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Influenza A virus (IAV) is a human respiratory pathogen that causes yearly global epidemics, as well as sporadic pandemics due to human adaptation of pathogenic strains. Efficient replication of IAV in different species is, in part, dictated by its ability to exploit the genetic environment of the host cell. To investigate IAV tropism in human cells, we evaluated the replication of IAV strains in a diverse subset of epithelial cell lines. HeLa cells were refractory to the growth of human H1N1 and H3N2 viruses and low-pathogenic avian influenza (LPAI) viruses. Interestingly, a human isolate of the highly pathogenic avian influenza (HPAI) H5N1 virus successfully propagated in HeLa cells to levels comparable to those in a human lung cell line. Heterokaryon cells generated by fusion of HeLa and permissive cells supported H1N1 virus growth, suggesting the absence of a host factor(s) required for the replication of H1N1, but not H5N1, viruses in HeLa cells. The absence of this factor(s) was mapped to reduced nuclear import, replication, and translation, as well as deficient viral budding. Using reassortant H1N1:H5N1 viruses, we found that the combined introduction of nucleoprotein (NP) and hemagglutinin (HA) from an H5N1 virus was necessary and sufficient to enable H1N1 virus growth. Overall, this study suggests that the absence of one or more cellular factors in HeLa cells results in abortive replication of H1N1, H3N2, and LPAI viruses, which can be circumvented upon the introduction of H5N1 virus NP and HA. Further understanding of the molecular basis of this restriction will provide important insights into the virus-host interactions that underlie IAV pathogenesis and tropism.IMPORTANCE Many zoonotic avian influenza A viruses have successfully crossed the species barrier and caused mild to life-threatening disease in humans. While human-to-human transmission is limited, there is a risk that these zoonotic viruses may acquire adaptive mutations enabling them to propagate efficiently and cause devastating human pandemics. Therefore, it is important to identify viral determinants that provide these viruses with a replicative advantage in human cells. Here, we tested the growth of influenza A virus in a subset of human cell lines and found that abortive replication of H1N1 viruses in HeLa cells can be circumvented upon the introduction of H5N1 virus HA and NP. Overall, this work leverages the genetic diversity of multiple human cell lines to highlight viral determinants that could contribute to H5N1 virus pathogenesis and tropism.

Distributed Denial of Service (DDoS) attacks continue to pose significant threats to network infrastructure and services. As the complexity and scale of these attacks grow, traditional methods of defense are becoming less effective. This research paper presents a comprehensive analysis of DDoS attack mitigation using Software-Defined Networking (SDN) strategies, shedding light on the challenges faced and the key factors that influence the effectiveness of SDN-based solutions. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is the most common sustained supraventricular arrhythmia encountered in clinical practice. Due to the higher prevalence of rheumatic fever in several regions of India, rheumatic heart disease (RHD) is the most common etiological factor of AF. Aims and Objectives: The objective of the study was to study clinical features, electrocardiographic (ECG) and echocardiographic (ECHO) findings, complications, and incidence of AF in rheumatic mitral valve disease (R-MVD). Methods: It is an observational cross-sectional study of 40 indoor patients in a Tertiary Care Hospital in Vadodara, Gujarat, carried over a period of a year. Clinical data including symptoms, signs, systemic examination, and relevant investigations were studied. Results: 67.5% (n = 27) of patients having AF were below the age of 50 years with higher incidence among females (72.50%) as compared to males (27.5%). Fifteen (37.5%) had mitral stenosis (MS) and 13 (32.5%) had MS with regurgitation. Most of the patients 35 (87.5%) presented with breathlessness, followed by palpitation 28 (70%). The most commonly heard murmur was mid-diastolic (65%, n = 26), followed by pansystolic murmur (40%, n = 16) at the apex. Out of 40 patients, 15 (37.5%) had evidence of left ventricular hypertrophy on ECG, whereas only 5 (12.5%) had right ventricular hypertrophy. Four out of five patients with the evidence of cardioembolic stroke had left atrium (LA) size >45 mm which suggests an increased risk of embolic stroke with increased LA size. Only 3 (7.5%) patients had a visible LA clot in LA on two-dimensional ECHO, whereas only one patient had vegetation on valves. Twenty-seven out of 30 patients treated with diltiazem show good response. Heart failure was the most common complication affecting 85% (n = 34) of the patients with AF with R-MVD. Four (10%) patients out of 40 expired including 1 (25%) of the four pregnant patients, suggesting higher mortality among pregnant females due to superimposed physiological changes occurring during pregnancy. Conclusion: In developing countries like India, RHD is a major cause of AF affecting the younger population and more commonly females. Most of the patients in our study presented with breathlessness and palpitation. LA size was directly proportional to the risk of cardioembolic stroke and most of the patients developed heart failure as a complication. [ABSTRACT FROM AUTHOR]

Central composite design (CCD) based RP-HPLC method optimization for the synchronized analysis of Efonidipine Hydrochloride Ethanolate (EFE) and Chlorthalidone (CHL) in Tablet. The effective separation was performed using Inertsil ODS C18 column (250 x 4.6 mm, 5µm), PDA detector with 0.05M KH2PO4 Buffer (pH 4.5): Acetonitrile (40:60%v/v) mobile phase. Independent variables were investigated include the concentration of KH2PO4 (X1) and flow rate of mobile phase (X2). Based on responses obtained (retention time, resolution and tailing factor), the optimum condition selected was X1 = 40% and X2 = 1 ml.ml-1. Optimized HPLC condition was validated by assessing validation parameters and it meet the acceptance criteria set by ICH. It was showed linear calibration curve in the quantity range 6.25-18.75 µg.ml-1 and 20-60 µg.ml-1. % for CHL & EFE. Assay of drugs was 100.94% and 100.06% for CHL & EFE. The validated RP-HPLC-PDA method can be used for routine analysis of EFE and CHL in tablet. [ABSTRACT FROM AUTHOR]

Women have a high stake in dairying; they account for 93 per cent of total employment in dairy production. A woman plays an important role in dairy enterprises as manager, decision makers and skilled workers in spite of that her hard work is mostly been unpaid and their considerable involvement or contribution in dairy production has been underestimated or ignored. The low participation of farm women was observed in decision making about economic aspects of animal husbandry farming. The knowledge and skill of women dairy occupation and their participation on decision making certainly aff ects their effi ciency work and the development of dairy enterprise. In order to fi nd out the relationship between the selected characteristic of respondents with their decision making patt ern regarding overall improved dairy farming practices correlation was worked out. The analysis of data showed that education land holding, herd size and annual income were signifi cant and positively correlated with their decision making patt ern. [ABSTRACT FROM AUTHOR]

Despite promising results, limited data exist regarding patient characteristics leading to discontinuation of sacubitril/valsartan (S/V) in larger community centers. From July 2016 to March 2018, 193 consecutive patients prescribed S/V were identified by the Slicer/Dicer tool within EPIC EMR platform (Madison, WI). Patients who died prior to agent discontinuation were excluded from the analyses. For nominal data, Chi-squared and Fisher Exact tests were used while one-way ANOVA and linear regression models were used to explore continuous variable associations. A total of 178 eligible patients were identified. Baseline patient characteristics are described in the Table. S/V discontinuation rate was 19.7% (n=35), of which 31.4% were primarily attributed to high cost of the agent (n=11), while symptomatic hypotension was the most commonly reported clinical side-effect (37.1%, n=13). Of the patients who discontinued S/V, 94.2% initiated low dose therapy. Lack of S/V dose reduction (OR: 15.1, p<0.001) and high beta-blocker dose (OR 0.26, p<0.001) were associated with lower rates of discontinuation. Continuous variables associated with S/V discontinuation included higher BUN (24.3 vs. 20.5; p=0.031) and lower number of S/V adjustments (0.5 vs. 2.2; P<0.001), while higher BNP (726.6 vs. 468.6; p=0.054) and lower diastolic blood pressure [(DBP), 71.4 vs. 75.2; p=0.122] trended toward significance. Higher rates of S/V discontinuation were noted compared to clinical trials with high cost as a notable cause. Clinical factors such as higher BUN and BNP and lower DBP may be important adjudicators for appropriate clinical use while patients tolerating higher beta-blocker dose may represent a robust cohort in whom S/V may be better tolerated. Our observed higher rates of intolerance despite conservative low dose S/V initiation may call for more concerted efforts for clinical assessment and non-traditional dose initiation. Confirmation of these observations are warranted with larger registries and prospective studies. [ABSTRACT FROM AUTHOR]

Sacubitril/valsartan (ARNI) effects on outcome and quality of life in patients with HFrEF are well established. Limited data exist regarding which patient characteristics predict ARNI-mediated improvements in left ventricular function (EF). Our cohort included 131 patients prescribed ARNI who had serial assessments of EF derived from 2D echocardiography at a community-based practice, Franciscan Health Indianapolis, from July 2016 to April 2018. Baseline patient characteristics predicting improvements in EF were assessed using univariate analysis. For continuous variables, logistic regression was used to determine predictors of EF improvement. Mean absolute EF improvement for the cohort was 6.7%. Presence of non-ischemic cardiomyopathy (NICM) vs ischemic cardiomyopathy (ICM) and absence of coronary artery disease (CAD) vs CAD were predictors of significant improvements in EF (3.5% vs 9.2%, p=0.003; and 4.6% vs 9.8%, p=0.009, respectively), while initiation of intermediate-dose vs low-dose ARNI and black vs caucasian trended toward significance (p=0.059 and 0.113, respectively) (see Table). No significant differences between NICM and ICM patients were observed with respect to baseline diastolic blood pressure (DBP), baseline EF, ARNI/beta-blocker dosing, duration of ARNI exposure, or presence of biventricular implantable defibrillator. Furthermore, higher baseline DBP (p=0.036) and lower baseline EF (p=0.0006) correlated with greater improvements in EF on ARNI. In this retrospective cohort of HFrEF patients treated with ARNI, we observed greater improvements in EF in patients with a non-ischemic etiology as well as lower baseline EF and higher DBP. Interestingly, despite very low numbers of black patients, the largest absolute mean EF increase occurred in this group. Future studies exploring the mechanistic underpinnings for these findings and validation in a larger cohort are warranted. [ABSTRACT FROM AUTHOR]

The density ( ρ ), viscosity ( η ) and ultrasonic velocity ( U ) of pure solvents (chloroform (CF), N , N -dimethyl formamide (DMF)) and solutions of 2-((4-acetyl-5-(2-hydroxyphenyl)-5-methyl-4,5-dihydro-1,3,4-oxadiazol-2-yl)methylthio)-3- o -tolylquinazolin-4(3 H )-one (PD I-C ) (0.001, 0.002, 0.004, 0.006, 0.008, and 0.010 mol dm −3 ) in CF and DMF are investigated at 303, 308 and 313 K at atmospheric pressure. Various thermodynamic parameters such as acoustical impedance ( Z ), adiabatic compressibility ( κ a ), inter molecular free path length ( L f ), Rao's molar sound function ( R m ), Van der Waals constant ( b ), internal pressure ( π ), relaxation time ( τ ), free volume ( V f ) and solvation number ( S n ) are calculated by using ρ , η and U data. The results obtained are interpreted in terms of solute – solvent and solute – solute interactions. The structure making or structure-breaking abilities of the solute in CF and DMF solvent are also studied. [ABSTRACT FROM AUTHOR]

A series of compounds 4-oxo-thiazolidine derivatives AJ5 a–j were synthesized by condensation reactions. The structure of synthesized compounds was characterized by IR, 1 H NMR, 13 C NMR and mass spectroscopy. The present paper deals with newly synthesized thiazolidine compounds AJ5 a –AJ5 j that were screened for their antimicrobial activity against different strains of bacteria and fungi using serial broth dilution method (Mueller–Hinton broth dilution method). In vitro antitubercular activity of compounds AJ5 a–j was carried out against Mycobacterium tuberculosis H 37 Rv. Compounds AJ5 a , AJ5 d , AJ5 e , AJ5 f and AJ5 g were found most active against selected bacterial strains (MIC = 62.5 μg/mL) and compounds AJ5 a–j were found moderately active against M. tuberculosis . [ABSTRACT FROM AUTHOR]

Human paraoxonase 1 (hPON1) is a Ca2+-dependent metalloenzyme with multifunctional properties. Due to its diverse roles as arylesterase, phosphotriesterase, and lactonase, it plays a significant role in disease conditions. Researchers across the globe have demonstrated different properties of PON1, like anti-oxidant, anti-inflammatory, anti-atherogenic, anti-diabetic, and OPneutralization. Due to its pleotropic role in disease conditions like atherosclerosis, diabetes, cardiovascular diseases, neurodegenerative disorders, and OP-poisoning, it can be considered as a potential candidate for the development of therapeutic interventions. Attempts are being made in this direction to identify the exact role of PON1 in these disease conditions. Different approaches like directed evolution, genetic as well as chemical fusion, liposomal delivery of PON1, etc., are being developed and evaluated for their therapeutic effects in different pathological pathways. In this review, we outline the exact role and involvement of different properties of PON1 in the pathophysiology of different diseases and how it can be utilized and developed as a therapeutic intervention in PON1-associated disease conditions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The endogenous opioid system regulates pain through local release of neuropeptides and modulation of their action on opioid receptors. However, the effect of opioid peptides, the enkephalins, is short-lived due to their rapid hydrolysis by enkephalin-degrading enzymes. In turn, an innovative approach to the management of pain would be to increase the local concentration and prolong the stability of enkephalins by preventing their inactivation by neural enkephalinases such as puromycin-sensitive aminopeptidase (PSA). Our previous structure-activity relationship studies offered the S-diphenylmethyl cysteinyl derivative of puromycin (20) as a nanomolar inhibitor of PSA. This chemical class, however, suffered from undesirable metabolism to nephrotoxic puromycin aminonucleoside (PAN). To prevent such toxicity, we designed and synthesized 5'-chloro substituted derivatives. The compounds retained the PSA inhibitory potency of the corresponding 5'-hydroxy analogs and had improved selectivity toward PSA. In vivo treatment with the lead compound 19 caused significantly reduced pain response in antinociception assays, alone and in combination with Met-enkephalin. The analgesic effect was reversed by the opioid antagonist naloxone, suggesting the involvement of opioid receptors. Further, PSA inhibition by compound 19 in brain slices caused local increase in endogenous enkephalin levels, corroborating our rationale. Pharmacokinetic assessment of compound 19 showed desirable plasma stability and identified the cysteinyl sulfur as the principal site of metabolic liability. We gained additional insight into inhibitor-PSA interactions by molecular modeling, which underscored the importance of bulky aromatic amino acid in puromycin scaffold. The results of this study strongly support our rationale for the development of PSA inhibitors for effective pain management., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Robert Vince, Swati S. More, and Rohit Singh have a patent pending to the University of Minnesota. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Rapid global urbanization and economic growth have significantly increased solid waste volumes, with hazardous waste posing substantial health and environmental risks. Co-processing strategies for industrial solid and hazardous waste as alternative fuels highlight the importance of integrated waste management for energy and material recovery. This study identifies and characterizes solid and hazardous industrial wastes with high calorific values from various industrial processes at Nirma Industries Limited. Nine types of combustible industrial wastes were analyzed: discarded containers (W1), plastic waste (W2), spent ion exchange resins from RO plants (W3), sludge from effluent treatment in soap plants (W4), glycerine foot from soap plants (W5), rock wool puff material (W6), fiber-reinforced plastic waste (W7), spent activated carbon (W8), and spent cartridges from reverse osmosis plants (W9). Physical characterization, proximate and ultimate analysis, heavy metal concentration evaluation, and thermogravimetric analysis were conducted to assess their properties, revealing high calorific values exceeding 2500 kcal/kg. Notably, W1 and W2 exhibited the highest calorific values (∼10,870 kcal/kg), followed by W6 and W8 (∼6000 kcal/kg) and W9 (∼8727 kcal/kg). Safe heavy metal levels are safe, and high calorific values support the prospects of energy recovery and economic and environmental benefits, reducing landfill reliance and enhancing sustainable waste management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The renin-angiotensin system (RAS) is known to affect diverse physiological processes that affect the functioning of many key organs. Angiotensin-converting enzyme (ACE) modulates a variety of bioactive peptides associated with pain. ACE inhibitors (ACEis) have found applications in the treatment of cardiovascular, kidney, neurological and metabolic disorders. However, ACEis also tend to display undesirable effects, resulting in increased pain sensitization and mechanical allodynia. In this review, we provide comprehensive discussion of preclinical and clinical studies involving the evaluation of various clinically approved ACEis. With the emerging knowledge of additional factors involved in RAS signaling and the indistinct pharmacological role of ACE substrates in pain, extensive studies are still required to elucidate the mechanistic role of ACE in pain perception., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Molecularly woven materials with striking mechanical resilience, and 2D controlled topologies like textiles, fishing nets, and baskets are highly anticipated. Molecular weaving exclusively apprehended by the secondary interactions expanding to laterally grown 2D self-assemblies with retained crystalline arrangement is stimulating. The interlacing entails planar molecules screwed together to form 2D woven thin films. Here, secondary interactions led 2D interlaced molecularly woven material (2 ° MW) built by 1D helical threads of organic chromophores twisted together via end-to-end CH···O connections, held strongly at inter-crossing by multiple OH···N interactions to prevent slippage is presented. Whereas, 1D helical threads with face-to-face O-H···O connections sans interlacing led the non-woven material (2 ° NW). The polarity-driven directionality in 2 ° MW led the water-actuated epitaxial growth of 2D-sheets to lateral thin films restricted to nano-scale thickness. The molecularly woven thin film is self-healing, flexible, and mechanically resilient in nature, while maintaining the crystalline regularity is attributed to the supple secondary interactions (2 ° )., (© 2024 Wiley‐VCH GmbH.)

Acetaminophen (APAP) overdose triggers a cascade of intracellular oxidative stress events, culminating in acute liver injury. The clinically used antidote, N-acetylcysteine (NAC), has a narrow therapeutic window, and early treatment is essential for a satisfactory therapeutic outcome. For more versatile therapies that can be effective even at late presentation, the intricacies of APAP-induced hepatotoxicity must be better understood. Accumulation of advanced glycation end products (AGEs) and the consequent activation of the receptor for AGEs (RAGE) are considered one of the key mechanistic features of APAP toxicity. Glyoxalase 1 (Glo-1) regulates AGE formation by limiting the levels of methylglyoxal (MEG). In this study, we studied the relevance of Glo-1 in the APAP-mediated activation of RAGE and downstream cell death cascades. Constitutive Glo-1-knockout mice (GKO) and a cofactor of Glo-1, ψ-GSH, were used as tools. Our findings showed elevated oxidative stress resulting from the activation of RAGE and hepatocyte necrosis through steatosis in GKO mice treated with high-dose APAP compared to wild-type controls. A unique feature of the hepatic necrosis in GKO mice was the appearance of microvesicular steatosis as a result of centrilobular necrosis, rather than the inflammation seen in the wild type. The GSH surrogate and general antioxidant ψ-GSH alleviated APAP toxicity irrespective of the Glo-1 status, suggesting that oxidative stress is the primary driver of APAP toxicity. Overall, the exacerbation of APAP hepatotoxicity in GKO mice suggests the importance of this enzyme system in antioxidant defense against the initial stages of APAP overdose.

Inspired by the uranyl-imidazole interactions via nitrogen's (N's) of histidine residues in single helical protein assemblies with open framework geometry that allows through migration/coordination of metal ions. Here, preliminary components of a stable hydrogen-bonded organic framework (HOF) are designed to mimic the stable single helical open framework with imidazole residues available for Uranium (U) binding. The imidazolate-HOF ( CSMCRI HOF2-S) is synthesized with solvent-directed H-bonding in 1D array and tuned hydrophobic CH-π interactions leading to single helix pattern having enhanced hydrolytic stability. De-solvation led CSMCRI HOF2-P with porous helical 1D channels are transformed in a freestanding thin film that showcased improved mass transfer and adsorption of uranyl carbonate. CSMCRI HOF2-P thin film can effectively extract ≈14.8 mg g -1 in 4 weeks period from natural seawater, with > 1.7 U/V (Uranium to Vanadium ratio) selectivity. This strategy can be extended for rational designing of hydrolytically stable, U selective HOFs to realize the massive potential of the blue economy toward sustainable energy., (© 2023 Wiley‐VCH GmbH.)