Impact of polyamine supplementation on GnRH expression, folliculogenesis, and puberty onset in young mice.

BACKGROUND: The hypothalamic-pituitary-gonadal (HPG) axis is pivotal in regulating reproductive functions, with gonadotropin-releasing hormone (GnRH) acting as a central regulator. Recently, polyamines have been shown to regulate the HPG axis, including GnRH expression and ovarian biology in old and adult rodents. The present study firstly highlights the age-specific variation in the polyamine and their corresponding biosynthetic enzymes in the ovary during aging, and further, the study focuses on the effect of polyamines, putrescine, and agmatine, in young female mice. METHOD AND RESULT: Immunofluorescence analysis revealed age-related differences in the expression of ornithine decarboxylase 1 (ODC1), spermine (SPM), and spermidine (SPD) in the ovaries, with adult mice exhibiting significantly higher expression levels compared to young and old mice. Likewise, qPCR analysis showed the mRNA levels of Odc1, Spermidine synthase (Srm), and Spermine synthase (Sms) show a significant increase in adult ovaries, which is then followed by a significant decline in old age. Histological examination demonstrated morphological alterations in the ovaries with age, including decreased follicle numbers and increased stromal cells in old mice. Furthermore, treatment with putrescine, a polyamine, in young mice resulted in larger ovaries and increased follicle numbers compared to controls. Additionally, serum levels of gonadotropin-releasing hormone (GnRH) and progesterone (P4) were measured, showing elevated levels in polyamine-treated mice. GnRH mRNA expression also increased significantly. Gene expression analysis revealed upregulation of genes associated with folliculogenesis such as Fshr, Bmp15, Gdf9, Amh, Star, Hsdb3, and Plaur in the ovaries and onset of puberty such as Tac2, and Kiss1, and a decrease in Mkrn3 in the hypothalamus of polyamine-treated mice. CONCLUSION: This study investigates the effect of polyamines in young immature female mice, shedding light on their role in upregulating GnRH, and enhancing folliculogenesis. Overall, these findings suggest that polyamines play a crucial role in ovarian aging and HPG axis regulation, offering potential therapeutics to reinstate fertility in reproductively challenged individuals.

Adipocytes Promote Endometrial Cancer Progression Through Activation of the SIRT1-HMMR Signaling Axis.

Adipocyte is a predominant component of the omental adipose tissue that influences the tumor microenvironment and increases the risk of endometrial cancer progression (EC), however, little is known about the underlying mechanism. In this study, using a co-culture model, we found that the adipocyte-EC cell interaction promoted SIRT1 signaling in vitro and in vivo xenograft mice models. Furthermore, immunostaining of SIRT1 protein showed significantly higher expression of SIRT1 in endometrial cancer patients than in normal endometria. RNA sequencing analysis revealed HMMR (hyaluronan-mediated motility receptor), an oncogene, as a downstream effector of SIRT1 in adipocyte-associated EC. Transient knockdown and chromatin immunoprecipitation assays showed that SIRT1 inhibition impedes transcription of the HMMR gene via FOXM1, and reduced expression of HMMR in co-cultured EC cells blocks AURKA activation via TPX2, leading to cell cycle arrest. This is the first study to report the positive correlation between SIRT1 and HMMR in EC patient tumors and might be used as a potential biomarker in EC. Notably, SIRT1 regulates HMMR expression in a FOXM1-dependent manner, and interfering with SIRT1 may provide a promising strategy for the management of endometrial cancer.

The potential antibacterial effects of tea polyphenols.

The current review of tea and its parts is focused on the antibacterial properties, considering the possible applications and modes of action against bacterial illnesses. It shows the backdrop of antibiotic resistance and the huge demand for antibacterial treatments out there. From the interactions with bacterial components, the theory presented that tea polyphenols are antibacterial and therefore would be a substitute or supplementary therapy to the usual antibiotics. The study highlighted the role of tea polyphenols as potential antibacterial compounds that may interact with various bacterial components and different polyphenolic compounds occurring in tea. Future research directions may be directed toward testing more plant-based sources for antibacterial properties, in vivo validation of the studies, and possible synergistic effects with classical antibiotics. By addressing the controversies and disagreements involved, the present understanding of the topic of tea's antibacterial properties and enable the entry of new ways for fighting microorganisms resistant to antibiotics. In conclusion, this review adds to the growing body of evidence regarding the antimicrobial properties of tea and emphasizes the need for further studies that will allow the full exploitation of its therapeutic potential for countering the rising problem of antibiotic resistance in healthcare.

Uncovering the coronavirus outbreak: present understanding and future research paths.

INTRODUCTION: The review discusses the pathophysiological mechanisms of SARS-CoV-2, the modes of transmission, and the long-term health consequences of COVID-19, emphasizing the importance of research and successful public health initiatives. CONTENT: COVID-19 taxonomy, pathophysiology, symptomatology, and epidemiological importance are the key objects of this research paper. This review explains how COVID-19 affects different systems of the body, including respiratory, cardiovascular, and reproductive systems of the human body. It describes the modes of entry of the virus into the cell; more precisely, ACE2 and TMPRSS2 in viral entry. In addition, the present study analyzes the situation of COVID-19 in India regarding vaccine development and the transmission rate related to socioeconomic factors. SUMMARY: The manifestation of COVID-19 presents a lot of symptoms and post-acute problems, issues which are seriously impacting mental health and physical health as well. The present review summarizes current research into pathogenicity and the mode of virus transmission, together with immunological responses. Coupled with strong vaccination programs, public health initiatives should hold the key to fighting this pandemic. OUTLOOK: Long-term effects and the development of treatment methods will need further study, as ambiguities on COVID-19 remain. Multidisciplinary collaboration across healthcare sectors in this respect is of paramount importance for the prevention of further spread and protection of public health.

Exploring Sperm Cell Rheotaxis in Microfluidic Channel: The Role of Flow and Viscosity.

Rheotaxis is a fundamental mechanism of sperm cells that guides them in navigating towards the oocyte. The present study investigates the phenomenon of sperm rheotaxis in Newtonian and non-Newtonian fluid media, which for the first time explores a viscosity range equivalent to that of the oviductal fluid of the female reproductive tract in rectilinear microfluidic channels. Three parameters, the progressive velocity while performing rheotaxis, the radius of rotation during rheotaxis, and the percentage of rheotactic sperm cells in the bulk and near-wall regions of the microfluidic channel, were measured. Numerical simulations of the flow were conducted to estimate the shear rate, flow velocity, and the drag force acting on the sperm head at specific locations where the sperms undergo rheotaxis. Increasing the flow velocity resulted in a change in the position of rheotactic sperm from the bulk center to the near wall region, an increase and subsequent decrease in the sperm's upstream progressive velocity, and a decrease in the radius of rotation. We observed that with an increase in viscosity, rheotactic sperms migrate to the near wall regions at lower flow rates, the upstream progressive velocity of the sperm decreases for Newtonian and increases for non-Newtonian media, and the radius of rotation increases for Newtonian and decreases for non-Newtonian media. These results quantify the effects of fluid properties such as viscosity and flow rate on sperm rheotaxis and navigation, thereby paving the way for manipulating sperm behavior in microfluidic devices, potentially leading to advancements in assisted reproduction techniques. .

Structure of higher-order interactions in social-ecological networks through Q-analysis of their neighbourhood and clique complex.

This paper studies higher-order interactions in social-ecological networks, which formally represent interactions within the social and ecological units of an ecosystem. Many real-world social ecosystems exhibit not only pairwise interactions but also higher-order interactions among their units. Therefore, the conventional graph-theoretic description of networks falls short of capturing these higher-order interactions due to the inherent limitations of the graph definition. In this work, a mathematical framework for capturing the higher-order interactions of a social-ecological system has been given by incorporating notions from combinatorial algebraic topology. In order to achieve this, two different simplicial complexes, the clique and the neighbourhood complex, have been constructed from a pairwise social-ecological network. As a case study, the Q-analysis and a structural study of the interactions in the rural agricultural system of southern Madagascar have been done at various structural levels denoted by q. The results obtained by calculating all the structural vectors for both simplicial complexes, along with exciting results about the participation of facets of the clique complex at different q-levels, have been discussed. This work also establishes significant theorems concerning the dimension of the neighbourhood complex and clique complex obtained from the parent pairwise network.

The First Generative AI Prompt-A-Thon in Healthcare: A Novel Approach to Workforce Engagement with a Private Instance of ChatGPT.

BACKGROUND: Healthcare crowdsourcing events (e.g. hackathons) facilitate interdisciplinary collaboration and encourage innovation. Peer-reviewed research has not yet considered a healthcare crowdsourcing event focusing on generative artificial intelligence (GenAI), which generates text in response to detailed prompts and has vast potential for improving the efficiency of healthcare organizations. Our event, the New York University Langone Health (NYULH) Prompt-a-thon, primarily sought to inspire and build AI fluency within our diverse NYULH community, and foster collaboration and innovation. Secondarily, we sought to analyze how participants' experience was influenced by their prior GenAI exposure and whether they received sample prompts during the workshop. METHODS: Executing the event required the assembly of an expert planning committee, who recruited diverse participants, anticipated technological challenges, and prepared the event. The event was composed of didactics and workshop sessions, which educated and allowed participants to experiment with using GenAI on real healthcare data. Participants were given novel "project cards" associated with each dataset that illuminated the tasks GenAI could perform and, for a random set of teams, sample prompts to help them achieve each task (the public repository of project cards can be found at https://github.com/smallw03/NYULH-Generative-AI-Prompt-a-thon-Project-Cards). Afterwards, participants were asked to fill out a survey with 7-point Likert-style questions. RESULTS: Our event was successful in educating and inspiring hundreds of enthusiastic in-person and virtual participants across our organization on the responsible use of GenAI in a low-cost and technologically feasible manner. All participants responded positively, on average, to each of the survey questions (e.g., confidence in their ability to use and trust GenAI). Critically, participants reported a self-perceived increase in their likelihood of using and promoting colleagues' use of GenAI for their daily work. No significant differences were seen in the surveys of those who received sample prompts with their project task descriptions. CONCLUSION: The first healthcare Prompt-a-thon was an overwhelming success, with minimal technological failures, positive responses from diverse participants and staff, and evidence of post-event engagement. These findings will be integral to planning future events at our institution, and to others looking to engage their workforce in utilizing GenAI.

A multifaceted approach to identifying and managing juvenile delinquency by integrating psycho-physiological indicators.

To understand and treat juvenile delinquency, the study explores the relevance of psycho-physiological indicators. It also emphasizes the necessity for thorough research to minimize the gap existing between psycho-physiological measurements and conventional psychosocial components. The study focuses on the relevance of personality features, habituation, and autonomic arousal required to monitor the proper management of delinquent conduct. Through the integration of biological, psychological, and social elements into a multidimensional approach, researchers can uncover novel insights and create cutting-edge therapies for youths who are at risk of delinquent behavior. The study proposes to develop a comprehensive framework that considers biological antecedents in addition to conventional metrics to reach the root cause of delinquency; thereby drawing special attention to current literature and research that emphasizes the psycho-physiological correlates of delinquency. By examining the complex interactions between stress, physiology, emotions, behavior, and social structures, the study highlights the intricacy of delinquent conduct and the necessity for adopting a multifaceted strategy to fully address the problematic areas. Future research paths are emphasized, with a focus on the significance of longitudinal studies, moderating and mediating variables, and creative treatment techniques. By utilizing psycho-physiological markers and psychosocial traits, researchers can tailor intervention strategies to meet individual needs effectively. Early identification of psycho-physiological deficits in children is crucial for implementing successful behavior modification techniques and promoting the well-being of future generations. This is expected to help the government agencies to save time and public money.

Landfill-mined soil-like fraction (LMSF) use in biopolymer composting: Material pre-treatment, bioaugmentation and agricultural prospects.

Polylactic Acid (PLA) based compostable bioplastic films degrade under thermophilic composting conditions. The purpose of our study was to understand whether sample pre-treatment along with bioaugmentation of the degradation matrix could reduce the biodegradation time under a simulated composting environment. Sepcifically, we also explored whether the commercial composts could be replaced by landfill-mined soil-like fraction (LMSF) for the said application. The effect of pre-treatment on the material was analysed by tests like tensile strength analysis, hydrophobicity analysis, morphological analysis, thermal degradation profiling, etc. Subsequently, the degradation experiment was performed in a simulated composting environment following the ASTM D5338 standard, along with bioaugmentation in selected experimental setups. When the novel approach of material pre-treatment and bioaugmentation were applied in combination, the time necessary for 90% degradation was reduced by 27% using compost and by 23% using LMSF. Beyond the improvement in degradation rate, the water holding capacity increased significantly for the degradation matrices. With pH, C: N ratio and microbial diversity tested to be favourable through 16s metabarcoding studies, material pre-treatment and bioaugmentation allow LMSF to not only replace commercial compost in polymer degradation but also find immense application in the agricultural sector of drought-affected areas (for better water retention) after it has been used for PLA degradation.

Comprehensive study of the interplay between immunological and metabolic factors in hepatic steatosis.

The pathophysiology of hepatic steatosis is thoroughly reviewed in this comprehensive report, with particular attention to the complex interactions between inflammatory pathways, insulin resistance, lipid metabolism, metabolic dysregulation, and immunological responses in the liver including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma (HCC). The study highlights the role of immune cell regulation in disease progression and explores the potential of immune cell-specific treatments for treating hepatic disorders. The development of liver disorders is significantly influenced by immune cells, including dendritic cells, T cells, and natural killer cells. Clinical investigations show that immune cell-specific treatments can effectively reduce liver fibrosis and inflammation. Future research should focus on finding new immunological targets for therapeutic interventions, as well as addressing the management challenges associated with NAFLD/NASH. Hepatic immune microorganisms also impact liver homeostasis and disorders. Improvements in immune cell regulation and liver transplantation methods give patients hope for better prognoses. Important phases include optimizing the selection of donors for malignancy of the liver, using machine perfusion for organ preservation, and fine-tuning immunosuppressive strategies. For focused treatments in hepatic steatosis, it is imperative to understand the intricate interactions between immune and metabolic variables. Understanding the liver's heterogeneous immune profile, encompassing a range of immune cell subpopulations, is crucial for formulating focused therapeutic interventions. To improve patient care and outcomes in hepatic illnesses, there is an urgent need for further research and innovation. Therefore, to effectively treat hepatic steatosis, it is important to enhance therapeutic techniques and maximize liver transplantation strategies.

Intrathecal ropivacaine versus bupivacaine in a non-obstetric population- A meta-analysis and trial sequential analysis.

Background and Aims: Intrathecal bupivacaine is used for anaesthesia and analgesia but is associated with hypotension. Ropivacaine is an alternative drug that may have fewer cardiotoxic and neurotoxic events. This meta-analysis investigated whether intrathecal ropivacaine is associated with reduced hypotension as compared to bupivacaine. Methods: The meta-analysis is registered in the International Prospective Register of Systematic Reviews (PROSPERO). The databases PubMed, Cinahl Plus, Google Scholar, and Scopus were searched, and papers from January 1980 to January 2023 were deemed eligible and filtered using predetermined inclusion and exclusion criteria. The primary outcome was the incidence of hypotension. Secondary outcomes were the duration of sensory block, duration of motor block, incidence of bradycardia, ephedrine usage, and duration of analgesia. Jadad scores were used to evaluate the quality of the papers. RevMan statistical software® utilised inverse variance and a random effect model to calculate the standardised mean difference with 95% confidence intervals for continuous variables and the Mantel-Haenszel test and the random effect model to calculate the odds ratio for dichotomous variables. Results: Thirty-three papers, including 2475 patients in total, were included. The Jadad score was between 1 and 5. The incidence of hypotension was significantly higher with intrathecal bupivacaine than with ropivacaine (P = 0.02). The duration of sensory block (P < 0.001) and motor block (P < 0.001) was prolonged with intrathecal bupivacaine. The duration of analgesia favoured intrathecal bupivacaine (P = 0.003). Conclusion: Intrathecal ropivacaine has a reduced incidence of hypotension and a reduced duration of sensory block compared to bupivacaine.

Improving newborn screening in India: Disease gaps and quality control.

In India, newborn screening (NBS) is essential for detecting health problems in infants. Despite significant progress, significant gaps and challenges persist. India has made great strides in genomics dueto the existence of the National Institute of Biomedical Genomics in West Bengal. The work emphasizes the challenges NBS programs confront with technology, budgetary constraints, insufficient counseling, inequality in illness panels, and a lack of awareness. Advancements in technology, such as genetic testing and next-generation sequencing, are expected to significantly transform the process. The integration of analytical tools, artificial intelligence, and machine learning algorithms could improve the efficiency of newborn screening programs, offering a personalized healthcare approach. It is critical to address gaps in information, inequities in illness incidence, budgetary restrictions, and inadequate counseling. Strengthening national NBS programs requires increased public awareness and coordinated efforts between state and central agencies. Quality control procedures must be used at every level for implementation to be successful. Additional studies endeavor to enhance NBS in India through public education, illness screening expansion, enhanced quality control, government incentive implementation, partnership promotion, and expert training. Improved neonatal health outcomes and the viability of the program across the country will depend heavily on new technology and counseling techniques.

Quercetin counteracts monosodium glutamate to mitigate immunosuppression in the thymus and spleen via redox-guided cellular signaling.

BACKGROUND: Chronic inflammation brought on by oxidative stress can result in several immunopathologies. Natural compounds with antioxidant characteristics, like quercetin, have shown effectiveness in reducing oxidative damage and regulating the immune response. PURPOSE: The commonly used food additive monosodium glutamate (M) causes immunosuppression by disrupting redox equilibrium and inducing oxidative stress. The goal of this work is to examine the therapeutic potential of quercetin against immunotoxicity brought on by M, revealing the molecular route implicated in such immunopathology by targeting the thymus and spleen, to support the development of future anti-inflammatory and antioxidant therapies. STUDY DESIGN AND METHODS: M-fed rats were employed as an immunotoxicity model and were supplemented with quercetin for four weeks. Hematological and biochemical parameters were measured; H&E staining, immunohistochemistry, flow cytometry, real-time quantitative PCR, and western blotting were performed. RESULTS: Based on the findings, TLR4 was activated by M to cause oxidative stress-mediated inflammation, which was alleviated by the supplementation of quercetin by modulating redox homeostasis to neutralize free radicals and suppress the inflammatory response. To prevent M-induced inflammation, quercetin demonstrated anti-inflammatory functions by blocking NF-kB activation, lowering the production of pro-inflammatory cytokines, and increasing the release of anti-inflammatory cytokines. By normalizing lipid profiles and lowering the potential risk of immunological deficiency caused by M, quercetin also improves lipid metabolism. Additionally, it has shown potential for modifying insulin levels, suggesting a possible function in controlling M-induced alteration in glucose metabolism. The addition of quercetin to M enhanced the immune response by improving immunoglobulin levels and CD4/CD8 expression in the thymus and spleen. Additionally, quercetin inhibited apoptosis by controlling mitochondrial caspase-mediated cellular signaling, suggesting that it may be able to halt cell death in M-fed rats. CONCLUSION: The results of this study first indicate that quercetin, via modulating redox-guided cellular signaling, has a promising role in reducing immune disturbances. This study illuminates the potential of quercetin as a safe, natural remedy for immunopathology caused by M, including thymic hypoplasia and/or splenomegaly, and paves the way for future anti-inflammatory and antioxidant supplements.

Dimension and Flexibility of Polystyrenesulfonate Chains in Methanol-Water.

The influence of the relative permittivity of the solvent medium on the single-chain dimension and flexibility of sodium polystyrenesulfonate chains has been investigated in mixed solvent media of methanol and water using viscosity experiments. Particular attention has been paid to explore the effect of the added low-molar-mass electrolyte. The root-mean-square (rms) radii of gyration of the chains in the unperturbed state have been calculated by applying the Flory model, while the intrinsic persistence lengths by the Benoit-Doty equation on the basis of the Kratky-Porod worm-like chain model. Estimation of the expansion factors for the rms radius of gyration, and the electrostatic persistence length helps evaluate the rms radii of gyration and the total persistence length of polystyrenesulfonate chains in the presence of varying amount of the supporting electrolyte. The polyion chains are highly extended at low ionic strengths but exhibit coil-like behavior with small persistence lengths when an excess of the supporting electrolyte is added in all the methanol-water mixtures investigated. Specifically, in the investigated solvent media, the polystyrenesulfonate chains have been found to shrink by ∼63-65% in the θ-state from their expanded conformation in the presence of 0.0001 mol L-1 NaCl. The chain dimensions pass through a maximum as the medium becomes richer in methanol, which could be explained by the formation and breakup of internal rings involving the polyion chain and water and/or methanol molecules. The intrinsic persistence length of sodium polystyrenesulfonate in a methanol-water mixture containing 0.1 mole fraction of methanol is ca. 1.3 times that in a medium with 0.3 mole fraction of methanol, indicating that flexibility of the polyion depends appreciably on the relative permittivity of the medium.

Surface Charge-Switchable Antifouling Block Copolymer with Bacteriostatic Properties.

Zwitterionic polymers are an emerging family of effective, low-fouling materials that can withstand unintended interactions with biological systems while exhibiting enhanced activity in bacterial matrix deterioration and biofilm eradication. Herein, we modularly synthesized an amphiphilic block copolymer, ZABCP, featuring potential bacteriostatic properties composed of a charge-switchable polyzwitterionic segment and a redox-sensitive pendant disulfide-labeled polymethacrylate block. The leucine-appended polyzwitterionic segment with alternatively positioned cationic amine and anionic carboxylate functionalities undergoes charge alterations (+ve → 0 → -ve) on pH variation. By introducing appropriate amphiphilicity, ZABCP forms distinct vesicles with redox-sensitive bilayer membranes and zwitterionic shielding coronas, enabling switching of surface charge. ZABCP vesicles exhibit 180 ± 20 nm hydrodynamic diameter, and its charge switching behavior in response to pH was confirmed by the change of zeta potential value from -23 to +36 mV. The binding interaction between ZABCP vesicles with lysozyme and pepsin proteins strengthens when the surface charge shifts from neutral (pH 7.4) to either anionic or cationic. This surface-charge-switchable phenomenon paves the way for implementing cationic ZABCP vesicles for bacterial cell growth inhibition, which is shown by the pronounced transition of cellular morphology, including clustering, aggregation, or elongation as well as membrane disruption for both Bacillus subtilis (Gram-positive) and Escherichia coli (Gram-negative). Such enhanced bacteriostatic activity could be ascribed to a strong electrostatic interaction between cationic vesicles and negatively charged bacterial membranes, leading to cell membrane disruption. Overall, this study provides a tailor-made approach to adopt low-fouling properties and potential bacteriostatic activity using zwitterionic polymers through precise control of pH.

Quercetin inhibits NF-kB and JAK/STAT signaling via modulating TLR in thymocytes and splenocytes during MSG-induced immunotoxicity: an in vitro approach.

BACKGROUND: The most widely used food additive monosodium glutamate (MSG) has been linked to immunopathology. Conversely, quercetin (Q), a naturally occurring flavonoid has been demonstrated to have immunomodulatory functions. Therefore, the purpose of the study is to determine if quercetin can mitigate the deleterious effects of MSG on immune cells, and the possible involvement of TLR, if any.  METHODS AND RESULTS: This study was conducted on Q, to determine how it affects the inflammatory response triggered by MSG in primary cultured thymocytes and splenocytes from rats (n = 5). Q shielded cells by augmenting cell survival and decreasing lactate dehydrogenase leakage during MSG treatment. It decreased IL-1ß, IL-6, IL-8, and TNF-α expression and release by hindering NF-kB activation and by inhibiting the JAK/STAT pathway. Moreover, Q prevented NLRP3 activation, lowered IL-1ß production, and promoted an anti-inflammatory response by increasing IL-10 production. Q reduced MSG-induced cellular stress and inflammation by acting as an agonist for PPAR-γ and LXRα, preventing NF-kB activation, and lowering MMP-9 production via increasing TIMP-1. Additionally, Q neutralized free radicals, elevated intracellular antioxidants, and impeded RIPK3, which is involved in inflammation induced by oxidative stress, TNF-α, and TLR agonists in MSG-treated cells. Furthermore, it also modulated TYK2 and the JAK/STAT pathway, which exhibited an anti-inflammatory effect. CONCLUSIONS: MSG exposure is associated with immune cell dysfunction, inflammation, and oxidative stress, and Q modulates TLR to inhibit NF-kB and JAK/STAT pathways, providing therapeutic potential. Further research is warranted to understand Q's downstream effects and explore its potential clinical applications in inflammation.

Zwitterionic Polysulfobetaine Inhibits Cancer Cell Migration Owing to Actin Cytoskeleton Dynamics.

Cell migration is an essential dynamic process for most living cells, mainly driven by the reorganization of actin cytoskeleton. To control actin dynamics, a molecular architecture that can serve as a nucleator has been designed by polymerizing sulfobetaine methacrylate. The synthesized zwitterionic polymer, poly(sulfobetaine methacrylate) (PZI), effectively nucleates the polymerization process of G-actin and substantially accelerates the rate of polymerization. Isothermal titration calorimetry (ITC) and bioinformatics analysis indicated binding between PZI and monomeric G-actin. Thus, in vitro actin dynamics was studied by dynamic light scattering (DLS), pyrene-actin polymerization assay, and total internal reflection fluorescence microscopy (TIRFM). Furthermore, a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) fluorophore-containing monomeric unit was incorporated into the sulfobetaine zwitterionic architecture to visualize the effect of polymer in the cellular environment. The BODIPY-containing zwitterionic sulfobetaine polymer (PZI-F) successfully penetrated the cell and remained in the lysosome with minimal cytotoxicity. Confocal microscopy revealed the influence of this polymer on the cellular actin cytoskeleton dynamics. The PZI-F polymer was successfully able to inhibit the collective migration of the human cervical cancer cell line (HeLa cell) and breast cancer cell line (MDA-MB-231 cell), as confirmed by a wound healing assay. Therefore, polyzwitterionic sulfobetaine could be explored as an inhibitor of cancer cell migration.

Flavone-based dual PARP-Tubulin inhibitor manifesting efficacy against endometrial cancer.

Structural tailoring of the flavone framework (position 7) via organopalladium-catalyzed C-C bond formation was attempted in this study. The impact of substituents with varied electronic effects (phenyl ring, position 2 of the benzopyran scaffold) on the antitumor properties was also assessed. Resultantly, the efforts yielded a furyl arm bearing benzopyran possessing a 4-fluoro phenyl ring (position 2) (14) that manifested a magnificent antitumor profile against the Ishikawa cell lines mediated through dual inhibition of PARP and tubulin [(IC50 (PARP1) = 74 nM, IC50 (PARP2) = 109 nM) and tubulin (IC50 = 1.4 µM)]. Further investigations confirmed the ability of 14 to induce apoptosis as well as autophagy and cause cell cycle arrest at the G2/M phase. Overall, the outcome of the study culminated in a tractable dual PARP-tubulin inhibitor endowed with an impressive activity profile against endometrial cancer.

Small extracellular vesicles administered directly in the brain promote neuroprotection and decreased microglia reactivity in a stroke mouse model.

Herein, we investigate the bioactivity of small extracellular vesicles (sEVs), focusing on their local effect in the brain. sEVs from mononuclear cells (MNCs) showed superior effects in vitro to sEVs from mesenchymal stem cells (MSCs) and were able to promote neuroprotection and decrease microglia reactivity in a stroke mouse model.

Biomass, carbon stock, CO2 mitigation and carbon credits of coffee-based multitier cropping model in Central India.

The present work was conducted in the forest-based ecosystem of Chhattisgarh in order to assess the varietal performance of coffee varieties along with silver oak in terms of growth, biomass, and carbon dynamics. Five coffee varieties were planted in silver oak shade in a randomized block design with four replications. The aim of the present investigation is to assess the economic and ecological feasibility of forest-based coffee plantations in the Bastar region of Chhattisgarh. Findings reflect the maximum under-storied plant height in Chandragiri Dwarf (1.85 m) which was at par with CxR (1.82 m) and San Ramon (1.71 m). The maximum above and below-ground carbon stock (48.40 and 12.09 Mg ha-1, respectively), as well as carbon dioxide (CO2) mitigation (177.63 and 44.41 Mg ha-1, respectively) from the under-storied coffee plantation, was recorded in CxR. In the upper-storied plantation, the above and below-ground biomass of silver oak recorded the maximum carbon stock (201.24 and 50.31 Mg ha-1, respectively) and CO2 mitigation (738.54 and 184.63 Mg ha-1) in S-8 intercropped lines. The highest value of carbon credit was recorded under the coffee variety S-8 and silver oak agroecosystem. The S-8, CxR, and Chandragiri Dwarf varieties performed quite well in terms of the expected value of carbon credit.