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The function of the gonadotropin-releasing hormone (GnRH) neuron is critical to maintain reproductive function and a significant decrease in GnRH can lead to disorders affecting fertility, including hypogonadotropic hypogonadism. Spexin (SPX) is a novel hypothalamic neuropeptide that exerts inhibitory effects on reproduction and feeding by acting through galanin receptor 2 (GALR2) and galanin receptor 3 (GALR3). Fatty acids can act as nutritional signals that regulate the hypothalamic-pituitary-gonadal (HPG) axis, and elevated levels of circulating saturated fatty acids associated with high fat diet (HFD)-feeding have been shown to induce neuroinflammation, endoplasmic reticulum stress and hormonal resistance in the hypothalamus, as well as alter neuropeptide expression. We previously demonstrated that palmitate, the most common saturated fatty acid in a HFD, elevates the expression of Spx, Galr2 and Galr3 mRNA in a model of appetite-regulating neuropeptide Y hypothalamic neurons. Here, we found that Spx, Galr2 and Galr3 mRNA were also significantly induced by palmitate in a model of reproductive GnRH neurons, mHypoA-GnRH/GFP. As a follow-up to our previous report, we examined the molecular pathways by which Spx and galanin receptor mRNA was regulated in this cell line. Furthermore, we performed inhibitor studies, which revealed that the effect of palmitate on Spx and Galr3 mRNA involved activation of the innate immune receptor TLR4, and we detected differential regulation of the three genes by the protein kinases PKC, JNK, ERK, and p38. However, the intracellular metabolism of palmitate to ceramide did not appear to be involved in the palmitate-mediated gene regulation. Overall, this suggests that SPX may play a role in reproduction at the level of the hypothalamus and the pathways by which Spx, Galr2 and Galr3 are altered by fatty acids could provide insight into the mechanisms underlying reproductive dysfunction in obesity.The hypothalamic-pituitary axis (HP axis) plays a critical and integrative role in the endocrine system control to maintain homeostasis. The HP axis is responsible for the hormonal events necessary to regulate the thyroid, adrenal glands, gonads, somatic growth, among other functions. Endocrine-disrupting chemicals (EDCs) are a worldwide public health concern. There is growing evidence that exposure to EDCs such as bisphenol A (BPA), some phthalates, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and biphenyls (PBBs), dichlorodiphenyltrichloroethane (DDT), tributyltin (TBT), and atrazine (ATR), is associated with HP axis abnormalities. EDCs act on hormone receptors and their downstream signaling pathways and can interfere with hormone synthesis, metabolism, and actions. Because the HP axis function is particularly sensitive to endogenous hormonal changes, disruptions by EDCs can alter HP axis proper function, leading to important endocrine irregularities. Here, we review the evidence that EDCs could directly affect the mammalian HP axis function.Wheat aphids are major wheat sap sucking pests found throughout the world. The analysis of wheat aphid population dynamics to develop aphid control strategies is therefore important. Even if all factors that control the size of aphid populations are known, several mathematical tools are needed to help us understand their combined effect. Based on the knowledge of population ecology and catastrophe theory, we proposed a generalized population dynamics model to describe variation of wheat aphid populations and obtained a dynamic threshold function for aphid control. Field survey data from 1997 to 2002 were used to validate this model. The results indicated the model could predict the results of practical measures against a pest if the factors of their immediate effects are known or could be estimated. By explaining and forecasting the size of an aphid outbreak and its probability of occurrence, this catastrophe model can provide a scientific basis for wheat aphid control.A new nonlinear phenomenon has been studied theoretically on one of the main cytoskeletal element of eukaryotic cells, namely chaos in microtubules vibrations. The general model of microtubules is used to draw phase portraits and Lyapunov spectra. The examination of numerical results reveals that the velocity of the chaotic wave could be the physical parameter that governs chaos. The energy released after the hydrolysation of guanosine triphosphate is converted to active turbulence leading to chaos. The high values of the Lyapunov exponents give hints that there are strong dissipations yielding in the lessening of the velocity of chaotic wave propagation in the microtubules. Moreover, the role of chaos in information processing has been established in microtubules. The energy coming from hydrolysis of guanosine triphosphate stimulates the tubulin leading it to probe its environment and collect information. The net sum of Lyapunov exponents is found to be positive in this stage of the process. CA-074 methyl ester order Also, the collected information is compressed with a negative sum of Lyapunov exponents. Eventually, the compressibility rate has been estimated to be η=67.2%, and 1.11 bit is lost.Sickle cell disease is prevalent in several parts of the world. Most hospitalizations of these patients are related to pain crisis episodes. Moreover, levels of hemoglobin are lower in sickle cell disease patients as compared with the general population. Complications related to sickle cell disease are managed with blood transfusions, hydroxyurea, and opioids. Despite these therapies, patients with sickle cell disease experience multiple pain crisis episodes leading to hospitalizations and end-organ damage. The US Food and Drug Administration has approved three new drugs-L-glutamine, voxelotor, and crizanlizumab-for the prophylaxis and treatment of complications related to sickle cell disease. This review was aimed at assessing the efficacy and safety of recently approved drugs for the treatment of sickle cell disease. A comprehensive search was made on PubMed and clinicaltrials.gov to look for clinical trials reporting the efficacy and safety of recently approved drugs for sickle cell disease. Based on the results of clinical trials, L-glutamine, voxelotor, and crizanlizumab were well tolerated by sickle cell disease patients. L-Glutamine and crizanlizumab reduced the number of sickle cell crisis episodes, while voxelotor improved the level of hemoglobin in sickle cell disease patients. These drugs were effective alone and in combination with hydroxyurea.

In pandemics such as COVID-19, shortages of personal protective equipment are common. One solution may be to decontaminate equipment such as facemasks for reuse.

To collect and synthesize existing information on decontamination of N95 filtering facepiece respirators (FFRs) using microwave and heat-based treatments, with special attention to impacts on mask function (aerosol penetration, airflow resistance), fit, and physical traits.

A systematic review (PROSPERO CRD42020177036) of literature available from Medline, Embase, Global Health, and other sources was conducted. Records were screened independently by two reviewers, and data was extracted from studies that reported on effects of microwave- or heat-based decontamination on N95 FFR performance, fit, physical traits, and/or reductions in microbial load.

Thirteen studies were included that used dry/moist microwave irradiation, heat, or autoclaving. All treatment types reduced pathogen load by a log

reduction factor of at least three when applied for sufficient duration (>30s microwave, >60min dry heat), with most studies assessing viral pathogens. Mask function (aerosol penetration <5% and airflow resistance <25 mmH

O) was preserved after all treatments except autoclaving. Fit was maintained for most N95 models, though all treatment types caused observable physical damage to at least one model.

Microwave irradiation and heat may be safe and effective viral decontamination options for N95 FFR reuse during critical shortages. The evidence does not support autoclaving or high-heat (>90°C) approaches. Physical degradation may be an issue for certain mask models, and more real-world evidence on fit is needed.

90°C) approaches. Physical degradation may be an issue for certain mask models, and more real-world evidence on fit is needed.Transmission of coronavirus disease 2019 (COVID-19) in healthcare settings has significant implications for patients and healthcare workers, may amplify local outbreaks, and may place additional burden on already stretched resources. Risk of missed or late diagnosis of COVID-19 was high during the UK's initial 'containment phase', because of strict criteria for testing. The risk remains due to asymptomatic/pre-symptomatic transmission, complicated by challenges faced with laboratory testing. We present a case study of potential nosocomial transmission associated with the first case of COVID-19 at a large acute NHS Trust in South-West London, and we describe the prevailing burden of nosocomial infections.

Scutellariabarbata D. Don extraction (SBE), a traditional Chinese medicine, has been proved effective against various malignant disorders in clinics with tolerable side-effects when administered alone or in combination with conventional chemotherapeutic regimens.

Multi-drug resistance of cancer is attributed to existence of cancer stemness-prone cells that harbor aberrantly high activation of Sonic Hedgehog (SHH) cascade. Our previous study has demonstrated that SBE sensitized non-small cell lung cancer (NSCLC) cells to Cisplatin (DDP) treatment by downregulating SHH pathway. Yet, whether SBE could prohibit proliferation of cancer stemness-prone cells and its underlying molecular mechanisms remain to be investigated. In this article, we further investigated intervention of SBE on NSCLC cell stemness-associated phenotypes and its potential mode of action.

CCK-8 and clonal formation detection were used to measure the anti-proliferative potency of SBE against NSCLC and normal epithelial cells. Sphere formaness-related features of NSCLC cells via targeting SOX2 and may serve as an alternative therapeutic option for clinic treatment.

Plumeria rubra L. (Apocynaceae) is a deciduous, commonly ornamental, tropical plant grown in home premises, parks, gardens, graveyards, because of its beautiful and attractive flowers of various colours and size. The different parts of the plant are used traditionally to treat various diseases and conditions like leprosy, inflammation, diabetic mellitus, ulcers, wounds, itching, acne, toothache, earache, tongue cleaning, pain, asthma, constipation and antifertility.

The main aim of this review is to provide an overview and critically analyze the reported ethnomedical uses, phytochemistry, pharmacological activities and toxicological studies of P. rubra and to identify the remaining gaps and thus supply a basis for further investigations. The review also focuses towards drawing attention of people and researchers about the wide spread pharmaceutical properties of the plant for its better utilization in the coming future.

All the relevant data and information on P. rubra was gathered using various databases such as PubMed, Springer, Taylor and Francis imprints, NCBI (National Center for Biotechnology Information), Science direct, Google scholar, Chemspider, SciFinder, research and review articles from peer-reviewed journals and unpublished data such as Phd thesis, etc.

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