Crosstalk involving two-component systems in Staphylococcus aureus signaling networks.

Staphylococcus aureus poses a serious global threat to human health due to its pathogenic nature, adaptation to environmental stress, high virulence, and the prevalence of antimicrobial resistance. The signaling network in S. aureus coordinates and integrates various internal and external inputs and stimuli to adapt and formulate a response to the environment. Two-component systems (TCSs) of S. aureus play a central role in this network where surface-expressed histidine kinases (HKs) receive and relay external signals to their cognate response regulators (RRs). Despite the purported high fidelity of signaling, crosstalk within TCSs, between HK and non-cognate RR, and between TCSs and other systems has been detected widely in bacteria. The examples of crosstalk in S. aureus are very limited, and there needs to be more understanding of its molecular recognition mechanisms, although some crosstalk can be inferred from similar bacterial systems that share structural similarities. Understanding the cellular processes mediated by this crosstalk and how it alters signaling, especially under stress conditions, may help decipher the emergence of antibiotic resistance. This review highlights examples of signaling crosstalk in bacteria in general and S. aureus in particular, as well as the effect of TCS mutations on signaling and crosstalk.

Nitrogen and phosphorus eutrophication enhance biofilm-related drug resistance in Enterococcus faecalis isolated from Water Sources.

Antibiotic resistance is a critical topic worldwide with important consequences for public health. So considering the rising issue of antibiotic-resistance in bacteria, we explored the impact of nitrogen and phosphorus eutrophication on drug resistance mechanisms in Enterococcus faecalis, especially ciprofloxacin, oxytetracycline, and ampicillin. For this purpose we examined the antibiotic-resistance genes and biofilm formation of Enterococcus faecalis under different concentration of nitrogen and phosphorus along with mentioned antibiotics. Mesocosms were designed to evaluate the impact of influence of eutrophication on the underlying mechanism of drugn resistence in Enterococcus faecalis. For this purpose, we explored the potential relation to biofilm formation, adhesion ability, and the expression levels of the regulatory gene fsrA and the downstream gene gelEI. Our results demonstrated that the isolates of all treatments displayed high biofilm forming potential, and fsrA and gelE genes expression. Additionally, the experimental group demonstrated substantially elevated Enterococcus faecalis gelE expression. Crystal violet staining was applied to observe biofilm formation during bacterial development phase and found higher biofilm formation. In conclusion, our data suggest that E. faecalis resistance to ciprofloxacin, oxytetracycline, and ampicillin is related to biofilm development. Also, the high level of resistance in Enterococcus faecalis is linked to the expression of the fsrA and gelE genes. Understanding these pathways is vital in tackling the rising problem of bacterial resistance and its potential effect on human health.

Evaluation Health Risks and Sorption of Hexavalent Chromium (Cr(VI) by Biochar and Iron Doped Zinc Oxide Modified Biochar (Fe-ZnO@BC) Using Trifolium: A Green Synthesis Technique.

Contamination of aquatic and terrestrial environment with hexavalent chromium Cr(VI) is one of the major hazards worldwide due its carcinogenicity, persistency and immobility. Different research techniques have been adopted for Cr(VI) remediation present in terrestrial and aquatic media, while adsorption being the most advance, low cost, environmentally friendly and common method. The present study discussed the mechanisms of Parthenium hysterophorus derived biochar, iron-doped zinc oxide nanoparticles (nFe-ZnO) and Fe-ZnO modified biochar (Fe-ZnO@BC) involved in Cr(VI) mobility and bioavailability. Pot experiments were conducted to study the effect of Parthenium hysterophorus derived biochar, nFe-ZnO and Fe-ZnO@BC application rates (2%, 2 mg/kg, 10 mg/kg, respectively). The results indicated that the addition of soil amendments reduced Cr(VI) mobility. The findings revealed that the reduction in chromium mobility was observed by P. hysterophorus BC, and Fe-ZnO@BC but nFe-ZnO application significantly (p = 0.05) reduced Cr(VI) and CrT uptake as compared to the control treatments. The results of SEM coupled with EDS showed a high micropores and channel, smooth surface which helped in adsorption, and may enhance soil conditions. The concentration index (CI) by different amendments in trifolium plant was followed the descending order as: nFe-ZnO > Fe-ZnO@BC > P. hysterophorus BC after 30, 60 and 90 days of harvesting, respectively. In addition, human health risk index was found less than one (H1 < 1.0) in amended soils as compared to control treatments.

Modulation of sunflower growth via regulation of antioxidants, oil content and gas exchange by arbuscular mycorrhizal fungi and quantum dot biochar under chromium stress.

Chromium (Cr) toxicity significantly threatens sunflower growth and productivity by interfering with enzymatic activity and generating reactive oxygen species (ROS). Zinc quantum dot biochar (ZQDB) and arbuscular mycorrhizal fungi (AMF) have become popular to resolve this issue. AMF can facilitate root growth, while biochar tends to minimize Cr mobility in soil. The current study aimed to explore AMF and ZQDB combined effects on sunflower plants in response to Cr toxicity. Four treatments were applied, i.e. NoAMF + NoZQDB, AMF + 0.40%ZQDB, AMF + 0.80%ZQDB, and AMF + 1.20%ZQDB, under different stress levels of Cr, i.e. no Cr (control), 150 and 200 mg Cr/kg soil. Results showed that AMF + 1.20%ZQDB was the treatment that caused the greatest improvement in plant height, stem diameter, head diameter, number of leaves per plant, achenes per head, 1000 achenes weight, achene yield, biological yield, transpiration rate, stomatal conductance, chlorophyll content and oleic acid, relative to the condition NoAMF + No ZQDB at 200 mg Cr/kg soil. A significant decline in peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) while improvement in ascorbate peroxidase (APx), oil content, and protein content further supported the effectiveness of AMF + 1.20%ZQDB against Cr toxicity. Our results suggest that the treatment AMF + 1.20%ZQDB can efficiently alleviate Cr stress in sunflowers.

Comparative efficacy of silicon and iron oxide nanoparticles towards improving the plant growth and mitigating arsenic toxicity in wheat (Triticum aestivum L.).

Nano-enabled agriculture has emerged as an attractive approach for facilitating soil pollution mitigation and enhancing crop production and nutrition. In this study, we conducted a greenhouse experiment to explore the efficacy of silicon oxide nanoparticles (SiONPs) and iron oxide nanoparticles (FeONPs) in alleviating arsenic (As) toxicity in wheat (Triticum aestivum L.) and elucidated the underlying mechanisms involved. The application of SiONPs and FeONPs at 25, 50, and 100 mg kg-1 soil concentration significantly reduced As toxicity and concurrently improved plant growth performance, including plant height, dry matter, spike length, and grain yield. The biochemical analysis showed that the enhanced plant growth was mainly due to stimulated antioxidative enzymes (catalase, superoxide dismutase, peroxidase) and reduced reactive oxygen species (electrolyte leakage, malondialdehyde, and hydrogen peroxide) in wheat seedlings under As stress upon NPs application. The nanoparticles (NPs) exposure also enhanced the photosynthesis efficiency, including the total chlorophyll and carotenoid contents as compared with the control treatment. Importantly, soil amendments with 100 mg kg-1 FeONPs significantly reduced the acropetal As translocation in the plant root, shoot and grains by 74%, 54% and 78%, respectively, as compared with the control treatment under As stress condition, with relatively lower reduction levels (i.e., 64%, 37% and 58% for the plant root, shoot and grains, respectively) for SiONPs amendment. Overall, the application of NPs especially the FeONPs as nanoferlizers for agricultural crops is a promising approach towards mitigating the negative impact of HMs toxicity, ensuring food safety, and promoting future sustainable agriculture.

Comparative efficacy of Parthenium hysterophorus (L.) derived biochar and iron doped zinc oxide nanoparticle on heavy metals (HMs) mobility and its uptake by Triticum aestivum (L.) in chromite mining contaminated soils.

In this study we investigated the efficacy of a novel material parthenium weed (Parthenium hysterophorus L.) biochar (PBC), iron doped zinc oxide nanoparticles (nFe-ZnO), and biochar modified with nFe-ZnO (Fe-ZnO@BC) to adsorb heavy metals (HMs) and reduce their uptake by wheat (Triticum aestivum L.) in a highly chromite mining contaminated soil. The co-application of the applied soil conditioners exhibited a positive effect on the immobilization and restricted the HMs uptake below their threshold levels in shoot content of wheat. The maximum adsorption capacity was because of large surface area, cation exchange capacity, surface precipitation, and complexation of the soil conditioners. The scanning electron microscopy (SEM) coupled with energy dispersive spectroscopy (EDS) showed porous smooth structure of parthenium weed derived biochar that helped in HMs adsorption, increase the efficiency of soil fertilizers and nutrients retention which help in the enhancement soil condition. Under different application rates the highest translocation factor (TFHMs) was obtained at 2 g nFe-ZnO rate followed the descending order: Mn > Cr > Cu > Ni > Pb. The overall TFHMs was found <1.0 indicating that low content of HMs accumulation in roots from soil slight transferred to shoot, thus satisfying the remediation requirements.

Wheat is considered as an important staple food which is grown in a chromite mining contaminated soil containing toxic HMs releasing from weathering of mafic and ultramafic rocks in the study area. The present research work is significantly beneficial in identifying the efficiency of treatment technologies to immobilize toxic HMs in soil. Parthenium weed derived biochar and biochar modified with nFe-ZnO (Fe-ZnO@BC) reduce the HMs uptake by wheat plant.

Hydrochemical evaluation of groundwater for drinking and irrigation purposes using multivariate indices along Indus Suture Zone, North Pakistan.

The present study is aimed to investigate the hydrochemical characteristics, spatial distribution and suitability of groundwater for drinking and irrigation purposes along the Indus Suture Zone (ISZ), north Pakistan. Physicochemical parameters and hazardous trace elements (HTEs) like Cd, Co, Cu and Mn were determined following standard methods. The mean and median concentrations were found below the World Health Organization (WHO) drinking water guidelines values. Hydrochemical results indicate that groundwater sources were mainly attributed to rock-water interaction category. Piper diagram shows that most of the groundwater samples fall in Ca-HCO3─ class presenting weak-alkaline proportion type. The drinking water quality index (DWQI) ranking was categorized as good to excellent, indicating the overall quality of the groundwater may pose no health hazard concern. Based on irrigation WQI (SAR, Na%, MAR, KR), the groundwater was found fit for irrigation except SAR whereas 36% of the groundwater samples fall within the poor class. The total HI values through dermal contact exceeded the safe non-carcinogenic threshold of HI = 1. Therefore, there is required an effective groundwater monitoring and management facility in the study area to safeguard residents from various illnesses associated with varying HTEs concentrations in drinking water. The major response actions needed for groundwater bodies restoration are including the installation of a continuous groundwater monitoring network and control of agricultural fertilizers that seems to be the most effective and tangible for immediate action.

Exploring the medicinal potential of Dark Chemical Matters (DCM) to design promising inhibitors for PLpro of SARS-CoV-2 using molecular screening and simulation approaches.

The growing concerns and cases of COVID-19 with the appearance of novel variants i.e., BA.2.75. BA.5 and XBB have prompted demand for more effective treatment options that could overcome the risk of immune evasion. For this purpose, discovering novel small molecules to inhibit druggable proteins such as PLpro required for viral pathogenesis, replication, survival, and spread is the best choice. Compounds from the Dark chemical matter (DCM) database is consistently active in various screening tests and offer intriguing possibilities for finding drugs that are extremely selective or active against uncommon targets. Considering the essential role of PLpro, the current study uses DCMdatabase for the identification of potential hits using in silico virtual molecular screening and simulation approaches to inhibit the current and emerging variants of SARS-CoV-2. Our results revealed the 10 best compounds with docking scores between -7.99 to -7.03 kcal/mol better than the control drug (GRL0617) among which DC 5977-0726, DC 6623-2024, DC C879-0379 and DC D135-0154 were observed as the best hits. Structural-dynamics properties such as dynamic stability, protein packing, and residue flexibility demonstrated the pharmacologically favorable properties of these top hits in contrast to GRL0617. The hydrogen bonding half-life revealed that Asp164, Arg166, Tyr264, and Tyr268 have major contributions to the hydrogen bonding during the simulation. However, some of the important hydrogen bonds were missing in the control drug (GRL0617). Finally, the total binding free energy was reported to be -34.41 kcal/mol for GRL0617 (control), -41.03 kcal/mol for the DC5977-0726-PLpro, for the DC6623-2024-Plpro complex the TBE was -48.87 kcal/mol, for the for DCC879-0379-Plpro complex the TBE was -45.66 kcal/mol while for the DCD135-0154-PLpro complex the TBE was calculated to be -40.09 kcal/mol respectively, which shows the stronger potency of these compounds against PLpro and further in in vivo and in vitro test are required for the possible usage as potential drug against SARS-CoV-2.

Chemically Gradient Hydrogen-Bonded Organic Framework Crystal Film.

Hydrogen-bonded organic frameworks (HOFs) are ordered supramolecular solid structures, however, nothing much explored as centimetre-scale self-standing films. The fabrication of such crystals comprising self-supported films is challenging due to the limited flexibility and interaction of the crystals, and therefore studies on two-dimensional macrostructures of HOFs are limited to external supports. Herein, we introduce a novel chemical gradient strategy to fabricate a crystal-deposited HOF film on an in situ-formed covalent organic polymer film (Tam-Bdca-CGHOF). The fabricated film showed versatility in chemical bonding along its thickness from covalent to hydrogen-bonded network. The kinetic-controlled Tam-Bdca-CGHOF showed enhanced proton conductivity (8.3×10-5  S cm-1 ) compared to its rapid kinetic analogue, Tam-Bdca-COP (2.1×10-5  S cm-1 ), which signifies the advantage of bonding-engineering in the same system.

Quinoxaline derivatives as attractive electron-transporting materials.

This review article provides a comprehensive overview of recent advancements in electron transport materials derived from quinoxaline, along with their applications in various electronic devices. We focus on their utilization in organic solar cells (OSCs), dye-sensitized solar cells (DSSCs), organic field-effect transistors (OFETs), organic-light emitting diodes (OLEDs) and other organic electronic technologies. Notably, the potential of quinoxaline derivatives as non-fullerene acceptors in OSCs, auxiliary acceptors and bridging materials in DSSCs, and n-type semiconductors in transistor devices is discussed in detail. Additionally, their significance as thermally activated delayed fluorescence emitters and chromophores for OLEDs, sensors and electrochromic devices is explored. The review emphasizes the remarkable characteristics and versatility of quinoxaline derivatives in electron transport applications. Furthermore, ongoing research efforts aimed at enhancing their performance and addressing key challenges in various applications are presented.

Linker residues regulate the activity and stability of hexokinase 2, a promising anticancer target.

Hexokinase (HK) catalyzes the first step in glucose metabolism, making it an exciting target for the inhibition of tumor initiation and progression due to their elevated glucose metabolism. The upregulation of hexokinase-2 (HK2) in many cancers and its limited expression in normal tissues make it a particularly attractive target for the selective inhibition of cancer growth and the eradication of tumors with limited side effects. The design of such safe and effective anticancer therapeutics requires the development of HK2-specific inhibitors that will not interfere with other HK isozymes. As HK2 is unique among HKs in having a catalytically active N-terminal domain (NTD), we have focused our attention on this region. We previously found that NTD activity is affected by the size of the linker helix-α13 that connects the N- and C-terminal domains of HK2. Three nonactive site residues (D447, S449, and K451) at the beginning of the linker helix-α13 have been found to regulate the NTD activity of HK2. Mutation of these residues led to increased dynamics, as shown via hydrogen deuterium exchange analysis and molecular dynamic simulations. D447A contributed the most to the enhanced dynamics of the NTD, with reduced calorimetric enthalpy of HK2. Similar residues exist in the C-terminal domain (CTD) but are unnecessary for HK1 and HK2 activity. Thus, we postulate these residues serve as a regulatory site for HK2 and may provide new directions for the design of anticancer therapeutics that reduce the rate of glycolysis in cancer through specific inhibition of HK2.

Taurine treatment of retinal degeneration and cardiomyopathy in a consanguineous family with SLC6A6 taurine transporter deficiency.

In a consanguineous Pakistani family with two affected individuals, a homozygous variant Gly399Val in the eighth transmembrane domain of the taurine transporter SLC6A6 was identified resulting in a hypomorph transporting capacity of ~15% compared with normal. Three-dimensional modeling of this variant has indicated that it likely causes displacement of the Tyr138 (TM3) side chain, important for transport of taurine. The affected individuals presented with rapidly progressive childhood retinal degeneration, cardiomyopathy and almost undetectable plasma taurine levels. Oral taurine supplementation of 100 mg/kg/day resulted in maintenance of normal blood taurine levels. Following approval by the ethics committee, a long-term supplementation treatment was introduced. Remarkably, after 24-months, the cardiomyopathy was corrected in both affected siblings, and in the 6-years-old, the retinal degeneration was arrested, and the vision was clinically improved. Similar therapeutic approaches could be employed in Mendelian phenotypes caused by the dysfunction of the hundreds of other molecular transporters.

χ2-BidLSTM: A Feature Driven Intrusion Detection System Based on χ2 Statistical Model and Bidirectional LSTM.

In a network architecture, an intrusion detection system (IDS) is one of the most commonly used approaches to secure the integrity and availability of critical assets in protected systems. Many existing network intrusion detection systems (NIDS) utilize stand-alone classifier models to classify network traffic as an attack or as normal. Due to the vast data volume, these stand-alone models struggle to reach higher intrusion detection rates with low false alarm rates( FAR). Additionally, irrelevant features in datasets can also increase the running time required to develop a model. However, data can be reduced effectively to an optimal feature set without information loss by employing a dimensionality reduction method, which a classification model then uses for accurate predictions of the various network intrusions. In this study, we propose a novel feature-driven intrusion detection system, namely χ2-BidLSTM, that integrates a χ2 statistical model and bidirectional long short-term memory (BidLSTM). The NSL-KDD dataset is used to train and evaluate the proposed approach. In the first phase, the χ2-BidLSTM system uses a χ2 model to rank all the features, then searches an optimal subset using a forward best search algorithm. In next phase, the optimal set is fed to the BidLSTM model for classification purposes. The experimental results indicate that our proposed χ2-BidLSTM approach achieves a detection accuracy of 95.62% and an F-score of 95.65%, with a low FAR of 2.11% on NSL-KDDTest+. Furthermore, our model obtains an accuracy of 89.55%, an F-score of 89.77%, and an FAR of 2.71% on NSL-KDDTest-21, indicating the superiority of the proposed approach over the standard LSTM method and other existing feature-selection-based NIDS methods.

An overview of dengue viral infection circulating in Pakistan.

BACKGROUND & OBJECTIVES: Dengue virus (DENV) is an RNA virus that infects approximately 2.5 billion people around the world. The incidence of dengue fever has rapidly increased at an alarming rate in the last few years and has affected thousands of people in Pakistan. This review explores the prevalence, serotypes and pathogenesis of dengue virus circulating in Pakistan. METHODS: A systematic review of observational studies published between 1994 and December 2019 was performed. All records of the confirmed outbreak of dengue fever in Pakistan were reviewed and articles containing no primary data were excluded. RESULTS: Four identified serotypes of dengue virus (DENV 1-4) circulate in different regions of the world causing epidemics. The most prevalent serotype, which is still epidemic and dominant in Pakistan, is DENV-2. Many factors like over-population, rapid urbanization, travelling, lack of vector control in dengue endemic areas and inadequate health-care are responsible of dynamic and huge raise of dengue in Pakistan. INTERPRETATION & CONCLUSION: Currently there is no specific treatment for prevention of dengue virus. Recently some antiviral compounds were being tested to eradicate this disease. There is a need to develop an efficient and safe vaccine for all four serotypes to combat dengue viral infection globally and particularly in Pakistan.

Elemental analysis of carrageenans isolated from Hypnea musciformis red algae of Karachi coast using SEM-EDX.

The carrageenans with high molecular weight, crude and dialysed polysaccharide fractions obtained from Hypnea musciformis red algae of Karachi coast in Pakistan. The elemental composition was determined by using SEM-EDX technique which is one of the modern, reliable and accurate techniques. After analyzing multiple mineral elements were detected in different quantities. The numbers of elements found in crude extracts were greater than that in the dialysed extracts. All extracts contained the higher concentrations of C followed by O (except dialysed acidic extract). Among other elements, Cl and K were present in the highest amounts (>25.0%) in dialysed acidic extracts. However, Al was detected in low concentrations in only crude aqueous and acidic extracts. The mineral concentrations ranges were 30.34-52.46%, 17.00-43.46%, 0.63-4.05%, 0.49-3.35%, 0-0.33%, 0.74-17.92%, 0.59-25.31%, 0.58-25.46%, 1.10-6.72%, 0-2.60% for C, O, Na, Mg, Al, S, Cl, K, Ca and Zn in these crude and dialyzed extracts respectively. The study confirmed the presence of major elements such that Na, Mg, Ca, K and Zn in high quantities. However, there was no toxic element identified like Cd, Hg and Pb which show that these carrageenans are safer to utilize in food and pharmaceutical industries.

Decrease of core 2 O-glycans on synovial lubricin in osteoarthritis reduces galectin-3 mediated crosslinking.

The synovial fluid glycoprotein lubricin (also known as proteoglycan 4) is a mucin-type O-linked glycosylated biological lubricant implicated to be involved in osteoarthritis (OA) development. Lubricin's ability to reduce friction is related to its glycosylation consisting of sialylated and unsialylated Tn-antigens and core 1 and core 2 structures. The glycans on lubricin have also been suggested to be involved in crosslinking and stabilization of the lubricating superficial layer of cartilage by mediating interaction between lubricin and galectin-3. However, with the spectrum of glycans being found on lubricin, the glycan candidates involved in this interaction were unknown. Here, we confirm that the core 2 O-linked glycans mediate this lubricin-galectin-3 interaction, shown by surface plasmon resonance data indicating that recombinant lubricin (rhPRG4) devoid of core 2 structures did not bind to recombinant galectin-3. Conversely, transfection of Chinese hamster ovary cells with the core 2 GlcNAc transferase acting on a mucin-type O-glycoprotein displayed increased galectin-3 binding. Both the level of galectin-3 and the galectin-3 interactions with synovial lubricin were found to be decreased in late-stage OA patients, coinciding with an increase in unsialylated core 1 O-glycans (T-antigens) and Tn-antigens. These data suggest a defect in crosslinking of surface-active molecules in OA and provide novel insights into OA molecular pathology.

Nanoparticle-based amelioration of drought stress and cadmium toxicity in rice via triggering the stress responsive genetic mechanisms and nutrient acquisition.

Cadmium and drought are the most destructive of the abiotic stresses with negative consequences in terms of impaired metabolism, restricted nutrient use efficiency and disruptive photosynthesis of plants. The present study investigated the mitigation strategy of both aforementioned stresses by the application of iron oxide (IONPs) and hydrogel nanoparticles (HGNPs) simultaneously probably for the first time. IONPs were biofabricated by using a locally identified Bacillus strain RNT1, while HGNPs were produced chemically followed by the confirmation and characterization of both NPs through nanomaterials characterization techniques. Results of FTIR and XRD showed the capping of NPs by different functional groups together with their crystalline structure, respectively. SEM and TEM analysis showed the spherical shape along with the particle size ranging from 18 to 94 nm of both NPs, while EDS analysis confirmed the elemental purity of NPs. The results revealed that IONPs-treated rice plants increased biomass, antioxidant enzyme contents, photosynthesis efficiency, nutrient acquisition together with the decrease in reactive oxygen species and acropetal Cd translocation under normal and drought stress conditions as compared with control plants. Furthermore, the expression of the Cd transporter genes, OsHMA2, OsHMA3 and OsLCT1 were curtailed in NPs-treated rice plants under normal and drought stress conditions. The overall significance of the study lies in devising the NPs-based solutions of increasing heavy metal pollution and water availability challenges being faced the farmers around the world.

Fatigue Crack Monitoring of T-Type Joints in Steel Offshore Oil and Gas Jacket Platform.

Several approaches have been used in the past to predict fatigue crack growth rates in T-joints of the offshore structures, but there are relatively few cases of applying structural health monitoring during the non-destructive testing of jacket platforms. This paper presents an experimental method based on the sensing of the piezoelectric sensors and finite element analysis method for studying the fatigue cracks in the offshore steel jacket structure. Three types of joints are selected in the current research work: T-type plate, T-type tube-plate, and T-type tube joints. The finite element analysis model established in the current study computes and analyzes the high stress and high strain regions in the T-type joints. The fatigue damage in the T-type joints was successfully detected by utilizing both the finite element analysis and experimental methods. The results showed that fatigue cracks of the three types of joints are prone to appear at the weld toe and spread in the welding direction. The fatigue damage location of T-type plate and T-type tube-plate joints is more concentrated in the upper weld toe area, and the fatigue damage location of the T-type tube joint is closer to the lower weld toe area.

New Carbonic Anhydrase-II Inhibitors from Marine Macro Brown Alga Dictyopteris hoytii Supported by In Silico Studies.

In continuation of phytochemical investigations of the methanolic extract of Dictyopteris hoytii, we have obtained twelve compounds (1-12) through column chromatography. Herein, three compounds, namely, dimethyl 2-bromoterepthalate (3), dimethyl 2,6-dibromoterepthalate (4), and (E)-3-(4-(dimethoxymethyl)phenyl) acrylic acid (5) are isolated for the first time as a natural product, while the rest of the compounds (1, 2, 6-12) are known and isolated for the first time from this source. The structures of the isolated compounds were elucidated by advanced spectroscopic 1D and 2D NMR techniques including 1H, 13C, DEPT, HSQC, HMBC, COSY, NEOSY, and HR-MS and comparison with the reported literature. Furthermore, eight compounds (13-20) previously isolated by our group from the same source along with the currently isolated compounds (1-12) were screened against the CA-II enzyme. All compounds, except 6, 8, 14, and 17, were evaluated for in vitro bovine carbonic anhydrase-II (CA-II) inhibitory activity. Eventually, eleven compounds (1, 4, 5, 7, 9, 10, 12, 13, 15, 18, and 19) exhibited significant inhibitory activity against CA-II with IC50 values ranging from 13.4 to 71.6 µM. Additionally, the active molecules were subjected to molecular docking studies to predict the binding behavior of those compounds. It was observed that the compounds exhibit the inhibitory potential by specifically interacting with the ZN ion present in the active site of CA-II. In addition to ZN ion, two residues (His94 and Thr199) play an important role in binding with the compounds that possess a carboxylate group in their structure.

Phylogenetic Characterization of the 5' Untranslated Region of Untypable HCV Genotypes Circulating in Pakistan.

INTRODUCTION: Commercial methods for HCV genotyping is challenged by the increased prevalence of untypable genotypes in Pakistan. OBJECTIVE: The aim of the current study was to perform nucleotide sequencing of 5' UTR region for genotyping of viral isolates circulating in Peshawar, Pakistan. METHODS: The total number of commercially untypable samples were 94 in which 18 samples were sequenced for the characterization of 5' UTR region. Post-sequencing analysis was performed for genotype identification (n = 18) and molecular phylogenetic analysis. RESULTS: The current study reveals different genotypes, that is, 10/18 viral isolates were found to be genotype 3a (55.55%), 3 isolates (genotype 3b, 16.66%), 2 isolates (genotype 6h/6g, 11.11%), 2 (6g/d, 11.11%), and 1 sample (genotype 1c, 5.55%). In addition, genotype 3a is the dominant representative of HCV circulating in Pakistan and has been increasing across the country. CONCLUSION: The current study also reveals that genotype 6 (2 were genotype 6h/6g and 2 were 6g/d) is also circulating in Pakistan and not restricted to South China and Hong Kong.