Academic publishing requires linguistically inclusive policies.

Scientific knowledge is produced in multiple languages but is predominantly published in English. This practice creates a language barrier to generate and transfer scientific knowledge between communities with diverse linguistic backgrounds, hindering the ability of scholars and communities to address global challenges and achieve diversity and equity in science, technology, engineering and mathematics (STEM). To overcome those barriers, publishers and journals should provide a fair system that supports non-native English speakers and disseminates knowledge across the globe. We surveyed policies of 736 journals in biological sciences to assess their linguistic inclusivity, identify predictors of inclusivity, and propose actions to overcome language barriers in academic publishing. Our assessment revealed a grim landscape where most journals were making minimal efforts to overcome language barriers. The impact factor of journals was negatively associated with adopting a number of inclusive policies whereas ownership by a scientific society tended to have a positive association. Contrary to our expectations, the proportion of both open access articles and editors based in non-English speaking countries did not have a major positive association with the adoption of linguistically inclusive policies. We proposed a set of actions to overcome language barriers in academic publishing, including the renegotiation of power dynamics between publishers and editorial boards.

Misalignment of plastic and evolutionary responses of lifespan to novel carbohydrate diets.

Diet elicits varied effects on longevity across a wide range of animal species where dietary discordance between an organisms' evolutionary and developmental dietary history is increasingly recognized to play a critical role in shaping lifespan. However, whether such changes, predominantly assessed in a single generation, lead to evolutionary shifts in lifespan remains unclear. In this study, we used an experimental evolution approach to test whether changes in an organisms' evolutionary and developmental dietary history, specifically carbohydrate content, causes lifespan evolution in Drosophila serrata. After 30 generations, we investigated the evolutionary potential of lifespan in response to four novel diets that varied systematically in their ratio of carbohydrate-protein content. We also examined developmental plasticity effects using a set of control populations that were raised on the four novel environments allowing us to assess the extent to which plastic responses of lifespan mirrored adaptive responses observed following experimental evolution. Both high- and low-carbohydrate diets elicited plastic effects on lifespan; however, the plastic responses for lifespan to developmental diets bore little resemblance to the evolved responses on evolutionary diets. Understanding the dietary conditions regulating the match/mismatch of plastic and evolved responses will be important in determining whether a particular match/mismatch combination is adaptive for lifespan. While the differences in evolutionary diet by developmental diet interactions are only beginning to be elucidated, this study lays the foundation for future investigations of carbohydrate contributions to evolved and plastic effects on health and lifespan.

Updated Intrinsic Role of Phytochemicals against Glyphosate-induced Neurotoxicity: Systematic Review.

BACKGROUND: Glyphosate-based herbicide (GBH) formulations are organophosphorus pesticides implicated for agricultural use. Several epidemiological reports have reported that the occupational exposure of farmers to glyphosate can cause age-related neurodegeneration. OBJECTIVE: the objective of this study is to examine the neurotoxic effects of glyphosate and its intricate role in triggering several neurodegenerative diseases like dementia, nootropic defects, Parkinson's disease, and neurological teratogenic effects due to its negative effects on the nervous system. Furthermore, the efficacy of phytochemicals against glyphosate-induced neurotoxicity was discussed. METHODS: We have searched public databases such as NLM, Pubmed, google scholar and collected a total of 103 articles including reviews, original articles, and obtained information related to glyphosate-induced neurotoxicity and novel phytochemicals implicated to ameliorate the glyphosate-induced neurotoxicity. We performed a systematic review without comprehensive meta-analysis. RESULTS: the efficacy of several phytochemicals as a nutritional intervention against glyphosate-induced neurotoxicity including Parkinsonism was elucidated by vivid review analysis of neurobehavioral alterations from in vitro and in vivo study models. CONCLUSION: These kinds of research projects will bring awareness about the neurotoxic effects of glyphosate and the protective nutritional intervention strategies against glyphosate-induced neurotoxicity including Parkinsonism for farmers.

Screening fructosamine-3-kinase (FN3K) inhibitors, a deglycating enzyme of oncogenic Nrf2: Human FN3K homology modelling, docking and molecular dynamics simulations.

Fructosamine-3-kinase (FN3K) is involved in the deglycation of Nrf2, a significant regulator of oxidative stress in cancer cells. However, the intricate functional aspects of FN3K and Nrf2 in breast cancers have not been explored vividly. The objectives of this study are to design the human FN3K protein using homology modeling followed by the screening of several anticancer molecules and examining their efficacy to modulate FN3K activity, Nrf2-mediated antioxidant signalling. Methods pertinent to homology modeling, virtual screening, molecular docking, molecular dynamics simulations, assessment of ADME properties, cytotoxicity assays for anticancer molecules of natural/synthetic origin in breast cancer cells (BT-474, T-47D), and Western blotting were used in this study. The screened anticancer molecules including kinase inhibitors of natural and synthetic origin interacted with the 3-dimensional structure of the catalytic domain in human FN3K protein designed through homology modeling by significant CDOCKER interaction energies. Subsequently, gefitinib, sorafenib, neratinib, tamoxifen citrate, and cyclosporine A enhanced the expression of FN3K in BT-474 cell lines with simultaneous alteration in Nrf2-driven antioxidant signalling. Oxaliplatin significantly downregulated FN3K expression and modulated Nrf2-driven antioxidant signalling when compared to cisplatin and other anticancer drugs. Hence, the study concluded the potential implications of existing anticancer drugs to modulate FN3K activity in breast cancers.

Inflammation and Stem Cell Stochasticity of HPV-induced Cervical Cancer: Epigenetics Based Biomarkers through Microbiome and Metabolome for Personalized Medicine: A Systematic Review.

BACKGROUND: Chemoresistance by stemness in HPV-induced cervical carcinogenesis has significant implications for the overall disease-specific survival of the patients. To date, there are no reports related to the implications of significant aspects of inflammation and microbiome-- mediated epigenetics in cervical cancers. OBJECTIVE: The current systematic review delineates the significant aspects of the inflammation-related pathophysiology, cervical cancer diagnosis based on the HPV-indued stemness, and microbiome- mediated epigenetic markers to develop personalized therapies to target the stemness-acquired indefinitely dividing cancer stem cells. METHODS: We performed a systematic review without a meta- analysis. We searched several public databases, such as Pubmed, ReleMed, National Library of Medicine, and Scopus, related to inflammation, metabolomics, microbiome-mediated epigenetic markers, and HPV-induced stemness. RESULTS AND CONCLUSION: The review significantly described the correlation between microbial inflammation and stem cell stochasticity of HPV-Induced cervical cancer and the expression of epigenetics- based biomarkers through microbiome and metabolome to foster the cervical cancer progression. These are major risk factors that can cause cervical dysplasia with substantial therapy resistance in cervical cancer patients. The qualitative and quantitative examination of the spatial transcriptomic expression of these stemness markers in the dividing cervical cancer stem cells has significant implications in the clinical sector to develop early personalized medicine to prevent cervical precancerous lesions depending on the prognosis of the cervical cancer patients. Mainly, the combinatorial regimen of current therapeutic modalities, along with microbiome-related therapies with future landscape of epigenetics-modulated therapies, may enhance overall disease-specific survival by modulating the stochastic dynamics of basal epithelial cells across the cervical region.

Systems biology and machine learning approaches identify metabolites that influence dietary lifespan and healthspan responses across flies and humans.

Dietary restriction (DR) is a potent method to enhance lifespan and healthspan, but individual responses are influenced by genetic variations. Understanding how metabolism-related genetic differences impact longevity and healthspan are unclear. To investigate this, we used metabolites as markers to reveal how different genotypes respond to diet to influence longevity and healthspan traits. We analyzed data from Drosophila Genetic Reference Panel strains raised under AL and DR conditions, combining metabolomic, phenotypic, and genome-wide information. Employing two computational methods across species-random forest modeling within the DGRP and Mendelian randomization in the UK Biobank-we pinpointed key traits with cross-species relevance that influence lifespan and healthspan. Notably, orotate was linked to parental age at death in humans and counteracted DR effects in flies, while threonine extended lifespan, in a strain- and sex-specific manner. Thus, utilizing natural genetic variation data from flies and humans, we employed a systems biology approach to elucidate potential therapeutic pathways and metabolomic targets for diet-dependent changes in lifespan and healthspan.

Design, synthesis, and application of thermally responsive draw solutes for sustainable forward osmosis desalination: A review.

Forward osmosis (FO) is an emerging sustainable desalination technology; however, it is not a stand-alone process and requires an additional step to recover the water or regenerate the draw solute (DS), making it energy extensive. Therefore, incorporating inexpensive energy sources for DS regeneration is a viable solution to compete with reverse osmosis desalination technology. Hence, selecting suitable DS and its regeneration became a crucial research focus in FO desalination. Among various DSs reported, thermally responsive DSs (TRDS) provide an opportunity to integrate low-grade energy sources for DS regeneration. Utilizing such inexpensive energy will reduce fossil fuel energy demand, lower the cost of desalination, and minimize the carbon footprint. Hence, this review explores the TRDS for FO-based desalination with its design, synthesis, and applications. The manuscript has discussed the classification and selection criteria for the DSs, and how traditional and new-generation TRDSs are designed and synthesized from cationic and anionic moieties of ionic liquids, hydrogels, and other chemicals. The manuscript has also given importance to design criteria such as osmotic strength, viscosity, toxicity, and thermal stability for TRDSs. Furthermore, a detailed discussion on the FO performance, energy, and economic aspects of TRDSs has been reviewed, along with a discussion on the possible low-grade energy sources for the recovery of TRDS. Finally, the challenges and future directions for TRDSs have been discussed to drive FO toward sustainable desalination technology.

Laser-induced graphene-based electrochemical biosensors for environmental applications: a perspective.

Biosensors are miniaturized devices that provide the advantage of in situ and point-of-care monitoring of analytes of interest. Electrochemical biosensors use the mechanism of oxidation-reduction reactions and measurement of corresponding electron transfer as changes in current, voltage, or other parameters using different electrochemical techniques. The use of electrochemically active materials is critical for the effective functioning of electrochemical biosensors. Laser-induced graphene (LIG) has garnered increasing interest in biosensor development and improvement due to its high electrical conductivity, specific surface area, and simple and scalable fabrication process. The effort of this perspective is to understand the existing classes of analytes and the mechanisms of their detection using LIG-based biosensors. The manuscript has highlighted the potential use of LIG, its modifications, and its use with various receptors for sensing various environmental pollutants. Although the conventional graphene-based sensors effectively detect trace levels for many analytes in different applications, the chemical and energy-intensive fabrication and time-consuming processes make it imperative to explore a low-cost and scalable option such as LIG for biosensors production. The focus of these potential biosensors has been kept on detection analytes of environmental significance such as heavy metals ions, organic and inorganic compounds, fertilizers, pesticides, pathogens, and antibiotics. The use of LIG directly as an electrode, its modifications with nanomaterials and polymers, and its combination with bioreceptors such as aptamers and polymers has been summarized. The strengths, weaknesses, opportunities, and threats analysis has also been done to understand the viability of incorporating LIG-based electrochemical biosensors for environmental applications.

Multivariate Optimization for Determination of Favipiravir, a SARS-CoV-2 Molecule, by the Reverse-Phase Liquid Chromatographic Method Using a QbD Approach.

The object of the analytical work is to develop an analytical multivariate optimization for the determination of Favipiravir (FAV), a SARS-CoV-2 molecule, by the reverse-phase liquid chromatographic method using the analytical quality by design approach. FAV is used as an antiviral drug. Box-Behnken design is utilized for the optimization of the experiment and to identify the critical method parameters like the volume of acetonitrile, temperature and flow rate. Further, these factors are used to design the suitable mathematical models and illustrate their effect on various responses. This newly developed method utilized C18 column (5µm, 100 × 4.6 mm) and a temperature of 40°C with a flow rate of 0.5 mL/min. The mobile phase is composed of acetonitrile and ammonium acetate buffer (pH 4), in the ratio of 20:80v/v and the wavelength of HPLC UV-Detector was fixed to 323nm. This method is validated according to International Council for Harmonization Q2 (R1) guidelines. The System suitability is performed and the retention time of Favipiravir is 3.4min. The linearity range is obtained at 0.062 - 4 µg/mL with a correlation coefficient (r2 = 0.9979). The recovery is found to be in the range of 98.84-100%. Thus, the intended method is found to be simple and robust.

Updates on Molecular Targets and Epigenetic-Based Therapies for PCOS.

Polycystic ovarian syndrome (PCOS) can cause infertility in females due to hyperandrogenism and neuroendocrine abnormalities. The aim of this study is to decipher the impact of endocrine variables, hyperandogenism, insulin resistance, oxidative stress, and dietary conditions in PCOS conditions, subsequently to depict the role of epigenetic factors relative to phenotypic manifestations in PCOS conditions. We have reviewed several metabolic milieus pertinent to PCOS conditions. Comparative efficacies of various PCOS therapies, and recent clinical recommendations for the effective management of PCOS and role of metabolic/endocrine variables in PCOS conditions were described. Comparative therapeutic effects were vividly delineated according to the variable pathophysiology and internal variables during PCOS syndrome on the female body through the formation of cascade of endocrine pathology, which affects working capacity and fosters redox stress-induced cardiovascular, neural, and liver abnormalities. GLP-1 agonists, insulin sensitizers (metformin), and diet and exercise regimens efficacy were explained in enhancing the fertility outcomes among the overweight or obese females with PCOS. Comprehensive appraisal of DNA methylation as epigenetic changes and the manifestations of methylated genes in PCOS conditions were discussed particularly to screen novel molecular targets for developing efficient diagnostic indicators for predicting PCOS risk or its progression. Due to the reversible nature of epigenetic modifications, it is possible to screen the "druggable" regions to target or to correct abnormalities in the gene expression subsequently to develop chromatin-modifying therapies against PCOS.

A novel RP-HPLC method development and validation for simultaneous quantification of gefitinib and resveratrol in polymeric hybrid lipid nanoparticles and glioma cells.

Resveratrol and Gefitinib are adjunct therapies for various cancers; however, both have been limited by low solubility, low cellular uptake, and bioavailability issues. As a result, this research aimed to develop an accurate, precise, selective, and sensitive reverse-phase high-performance liquid chromatography (RP-HPLC) method to simultaneously determine both compounds in nanoformulation and Glioma cells. The phenomenex luna C8 column, a mobile phase (80: 20 ratios of acetonitrile: 200 mM ammonium acetate) with a flow rate of 1 mL. min-1, 40 ± 0.2 °C as a column temperature, and the injection volume was 20 µl were selected as optimized chromatographic conditions. Retention time (RT) of resveratrol (1.80 min) and gefitinib (2.56 min) were identified using an optimized analytical method and detected at 345 nm (isosbestic point). The approach was proven to be specific for resveratrol and gefitinib analysis in the existence of PHLNPs, precise (RSD 2 %), and accurate (>90 %). The simultaneous analytical method was successfully developed to identify percentage drug entrapment efficiency (% DEE), % drug loading (% DL) of resveratrol and gefitinib in PHLNPs, and secondary estimates of in-vitro drug release profile and percentage cellular uptake studies. The in-vitro results revealed that the developed analytical method could simultaneously detect and quantify these drugs in other nanoformulations and in-vivo studies.

Genetically predicted glucosamine and longevity: A Mendelian randomization study.

BACKGROUND & AIMS: Glucosamine is known to affect different health outcomes, however its effect on male and female lifespan is still unclear. We conducted a two-sample Mendelian randomization (MR) study to investigate the association of genetically proxied glucosamine with longevity. METHODS: Using genetic data from the Medical Research Council Integrative Epidemiology Unit (MRC-IEU) consortium for 461,384 individuals, we identified five genetic variants as instrumental variables for genetically predicted glucosamine. We obtained genetic associations of these variants with parental longevity as combined parental age at death (n = 208,118), mother's age at death (n = 246,941) and father's age at death (n = 317,652). We used the inverse-variance weighted method to estimate the effect of a 1-standard deviation (SD) increase in genetically predicted glucosamine on parental longevity. RESULTS: We found a positive effect of genetically predicted higher glucosamine status on life expectancy using combined parental age at death. A 1-SD increase in genetically predicted glucosamine was associated with higher odds of combined parental age at death (odds ratio, 2.64; 95% CI 1.26, 5.54; P = 0.01), and maternal age at death (odds ratio, 1.73; 95 CI 1.04, 2.89; P = 0.03), but not paternal age at death (odds ratio, 1.32; 95% CI 0.81, 2.15; P = 0.27). Based on follow-up sensitivity analyses, we did not find evidence of pleiotropic effects of the genetic variants. CONCLUSIONS: Lifelong higher levels of glucosamine may increase life expectancy. Positive effects of glucosamine were associated with maternal age at death only. The clinical implications of this sex-specific finding warrant further investigation.

Immune Repertoire and Advancements in Nanotherapeutics for the Impediment of Severe Steroid Resistant Asthma (SSR).

Severe steroid-resistant asthma (SSR) patients do not respond to the corticosteroid therapies due to the heterogeneity, and genome-wide variations. However, there are very limited reports pertinent to the molecular signaling underlying SSR and making pharmacologists, and formulation scientists to identify the effective therapeutic targets in order to produce novel therapies using novel drug delivery systems (NDDS). We have substantially searched literature for the peer-reviewed and published reports delineating the role of glucocorticoid-altered gene expression, and the mechanisms responsible for SSR asthma, and NDDS for treating SSR asthma using public databases PubMed, National Library of Medicine (NLM), google scholar, and medline. Subsequently, we described reports underlying the SSR pathophysiology through several immunological and inflammatory phenotypes. Furthermore, various therapeutic strategies and the role of signaling pathways such as mORC1-STAT3-FGFBP1, NLRP3 inflammasomes, miR-21/PI3K/HDAC2 axis, PI3K were delineated and these can be considered as the therapeutic targets for mitigating the pathophysiology of SSR asthma. Finally, the possibility of nanomedicine-based formulation and their applications in order to enhance the long term retention of several antioxidant and anti-asthmatic drug molecules as a significant therapeutic modality against SSR asthma was described vividly.

Genetic and social contributions to sex differences in lifespan in Drosophila serrata.

Sex differences in lifespan remain an intriguing puzzle in evolutionary biology. While explanations range from sex differences in selection to sex differences in the expression of recessive lifespan-altering mutations (via X-linkage), little consensus has been reached. One unresolved issue is the extent to which genetic influences on lifespan dimorphism are modulated by the environment. For example, studies have shown that sex differences in lifespan can either increase or decrease depending upon the social environment. Here, we took an experimental approach, manipulating multiple axes of the social environment across inbred long- and short-lived genotypes and their reciprocal F1s in the fly Drosophila serrata. Our results reveal strong genetic effects and subtle yet significant genotype-by-environment interactions for male and female lifespan, specifically due to both population density and mating status. Further, our data do not support the idea that unconditional expression of deleterious X-linked recessive alleles in heterogametic males accounts for lower male lifespan.

Digest: Deprivation of parental care reveals the value of sibling cooperation in burying beetles.

What conditions favor cooperation in sibling interactions? In burying beetles of the genus Nicrophorus, Prang et al. found that dependence on parental care cannot solely explain the degree of offspring cooperation. While only larvae of independent species cooperated when receiving pre-hatching care, both independent and dependent species cooperated in the absence of pre-hatching care. This finding suggests that offspring cooperation has persisted from an early ancestor of the genus Nicrophorus to the present species, highlighting the evolution from facultative to obligatory social behavior.

Digest: Nature and nurture: Influences of parental care and rearing environment on phenotypic plasticity in Nicrophorus vespilloides.

What conditions favor niche expansion in nature? In the burying beetle Nicrophorus vespilloides, Schrader et al. found that larvae reared with parental care on larger carcasses were better equipped for resource use than individuals reared without parental care on smaller carcasses. This finding illustrates that developmental plasticity induced by parental care and carcass size has the potential to influence adaptive diversification.

Leveraging Rapid Response Activities to Build Public Health Capacity: Development of the Opioid Rapid Response Team Model.

As part of the federal response to the opioid crisis, the Opioid Rapid Response Team project (2018-2019) was created to provide rapid short-term assistance to requesting US jurisdictions responding to an acute opioid-related event. The project used an approach that maximized overall value by leveraging existing federal resources and harnessing opportunities to meet project-specific objectives while also enhancing general response capacity at the federal, state, and local levels. This tandem capacity building for both opioid rapid response and general response focused on systems and operations, workforce readiness, technical assistance, and partnerships. In this article, we demonstrate the ancillary value that issue-specific response activities can contribute to broader public health response capacity.

Recent Investigations on Neurotransmitters' Role in Acute White Matter Injury of Perinatal Glia and Pharmacotherapies-Glia Dynamics in Stem Cell Therapy.

Periventricular leukomalacia (PVL) and cerebral palsy are two neurological disease conditions developed from the premyelinated white matter ischemic injury (WMI). The significant pathophysiology of these diseases is accompanied by the cognitive deficits due to the loss of function of glial cells and axons. White matter makes up 50% of the brain volume consisting of myelinated and non-myelinated axons, glia, blood vessels, optic nerves, and corpus callosum. Studies over the years have delineated the susceptibility of white matter towards ischemic injury especially during pregnancy (prenatal, perinatal) or immediately after child birth (postnatal). Impairment in membrane depolarization of neurons and glial cells by ischemia-invoked excitotoxicity is mediated through the overactivation of NMDA receptors or non-NMDA receptors by excessive glutamate influx, calcium, or ROS overload and has been some of the well-studied molecular mechanisms conducive to the injury of white matter. Expression of glutamate receptors (GluR) and transporters (GLT1, EACC1, and GST) has significant influence in glial and axonal-mediated injury of premyelinated white matter during PVL and cerebral palsy. Predominantly, the central premyelinated axons express extensive levels of functional NMDA GluR receptors to confer ischemic injury to premyelinated white matter which in turn invoke defects in neural plasticity. Several underlying molecular mechanisms are yet to be unraveled to delineate the complete pathophysiology of these prenatal neurological diseases for developing the novel therapeutic modalities to mitigate pathophysiology and premature mortality of newborn babies. In this review, we have substantially discussed the above multiple pathophysiological aspects of white matter injury along with glial dynamics, and the pharmacotherapies including recent insights into the application of MSCs as therapeutic modality in treating white matter injury.

Digest: More than just a pretty fin: The evolution of sexual ornaments in killifish.

What conditions favor the evolution of elaborate sexual ornaments? In freshwater killifishes, Sowersby et al. found that larger sexual ornaments were negatively associated with locomotive performance. Although selection clearly favored large ornamental fins in environments with fewer predators, there was no clear association between large ornamental fins and differences in life-history strategy. This finding illustrates that habitat differences in predation risk have the potential to influence the evolution of secondary sexual traits such as ornaments through natural selection.