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Moringa oleifera Lam. leaves are rich in nutritionally and therapeutically important bioactive compounds. As the knowledge on natural population genetic diversity is a prerequisite for further leaf biomass improvement, the morphological and molecular diversity were assessed among 55 South Indian ecotypes of M. oliefera. Leaf traits such as leaf length, breadth, fresh weight, dry weight and number of leaves were evaluated for morphological diversity and for genetic diversity, a total of 116 Simple Sequence Repeats (SSR; including 75 Genomic- and 41 Genic-SSR) were used. Polymorphic information content (PIC) for those SSRs had ranged from 0.0 (for SSR19876) to 0.96 for (SSR25987) with an average of 0.886. The heterozygosity ranged from 0.0 to 0.96 with an average of 0.215 and those allelic data clustered the investigated accessions into three main clusters using the Unweighted Pair Group Method with Arithmetic mean (UPGMA). Analysis of molecular variance (AMOVA) indicated that 71% of diversity was attributed to differences among individuals of population. Cluster analysis, Principal coordinate analysis (PCoA) and structure-based population study showed that, there was no geographical distribution among the genotypes. Marker-trait associations was also implemented with general and mixed linear models and 65 SSR markers were found to be associated with investigated leaf traits at p

Wireless Sensor Network (WSN) is infrastructure- less. This is mainly used for target monitoring, target detection by setting in an ad-hoc style. So, in a wireless network target want to be protected. But the network cannot hide source permanently but it is capable of increasing the safety time. Both data privacy and location privacy are important to WSN security. In the case of data privacy there are many encrypting algorithm to protect data.But it is not possible in the case of source location privacy. When taking source location privacy there is source location privacy and sink location privacy.Source location privacy techniques will collapse generally by tracing back by the attacker.Hiding the source location is a crucial challenge in WSNs since the location of a source sensor gives contextual information about an event. In WSNs, a variety of approaches are utilised to safeguard the source location.One of these methods concealed the source location by using fakesources. Phantom nodes were utilised in another method to shield the source location. Although the current systems operate pretty well with the use of fake sources and phantom nodes.The efficient way to protect source location privacy is using of both phantom nodes and fake nodes.There is determination of fake source to protect from adversary which is chosen by randomly.So determining fake sources by path extension which helps to increase the safety time.PEM is done after the initialfake sources are determined, each of them will choose a newfake source from its neighbor. There by can increase the safety time.Wireless Sensor Network (WSN) is infrastructure- less. This is mainly used for target monitoring, target detection by setting in an ad-hoc style. So, in a wireless network target want to be protected. But the network cannot hide source permanently but it is capable of increasing the safety time. Both data privacy and location privacy are important to WSN security. In the case of data privacy there are many encrypting algorithm to protect data.But it is not possible in the case of source location privacy. When taking source location privacy there is source location privacy and sink location privacy.Source location privacy techniques will collapse generally by tracing back by the attacker.Hiding the source location is a crucial challenge in WSNs since the location of a source sensor gives contextual information about an event. In WSNs, a variety of approaches are utilised to safeguard the source location.One of these methods concealed the source location by using fakesources. Phantom nodes were utilised in another method to shield the source location. Although the current systems operate pretty well with the use of fake sources and phantom nodes.The efficient way to protect source location privacy is using of both phantom nodes and fake nodes.There is determination of fake source to protect from adversary which is chosen by randomly.So determining fake sources by path extension which helps to increase the safety time.PEM is done after the initialfake sources are determined, each of them will choose a newfake source from its neighbor. There by can increase the safety time., {"references":["1.\tM. Bradbury, A. Jhumka and M. Leeke (2018). Hybrid online protocols for source location privacy in wireless sensor networks. Journal of Parallel and Distributed Computing, 115, 67–81.","2.\tJ. Chen, Z. Lin, Y. Hu and B.Wang (2015). Hiding the source based on limited flooding for sensor networks. Sensors, 15(11), 29129–29148.","3.\tG. Han, X. Miao, H. Wang, M. Guizani and W. Zhang (2019). Cpslp: A cloud-based scheme for protecting source location privacy in wireless sensor networks using multisinks. IEEE Transactions on Vehicular Technology, 68(3), 2739–2750.","4.\tH. Wang, G. Han, W. Zhang, M. Guizani and S. Chan (2019). A probabilistic source location privacy protection scheme in wireless sensor networks. IEEE Transactions on Vehicular Technology, 68(6), 5917– 5927.","5.\tNa Wang, Junsong Fu, Jian Li, Bharat K. Bhargava, \"Source-Location Privacy Protection based on Anonymity Cloud in Wireless Sensor Networks , IEEE Transactions on Information Forensics and Security, 15(2019), 100-114","6.\tOzturk, C.; Zhang, Y.; Trappe, W. Source-location privacy in energy constrained sensor networks routing, In Proceedings of the 2nd ACM Workshop on Security of Ad Hoc and Sensor Networks, Washington,","7.\tDC, USA, 25–29 October 2004; pp. 88–93","8.\tA. Thomason, M. Leeke, M. Bradbury, A. Jhumka, Evaluating the impact of broadcast rates and collisions on fake source protocols for source location privacy, 12th IEEE International Conference on Trust, Security and Privacy in Computing and Communications (TrustCom), 2013, pp. 667–674. doi:10.1109/TrustCom.2013.81.","9.\tLong, J., Dong, M., Ota, K. and Liu, A. Achieving source location pri- vacy and network lifetime maximization through tree-based diversionary routing in wireless sensor networks. IEEE Access, 2, 2004, pp.633-651.","10.\tRoy, Pradeep Kumar, Jyoti Prakash Singh, Prabhat Kumar, and M. P. Singh. Source location privacy using fake source and phantom routing (FSAPR) technique in wireless sensor networks. Procedia Computer Science 57 (2015): 936-941."]}

Scorpion stings are major public health problem especially in rural parts of India. Envenomation from Scorpions if estimating on yearly basis it is about 12 lakh people per year and is responsible for nearly about 3250 deaths. There are about 1400 species of scorpions identified worldwide out of this only 53 are reported to be dangerous to humans, In India we have identified around 86 species. Poison due to insect bite is common and can be accompanied with a variety of symptoms ranging from simple itching to life threatening situations. Many may go through minor problems like swelling, tingling or numbness due to the sting. Scorpion sting usually results in severe symptoms, as its venom is more potent. Young children and older adults may require immediate treatment. Vrischikadamsha is such a specific envenomation that requires medical attention. There are ample references treatment modalities and medicines in Keraleeyavisha chikitsa granthas and ayurvedic classics which are described for managing vrischikavisha. Many of the keraliyavishagrantha are written in Malayalam hence there is a need to explore and bring out the remedies. So in this article a humble effort is made to bring out the different vrischika and treatment modalities described in keraleeyagrandhas along with the specific symptoms.

Ayurveda is attaining the attraction globally not only as an ancient life science but also as a successful aid to treat and manage the ailments in style, Apart from the common sayings that Ayurveda does not have quick-acting treatment modality, Nowadays Ayurveda is successfully managing sports medicine effectively and smoothly, as far as sports medicine and athletes are concerned Injuries are part & parcel of a sportsperson’s life. They are a class of people who torture their body to the maximum to get the maximum result. Injuries are sustained due to faulty techniques, accidents as in the case of contact sports. In the process, they sustain a lot of injuries. Despite advanced treatment techniques injuries tend to recur. It severely hampers the progress of their career & shortens their active sports life. It forces them for early retirement. Ayurvedic treatment like sringavacharana & bandaging technique help to heal the injuries more effectively. Sringavacharana is an essential tool in the armarium of Ayurvedic physician to deal as emergency care in low back pain.here the technique and step involved in executing the Sringavacharana in the modern era and swastika bandhana is explained with essential photographs and also with the help of a clinical study.

According to Ayurveda health is having an inseparable relation between tridoshas, sapta dhatus, trimalasmalas srotases and agnis. The normalcy of these components is essential for a healthy life and any alteration or change in the equilibrium of these components will give raise to vyaadi or disease. In our body we have got so many dosha gatis like vriddhikshaya bheda, ashayapakarsha bheda urdhvadhar, tiryak bheda koshta shakha, Marathi sandhi bheda avarna bheda. So because of this we need to study the roga marga in detail for understanding the rogas in a better way so a study have been put forth with the heading “A Study On Roga marga W.S.R. To Madhyama Roga marga” with its role in diagnosis, prognosis and treatment formed the objectives. In this study we have done the Collection, compilation sorting and analysis of various documentations right from Vedic scriptures to the latest dissertations, journals and websites on trividha roga marga were done. After screening through all the literatures collected on the matter we came to a conclusion that there exists lot of similarity between roga marga and srotas. But they seem to be different. Roga marga are the place where roga exists. Khavaigunya when takes place in srotas disease manifests. Different diseases have been included in different roga marga according to the samprapti and the udbhava sthana of the disease. Roga marga is the place where khavaigunya does occur and acts as the point of ignition and directs the samprapti to propagate in a definite manner. So we have concluded the study as the Roga marga plays an important role in the sub clinical and clinical stages of raj samprathi.

Fatal human rabies infections can be prevented through appropriate rabies postexposure prophylaxis (PEP). Errors in patient selection and administration of human rabies immune globulin in the emergency department (ED) setting were identified in a previous study of rabies PEP administration.To test the a priori hypothesis that implementation of a rabies PEP bundle in the ED would improve full adherence to 6 human rabies immune globulin quality indicators compared with preimplementation controls.This quality improvement study was conducted in 15 EDs in a US multihospital health system. Patients who received human rabies immune globulin or rabies vaccine in the ED from January 2015 to June 2018 were included in the preimplementation control group and from December 2019 to November 2020 were included in the postimplementation intervention group. Data were analyzed in January 2021.The PEP bundle was implemented in December 2019 and consisted of electronic health record enhancements, including clinical decision support, ED staff education, and patient education.Full adherence to 6 human rabies immune globulin quality indicators: patient selection, dose, timing, infiltration into wounds, administration distant from rabies vaccine site, and administration that avoids the buttock.The study included 324 patients; 254 patients were in preimplementation group (mean [SD] age, 39 [21] years; 135 [53%] women) and 70 in the postimplementation group (mean [SD] age, 38 [19] years; 33 [47%] women). Most patients presented to EDs embedded in a community hospital (231 patients [71%]). Full adherence increased from 37% in the preimplementation group to 61% postimplementation (absolute increase, 24%; 95% CI, 11% to 37%; P .001). Adherence improved for quality indicators for infiltration into wounds (137 of 254 patients [54%] to 50 of 70 patients [71%]; P = .009), administration distant from rabies vaccine site (180 of 254 [71%] to 58 of 70 [83%]; P = .04), and administration that avoids the buttock (168 of 254 [66%] to 58 of 70 [83%]; P = .007). No instances of sciatic nerve injury or compartment syndrome were observed.In this quality improvement study, implementation of a rabies PEP bundle was associated with improved patient selection and delivery of human rabies immune globulin in EDs across a multihospital health system. Although the bundle included ED staff education and patient discharge education, the observed improvement was likely driven by clinical decision support from the rabies PEP ED order set. Future research should evaluate implementation of this clinical decision support at other health systems.

HIV-1 protease inhibitors (PIs), such as darunavir (DRV), are the key component of antiretroviral therapy. However, HIV-1 often acquires resistance to PIs. Here, seven novel PIs were synthesized, by introducing single atom changes such as an exchange of a sulfur to an oxygen, scission of a single bond in P2′-cyclopropylaminobenzothiazole (or -oxazole), and/or P1-benzene ring with fluorine scan of mono- or bis-fluorine atoms around DRV’s scaffold. X-ray structural analyses of the PIs complexed with wild-type Protease (PRWT) and highly-multi-PI-resistance-associated PRDRVRP51 revealed that the PIs better adapt to structural plasticity in PR with resistance-associated amino acid substitutions by formation of optimal sulfur bond and adaptation of cyclopropyl ring in the S2′-subsite. Furthermore, these PIs displayed increased cell permeability and extreme anti-HIV-1 potency compared to DRV. Our work provides the basis for developing novel PIs with high potency against PI-resistant HIV-1 variants with a high genetic barrier.

In a radical departure from the classical E1–E2–E3 three-enzyme mediated ubiquitination of eukaryotes, the recently described bacterial enzymes of the SidE family of Legionella pneumophila effectors utilize NAD(+) to ligate ubiquitin onto target substrate proteins. This outcome is achieved via a two-step mechanism involving (1) ADP ribosylation of ubiquitin followed by (2) phosphotransfer to a target serine residue. Here, using fluorescent NAD(+) analogues as well as synthetic substrate mimics, we have developed continuous assays enabling real-time monitoring of both steps of this mechanism. These assays are amenable to biochemical studies and high-throughput screening of inhibitors of these effectors, and the discovery and characterization of putative enzymes similar to members of the SidE family in other organisms. We also show their utility in studying enzymes that can reverse and inhibit this post-translational modification.

A four-step synthesis of the FDA-approved anticancer agent gefitinib was developed starting from 2,4-dichloro-6,7-dimethoxyquinazoline. Reaction temperatures were highly practical (0–55 °C), and chromatographic purifications were avoided. The ionic liquid trimethylammonium heptachlorodialuminate was used to monodemethylate the dimethoxyquinazoline core. In the final step, a selective dehalogenation was employed to provide gefitinib in 14% overall yield on a gram scale.

The design, synthesis, and biological evaluation of a new class of HIV-1 protease inhibitors containing stereochemically defined fused tricyclic polyethers as the P2 ligands and a variety of sulfonamide derivatives as the P2′ ligands, are described. A number of ring sizes and various substituent effects were investigated to enhance the ligand-backbone interactions in the protease active site. Inhibitors 5c and 5d containing this unprecedented fused 6-5-5 ring system as the P2 ligand, an aminobenzothiazole as the P2′ ligand and a difluorophenylmethyl as the P1 ligand exhibited exceptional enzyme inhibitory potency and maintained excellent antiviral activity against a panel of highly multidrug-resistant HIV-1 variants. The umbrella-like P2 ligand for these inhibitors has been synthesized efficiently in an optically active form using a Pauson-Khand cyclization reaction as the key step. The racemic alcohols were resolved efficiently using a lipase catalyzed enzymatic resolution. Two high resolution X-ray structures of inhibitor-bound HIV-1 protease revealed extensive interactions with the backbone atoms of HIV-1 protease and provided molecular insight into the binding properties of these new inhibitors.

Herein we report the design, synthesis, X-ray structural, and biological studies of an exceptionally potent HIV-1 protease inhibitor, compound 5 ((3S,7aS,8S)-hexahydro-4H-3,5-methanofuro[2,3-b]pyran-8-yl ((2S,3R)-4-((2-(cyclopropylamino)-N-isobutylbenzo[d]thiazole)-6-sulfonamido)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl)carbamate). Using structure-based design, we incorporated an unprecedented 6-5-5-ring-fused crown-like tetrahydropyranofuran as the P2-ligand, a cyclopropylaminobenzothiazole as the P2'-ligand, and a 3,5-difluorophenylmethyl group as the P1-ligand. The resulting inhibitor 5 exhibited exceptional HIV-1 protease inhibitory and antiviral potency at the picomolar level. Furthermore, it displayed antiviral IC50 values in the picomolar range against a wide panel of highly multidrug-resistant HIV-1 variants. The inhibitor shows an extremely high genetic barrier against the emergence of drug-resistant variants. It also showed extremely potent inhibitory activity toward dimerization as well as favorable central nervous system penetration. We determined a high-resolution X-ray crystal structure of the complex between inhibitor 5 and HIV-1 protease, which provides molecular insight into the unprecedented activity profiles observed.

The total syntheses of (−)-amphirionin-4 and (+)-amphirionin-4 have been achieved in a convergent and enantioselective manner. The tetrahydrofuranol cores of amphirionin-4 were constructed in optically active form by enzymatic resolution of racemic cis-3-hydroxy-5-methyldihydrofuran-2(3H)-one. The polyene side chain was efficiently synthesized using Stille coupling. The remote C8-stereocenter was constructed using the Nozaki-Hiyama-Kishi coupling reaction. Detailed 1H NMR studies of Mosher esters of (−)-amphirionin-4 and (+)-amphirionin-4 were carried out to support the assignment of the absolute configurations of the C-4 and C-8 asymmetric centers of amphirionin-4.

Three cis-selective Co(II)-salen complexes have been developed for the asymmetric cyclopropanation of para-fluorinated styrenes with ethyl diazoacetate. Increasing the steric reach of the C2 -symmetric ligand side chains improved the enantiomeric ratio of the reaction from 28:1 to 66:1. The methodology was exemplified by the gram-scale synthesis of a lead compound for the treatment of castration-resistant prostate cancer (CRPC), as well as a structurally related analog.

We generated two novel nonpeptidic HIV-1 protease inhibitors (PIs), GRL-001-15 and GRL-003-15, which contain unique crown-like tetrahydropyranofuran (Crn-THF) and P2′-cyclopropyl-aminobenzothiazole (Cp-Abt) moieties as P2 and P2′ ligands, respectively. GRL-001-15 and GRL-003-15 have meta-monofluorophenyl and para-monofluorophenyl at the P1 site, respectively, exert highly potent activity against wild-type HIV-1 with 50% effective concentrations (EC(50)s) of 57 and 50 pM, respectively, and have favorable cytotoxicity profiles with 50% cytotoxic concentrations (CC(50)s) of 38 and 11 μM, respectively. The activity of GRL-001-15 against multi-PI-resistant HIV-1 variants was generally greater than that of GRL-003-15. The EC(50) of GRL-001-15 against an HIV-1 variant that was highly resistant to multiple PIs, including darunavir (DRV) (HIV-1(DRV)(R)(P30)), was 0.17 nM, and that of GRL-003-15 was 3.3 nM, while DRV was much less active, with an EC(50) of 216 nM. The emergence of HIV-1 variants resistant to GRL-001-15 and GRL-003-15 was significantly delayed compared to that of variants resistant to selected PIs, including DRV. Structural analyses of wild-type protease (PR(WT)) complexed with the novel PIs revealed that GRL-001-15’s meta-fluorine atom forms halogen bond interactions (2.9 and 3.0 Å) with Gly49 and Ile50, respectively, of the protease flap region and with Pro81′ (2.7 and 3.2 Å), which is located close to the protease active site, and that two fluorine atoms of GRL-142-13 form multiple halogen bond interactions with Gly49, Ile50, Pro81′, Ile82′, and Arg8′. In contrast, GRL-003-15 forms halogen bond interactions with Pro81′ alone, suggesting that the reduced antiviral activity of GRL-003-15 is due to the loss of the interactions with the flap region.

Based upon molecular insights from the X-ray structures of inhibitor-bound HIV-1 protease complexes, we have designed a series of isophthalamide-derived inhibitors incorporating substituted pyrrolidines, piperidines and thiazolidines as P2-P3 ligands for specific interactions in the S2-S3 extended site. Compound 4b has shown an enzyme K i of 0.025 nM and antiviral IC 50 of 69 nM. An X-ray crystal structure of inhibitor 4b -HIV-1 protease complex was determined at 1.33 A resolution. We have also determined X-ray structure of 3b -bound HIV-1 protease at 1.27 A resolution. These structures revealed important molecular insight into the inhibitor–HIV-1 protease interactions in the active site.

We report here that GRL-0739, a novel nonpeptidic HIV-1 protease inhibitor containing a tricycle (cyclohexyl- bis -tetrahydrofuranylurethane [THF]) and a sulfonamide isostere, is highly active against laboratory HIV-1 strains and primary clinical isolates (50% effective concentration [EC 50 ], 0.0019 to 0.0036 μM), with minimal cytotoxicity (50% cytotoxic concentration [CC 50 ], 21.0 μM). GRL-0739 blocked the infectivity and replication of HIV-1 NL4-3 variants selected by concentrations of up to 5 μM ritonavir or atazanavir (EC 50 , 0.035 to 0.058 μM). GRL-0739 was also highly active against multidrug-resistant clinical HIV-1 variants isolated from patients who no longer responded to existing antiviral regimens after long-term antiretroviral therapy, as well as against the HIV-2 ROD variant. The development of resistance against GRL-0739 was substantially delayed compared to that of amprenavir (APV). The effects of the nonspecific binding of human serum proteins on the anti-HIV-1 activity of GRL-0739 were insignificant. In addition, GRL-0739 showed a desirable central nervous system (CNS) penetration property, as assessed using a novel in vitro blood-brain barrier model. Molecular modeling demonstrated that the tricyclic ring and methoxybenzene of GRL-0739 have a larger surface and make greater van der Waals contacts with protease than in the case of darunavir. The present data demonstrate that GRL-0739 has desirable features as a compound with good CNS-penetrating capability for treating patients infected with wild-type and/or multidrug-resistant HIV-1 variants and that the newly generated cyclohexyl- bis -THF moiety with methoxybenzene confers highly desirable anti-HIV-1 potency in the design of novel protease inhibitors with greater CNS penetration profiles.

Design, synthesis, biological and X-ray crystallographic studies of a series of potent HIV-1 protease inhibitors are described. Various polar functionalities have been incorporated on the tetrahydropyranyl-tetrahydrofuran-derived P2 ligand to interact with the backbone atoms in the S2-subsite. The majority of the inhibitors showed very potent enzyme inhibitory and antiviral activity. Two high-resolution X-ray structures of 30b- and 30j-bound HIV-1 protease provide insight into ligand-binding site interactions. In particular, the polar functionalities on the P2-ligand appear to form unique hydrogen bonds with Gly48 amide NH and amide carbonyl groups in the flap region.

Antiretroviral therapy for HIV-1 infection/AIDS has significantly extended the life expectancy of HIV-1-infected individuals and reduced HIV-1 transmission at very high rates. However, certain individuals who initially achieve viral suppression to undetectable levels may eventually suffer treatment failure mainly due to adverse effects and the emergence of drug-resistant HIV-1 variants. Here, we report GRL-142, a novel HIV-1 protease inhibitor containing an unprecedented 6-5-5-ring-fused crown-like tetrahydropyranofuran, which has extremely potent activity against all HIV-1 strains examined with IC50 values of attomolar-to-picomolar concentrations, virtually no effects on cellular growth, extremely high genetic barrier against the emergence of drug-resistant variants, and favorable intracellular and central nervous system penetration. GRL-142 forms optimum polar, van der Waals, and halogen bond interactions with HIV-1 protease and strongly blocks protease dimerization, demonstrating that combined multiple optimizing elements significantly enhance molecular and atomic interactions with a target protein and generate unprecedentedly potent and practically favorable agents.