Degradation of lignin by Bacillus altitudinis SL7 isolated from pulp and paper mill effluent.

Lignin is a major by-product of pulp and paper industries, and is resistant to depolymerization due to its heterogeneous structure. Degradation of lignin can be achieved by the use of potential lignin-degrading bacteria. The current study was designed to evaluate the degradation efficiency of newly isolated Bacillus altitudinis SL7 from pulp and paper mill effluent. The degradation efficiency of B. altitudinis SL7 was determined by color reduction, lignin content, and ligninolytic activity from degradation medium supplemented with alkali lignin (3 g/L). B. altitudinis SL7 reduced color and lignin content by 26 and 44%, respectively, on the 5th day of incubation, as evident from the maximum laccase activity. Optimum degradation was observed at 40 °C and pH 8.0. FT-IR spectroscopy and GC-MS analysis confirmed lignin degradation by emergence of the new peaks and identification of low-molecular-weight compounds in treated samples. The identified compounds such as vanillin, 2-methyoxyhenol, 3-methyl phenol, oxalic acid and ferulic acid suggested the degradation of coniferyl and sinapyl groups of lignin. Degradation efficiency of B. altitudinis SL7 towards high lignin concentration under alkaline pH indicated the potential application of this isolate in biological treatment of the lignin-containing effluents.

The broad-spectrum antiviral recommendations for drug discovery against COVID-19.

Despite to outbreaks of highly pathogenic beta and alpha coronaviruses including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and human coronavirus, the newly emerged 2019 coronavirus (COVID-19) is considered as a lethal zoonotic virus due to its deadly respiratory syndrome and high mortality rate among the human. Globally, more than 3,517,345 cases have been confirmed with 243,401 deaths due to Acute Respiratory Distress Syndrome (ARDS) caused by COVID-19. The antiviral drug discovery activity is required to control the persistence of COVID-19 circulation and the potential of the future emergence of coronavirus. However, the present review aims to highlight the important antiviral approaches, including interferons, ribavirin, mycophenolic acids, ritonavir, lopinavir, inhibitors, and monoclonal antibodies (mAbs) to provoke the nonstructural proteins and deactivate the structural and essential host elements of the virus to control and treat the infection of COVID-19 by inhibiting the viral entry, viral RNA replication and suppressing the viral protein expression. Moreover, the present review investigates the epidemiology, diagnosis, structure, and replication of COVID-19 for better understanding. It is recommended that these proteases, inhibitors, and antibodies could be a good therapeutic option in drug discovery to control the newly emerged coronavirus.HighlightsCOVID-19 has more than 79.5% identical sequence to SARS-CoV and a 96% identical sequence of the whole genome of bat coronaviruses.Acute respiratory distress syndrome (ARDS), renal failure, and septic shock are the possible clinical symptoms associated with COVID-19.Different antivirals, including interferons, ribavirin, lopinavir, and monoclonal antibodies (mAbs) could be the potent therapeutic agents against COVID-19.The initial clinical trials on hydroquinone in combination with azithromycin showed an admirable result in the reduction of COVID-19.The overexpression of inflammation response, cytokine dysregulation, and induction of apoptosis could be an well-organized factors to reduce the pathogenicity of COVID-19.

A unique type of fully covered metal stent for the management of post liver transplant biliary anastomotic strictures.

BACKGROUND: We report our experience of treating anastomotic strictures using a novel type of fully covered metal stent (FCSEMS). This stent, known as the Kaffes Stent, is short-length with an antimigration waist and is easily removable due to long retrieval wires deployed within the duodenum. METHODS: Sixty-two patients underwent ERCP and Kaffes stent insertion for post-transplant anastomotic strictures following confirmation of a stricture on MRCP. These patients were retrospectively analysed for immediate and long-term stricture resolution, improvement in symptoms and liver function tests (LFTs), stricture recurrence and complication rates. RESULTS: Of the 56 patients who had their stent removed at the time of analysis, 54 (96%) had immediate stricture resolution and 42 continued to have long-term resolution (mean follow-up period was 548 days). Of the 16 patients with symptoms of biliary obstruction, 13 had resolution of their symptoms. Overall, there was a significant improvement in LFTs after stent removal compared to before stent insertion. Complication rates were 15% with only one patient requiring biliary reconstruction. CONCLUSIONS: The Kaffes stent is effective and safe at resolving post liver transplant biliary anastomotic strictures.

Synthesis and computational studies of highly selective inhibitors of human recombinant tissue non-specific alkaline phosphatase (h-TNAP): A therapeutic target against vascular calcification.

In this study, we have discovered small druglike molecules as selective inhibitors of human tissue-nonspecific alkaline phosphatase (h-TNAP), an enzyme critical for the regulation of extracellular matrix calcification. The upregulation of h-TNAP is associated with various pathologies particularly the vascular calcification (VC). Selective inhibition of h-TNAP over h-NPP1 may serve as a useful therapeutic strategy against vascular calcification. A series of novel triazolyl pyrazole derivatives (10a-y) in which thiol bearing triazole moiety as the zinc binding functional group was introduced to a pyrazole based pharmacophore was synthesized and evaluated as potent and selective inhibitors of h-TNAP over h-NPP1. The biological screening against h-TNAP, h-IAP, h-NPP1 and h-NPP3 showed that many of the synthesized compounds are selective inhibitors of TNAP. Particularly, the compounds 10a-h, 10j, 10m-q, 10u, 10w and 10x displayed high potency and complete selectivity towards h-TNAP over h-NPP1. Compound 10q emerged as a highly potent inhibitor (IC50 = 0.16 µM or 160 nM) against h-TNAP with 127-fold increased inhibition compared to levamisole. On the other hand, compound 10e was found to be most selective inhibitor against the tested APs and NPPs (IC50 = 1.59 ± 0.36 µM). Binding sites architecture analysis, molecular-docking and molecular dynamics simulations (MDS), revealed the basis for h-TNAP and h-IAP ligand selectivity as well as selectivity towards h-TNAP over h-NPP1. These newly discovered inhibitors are believed to represent valuable lead structures to further streamline the generation of candidate compounds to target VC.

Conjugates of degraded and oxidized hydroxyethyl starch and sulfonylureas: synthesis, characterization, and in vivo antidiabetic activity.

Orally administered drugs usually face the problem of low water solubility, low permeability, and less retention in bloodstream leading to unsatisfactory pharmacokinetic profile of drugs. Polymer conjugation has attracted increasing interest in the pharmaceutical industry for delivering such low molecular weight (Mw) drugs as well as some complex compounds. In the present work, degraded and oxidized hydroxyethyl starch (HES), a highly biocompatible semisynthetic biopolymer, was used as a drug carrier to overcome the solubility and permeability problems. The HES was coupled with synthesized N-arylsulfonylbenzimidazolones, a class of sulfonylurea derivatives, by creating an amide linkage between the two species. The coupled products were characterized using GPC, FT-IR, (1)H NMR, and (13)C NMR spectroscopy. The experiments established the viability of covalent coupling between the biopolymer and N-arylsulfonylbenzimidazolones. The coupled products were screened for their in vivo antidiabetic potential on male albino rats. The coupling of sulfonylurea derivatives with HES resulted in a marked increase of the hypoglycemic activity of all the compounds. 2,3-Dihydro-3-(4-nitrobenzensulfonyl)-2-oxo-1H-benzimidazole coupled to HES10100 was found most potent with a 67% reduction in blood glucose level of the rats as compared to 41% reduction produced by tolbutamide and 38% by metformin.

Phytochemical analysis of Hibiscus caesius using high performance liquid chromatography coupled with mass spectrometry.

Various species in genus Hibiscus are traditionally known for their therapeutic attributes. The present study focused on the phytochemical analysis of a rather unexplored species Hibiscus caesius (H. caesius), using high-pressure liquid chromatography coupled with mass spectrometry (HPLC-MS). The analysis revealed five major compounds in the aqueous extract, viz. vanillic acid, protocatechoic acid, quercetin, quercetin glucoside and apigenin, being reported for the first time in H. caesius. Literature suggests that these compounds have important pharmacological traits such as anti-cancer, anti-inflammatory, anti-bacterial and hepatoprotective etc. however, this requires further pharmacological investigations at in vitro and in vivo scale. The above study concluded the medicinal potential of H. caesius.

Synthesis, Spectral investigation (¹H, ¹³C) and Anti-microbial Screening of benzophenone imines.

New series of benzophenone imines with general formula Ph2-C=NR; R = Benzyl, 4-Fluorobenzyl, Naphthyl, Phenyl, 4-Nitrophenyl were synthesized by condensation of dichlorodiphenylmethane and different aromatic primary amines (1:1) Those imines were characterized by different physiochemical and spectroscopic techniques like melting point, elemental analysis, FT-IR, multinuclear NMR (¹H, ¹³C). After characterization, imines were subjected to anti-microbial activities. All compounds showed promising activity against different bacterial strains like Escherichia coli, Bacillussubtilis, Pasturellam ultocida and Staphylococcus aureus as well as fungal strains like Alternata alternaria, Ganoderma lucidium, Penicillium notatum and Trichoderma harzianum using Amoxicillin and Flucanazole as a standard drugs respectively.

Safety of primary percutaneous coronary intervention with and without (selective) thrombus aspiration.

OBJECTIVE: To determine the safety and efficacy of selective thrombus aspiration during Primary Percutaneous Coronary Intervention (PCI). METHODS: This observational prospective study was conducted in the catheterization laboratory of a tertiary care cardiovascular centre. A total of 150 consecutive patients who underwent primary PCI were enrolled. Aspiration was done only when thrombus burden was considered significant. After completion of procedure angiographic and electrocardiographic signs were recorded and clinical follow up was documented up to 1 year. RESULTS: No significant difference among the groups was found in age, height, weight and other risk factors like Hypertension, Diabetes Mellitus and Smoking. In general, left anterior descending artery was culprit in - 65% of patients and more than 90% of culprit vessels had visible thrombus. Multivessel disease was present in 38% of patients and 22.7% had past history of myocardial infarction. Out of 150 patients 117 (78%) underwent thrombus aspiration. No significant difference was found in ST resolution within 60 minutes (72.6 vs 81.8%; P < 0.285) and myocardial blush grade II & III (41.9 vs 27.3%; P < 0.128). No difference in event free survival was observed among the two groups (80.3 vs 84.8%; P < 0.708) at one year. CONCLUSION: Selective thrombus aspiration in definite thrombus laden arteries and no aspiration in low or negligible thrombus burden vessels may be a safe and effective strategy in patients undergoing primary PCI. Overall poor risk profile of our patients as compared to western population necessitates further evaluation of this matter in randomized studies.

Mathematical study of polycystic ovarian syndrome disease including medication treatment mechanism for infertility in women.

Among women of reproductive age, PCOS (polycystic ovarian syndrome) is one of the most prevalent endocrine illnesses. In addition to decreasing female fertility, this condition raises the risk of cardiovascular disease, diabetes, dyslipidemia, obesity, psychiatric disorders and other illnesses. In this paper, we constructed a fractional order model for polycystic ovarian syndrome by using a novel approach with the memory effect of a fractional operator. The study population was divided into four groups for this reason: Women who are at risk for infertility, PCOS sufferers, infertile women receiving therapy (gonadotropin and clomiphene citrate), and improved infertile women. We derived the basic reproductive number, and by utilizing the Jacobian matrix and the Routh-Hurwitz stability criterion, it can be shown that the free and endemic equilibrium points are both locally stable. Using a two-step Lagrange polynomial, solutions were generated in the generalized form of the power law kernel in order to explore the influence of the fractional operator with numerical simulations, which shows the impact of the sickness on women due to the effect of different parameters involved.

Fractional order model of MRSA bacterial infection with real data fitting: Computational Analysis and Modeling.

Bacterial infections in the health-care sector and social environments have been linked to the Methicillin-Resistant Staphylococcus aureus (MRSA) infection, a type of bacteria that has remained an international health risk since the 1960s. From mild colonization to a deadly invasive disease with an elevated mortality rate, the illness can present in many different forms. A fractional-order dynamic model of MRSA infection developed using real data for computational and modeling analysis on the north side of Cyprus is presented in this paper. Initially, we tested that the suggested model had a positively invariant region, bounded solutions, and uniqueness for the biological feasibility of the model. We study the equilibria of the model and assess the expression for the most significant threshold parameter, called the basic reproduction number (ℛ0). The reproductive number's parameters are also subjected to sensitivity analysis through mathematical methods and simulations. Additionally, utilizing the power law kernel and the fixed-point approach, the existence, uniqueness, and generalized Ulam-Hyers-Rassias stability are presented. Chaos Control was used to regulate the linear responses approach to bring the system to stabilize according to its points of equilibrium, taking into account a fractional-order system with a managed design where solutions are bound in the feasible domain. Finally, numerical simulations demonstrating the effects of different parameters on MRSA infection are used to investigate the impact of the fractional operator on the generalized form of the power law kernel through a two-step Newton polynomial method. The impact of fractional orders is emphasized in the study so that the numerical solutions support the importance of these orders on MRSA infection. With the application of fractional order, the significance of cognizant antibiotic usage for MRSA infection is verified.

A mathematical fractal-fractional model to control tuberculosis prevalence with sensitivity, stability, and simulation under feasible circumstances.

BACKGROUND: Tuberculosis, a global health concern, was anticipated to grow to 10.6 million new cases by 2021, with an increase in multidrug-resistant tuberculosis. Despite 1.6 million deaths in 2021, present treatments save millions of lives, and tuberculosis may overtake COVID-19 as the greatest cause of mortality. This study provides a six-compartmental deterministic model that employs a fractal-fractional operator with a power law kernel to investigate the impact of vaccination on tuberculosis dynamics in a population. METHODS: Some important characteristics, such as vaccination and infection rate, are considered. We first show that the suggested model has positive bounded solutions and a positive invariant area. We evaluate the equation for the most important threshold parameter, the basic reproduction number, and investigate the model's equilibria. We perform sensitivity analysis to determine the elements that influence tuberculosis dynamics. Fixed-point concepts show the presence and uniqueness of a solution to the suggested model. We use the two-step Newton polynomial technique to investigate the effect of the fractional operator on the generalized form of the power law kernel. RESULTS: The stability analysis of the fractal-fractional model has been confirmed for both Ulam-Hyers and generalized Ulam-Hyers types. Numerical simulations show the effects of different fractional order values on tuberculosis infection dynamics in society. According to numerical simulations, limiting contact with infected patients and enhancing vaccine efficacy can help reduce the tuberculosis burden. The fractal-fractional operator produces better results than the ordinary integer order in the sense of memory effect at diffract fractal and fractional order values. CONCLUSION: According to our findings, fractional modeling offers important insights into the dynamic behavior of tuberculosis disease, facilitating a more thorough comprehension of their epidemiology and possible means of control.

Computational and stability analysis of Ebola virus epidemic model with piecewise hybrid fractional operator.

In this manuscript, we developed a nonlinear fractional order Ebola virus with a novel piecewise hybrid technique to observe the dynamical transmission having eight compartments. The existence and uniqueness of a solution of piecewise derivative is treated for a system with Arzel'a-Ascoli and Schauder conditions. We investigate the effects of classical and modified fractional calculus operators, specifically the classical Caputo piecewise operator, on the behavior of the model. A model shows that a completely continuous operator is uniformly continuous, and bounded according to the equilibrium points. The reproductive number R0 is derived for the biological feasibility of the model with sensitivity analysis with different parameters impact on the model. Sensitivity analysis is an essential tool for comprehending how various model parameters affect the spread of illness. Through a methodical manipulation of important parameters and an assessment of their impact on Ro, we are able to learn more about the resiliency and susceptibility of the model. Local stability is established with next Matignon method and global stability is conducted with the Lyapunov function for a feasible solution of the proposed model. In the end, a numerical solution is derived with Newton's polynomial technique for a piecewise Caputo operator through simulations of the compartments at various fractional orders by using real data. Our findings highlight the importance of fractional operators in enhancing the accuracy of the model in capturing the intricate dynamics of the disease. This research contributes to a deeper understanding of Ebola virus dynamics and provides valuable insights for improving disease modeling and public health strategies.

Analysis and dynamical structure of glucose insulin glucagon system with Mittage-Leffler kernel for type I diabetes mellitus.

In this paper, we propose a fractional-order mathematical model to explain the role of glucagon in maintaining the glucose level in the human body by using a generalised form of a fractal fractional operator. The existence, boundedness, and positivity of the results are constructed by fixed point theory and the Lipschitz condition for the biological feasibility of the system. Also, global stability analysis with Lyapunov's first derivative functions is treated. Numerical simulations for fractional-order systems are derived with the help of Lagrange interpolation under the Mittage-Leffler kernel. Results are derived for normal and type 1 diabetes at different initial conditions, which support the theoretical observations. These results play an important role in the glucose-insulin-glucagon system in the sense of a closed-loop design, which is helpful for the development of artificial pancreas to control diabetes in society.

Mathematical modeling and control of lung cancer with IL2 cytokine and anti-PD-L1 inhibitor effects for low immune individuals.

Mathematical formulations are crucial in understanding the dynamics of disease spread within a community. The aim of this work is to examine that the Lung Cancer detection and treatment by introducing IL2 and anti-PD-L1 inhibitor for low immune individuals. Mathematical model is developed with the created hypothesis to increase immune system by antibody cell's and Fractal-Fractional operator (FFO) is used to turn the model into a fractional order model. A newly developed system TCDIL2Z is examined both qualitatively and quantitatively in order to determine its stable position. The boundedness, positivity and uniqueness of the developed system are examined to ensure reliable bounded findings, which are essential properties of epidemic models. The global derivative is demonstrated to verify the positivity with linear growth and Lipschitz conditions are employed to identify the rate of effects in each sub-compartment. The system is investigated for global stability using Lyapunov first derivative functions to assess the overall impact of IL2 and anti-PD-L1 inhibitor for low immune individuals. Fractal fractional operator is used to derive reliable solution using Mittag-Leffler kernel. In fractal-fractional operators, fractal represents the dimensions of the spread of the disease and fractional represents the fractional ordered derivative operator. We use combine operators to see real behavior of spread as well as control of lung cancer with different dimensions and continuous monitoring. Simulations are conducted to observe the symptomatic and asymptomatic effects of Lung Cancer disease to verify the relationship of IL2, anti-PD-L1 inhibitor and immune system. Also identify the real situation of the control for lung cancer disease after detection and treatment by introducing IL2 cytokine and anti-PD-L1 inhibitor which helps to generate anti-cancer cells of the patients. Such type of investigation will be useful to investigate the spread of disease as well as helpful in developing control strategies from our justified outcomes.

Physiological and chaos effect on dynamics of neurological disorder with memory effect of fractional operator: A mathematical study.

BACKGROUND AND OBJECTIVE: To study the dynamical system, it is necessary to formulate the mathematical model to understand the dynamics of various diseases that are spread worldwide. The main objective of our work is to examine neurological disorders by early detection and treatment by taking asymptomatic. The central nervous system (CNS) is impacted by the prevalent neurological condition known as multiple sclerosis (MS), which can result in lesions that spread across time and place. It is widely acknowledged that multiple sclerosis (MS) is an unpredictable disease that can cause lifelong damage to the brain, spinal cord, and optic nerves. The use of integral operators and fractional order (FO) derivatives in mathematical models has become popular in the field of epidemiology. METHOD: The model consists of segments of healthy or barian brain cells, infected brain cells, and damaged brain cells as a result of immunological or viral effectors with novel fractal fractional operator in sight Mittag Leffler function. The stability analysis, positivity, boundedness, existence, and uniqueness are treated for a proposed model with novel fractional operators. RESULTS: Model is verified the local and global with the Lyapunov function. Chaos Control will use the regulate for linear responses approach to bring the system to stabilize according to its points of equilibrium so that solutions are bounded in the feasible domain. To ensure the existence and uniqueness of the solutions to the suggested model, it makes use of Banach's fixed point and the Leray Schauder nonlinear alternative theorem. For numerical simulation and results the steps Lagrange interpolation method at different fractional order values and the outcomes are compared with those obtained using the well-known FFM method. CONCLUSION: Overall, by offering a mathematical model that can be used to replicate and examine the behavior of disease models, this research advances our understanding of the course and recurrence of disease. Such type of investigation will be useful to investigate the spread of disease as well as helpful in developing control strategies from our justified outcomes.

Qualitative analysis and chaotic behavior of respiratory syncytial virus infection in human with fractional operator.

Respiratory syncytial virus (RSV) is the cause of lung infection, nose, throat, and breathing issues in a population of constant humans with super-spreading infected dynamics transmission in society. This research emphasizes on examining a sustainable fractional derivative-based approach to the dynamics of this infectious disease. We proposed a fractional order to establish a set of fractional differential equations (FDEs) for the time-fractional order RSV model. The equilibrium analysis confirmed the existence and uniqueness of our proposed model solution. Both sensitivity and qualitative analysis were employed to study the fractional order. We explored the Ulam-Hyres stability of the model through functional analysis theory. To study the influence of the fractional operator and illustrate the societal implications of RSV, we employed a two-step Lagrange polynomial represented in the generalized form of the Power-Law kernel. Also, the fractional order RSV model is demonstrated with chaotic behaviors which shows the trajectory path in a stable region of the compartments. Such a study will aid in the understanding of RSV behavior and the development of prevention strategies for those who are affected. Our numerical simulations show that fractional order dynamic modeling is an excellent and suitable mathematical modeling technique for creating and researching infectious disease models.

Flip bifurcation analysis and mathematical modeling of cholera disease by taking control measures.

To study the dynamical system, it is necessary to formulate the mathematical model to understand the dynamics of various diseases which are spread in the world wide. The objective of the research study is to assess the early diagnosis and treatment of cholera virus by implementing remedial methods with and without the use of drugs. A mathematical model is built with the hypothesis of strengthening the immune system, and a ABC operator is employed to turn the model into a fractional-order model. A newly developed system SEIBR, which is examined both qualitatively and quantitatively to determine its stable position as well as the verification of flip bifurcation has been made for developed system. The local stability of this model has been explored concerning limited observations, a fundamental aspect of epidemic models. We have derived the reproductive number using next generation method, denoted as " R 0 ", to analyze its impact rate across various sub-compartments, which serves as a critical determinant of its community-wide transmission rate. The sensitivity analysis has been verified according to its each parameters to identify that how much rate of change of parameters are sensitive. Atangana-Toufik scheme is employed to find the solution for the developed system using different fractional values which is advanced tool for reliable bounded solution. Also the error analysis has been made for developed scheme. Simulations have been made to see the real behavior and effects of cholera disease with early detection and treatment by implementing remedial methods without the use of drugs in the community. Also identify the real situation the spread of cholera disease after implementing remedial methods with and without the use of drugs. Such type of investigation will be useful to investigate the spread of virus as well as helpful in developing control strategies from our justified outcomes.

Phytochemical, Geographical, and Pharmacological Retrospect of Genus Torilis.

BACKGROUND: Genus Torilis (Apiaceae) known as hedge parsley, encompasses 11-13 species distributed worldwide and shows potential pharmacological uses. Its phytochemical pattern is highly diversified including many phenolic and terpenic compounds. OBJECTIVE: This research-review provides new highlighting of structural organizations, structure-activity trends, taxonomical, tissue and geographical distribution of phytocompounds of Torilis genus from extensive statistical analyses of available data. METHODS: In extenso, exploration of documented literature and statistical data analyses were applied to update the phytochemical pool of the genus under several aspects including structural diversity, geographical distribution, biological compartmentations and pharmacological activities. RESULTS: Phytoconstituents were classified into homogeneous clusters that revealed to be associated with chemical constitutions (aglycone types, chemical groups) and distributions (through species, tissues, geographical). About bioactivities, terpenes were studied from a pharmacological point of view with relatively high frequencies for antifungal, antibacterial, cytotoxic and anti-inflammatory activities. Preliminary structure-activity relationships were highlighted implying opposite effects between hydroxylation and methylation in favor of different activities. Crude extracts and isolated compounds have shown several biological activities (antibacterial, anticancer, antiangiogenic, antiproliferative, etc.), thus providing authentic scientific proof for their diverse uses in folk medicines. CONCLUSION: The phytochemistry of the genus Torilis promises important perspectives in matters of pharmacological activities. These perspectives call for further investments in pharmacology because of (i) unbalance between phenolic and terpenic compounds according to the countries and (ii) more advanced current states of structural elucidations compared to biological evaluations.