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This study investigates the emergence of extreme events in two different coupled systems: the FitzHugh-Nagumo neuron model and the forced Liénard system, both based on time-varying interactions. The time-varying coupling function between the systems determines the duration and frequency of their interaction. Extreme events in the coupled system arise as a result of the influence of time-varying interactions within various parameter regions. We specifically focus on elucidating how the transition point between extreme events and regular events shifts in response to the duration of interaction time between the systems. By selecting the appropriate interaction time, we can effectively mitigate extreme events, which is highly advantageous for controlling undesired fluctuations in engineering applications. Furthermore, we extend our investigation to networks of oscillators, where the interactions among network elements are also time dependent. The proposed approach for coupled systems holds wide applicability to oscillator networks., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

In the present study, we investigate the dynamic behavior of the fractional-order Bonhoeffer-van der Pol (BVP) oscillator. Previous studies on the integer-order BVP have shown that it exhibits mixed-mode oscillations (MMOs) with respect to the frequency of external forcing. We explore the effect of fractional-order on these MMOs and observe interesting phenomena. For fractional-order q1, we find that as we vary the frequency of external forcing, the system exhibits increasingly small amplitude oscillations. Eventually, as q1 decreases, the MMOs disappear entirely, indicating that lower fractional orders eliminate the presence of MMOs in the BVP oscillator. On the other hand, for the fractional-order q2, we observe more complex MMOs compared to q1. However, we find that the elimination of MMOs occurs with less variation from the integer order 1. Intriguingly, as we change q2, the fractional-order BVP oscillator undergoes a phenomenon known as a crisis, where the attractor expands and extreme events occur. Overall, our study highlights the rich dynamics of the fractional-order BVP oscillator and its ability to display various modes of oscillations and crises as the order is changed., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Solar energy provides desired thermal energy for diverse applications, including industrial heating, domestic cooking, power generation, desalination, and agri-food preservation. Despite extensive research on solar drying from the scientific community, there are limited practical applications for small-scale use. This review attempts to analyze the design features of three specific types of dryers for food drying applications: solar evacuated tube dryers, biomass dryers, and hybrid solar dryers. The thermal performance of the three dryers is evaluated in terms of drying time, moisture removal, and temperature attained during drying. The review also assesses the prospects of solar dryers, highlighting the need for further research into innovative designs and advanced drying capabilities. The study provides valuable information for enhancing dryer performance with various integrated solutions., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Infectious complications following oesophagectomy are associated with significant morbidity. Early prediction of these complications may mitigate significant morbidity and mortality. Patients undergoing minimally invasive oesophagectomy for carcinoma oesophagus between January 2019 and June 2020 were included in the study. All patients underwent standard preoperative investigations and preparation. Post-operative complications including infectious complications were recorded. Association of post-operative serum interleukin-6 (IL-6) levels with post-operative complications were analysed. A total of twenty-two participants were included in the study (median age; 51 years, 13 (%) male). The tumour site was middle 1/3rd of oesophagus in 13 (59.1%), lower 1/3rd of oesophagus in 9 (40.9%). The tumour histology was squamous cell carcinoma in all patients. Eight (36.4 %) patients developed major complications and five of them developed anastomotic leak. IL-6 levels were significantly higher on POD 3 in patients who developed major complications ( p = 0.009) and anastomotic leak ( p = 0.031). At receiver operating characteristic curve (ROC curve) analysis, an IL-6 cut-off level of 36.4 pg/ml on POD 3 yielded a sensitivity of 87% and a specificity of 79% for the prediction of major complication and cut-off level of 44.3 pg/ml on POD 3 yielded a sensitivity of 80% and a specificity of 82% for the prediction of anastomotic leak. A high post-operative IL-6 level helps in the prediction of major complications and cervical oesophagogastric anastomotic leak., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Indian Association of Surgical Oncology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The tobacco cutworm, Spodoptera litura and cotton bollworm, Helicoverpa armigera (Lepidoptera: Noctuidae) are important pests of various agricultural crops that cause sevier economic loses throughout the world. Indiscriminate and frequent use of insecticide may lead to development of resistance in these pests. Nanotechnology has given an alternative to manage and overcome insecticide resistance for pest management strategies. In the present study the iron nanoparticles derived from Trigonella foenum-graecum leaf extract (FeNPs) was investigated for its ecofriendly management of pyrethroid resistance in two lepidopteron pest species at 24 h, 48 h and 72 h post treatment. The result showed high mortality (92.83% and 91.41%) of S. litura and H. armigera at 72 h treatment upon FeNPs and fenvalerate (Fen + FeNPs) teratment. Probit analysis revealed high LC 50 upon Fen + FeNPs treatment (130.31 and 89.32 mg/L) with a synergism ratio of 1.38 and 1.36. Antifeedant activity of six dofferent concentration of FeNPs revelaed increased antifeedant activity with respect to increasing concentration of nanoparticles ranging from 10 to 90% and 20-95% againt both insects (p<0.05). Detoxification activity of carboxylesterase was elevated at 630 μmol/mg protein/min (p<0.05) in fenvalerate treatment, whereas decreased activity was found (392umole/mg protein/min) in FeNPs and Fen + FeNPs treatment (P<0.001). GST and P450 activity was also increased in fenvalerate treatment, whereas decreased activity was observed in FeNPs and Fen + FeNPs. Esterase isoenzyme banding pattern revealed four bands in fenvalerate treatment and two bans (E3 and E4) in Fen + FeNPs combination. Hence the present study concludes that T. foenum-graecum synthesized iron nanoparticles could be an effective alternate for ecofriendly management of S. litura and H. armigera., 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 © 2023 Elsevier Inc. All rights reserved.)

Studies have investigating the detoxification and antioxidant enzymes with melatonin under pesticide stress in many vertebrates, whereas no reports produced in invertebrates. In this study possible role of melatonin and luzindole effect on fipronil toxicity and the detoxification, antioxidant enzymes in H. armigera has been reported. Result showed high toxicity of fipronil treatment (LC 50 4.24 ppm), followed by increased LC 50 value with melatonin pretreatment (6.44 ppm). Whereas decreased toxicity was observed with melatonin and luzindole combination (3.72 ppm). The detoxification enzymes AChE, esterase and P450 were increased in larval head and whole body with exogenous melatonin level compared to control 1-1.5 μmol/mg of protein. The antioxidant levels of CAT, SOD and GST in whole body and head tissue had been increased by melatonin and fipronil combination 1.1-1.4 unit/mg of protein followed by GPx and GR in larval head (1-1.2 μmol/mg of protein). Mean while the luzindole antagonist inhibits CAT, SOD, GST and GR oxidative enzyme level (1-1.5 fold) in most of the tissue compared to melatonin and fipronil treatment (p < 0.01). Hence this study concludes that the melatonin pretreatment can reduce the fipronil toxicity by enhanced detoxification and antioxidant enzyme system in H. armigera., 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 © 2023 Elsevier Inc. All rights reserved.)

The numerical, analytical, and experimental analyses are presented for synchronizing two rotors under the Yukawa interaction. We report that the rotors exhibit in-phase and mixed-phase measure synchronizations for a pair of coupled rotors. Here, the analytical condition for synchronization is derived, tested numerically, and confirmed experimentally using coupled camphor infused rotors as a test bed. Moreover, the concept of measure synchronization is discussed. We report that, in conservative systems, not only the critical coupling parameter but initial conditions also play an essential role for estimating the measure synchronization region.

Defects in insulin processing and granule maturation are linked to pancreatic beta-cell failure during type 2 diabetes (T2D). Phosphatidylinositol transfer protein alpha (PITPNA) stimulates activity of phosphatidylinositol (PtdIns) 4-OH kinase to produce sufficient PtdIns-4-phosphate (PtdIns-4-P) in the trans-Golgi network to promote insulin granule maturation. PITPNA in beta-cells of T2D human subjects is markedly reduced suggesting its depletion accompanies beta-cell dysfunction. Conditional deletion of Pitpna in the beta-cells of Ins-Cre, Pitpna flox/flox mice leads to hyperglycemia resulting from decreasing glucose-stimulated insulin secretion (GSIS) and reducing pancreatic beta-cell mass. Furthermore, PITPNA silencing in human islets confirms its role in PtdIns-4-P synthesis and leads to impaired insulin granule maturation and docking, GSIS, and proinsulin processing with evidence of ER stress. Restoration of PITPNA in islets of T2D human subjects reverses these beta-cell defects and identify PITPNA as a critical target linked to beta-cell failure in T2D., (© 2023. The Author(s).)

In this study, we report a rich variety of large-intensity pulses exhibited by a Zeeman laser model. The instabilities in the system occur via three different dynamical processes, such as quasiperiodic intermittency, Pomeau-Manneville intermittency, and the breakdown of quasiperiodic motion to chaos followed by an interior crisis. This Zeeman laser model is more capable of exploring the major possible types of instabilities when changing a specific system's parameter in a particular range. We exemplified distinct dynamical transitions of the Zeeman laser model. The statistical measures reveal the appearance of the low probability of large-intensity pulses above the qualifier threshold value. Moreover, they seem to follow an exponential decay that shows a Poisson-like distribution. The impact of noise and time delay effects have been analyzed near the transition point of the system.

Phase slips are a typical dynamical behavior in coupled oscillator systems: the route to phase synchrony is characterized by intervals of constant phase difference interrupted by abrupt changes in the phase difference. Qualitatively similar to stick-slip phenomena, analysis of phase slip has mainly relied on identifying remnants of saddle-nodes or "ghosts." We study sets of phase oscillators and by examining the dynamics in detail, offer a more precise, quantitative description of the phenomenon. Phase shifts and phase sticks, namely, the temporary locking of phases required for phase slips, occur at stationary points of phase velocities. In networks of coupled phase oscillators, we show that phase slips between pairs of individual oscillators do not occur simultaneously, in general. We consider additional systems that show phase synchrony: one where saddle-node ghosts are absent, one where the coupling is similarity dependent, and two cases of coupled chaotic oscillators.

The COVID-19 pandemic has exacerbated the existing challenges to achieving the WHO target of eliminating cervical cancer as a public health problem by working towards the target of fewer than four cases per 100 000 women. We reviewed the literature to identify potential recovery strategies to support cervical cancer prevention programs in lower-and middle-income countries (LMICs) following COVID-19 disruptions and the extent to which strategies have been implemented. Utilising the WHO health systems framework, we mapped these recovery strategies against the six building blocks to examine their reach across the health system. Most recovery strategies were focused on service delivery, while leadership and governance played a pivotal role in the continuity of cervical cancer prevention programs during the pandemic. Leadership and governance were the drivers for outcomes in the building blocks of health information systems, financing and critical support in operationalising service delivery strategies. In the aftermath of the COVID-19 pandemic with strained health resources and economies, stakeholders would significantly influence the coverage and sustainability of cervical cancer prevention programs. The support from multisectoral stakeholders would accelerate the recovery of cervical cancer prevention programs. To achieve the WHO target by 2030, we call for future studies to understand the barriers and facilitators from the perspectives of stakeholders in order to support the decision-making processes and information required to implement recovery strategies in LMICs., Competing Interests: This is a research project initiated by the research team and supported by Merck education grant. Merck has no financial interest, ownership, and intellectual property rights of the research project findings. SMG is supported by NHMRC APP1197951 Leadership Investigator grant level 3, a member of the advisory board for the nine valent HPV vaccine of Merck, received educational grant from Merck for study on HPV and young women through her institution and received Merck lecture fees. SK has served in advisory boards of both Merck & GSK and has received Merck lecture fees. IIP has received Roche lecture fees. DAM has received lecture fees from MSD. The other author reports no conflict of 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., (© 2023 Published by Elsevier Inc.)

This systematic review identified various bioactive compounds which have the potential to serve as novel drugs or leads against acute myeloid leukemia. Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy that arises from the dysregulation of cell differentiation, proliferation, and cell death. The risk factors associated with the onset of AML include long-term exposure to radiation and chemicals such as benzene, smoking, genetic disorders, blood disorders, advancement in age, and others. Although novel strategies to manage AML, including a refinement of the conventional chemotherapy regimens, hypomethylating agents, and molecular targeted drugs, have been developed in recent years, resistance and relapse remain the main clinical problems. In this study, three databases, PubMed/MEDLINE, ScienceDirect, and Google Scholar, were systematically searched to identify various bioactive compounds with antileukemic properties. A total of 518 articles were identified, out of which 59 were viewed as eligible for the current report. From the data extracted, over 60 bioactive compounds were identified and divided into five major groups: flavonoids, alkaloids, organosulfur compounds, terpenes, and terpenoids, and other known and emerging bioactive compounds. The mechanism of actions of the analyzed individual bioactive molecules differs remarkably and includes disrupting chromatin structure, upregulating the synthesis of certain DNA repair proteins, inducing cell cycle arrest and apoptosis, and inhibiting/regulating Hsp90 activities, DNA methyltransferase 1, and histone deacetylase 1., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Competing Interests: None

Hidden attractors are present in many nonlinear dynamical systems and are not associated with equilibria, making them difficult to locate. Recent studies have demonstrated methods of locating hidden attractors, but the route to these attractors is still not fully understood. In this Research Letter, we present the route to hidden attractors in systems with stable equilibrium points and in systems without any equilibrium points. We show that hidden attractors emerge as a result of the saddle-node bifurcation of stable and unstable periodic orbits. Real-time hardware experiments were performed to demonstrate the existence of hidden attractors in these systems. Despite the difficulties in identifying suitable initial conditions from the appropriate basin of attraction, we performed experiments to detect hidden attractors in nonlinear electronic circuits. Our results provide insights into the generation of hidden attractors in nonlinear dynamical systems.

Coronaviruses have caused enough devastation in the last two decades. These viruses have some rare features while sharing some common features. Novel coronavirus disease (nCoV-19) caused an outbreak with a fatality rate of 5%. It emerged from China and spread into many countries. The present research focused on genome analysis of Indian nCoV-19 Isolate and its translational product subjected to homology modeling and its subsequent molecular simulations to find out potent FDA approved drug for treating COVID-19. Phylogenetic analysis of SARS-CoV-2 Indian isolate shows close resemblance with 17 countries SARS-CoV-2 isolates. Homology modeling of four non-structural proteins translational product of Indian SARS-CoV-2 genome shows high similarity and allowed regions with the existing PDB deposited SARS-CoV-2 target proteins. Finally, these four generated proteins show more affinity with cobicistat, remdesivir and indinavir out of 14 screened FDA approved drugs in molecular docking which is further proven by molecular dynamics simulation and MMGBSA analysis of target ligand complex with best simulation trajectories. Overall our present research findings is that three proposed drugs namely cobicistat, remdesivir and indinavir showed higher interaction with the model SARS-CoV-2 viral target proteins from the Indian nCoV-19 isolate. These compounds could be used as a starting point for the creation of active antiviral drugs to combat the deadly COVID-19 virus during global pandemic and its subsequent viral infection waves across the globe.Communicated by Ramaswamy H. Sarma.

"Reverse cortical sign" is a rare entity described in lumbar burst fracture that corresponds to the fracture fragment of the posterior wall of vertebral body, which has rotated 180 degrees with the cortical surface facing anteriorly and the cancellous surface facing posteriorly in the canal. Identifying this sign is crucial in deciding the line of management as it is a contraindication for ligamentotaxis. The advent of computed tomography scans with axial and sagittal reconstruction has allowed us to better describe these rare entities. We present a lumbar burst fracture with a reverse cortical sign describing its appearance in axial computed tomography scans, sagittal reconstruction, and magnetic resonance imaging., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Despite the introduction of cervical cancer screening and human papillomavirus (HPV) vaccines, the utilization pattern was not standardized. The aim of this study was to elicit the current prevention care in Asia-Oceania., Methods: An online questionnaire was circulated to different countries/cities in Asia-Oceania. The primary objective was to evaluate the coverage of HPV vaccination and cervical screening programs. The secondary objectives were to study the structures of these programs. Five case scenarios were set to understand how the respondents manage the abnormal screening results., Results: Fourteen respondents from 10 countries/cities had participated. Cervical cancer ranked the first in Myanmar and Nepal. About 10%-15% did not have national vaccination or screening program. The estimated coverage rate for vaccination and screening varied from less than 1% to 70%, which the coverage ran in parallel with the incidence and mortality rates of cervical cancer. All regions approved HPV vaccines, although only four provided free or subsidized programs for nonavalent vaccine. Cervical cytology remained the most common screening tool, and 20%-30% relied heavily on visual inspection using acetic acid. The screening age groups varied in different regions. From the case scenarios, it was noted that some respondents tended to offer more frequent screening tests or colposcopy than recommended by international guidelines., Conclusion: This study revealed discrepancy in the practice of cervical cancer prevention in Asia-Oceania especially access to HPV vaccines. There is an urgent need for a global collaboration to eliminate cervical cancer by public education, reforming services, and medical training., (© 2023 Japan Society of Obstetrics and Gynecology.)

Extreme events are unusual and rare large-amplitude fluctuations can occur unexpectedly in nonlinear dynamical systems. Events above the extreme event threshold of the probability distribution of a nonlinear process characterize extreme events. Different mechanisms for the generation of extreme events and their prediction measures have been reported in the literature. Based on the properties of extreme events, such as those that are rare in the frequency of occurrence and extreme in amplitude, various studies have shown that extreme events are both linear and nonlinear in nature. Interestingly, in this Letter, we report on a special class of extreme events which are nonchaotic and nonperiodic. These nonchaotic extreme events appear in between the quasiperiodic and chaotic dynamics of the system. We report the existence of such extreme events with various statistical measures and characterization techniques.

One of the areas of science which has immensely advanced in the recent years is nanotechnology. This area broadly revolves around matter at scales between 1 and 100 nm, where peculiar phenomena make way for cutting-edge applications. Today, nanotechnology has a daily impact on human life with numerous and varied possible advantages. Nanosensors are one of the products of nanotechnology and any sensor that uses nanoscale phenomena qualifies to be known as a nanosensor. Nanosensors have proven very useful in a number of sectors including medical applications, food quality analysis and agricultural controlling process, etc. One of the major human healthcare applications of nanosensors is for disease diagnosis. With the aid of nanosensors, numerous neurodegenerative disorders and inflammatory diseases are commonly identified and treated of late. Alzheimer's disease (AD) and inflammatory bowel disease fall under the categories of neurodegenerative illnesses and inflammatory diseases. There are more than 20 million cases of (AD) making it the most prevalent neurological condition globally and "inflammatory bowel disease" (IBD) refers to a variety of conditions that cause persistent inflammation of the digestive tract. Here we present a comprehensive account on the utility of nanosensors for the diagnosis and treatment of (AD) and (IBD)., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

The genetic and molecular basis of developing high blood pressure and renal disease are not well known. Resp18 mutant Dahl salt-sensitive (SS- Resp18 mutant ) rats fed a 2% NaCl diet for six weeks have high blood pressure, increased renal fibrosis, and decreased mean survival time. Impairment of the dopaminergic system also leads to hypertension that involves renal and non-renal mechanisms. Deletion of any of the five dopamine receptors may lead to salt-sensitive hypertension. Therefore, we investigated the interaction between Resp18 and renal dopamine in SS- Resp18 mutant and Dahl salt-sensitive (SS) rats. We found that SS- Resp18 mutant rats had vascular dysfunction, as evidenced by a decrease in vasorelaxation in response to sodium nitroprusside. The pressure-natriuresis curve in SS- Resp18 mutant rats was shifted down and to the right of SS rats. SS- Resp18 mutant rats had decreased glomerular filtration rate and dopamine receptor subtypes, D1R and D5R. Renal dopamine levels were decreased, but urinary dopamine levels were increased, which may be the consequence of increased renal dopamine production, followed by secretion into the tubular lumen. The increased renal dopamine production in SS- Resp18 mutant rats in vivo was substantiated by the increased dopamine production in renal proximal tubule cells treated with L-DOPA. Overall, our study provides evidence that targeted disruption of the Resp18 locus in the SS rat dysregulates the renal dopaminergic system.

In recent times, the fractional-order dynamical networks have gained lots of interest across various scientific communities because it admits some important properties like infinite memory, genetic characteristics, and more degrees of freedom than an integer-order system. Because of these potential applications, the study of the collective behaviors of fractional-order complex networks has been investigated in the literature. In this work, we investigate the influence of higher-order interactions in fractional-order complex systems. We consider both two-body and three-body diffusive interactions. To elucidate the role of higher-order interaction, we show how the network of oscillators is synchronized for different values of fractional-order. The stability of synchronization is studied with a master stability function analysis. Our results show that higher-order interactions among complex networks help the earlier synchronization of networks with a lesser value of first-order coupling strengths in fractional-order complex simplices. Besides that, the fractional-order also shows a notable impact on synchronization of complex simplices. For the lower value of fractional-order, the systems get synchronized earlier, with lesser coupling strengths in both two-body and three-body interactions. To show the generality in the outcome, two neuron models, namely, Hindmarsh-Rose and Morris-Leccar, and a nonlinear Rössler oscillator are considered for our analysis.

We consider a system of coupled nonlinear oscillators in which the interaction is modulated by a measure of the similarity between the oscillators. Such a coupling is common in treating spatially mobile dynamical systems where the interaction is distance dependent or in resonance-enhanced interactions, for instance. For a system of Stuart-Landau oscillators coupled in this manner, we observe a novel route to oscillation death via a Hopf bifurcation. The individual oscillators are confined to inhomogeneous limit cycles initially and are damped to different fixed points after the bifurcation. Analytical and numerical results are presented for this case, while numerical results are presented for coupled Rössler and Sprott oscillators.

Insulin stores lipid in adipocytes and prevents lipolysis and the release of non-esterified fatty acids (NEFA). Excessive release of NEFA during sustained energy supply and increase in abdominal adiposity trigger systemic insulin resistance, including in the liver, a major site of insulin clearance. This causes a reduction in insulin clearance as a compensatory mechanism to insulin resistance in obesity. On the other hand, reduced insulin clearance in the liver can cause chronic hyperinsulinemia, followed by downregulation of insulin receptor and insulin resistance. Delineating the cause-effect relationship between reduced insulin clearance and insulin resistance has been complicated by the fact that insulin action and clearance are mechanistically linked to insulin binding to its receptors. This review discusses how NEFA mobilization contributes to the reciprocal relationship between insulin resistance and reduced hepatic insulin clearance, and how this may be implicated in the pathogenesis of non-alcoholic fatty liver disease.

The unavailability of vaccine and medicines raised serious issues during COVID-19 pandemic and peoples from different parts of world relied on traditional medicine for their immediate recovery from COVID-19 and it found effective also. The current research aims to target COVID-19 immunological human host receptors i.e. angiotensin-converting enzyme (ACE)-2, interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α) and protease-activated receptor (PAR)-1 using curcumin derivatives to prevent viral infection and control overproduction of early clinical responses of COVID-19. Targeting these host proteins will mitigate the infection and will filter out many complications caused by these proteins in COVID-19 patients. It is proven through computer-aided computational modeling approaches, total 30 compounds of curcumin and its derivatives were chosen. Drug-likeness parameters were calculated for curcumin and its derivatives and 20 curcumin analogs were selected for docking analysis. From docking analysis of 20 curcumin analogs against five chosen human host receptor targets reveals 11 curcumin analogs possess least binding affinity and best interaction at active sites subjected to absorption, distribution, metabolism, excretion (ADME) analysis. Density functional theory (DFT) analysis of five final shortlisted curcumin derivatives was done to show least binding affinity toward chosen host target protein. Molecular dynamics simulation (MDS) was performed to observe behavior and interaction of potential drug hydrazinocurcumin against target proteins ACE-2 and PAR-1. It was performed at 100 nanoseconds and showed satisfactory results. Finally, our investigation reveals that hydrazinocurcumin possesses immunomodulatory and anti-cytokine therapeutic potential against COVID-19 and it can act as COVID-19 warrior drug molecule and promising choice of drug for COVID-19 treatment, however, it needs further in vivo clinical evaluation to commercialize as COVID-19 drug.Communicated by Ramaswamy H. Sarma.

We present numerical and experimental results for the generation of aperiodic motion in coupled active rotators. The numerical analysis is presented for two point particles constrained to move on a unit circle under the Yukawa-like interaction. Simulations exhibit that the collision among the rotors results in chaotic motion of the rotating point particles. Furthermore, the numerical model predicts a route to chaotic motion. Subsequently, we explore the effect of separation between the rotors on their chaotic dynamics. The numerically calculated fraction of initial conditions which led to chaotic motion shed light on the observed effects. We reproduce a subset of the numerical observations with two self-propelled ribbons rotating at the air-water interface. A pinned camphor rotor moves at the interface due to the Marangoni forces generated by surface tension imbalance around it. The camphor layer present at the common water surface acts as chemical coupling between two ribbons. The separation distance of ribbons (L) determines the nature of coupled dynamics. Below a critical distance (L&#95;{T}), rotors can potentially, by virtue of collisions, exhibit aperiodic oscillations characterized via a mixture of co- and counterrotating oscillations. These aperiodic dynamics qualitatively matched the chaotic motion observed in the numerical model.

We report the appearance of strange nonchaotic attractors in a discrete FitzHugh-Nagumo neuron model with discontinuous resetting. The well-known strange nonchaotic attractors appear in quasiperiodically forced continuous-time dynamical systems as well as in a discrete map with a small intensity of noise. Interestingly, we show that a discrete FitzHugh-Nagumo neuron model with a sigmoidal recovery variable and discontinuous resetting generates strange nonchaotic attractors without external force. These strange nonchaotic attractors occur as intermittency behavior (locally unstable behavior in laminar flow) in the periodic dynamics. We use various characterization techniques to validate the existence of strange nonchaotic attractors in the considered system.

Background: The prognosis of glioblastoma (GBM) remains dismal because therapeutic approaches have limited effectiveness. A new targeted treatment using MEK inhibitors, including trametinib, has been proposed to improve GBM therapy. Trametinib had a promising preclinical effect against several cancers, but its adaptive treatment resistance precluded its clinical translation in GBM. Previously, we have demonstrated that protein arginine methyltransferase 5 (PRMT5) is upregulated in GBM and its inhibition promotes apoptosis and senescence in differentiated and stem-like tumor cells, respectively. We tested whether inhibition of PRMT5 can enhance the efficacy of trametinib against GBM., Methods: Patient-derived primary GBM neurospheres (GBMNS) with transient PRMT5 knockdown were treated with trametinib and cell viability, proliferation, cell cycle progression, ELISA, and western blot were analyzed. In vivo, NSG mice were intracranially implanted with PRMT5-intact and -depleted GBMNS, treated with trametinib by daily oral gavage, and observed for tumor progression and mice survival rate., Results: PRMT5 depletion enhanced trametinib-induced cytotoxicity in GBMNS. PRMT5 knockdown significantly decreased trametinib-induced AKT and ERBB3 escape pathways. However, ERBB3 inhibition alone failed to block trametinib-induced AKT activity suggesting that the enhanced antitumor effect imparted by PRMT5 knockdown in trametinib-treated GBMNS resulted from AKT inhibition and not ERBB3 inhibition. In orthotopic murine xenograft models, PRMT5-depletion extended the survival of tumor-bearing mice, and combination with trametinib further increased survival., Conclusion: Combined PRMT5/MEK inhibition synergistically inhibited GBM in animal models and is a promising strategy for GBM therapy., (Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology 2022.)

Contamination of aquatic systems with pharmaceuticals, personal care products, steroid hormones, and agrochemicals has been an immense problem for the earth's ecosystem and health impacts. The environmental issues of well-known persistence pollutants, their metabolites, and other micro-pollutants in diverse aquatic systems around the world were collated and exposed in this review assessment. Waste Water Treatment Plant (WWTP) influents and effluents, as well as industrial, hospital, and residential effluents, include detectable concentrations of known and undiscovered persistence pollutants and metabolites. These components have been found in surface water, groundwater, drinking water, and natural water reservoirs receiving treated and untreated effluents. Several studies have found that these persistence pollutants, and also similar recalcitrant pollutants, are hazardous to a variety of non-targeted creatures in the environment. In human and animals, they can also have severe and persistent harmful consequences. Because these pollutants are harmful to aquatic organisms, microbial degradation of these persistence pollutants had the least efficiency. Fortunately, only a few wild and Genetically Modified (GMOs) microbial species have the ability to degrade these PPCPs contaminants. Hence, researchers have been studying the degradation competence of microbial communities in persistence pollutants of Pharmaceutical and Personal Care Products (PPCPs) and respective metabolites for decades, as well as possible degradation processes in various aquatic systems. As a result, this review provides comprehensive information about environmental issues and the degradation of PPCPs and their metabolites, as well as other micro-pollutants, in aquatic systems., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Donning of personal protective equipment (PPE) in the healthcare sector has been intensified by the on-going COVID-19 pandemic around the globe. While extensive PPE provides protection, it typically limits moisture permeability and severely hinders the sweat evaporation process, resulting in greater heat stress on the personnel. Herein, a zinc-poly(vinyl alcohol) (Zn-PVA) composite film is fabricated by embedding a super-hygroscopic zinc-ethanolamine complex (Zn-complex) in the PVA matrix. By attaching the Zn-PVA composite film, the relative humidity (RH) inside the protective suit decreases from 91.0% to 48.2%. The reduced RH level, in turn, enhances evaporative cooling, hence bringing down the heat index from 64.6 to 40.0 °C at an air temperature of 35 °C, remarkably lowering the likelihood of heat stroke. The American Society for Testing and Materials tests conducted on a sweating manikin have also proven that the Zn-PVA composite films can significantly reduce the evaporative resistance of the protective suit by 90%. The low material cost, facile fabrication process, and reusability allow the Zn-PVA composition films to be readily available for healthcare workers worldwide. This application can be further extended to other occupations that are facing severe thermal discomfort and heat stress., (© 2022 Wiley-VCH GmbH.)

This study aims to develop an eco-friendly method for rapidly synthesizing silver nanoparticles (AgNPs) using Asafoetida ethanol extracts and to validate AgNPs synthesis using UV-vis spectroscopy (absorption spectrum), FTIR (functional groups), XRD (crystallinity), FE-SEM (size of the particles) and SEM-EDAX (Purity). Furthermore, to evaluate the anti-proliferative effect of Ag NPs against grown cultured L6 cell lines, studies have shown that AgNPs biosynthesis inhibits cancer cell growth compared to control cell lines. UV-vis absorption verified the existence of Ag NPs, and the spectrum was observed at 480 nm. Functional groups are present in the synthesized Ag NPs were shifted on 528.48 cm -1 confirmed using an FT-IR spectrum. Consequently, anti-cancer efficacy observed the IC 50 value of As Ag NPs against L6 cells was 1.0 μg/mL for 48 h. Finally, using a halogen lamp, studies explored the photocatalytic degradation of AgNPs against the methylene blue radioactive dye and achieved a 96 percent degradation rate in 90 min. Asafoetida mediated silver nanoparticles show grater photodegradation for methylene blue dye, which is present in textile industries, when exposed to solar light, and it has a wide range of potential applications in wastewater treatment. As a whole, biosynthesized silver nanoparticles showed excellent cytotoxic, antioxidant, and photocatalytic dye degradation effects., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Identifying patients with BRCA mutations is clinically important to inform on the potential response to treatment and for risk management of patients and their relatives. However, traditional referral routes may not meet clinical needs, and therefore, mainstreaming cancer genetics has been shown to be effective in some high-income and high health-literacy settings. To date, no study has reported on the feasibility of mainstreaming in low-income and middle-income settings, where the service considerations and health literacy could detrimentally affect the feasibility of mainstreaming., Methods: The Mainstreaming Genetic Counselling for Ovarian Cancer Patients (MaGiC) study is a prospective, two-arm observational study comparing oncologist-led and genetics-led counselling. This study included 790 multiethnic patients with ovarian cancer from 23 sites in Malaysia. We compared the impact of different method of delivery of genetic counselling on the uptake of genetic testing and assessed the feasibility, knowledge and satisfaction of patients with ovarian cancer., Results: Oncologists were satisfied with the mainstreaming experience, with 95% indicating a desire to incorporate testing into their clinical practice. The uptake of genetic testing was similar in the mainstreaming and genetics arm (80% and 79%, respectively). Patient satisfaction was high, whereas decision conflict and psychological impact were low in both arms of the study. Notably, decisional conflict, although lower than threshold, was higher for the mainstreaming group compared with the genetics arm. Overall, 13.5% of patients had a pathogenic variant in BRCA1 or BRCA2, and there was no difference between psychosocial measures for carriers in both arms., Conclusion: The MaGiC study demonstrates that mainstreaming cancer genetics is feasible in low-resource and middle-resource Asian setting and increased coverage for genetic testing., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aim: Lung as a target end organ for microvascular disease often remains underdiagnosed. This study aims to assess occurrence of pulmonary microangiopathy among Type 2 diabetes mellitus (T2DM) using dynamic diffusion lung capacity of carbon monoxide (DLCO)., Methods: A total of 120 participants aged >18 years were enrolled in this study. Group 1 comprised T2DM with microangiopathy (n = 40), group 2 include T2DM without microangiopathy (n = 40), group 3 were healthy controls (n = 40). Individuals with underlying lung disease, smoking history, heart failure, urinary tract infection, macrovascular complications of diabetes, microalbuminuria due to other causes were excluded from the study. Using electronic spirometry, Forced Expiratory Volume in first second (FEV1), Forced Vital Capacity (FVC) was measured and FEV1/FVC ratio calculated. DLCO (%predicted) using single breath method was measured in sitting position followed by supine position and delta DLCO was calculated. DLCO measured was compared between the three groups., Results: DLCO (median [IQR]) in sitting (78 [70-82.75]) and supine position (70 [62-84]) among group one was significantly decreased when compared to other two groups (p value < 0.001, p value < 0.001 respectively). Delta DLCO (median, [IQR]) among patients with diabetic microangiopathy (-6 [-8 to -2]) was significant on comparison with group two (4[2,6]) and control group (5[4,6]) (p < 0.001). Negative delta DLCO reflecting pulmonary microangiopathy was significantly associated with extrapulmonary microangiopathy (p value = 0.027)., Conclusion: Postural variation in DLCO is a useful non-invasive test for identifying pulmonary microangiopathy among T2DM patients. Presence of pulmonary microangiopathy has significant association with diabetic nephropathy and retinopathy., Competing Interests: Declaration of competing interest All authors declare that there is no conflict of interest., (Copyright © 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Expression of Regulated endocrine specific protein 18 (Resp18) is localized in numerous tissues and cell types; however, its exact cellular function is unknown. We previously showed that targeted disruption of the Resp18 locus in the Dahl SS (SS) rat (Resp18 mutant ) results in higher blood pressure (BP), increased renal fibrosis, increased urinary protein excretion, and decreased mean survival time following a chronic (6 weeks) 2% high salt (HS) diet compared with the SS rat. Based on this prominent renal injury phenotype, we hypothesized that targeted disruption of Resp18 in the SS rat promotes an early onset hypertensive-signaling event through altered signatures of the renal transcriptome in response to HS. To test this hypothesis, both SS and Resp18 mutant rats were exposed to a 7-day 2% HS diet and BP was recorded by radiotelemetry. After a 7-day exposure to the HS diet, systolic BP was significantly increased in the Resp18 mutant rat compared with the SS rat throughout the circadian cycle. Therefore, we sought to investigate the renal transcriptomic response to HS in the Resp18 mutant rat. Using RNA sequencing, Resp18 mutant rats showed a differential expression of 25 renal genes, including upregulation of Ren. Upregulation of renal Ren and other differentially expressed genes were confirmed via qRT-PCR. Moreover, circulating renin activity was significantly higher in the Resp18 mutant rat compared with the WT SS rat after 7 days on HS. Collectively, these observations demonstrate that disruption of the Resp18 gene in the SS rat is associated with an altered renal transcriptomics signature as an early response to salt load., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

We study the propagation of rare or extreme events in a network of coupled nonlinear oscillators, where counter-rotating oscillators play the role of the malfunctioning agents. The extreme events originate from the coupled counter-oscillating pair of oscillators through a mechanism of saddle-node bifurcation. A detailed study of the propagation and the destruction of the extreme events and how these events depend on the strength of the coupling is presented. Extreme events travel only when nearby oscillators are in synchronization. The emergence of extreme events and their propagation are observed in a number of excitable systems for different network sizes and for different topologies.

The accumulated bauxite mine soil had an acidic pH of 5.52 ± 0.12 and more heavy metals such as Cr, Cd, Zn, and Pb, which can cause severe soil and water pollution to the nearby farmlands and water reservoirs. Hence, the work was designed to find the possibility of reclamation of bauxite mine soil through Crotalaria juncea with the amalgamation of native metal degrading bacterial isolates. Out of 15 bacterial cultures, only 2 isolates (B3 and B14) showed excellent metal tolerance (for up to 750 mg L -1 ), solubilizing (15.27-38.7 mg kg -1 ) (including phosphate: 47.4 ± 1.79%), and degrading potential (22.8 ± 0.89 to 31.5 ± 1.6%) than the others. These B3 and B14 isolates were recognized as B. borstelensis UTM105 (1432 bp) and B. borstelensis AK2 (1494 bp) through molecular characterization. These isolates have produced a metal stress response protein (205-43 KDa molecular weight protein) during metal stress conditions. The phytoremediation competence of C. juncea under the influence of these bacterial isolates was assessed with various treatment (I-IV) schemes. The treatment IV (C. juncea with two bacterial isolates) showed substantial physiological and biochemical results compared with the control and the other treatments. The phytoremediation competence of C. juncea was also effective in treatment IV than the others. It reduced and extracted a reasonable quantity of metals from the bauxite mine soil. The intact results accomplished that these native metals tolerant, solubilizing, and degrading bacterial isolates, could be used as optimistic bacterial candidates in combination with C. juncea for the effective reclamation of metal enriched bauxite mine soil., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Slow and fast dynamics of unsynchronized coupled nonlinear oscillators is hard to extract. In this paper, we use the concept of perpetual points to explain the short duration ordering in the unsynchronized motions of the phase oscillators. We show that the coupled unsynchronized system has ordered slow and fast dynamics when it passes through the perpetual point. Our simulations of single, two, three, and 50 coupled Kuramoto oscillators show the generic nature of perpetual points in the identification of slow and fast oscillations. We also exhibit that short-time synchronization of complex networks can be understood with the help of perpetual motion of the network.

Rectal foreign bodies are not uncommon and often pose a serious challenge to surgeons. In majority, the objects are inserted by self in children, psychiatric patients and for sexual gratification in adults. Various rectal foreign bodies have been reported. Deodorant aerosol spray can in the rectum has not been reported previously. Danger of aerosol dispenser can is the risk of fire and explosion. Especially during any surgical procedures to remove the foreign body using cautery or any energy devices. We report of a rare foreign body of deodorant aerosol spray can in the rectum in a young male patient, which was removed under general anaesthesia., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Since the outbreak of COVID-19, there have already been over 26 million people being infected and it is expected that the pandemic will not end in near future. Not only the daily activities and lifestyles of individuals have been affected, the medical practice has also been modified to cope with this emergency catastrophe. In particular, the cancer services have faced an unprecedented challenge. While the services may have been cut by the national authorities or hospitals due to shortage of manpower and resources, the medical need of cancer patients has increased. Cancer patients who are receiving active treatment may develop various kinds of complications especially immunosuppression from chemotherapy, and they and their carers will need additional protection against COVID-19. Besides, there is also evidence that cancer patients are more prone to deteriorate from COVID-19 if they contract the viral infection. Therefore, it is crucial to establish guidelines so that healthcare providers can triage their resources to take care of the most needed patients, reduce less important hospitalization and visit, and to avoid potential complications from treatment. The Asia and Oceania Federation of Obstetrics and Gynecology (AOFOG) hereby issued this opinion statement on the management of gynecological cancer patients during the COVID-19., (© 2021 Japan Society of Obstetrics and Gynecology.)

Abandoned magnesite mine heap causing pollution to nearby farmland and water reservoir. Thus the intention of this research was to screening metal mobilizing and absorbing bacteria from the rhizosphere section of V. unguiculata from farmland nearby to magnesite mine. Further, studied their stimulus effect on growth, biomass, and phytoextraction prospective of V unguiculata in mine tailing. The results of the physicochemical properties of mine tailing shows that four metals (Pb, Mn, Cd, and Zn) were crossing the permissible limit. Out of 27 isolates, 2 isolates (MMS15 and MMS17) were identified with maximum metal tolerance for up to 700 mg L -1 (MIC) and metal mobilization (Pb 5.5 and 5.87, Mn 6.6 and 4.88, Cd 1.99 and 2.59, and Zn 6.55 and 6.94 mg kg -1 ) and biosorption efficiency as Pb 3.74 and 3.74, Mn 4.9 and 4.7, Cd 2.41 and 3.96, and Zn 4.3 and 4.9 mg g -1 . These two strains were identified as members of B. cereus and Kosakonia sp. using 16S rRNA technique and labelled strains NDRMN001 and MGR1, respectively. The Kosakonia sp. MGR1 effectively fixes the nitrogen in the rate of 81.94% and B. cereus NDRMN001 solubilizes 69.98 ± 2.31 mg L -1 of soluble phosphate. The experimental group's study results show that the group C (Kosakonia sp. MGR1 and B. cereus NDRMN001) has effectively stimulate the growth, biomass, and phytoextraction potential of V. unguiculata. The results conclude that the optimistic interaction between these two bacteria could be more significant to minimize the metal pollution in magnesite mine tailing.

Background: Cardiovascular diseases (CVD) are one of the leading causes of mortality and morbidity worldwide. Biological aging has been associated with the occurrence of adverse cardiovascular outcomes; however, the underlying mechanism of this process remains unknown., Objectives: This study sought to evaluate if peripheral blood mononuclear cell (PBMC) senescence and endothelial biomarkers could influence cardiovascular (CV) risk and be suitable markers for the early detection of cardiovascular diseases in adults., Methods: In this cross-sectional study patients free of CVD were classified as lower (n=32) and higher Interheart Risk (IHR) scores (n=28). PBMC senescence was assessed by estimating the telomerase activity (TA) and detecting the presence of senescent cells and endothelial dysfunction by estimating the concentration of nitrite and nitrate and of total antioxidant capacity (TAC). Statistical analysis was performed with SPSS version 16.0 (SPSS Inc., Chicago, IL). All p-values <0.05 were considered statistically significant., Results: PBMC senescence 0.95 [p-value = 0.0001; 95% CI (0.874-1.026)] was a significant predictor of patients with higher IHR scores with a cut-off value of 21.65 with a sensitivity and specificity of 92% and 88% respectively. PBMC senescence, nitrite and nitrate and TA were found to be independently associated with high IHR scores., Conclusion: PBMC senescence, TA and nitrite, and nitrate status are suitable measures to predict high cardiovascular risk in adults with CV risk. Nevertheless, long-term follow-up studies are needed to confirm these findings. (Arq Bras Cardiol. 2021; 116(1):37-47).

Background: Type 2 diabetes (adult onset diabetes) is the most common type of diabetes, accounting for around 90% of all diabetes cases with insulin resistance and insulin secretion defect. The key goal of anti-diabetic therapy is to increase the development of insulin, immunity and/or decrease the amount of blood glucose. While many synthetic compounds have been produced as antidiabetic agents, due to their side effects and limited effectiveness, their usefulness has been hindered., Methods: This systematic review investigated the bioactive compounds reported to possess activities against type 2 diabetes. Three (3) databases, PubMed, ScienceDirect and Google Scholar were searched for research articles published between January 2010 and October 2020. A total of 6464 articles were identified out of which 84 articles were identified to be elligible for the study., Result and Discussion: From the data extracted, it was found that quercetin, Kaempferol, Rosmarinic acid, Cyanidin, Rutin, Catechin, Luteolin and Ellagic acid were the most cited bioactive compounds which all falls within the class of polyphenolic compounds. The major sources of these bioactive compounds includes citrus fruits, grapes, onions, berries, cherries, broccoli, honey, apples, green tea, Ginkgo biloba, St. John's wort, green beans, cucumber, spinach, tea, Rosmarinus officinalis, Aloe vera, Moringa oleifera, tomatoes, potatoes, oregano, lemon balm, thyme, peppermint, Ocimum basilicum, red cabbage, pears, olive oil and walnut., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The prime aim of this study was to enumerate predominant bacteria from polluted lake soil samples, which possess polyhydroxybutyrate (PHB) fabricating potential and identify the suitable growth conditions and nutritional factors for PHB fabrication. From several numbers of bacterial cultures, one culture has the competence to yield PHB, and it was endorsed through Sudan Black B stain, Nile red staining, SEM analysis, and growth in PHB selective media. Under the microscopic observation, the fluorescent cells and polymeric granules were observed in the fluorescent microscope and SEM, respectively. This PHB fabricating isolate was recognized as Bacillus cereus NDRMN001 through 16S rRNA partial sequence analysis. The structural characteristics of PHB produced by B. cereus NDRMN001 were studied through FT-IR, 1 H NMR, and 13 C NMR analysis. The peak observed at 1759.27 cm -1 on FT-IR analysis is corresponding to the signal band of PHB. In 1 H NMR peaks were noticed at 1.67, 2.37 to 2.71, and 3.38 to 7.68 which corresponding to -CH3, -CH2, and -CH protons of PHB. About 4 notable peaks were noticed in 13 C NMR analysis at 19.62, 68.27, 40.68, and 169.11 ppm which appeared close to the carboxyl group of PHB. About 10% of inoculum, pH 7.5, 2 g L of yeast extract, 20 g L of rice bran, 35 °C, and 2 days of incubation were recognized as optimal growth conditions for B. cereus NDRMN001 to produce PHB. The identified B. cereus NDRMN001 has the potential to yield 91.48% of PHB as 33.19 g L of PHB from 36.26 g L of culture biomass. The complete results conclude that the B. cereus NDRMN001 screened from polluted lake soil has the competence to produce fine quality and quantity of PHB in a short duration of fabrication process under favorable conditions with the utilization of cheap nutritional factors., (© 2020 Published by Elsevier Ltd.)

Background Renal artery stenosis is a common cause of renal ischemia, contributing to the development of chronic kidney disease. To investigate the role of local CD40 expression in renal artery stenosis, Goldblatt 2-kidney 1-clip surgery was performed on hypertensive Dahl salt-sensitive rats (S rats) and genetically modified S rats in which CD40 function is abolished ( Cd40 mutant rats demonstrated significantly reduced blood pressure and renal fibrosis in the ischemic kidneys compared with S rat controls. Similarly, disruption of Cd40 resulted in reduced 24-hour urinary protein excretion in Cd40 rats versus S rat controls (46.2±1.9 versus 118.4±5.3 mg/24 h; mutant rats demonstrated significantly reduced blood pressure and renal fibrosis in the ischemic kidneys compared with S rat controls. Similarly, disruption of Cd40 resulted in reduced 24-hour urinary protein excretion in Cd40 rats versus S rat controls ( mutant rats versus S rat controls (46.2±1.9 versus 118.4±5.3 mg/24 h; P <0.01), as well as protection from oxidative stress, as indicated by increased paraoxonase activity in Cd40 mutant rats versus S rat controls ( P <0.01). Ischemic kidneys from Cd40 <0.001), compared with S rat ischemic kidneys, as assessed by quantitative PCR assay. Reciprocal renal transplantation documented that CD40 exclusively expressed in the kidney contributes to ischemia-induced renal fibrosis. Furthermore, human CD40-knockout proximal tubule epithelial cells suggested that suppression of CD40 signaling significantly inhibited expression of proinflammatory and -fibrotic genes. Conclusions Taken together, our data suggest that activation of CD40 induces a significant proinflammatory and -fibrotic response and represents an attractive therapeutic target for treatment of ischemic renal disease. mutant rats demonstrated a significant decrease in gene expression of the profibrotic mediator, plasminogen activator inhibitor-1 ( P <0.05), and the proinflammatory mediators, C-C motif chemokine ligand 19 ( P <0.01), C-X-C Motif Chemokine Ligand 9 ( P <0.01), and interleukin-6 receptor ( P <0.001), compared with S rat ischemic kidneys, as assessed by quantitative PCR assay. Reciprocal renal transplantation documented that CD40 exclusively expressed in the kidney contributes to ischemia-induced renal fibrosis. Furthermore, human CD40-knockout proximal tubule epithelial cells suggested that suppression of CD40 signaling significantly inhibited expression of proinflammatory and -fibrotic genes. Conclusions Taken together, our data suggest that activation of CD40 induces a significant proinflammatory and -fibrotic response and represents an attractive therapeutic target for treatment of ischemic renal disease.

Here we postulate that the heritability of complex disease traits previously ascribed solely to the inheritance of the nuclear and mitochondrial genomes is broadened to encompass a third component of the holobiome, the microbiome. To test this, we expanded on the selectively bred low capacity runner/high capacity runner (LCR/HCR) rat exercise model system into four distinct rat holobiont model frameworks including matched and mismatched host nuclear and mitochondrial genomes. Vertical selection of varying nuclear and mitochondrial genomes resulted in differential acquisition of the microbiome within each of these holobiont models. Polygenic disease risk of these novel models were assessed and subsequently correlated with patterns of acquisition and contributions of their microbiomes in controlled laboratory settings. Nuclear-mitochondrial-microbiotal interactions were not for exercise as a reporter of health, but significantly noted for increased adiposity, increased blood pressure, compromised cardiac function, and loss of long-term memory as reporters of disease susceptibility. These findings provide evidence for coselection of the microbiome with nuclear and mitochondrial genomes as an important feature impacting the heritability of complex diseases.

The present study describes the synthesis of a series of 22 chalcone analogs. These compounds were evaluated as potential human MAO-A and MAO-B inhibitors. The compounds showed varied selectivity against the two isoforms. The IC 50 values were found to be in the micromolar to submicromolar range. The K i values of compound 16 were determined to be 0.047 and 0.020 μM for the inhibition of MAO-A and MAO-B, respectively. Dialysis of enzyme-inhibitor mixtures indicated a reversible competitive mode of inhibition. Most of the synthesized chalcone analogs showed a better selectivity toward MAO-B. However, introducing of 2,4,6-trimethoxy substituents on ring B shifted the selectivity toward MAO-A. In addition, we investigated the molecular mechanism of MAO-B inhibition by selected chalcone analogs. Our results revealed that these selected chalcone analogs increased dopamine levels in the rat hepatoma (H4IIE) cells and decreased the relative mRNA expression of the MAO-B enzyme.