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Green marketing is the buzzword nowadays which focuses on the organic concept of the product with minimum residue and wastages. It also focuses on the recycling and the reusability of the product for further usage. This research paper focuses on ‘The Impact of Food Labelling on Consumer’s choice of Products – A Green Marketing Initiative’. It focuses on green marketing, how consumer perceives it and what are the real ingredients associated with it. This is the empirical research where the Likert scale is used to collect the primary data. A sample of 126 respondents was used to analyse the green marketing initiative. The various factors that used were nutrition information, green packaging, fitness labels like low fat, gluten free etc., allergen information and the product in which the product is made etc. also impact consumer choices. Correlation analysis is used as a statistical tool to analyse the data with the help of SPSS 28.0 software. The scope and application of the paper is that the suggestive framework for green marketing initiatives can be used by various marketing firms, and policymakers which will empower the consumers and the manufacturer both to make improved and better fitness, health and ecologically environmentally friendly choices.

Human resource management is included within an organisation for recruiting employees, guiding work procedures, providing training, and developing policies to motivate and satisfy employees for better productivity and profit. This study sheds light on the importance of human resource management to influence employee turnover and job satisfaction of the employees. The study provided an overview of the different factors which prove to have a dramatic influence on employee turnover and the job satisfaction of the workers. The strategies integrated by human resource management for the heightening such crucial aspects of employee turnover and job satisfaction was observed in the study.

The utilization of back-propagation neural network in identification of internal dynamics of chaotic motion is found appropriate. However, during its training through Rumelhart algorithm, it is found that, a high learning rate (α) leads to rapid learning but the weights may oscillate, while a lower value of 'α' leads to slower learning process in weight updating formula Δvjk = αδjxi Momentum factor (μ) is to accelerate the convergence of error during the training in the equation wjk(t+1) = wjk(t) + αδkzj + μ{wjk(t) - wjk(t - 1)} vjk(t+1) = vjk(t) + αδkz + μ{vjk(t) - vjk(t-1) while transfer function sigmoid f(x) = 1/1+e-δx+n. It is the most complicated and experimental task to identify optimum value of 'α' and 'μ' during the training. To identiαy optimum value of 'α' and 'μ', firstly the network is trained with 10³ epochs under different values of 'α' in the close interval 0 < α <1 and μ = 1. At α = 0.3the convergence of initial weights and minimization of error (i.e., mean square error) process is found appropriate. Afterwards to find optimum value of μ, the network was trained again with α = 0.3 (fixed) and with different values of μ in the close interval 0 <μ < 1 for 10³ epochs. It was observed that the convergence of initial weights and minimization of error was appropriate with α = 0.3 and μ = 0.9. On this optimum value of α and μ the network was trained successfully from local minima of error = 1.67029292416874E-03 at 10³ epochs to global minima of error = 4.99180426869658E-04 at 15 105 epochs. At the global minima, the network has exhibited excellent performance in identification of internal dynamics of chaotic motion and in prediction of future values by past recorded data series. These essentials are presented through this research paper. [ABSTRACT FROM AUTHOR]

Objective: This article aimed to study the various treatment options according to the grading scale for penile incarceration. Materials and Methods: A retrospective review, of all the case files of patients presented with penile incarceration with encircling metallic object was performed. The patients were analyzed for age, marital status, motive, object used, who applied it, trauma grade, duration of incarceration, removal technique, removal time, anesthesia used and recovery time. Result: A total of seven patients were identified. The average age was 46.71 years. Self-sexual gratification was the most common motive (five patients). Six patients presented within 24 hours. Grade II of injury was commonest type of injury seen in five patients. The technique of removal chosen was according to grade of penile injury, duration of incarceration and type of object used. Spinal anesthesia was used in most of the cases (five patients). Conclusion: Penile incarceration with encircling metallic objects is a rare presentation and requires urgent intervention according to trauma grade to prevent complications. [ABSTRACT FROM AUTHOR]

Rice ecosystem of Chattisgarh can be divided into three major farming situations such as low-land, mid-land and up-land. In the present investigation, two farming situations of rice viz, mid-land and low-land were selected to evaluate the production potential of spices like-coriander, fenugreek and black cumin over traditionally grown crop chickpea during the rainy and winter season of year 2003 and 2004. The result revaled that, in general, the chickpea equivalaent yield was found higher in mid-land situation than low-land situation. Total net income of rice-spice croppping system was higher under mid-land farming situation than low-land farming situation. Among the crops, rice fenugreek gave maximum net returns in both the cropping system followed by black cumin and coriander crop. [ABSTRACT FROM AUTHOR]

The article focuses on a Caribbean case study of water resources and food security. It shows the need for policymakers to come to terms with the realities of virtual water imports and the impending food insecurity, and thereby give high priority to the expansion and improvement of the irrigation infrastructure in the contemporary planning of the island's water resources. The neglect of agriculture in Trinidad has deep historical roots, which go back to the days of the transatlantic slave trade and the sugar cane plantations between the seventeenth and nineteenth centuries. It may also be noted that the island's topography, in its central and southwestern plains, permits mechanized rice production.

Presents a medical case of a woman suffering from pain in the abdomen. Performance of Barium Meal Examination in the abdomen which showed dilated stomach with filling defect towards the pylorus; Detection of a perforation in the pyloric region of the stomach and contamination of the peritoneal cavity by barium; Administration of omentopexy to close the perforation.

Copyright of Experientia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Experientia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Bezoars are conglomerates of food or fiber in the alimentary tract of humans and certain animals, mainly ruminants. A trichobezoar represents a mass of accumulated hair. Trichobezoars may present as an isolated gastric mass, as an extension into the small intestine, or as an independent fragmented mass in the small intestine. The presence of discrete coexisting gastric and ileal trichobezoars has been reported only rarely in the literature. This is a case report of a 10-year-old girl presenting with small-bowel obstruction secondary to synchronous trichobezoars in the stomach and ileum. The case highlights the role of imaging and importance of complete evaluation of the gastrointestinal tract at the time of surgical evacuation. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis ( M. tb ) is one of the most successful human pathogens, causing a severe and widespread infectious disease. The frequent emergence of multidrug-resistant (MDR) strains has exacerbated this public health crisis, particularly in underdeveloped regions. M. tb employs a sophisticated array of virulence factors to subvert host immune responses, both innate and adaptive. It utilizes the early secretory antigenic target (ESAT6) secretion system 1 (ESX-1) type VII secretion system (T7SS) and cell wall lipids to disrupt phagosomal integrity, inhibiting phagosome maturation, and fusion with lysosomes. Although host cells activate mechanisms such as ubiquitin (Ub), Ub-ligase, and cyclic GMP-AMP synthase-stimulator of interferon genes 1 (CGAS-STING1)-mediated autophagy to inhibit M. tb survival within macrophages, the pathogen counteracts these defenses with its own virulence factors, thereby inhibiting autophagy and dampening host-directed responses. T7SSs are critical for transporting proteins across the complex mycobacterial cell envelope, performing essential functions, including metabolite uptake, immune evasion, and conjugation. T7SS substrates fall into two main families: ESAT-6 system proteins, which are found in both Firmicutes and Actinobacteria, and proline-glutamic acid (PE) and proline-proline-glutamic acid (PPE) proteins, which are unique to mycobacteria. Recent studies have highlighted the significance of T7SSs in mycobacterial growth, virulence, and pathogenesis. Understanding the mechanisms governing T7SSs could pave the way for novel therapeutic strategies to combat mycobacterial diseases, including tuberculosis (TB).

Introduction: This study explored the efficacy of repeat blood cultures in bacteremic acute myeloid leukemia (AML) patients following allogeneic hematopoietic stem cell transplantation (HSCT)., Methods: This was a retrospective study of AML patients who experienced febrile neutropenia (FN) and bacteremia following HSCT at the Taussig Cancer Center from January 1, 2019, to December 31, 2022. The primary endpoint was the rate of positive repeat blood cultures following initial positive blood culture., Results: Fifty patients were included in the study. There were 50 occurrences of FN with positive initial blood cultures that were diagnosed following HSCT. Fifty initial sets of blood cultures and 96 sets of repeat blood cultures were drawn between the 50 occurrences of FN. Twelve of 96 (12.5%) repeat blood culture sets were positive for a pathogen, which occurred over nine of 50 (18.0%) episodes of FN. Three of 96 (3.2%) repeat blood culture sets grew a pathogen that differed from the pathogen that grew in the preceding positive blood culture., Conclusion: Among bacteremic AML patients in the post-HSCT period, the yield of repeat blood cultures for detecting previously detected and new pathogens was low., (© 2024 The Author(s). Transplant Infectious Disease published by Wiley Periodicals LLC.)

Vaccination is one of the most effective prophylactic public health interventions for the prevention of infectious diseases such as coronavirus disease (COVID-19). Considering the ongoing need for new COVID-19 vaccines, it is crucial to modify our approach and incorporate more conserved regions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to effectively address emerging viral variants. The nucleocapsid protein is a structural protein of SARS-CoV-2 that is involved in replication and immune responses. Furthermore, this protein offers significant advantages owing to the minimal accumulation of mutations over time and the inclusion of key T-cell epitopes critical for SARS-CoV-2 immunity. A novel strategy that may be suitable for the new generation of vaccines against COVID-19 is to use a combination of antigens, including the spike and nucleocapsid proteins, to elicit robust humoral and potent cellular immune responses, along with long-lasting immunity. The strategic use of multiple antigens aims to enhance vaccine efficacy and broaden protection against viruses, including their variants. The immune response against the nucleocapsid protein from other coronavirus is long-lasting, and it can persist up to 11 years post-infection. Thus, the incorporation of nucleocapsids (N) into vaccine design adds an important dimension to vaccination efforts and holds promise for bolstering the ability to combat COVID-19 effectively. In this review, we summarize the preclinical studies that evaluated the use of the nucleocapsid protein as antigen. This study discusses the use of nucleocapsid alone and its combination with spike protein or other proteins of SARS-CoV-2., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Noe Juvenal Mendoza-Ramírez et al.)

Introduction: High sustained anti-rhGAA antibody titers (HSAT; ≥12,800) are directly linked to reduced efficacy of enzyme replacement therapy (ERT) and subsequent clinical deterioration in infantile-onset Pompe disease (IOPD). We have previously demonstrated the safety and effectiveness of a bortezomib-based immune-tolerance induction (ITI) regimen (bortezomib, rituximab, methotrexate, and IVIG) in eliminating HSAT., Methods: Here, we describe two IOPD cases (patients 6 and 8) who developed HSAT at 8 and 10 weeks on ERT despite transient low-dose methotrexate ITI administration in the ERT-naïve setting and were treated with a bortezomib-based ITI regimen, and we compare their courses to a series of six historical patients (patients 1-5, and 7) with a similar presentation who exemplify our evolving approach to treatment., Results: In total, patients 6 and 8 received 16 and 8 doses of bortezomib (4 doses=1 cycle) respectively reducing titers from 25,600 to seronegative, but differences in the course of their therapy were instructive regarding the optimal approach to initial treatment of HSAT; specifically, patient 6 was treated initially with only a single course of bortezomib rescue therapy, while patient 8 received two back-to-back courses. Patient 8 received IVIG therapy throughout the immunosuppression whereas patient 6 received IVIG therapy and was switched to subcutaneous IgG replacement. Patient 6 had a transient reduction in anti-rhGAA antibodies, after receiving a single initial cycle of bortezomib, but had a recurrence of high anti-rhGAA antibody titer after 160 weeks that required 3 additional cycles of bortezomib to ultimately achieve tolerance. In contrast, patient 8 achieved tolerance after being given two consecutive cycles of bortezomib during their initial treatment and had B cell recovery by week 54. Since the reduction in anti-rhGAA antibodies, both patients are doing well clinically, and have decreasing ALT, AST, and CK. No major infections leading to interruption of treatment were observed in either patient. The bortezomib-based ITI was safe and well-tolerated, and patients continue to receive ERT at 40 mg/kg/week., Discussion: These case studies and our previous experience suggest that to achieve an effective reduction of anti-rhGAA antibodies in the setting of HSAT, bortezomib should be initiated at the earliest sign of high anti-rhGAA antibodies with a minimum of two consecutive cycles as shown in the case of patient 8. It is important to note that, despite initiation of ERT at age 2.3 weeks, patient 8 quickly developed HSAT. We recommend close monitoring of anti-rhGAA antibodies and early intervention with ITI as soon as significantly elevated anti-rhGAA antibody titers are noted., Competing Interests: AD has received grant support from Sanofi Genzyme and the Lysosomal Disease Network. AD has received honoraria from Sanofi Genzyme. CG has received Honoraria from Sanofi, Amicus Therapeutics, and RegenX Bio. RW serves on the Scientific Advisory Board for and owns equity in M6P Therapeutics. PK has received research/grant support from Sanofi Genzyme and Amicus Therapeutics. PK has received consulting fees and honoraria from Sanofi Genzyme, Amicus Therapeutics, Maze Therapeutics, Bayer, and Asklepios Biopharmaceutical, Inc. (AskBio). PK is a member of the Pompe and Gaucher Disease Registry Advisory Board for Sanofi Genzyme, Pompe Disease Advisory Board for Amicus Therapeutics, and Advisory Board for Babies. PK has equity with Maze Therapeutics and has held equity in Asklepios Biopharmaceuticals and may receive milestone payments related to that equity in the future. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2024 Desai, Shrivastava, Grant, Wang, Burt and Kishnani.)

Importance: During blood feeding, mosquitoes inject saliva into the host skin, preventing hemostasis and inflammatory responses. D7 proteins are among the most abundant components of the saliva of blood-feeding arthropods. Aedes aegypti , the vector of yellow fever and dengue, expresses two D7 long-form salivary proteins: D7L1 and D7L2. These proteins bind and counteract hemostatic agonists such as biogenic amines and leukotrienes. D7L1 and D7L2 knockout mosquitoes showed prolonged probing times and carried significantly less Plasmodium gallinaceum oocysts per midgut than wild-type mosquitoes. We hypothesize that reingested D7s play a vital role in the midgut microenvironment with important consequences for pathogen infection and transmission., Competing Interests: The authors declare no conflict of interest.

Mosquito borne flaviviruses such as dengue and Zika represent a major public health problem due to globalization and propagation of susceptible vectors worldwide. Vertebrate host responses to dengue and Zika infections include the processing and release of pro-inflammatory cytokines through the activation of inflammasomes, resulting in disease severity and fatality. Mosquito saliva can facilitate pathogen infection by downregulating the host's immune response. However, the role of mosquito saliva in modulating host innate immune responses remains largely unknown. Here, we show that mosquito salivary gland extract (SGE) inhibits dengue and Zika virus-induced inflammasome activation by reducing NLRP3 expression, Caspase-1 activation, and 1L-1β secretion in cultured human and mice macrophages. As a result, we observe that SGE inhibits virus detection in the early phase of infection. This study provides important insights into how mosquito saliva modulates host innate immunity during viral infection., Competing Interests: The authors declare no competing interests.

Objective: CivaSheet is a palladium-103, implantable, intraoperative radiation therapy device which emits unidirectional radiation that enables boost doses in patients who have otherwise received the maximum radiation dose. Here, we present our initial clinical experience with the first 10 cases using this new technology., Methods and Materials: A retrospective chart review of all patients with STS treated with surgical resection and CivaSheet placement at the University of Miami Hospital, a tertiary care center, from January 2018 to December 2019, was performed. Adjuvant radiation was administered by a palladium-103 implant, which delivered an average of 47 Gy (35-55) to a depth of 5 mm., Results: Nine patients underwent CivaSheet placement from January 2018 until December 2019 for a total of 10 CivaSheets placed (1 patient had 2 CivaSheets inserted) and followed for a mean of 27 months (4-45 months). Four tumors were located in the retroperitoneum, two in the chest, two in the groin, and two within the lower extremity. At the time of tumor resection and CivaSheet placement, tumor sizes ranged from 2.5 cm to 13.8 cm with an average of 7.6 cm. Four patients necessitated musculocutaneous tissue flaps for closure and reconstruction. All patients with Grade 4 complications had flap reconstruction and prior radiation. Four patients' tumors recurred locally for a local recurrence rate of 40%. Three patients had modified accordion Grade 4 complications necessitating additional surgery for CivaSheet removal. Extremity tumors unanimously developed modified accordion Grade 4 adverse events., Conclusions: CivaSheet may be an acceptable alternative treatment modality compared to prior brachytherapy methods., (Copyright © 2023. Published by Elsevier Inc.)

Background: Salivary glands from blood-feeding arthropods secrete several molecules that inhibit mammalian hemostasis and facilitate blood feeding and pathogen transmission. The salivary functions from Simulium guianense , the main vector of Onchocerciasis in South America, remain largely understudied. Here, we have characterized a salivary protease inhibitor (Guianensin) from the blackfly Simulium guianense ., Materials and Methods: A combination of bioinformatic and biophysical analyses, recombinant protein production, in vitro and in vivo experiments were utilized to characterize the molecula mechanism of action of Guianensin. Kinetics of Guianensin interaction with proteases involved in vertebrate inflammation and coagulation were carried out by surface plasmon resonance and isothermal titration calorimetry. Plasma recalcification and coagulometry and tail bleeding assays were performed to understand the role of Guianensin in coagulation., Results: Guianensin was identified in the sialotranscriptome of adult S. guianense flies and belongs to the Kunitz domain of protease inhibitors. It targets various serine proteases involved in hemostasis and inflammation. Binding to these enzymes is highly specific to the catalytic site and is not detectable for their zymogens, the catalytic site-blocked human coagulation factor Xa (FXa), or thrombin. Accordingly, Guianensin significantly increased both PT (Prothrombin time) and aPTT (Activated partial thromboplastin time) in human plasma and consequently increased blood clotting time ex vivo . Guianensin also inhibited prothrombinase activity on endothelial cells. We show that Guianensin acts as a potent anti-inflammatory molecule on FXa-induced paw edema formation in mice., Conclusion: The information generated by this work highlights the biological functionality of Guianensin as an antithrombotic and anti-inflammatory protein that may play significant roles in blood feeding and pathogen transmission., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer BB declared a past collaboration with the authors EC, IM to the handling editor., (Copyright At least a portion of this work is authored by Paola Carolina Valenzuela-Leon, Andrezza Campos Chagas, Ines Martin-Martin, Adeline E. Williams, Markus Berger, Gaurav Shrivastava, Andrew S. Page, Lucas Tirloni and Eric Calvo on behalf of the U.S. Government and as regards Dr. Valenzuela-Leon, Dr. Chagas, Dr. Martin-Martin, Dr. Williams, Dr. Berger, Dr. Shrivastava, Dr. Page, Dr.Tirloni and Dr. Calvo and the U.S. Government, is not subject to copyright protection in the United States. Foreign and other copyrights may apply.)

Blood-feeding arthropods secrete potent salivary molecules, which include platelet aggregation inhibitors, vasodilators, and anticoagulants. Among these molecules, Alboserpin, the major salivary anticoagulant from the mosquito vector Aedes albopictus , is a specific inhibitor of the human coagulation factor Xa (FXa). In this study, we investigated the anti-inflammatory properties of Alboserpin, in vitro and in vivo. In vitro, Alboserpin inhibited FXa-induced protease-activated receptor (PAR)-1, PAR-2, PAR-3, VCAM, ICAM, and NF-κB gene expression in primary dermal microvascular endothelial cells. Alboserpin also prevented FXa-stimulated ERK1/2 gene expression and subsequent inflammatory cytokine release (MCP-1, TNF-α, IL-6, IL-8, IL-1β, IL-18). In vivo, Alboserpin reduced paw edema induced by FXa and subsequent release of inflammatory cytokines (CCL2, MCP-1, IL-1α, IL-6, IL-1β). Alboserpin also reduced FXa-induced endothelial permeability in vitro and in vivo. These findings show that Alboserpin is a potent anti-inflammatory molecule, in vivo and in vitro, and may play a significant role in blood feeding., (Copyright © 2022 The Authors.)

Saliva from mosquitoes contains vasodilators that antagonize vasoconstrictors produced at the bite site. Sialokinin is a vasodilator present in the saliva of Aedes aegypti. Here, we investigate its function and describe its mechanism of action during blood feeding. Sialokinin induces nitric oxide release similar to substance P. Sialokinin-KO mosquitoes produce lower blood perfusion than parental mosquitoes at the bite site during probing and have significantly longer probing times, which result in lower blood feeding success. In contrast, there is no difference in feeding between KO and parental mosquitoes when using artificial membrane feeders or mice that are treated with a substance P receptor antagonist, confirming that sialokinin interferes with host hemostasis via NK1R signaling. While sialokinin-KO saliva does not affect virus infection in vitro, it stimulates macrophages and inhibits leukocyte recruitment in vivo. This work highlights the biological functionality of salivary proteins in blood feeding., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

The healthcare technologies in COVID-19 pandemic had grown immensely in various domains. Blockchain technology is one such turnkey technology, which is transforming the data securely; to store electronic health records (EHRs), develop deep learning algorithms, access the data, process the data between physicians and patients to access the EHRs in the form of distributed ledgers. Blockchain technology is also made to supply the data in the cloud and contact the huge amount of healthcare data, which is difficult and complex to process. As the complexity in the analysis of data is increasing day by day, it has become essential to minimize the risk of data complexity. This paper supports deep neural network (DNN) analysis in healthcare and COVID-19 pandemic and gives the smart contract procedure, to identify the feature extracted data (FED) from the existing data. At the same time, the innovation will be useful to analyse future diseases. The proposed method also analyze the existing diseases which had been reported and it is extremely useful to guide physicians in providing appropriate treatment and save lives. To achieve this, the massive data is integrated using Python scripting language under various libraries to perform a wide range of medical and healthcare functions to infer knowledge that assists in the diagnosis of major diseases such as heart disease, blood cancer, gastric and COVID-19., (© 2021 John Wiley & Sons Ltd.)

Aedes aegypti mosquitoes are important vectors of several debilitating and deadly arthropod-borne (arbo) viruses, including Yellow Fever virus, Dengue virus, West Nile virus and Zika virus (ZIKV). Arbovirus transmission occurs when an infected mosquito probes the host's skin in search of a blood meal. Salivary proteins from mosquitoes help to acquire blood and have also been shown to enhance pathogen transmission in vivo and in vitro. Here, we evaluated the interaction of mosquito salivary proteins with ZIKV by surface plasmon resonance and enzyme-linked immunosorbent assay. We found that three salivary proteins AAEL000793, AAEL007420, and AAEL006347 bind to the envelope protein of ZIKV with nanomolar affinities. Similar results were obtained using virus-like particles in binding assays. These interactions have no effect on viral replication in cultured endothelial cells and keratinocytes. Additionally, we found detectable antibody levels in ZIKV and DENV serum samples against the recombinant proteins that interact with ZIKV. These results highlight complex interactions between viruses, salivary proteins and antibodies that could be present during viral transmissions.

Background: Gangliosides are glycosphingolipids highly enriched in the brain, with important roles in cell signaling, cell-to-cell communication, and immunomodulation. Genetic defects in the ganglioside biosynthetic pathway result in severe neurodegenerative diseases, while a partial decrease in the levels of specific gangliosides was reported in Parkinson's disease and Huntington's disease. In models of both diseases and other conditions, administration of GM1-one of the most abundant gangliosides in the brain-provides neuroprotection. Most studies have focused on the direct neuroprotective effects of gangliosides on neurons, but their role in other brain cells, in particular microglia, is not known. In this study we investigated the effects of exogenous ganglioside administration and modulation of endogenous ganglioside levels on the response of microglia to inflammatory stimuli, which often contributes to initiation or exacerbation of neurodegeneration., Methods: In vitro studies were performed using BV2 cells, mouse, rat, and human primary microglia cultures. Modulation of microglial ganglioside levels was achieved by administration of exogenous gangliosides, or by treatment with GENZ-123346 and L-t-PDMP, an inhibitor and an activator of glycolipid biosynthesis, respectively. Response of microglia to inflammatory stimuli (LPS, IL-1β, phagocytosis of latex beads) was measured by analysis of gene expression and/or secretion of pro-inflammatory cytokines. The effects of GM1 administration on microglia activation were also assessed in vivo in C57Bl/6 mice, following intraperitoneal injection of LPS., Results: GM1 decreased inflammatory microglia responses in vitro and in vivo, even when administered after microglia activation. These anti-inflammatory effects depended on the presence of the sialic acid residue in the GM1 glycan headgroup and the presence of a lipid tail. Other gangliosides shared similar anti-inflammatory effects in in vitro models, including GD3, GD1a, GD1b, and GT1b. Conversely, GM3 and GQ1b displayed pro-inflammatory activity. The anti-inflammatory effects of GM1 and other gangliosides were partially reproduced by increasing endogenous ganglioside levels with L-t-PDMP, whereas inhibition of glycolipid biosynthesis exacerbated microglial activation in response to LPS stimulation., Conclusions: Our data suggest that gangliosides are important modulators of microglia inflammatory responses and reveal that administration of GM1 and other complex gangliosides exerts anti-inflammatory effects on microglia that could be exploited therapeutically., (© 2022. The Author(s).)

The PIWI-interacting RNA (piRNA) pathway provides an RNA interference (RNAi) mechanism known from Drosophila studies to maintain the integrity of the germline genome by silencing transposable elements (TE). Aedes aegypti mosquitoes, which are the key vectors of several arthropod-borne viruses, exhibit an expanded repertoire of Piwi proteins involved in the piRNA pathway, suggesting functional divergence. Here, we investigate RNA-binding dynamics and subcellular localization of A. aegypti Piwi4 (AePiwi4), a Piwi protein involved in antiviral immunity and embryonic development, to better understand its function. We found that AePiwi4 PAZ (Piwi/Argonaute/Zwille), the domain that binds the 3' ends of piRNAs, bound to mature (3' 2' O-methylated) and unmethylated RNAs with similar micromolar affinities (K D = 1.7 ± 0.8 μM and K D of 5.0 ± 2.2 μM, respectively; p = 0.05) in a sequence independent manner. Through site-directed mutagenesis studies, we identified highly conserved residues involved in RNA binding and found that subtle changes in the amino acids flanking the binding pocket across PAZ proteins have significant impacts on binding behaviors, likely by impacting the protein secondary structure. We also analyzed AePiwi4 subcellular localization in mosquito tissues. We found that the protein is both cytoplasmic and nuclear, and we identified an AePiwi4 nuclear localization signal (NLS) in the N-terminal region of the protein. Taken together, these studies provide insights on the dynamic role of AePiwi4 in RNAi and pave the way for future studies aimed at understanding Piwi interactions with diverse RNA populations.

The mortality and morbidity rates for prostate cancer have recently increased to alarming levels, rising higher than lung cancer. Due to a lack of drug targets and molecular probes, existing theranostic techniques are limited. Human LIN28A and its paralog LIN28B overexpression are associated with a number of tumors resulting in a remarkable increase in cancer aggression and poor prognoses. The current review aims to highlight recent work identifying the key roles of LIN28A and LIN28B in prostate cancer, and to instigate further preclinical and clinical research in this important area.

Importance: A large proportion of extremity soft-tissue sarcomas (ESS) occur among young adults, yet this group is underrepresented in clinical trials, resulting in limited data on this population. Younger patients present many complex challenges that affect clinical management., Objective: To investigate variations in treatment management in young adults vs older adults with ESS., Design, Setting, and Participants: This multicenter retrospective cohort study used the National Cancer Data Base (NCDB) to identify patients 18 years and older with ESS who received definitive treatment (ie, limb-sparing surgery [LSS] or amputation) between 2004 and 2014. Data analysis was conducted in November 2019., Exposures: Treatment regimen received among young adults (aged 18-39 years) and older adults (≥40 years) after diagnosis with ESS., Main Outcomes and Measures: To detect unique factors associated with treatment decisions in young adults with ESS, multivariable analyses used logistic regressions for patterns of treatment and their association with demographic factors and tumor characteristics., Results: Overall, 8953 patients were identified, and among these, 1280 (14.3%) were young adults. From the full cohort, 4796 patients (53.6%) identified as male and 6615 (73.9%) identified as non-Hispanic White. More young adults than older adults underwent amputation (age 18-39 years, 104 of 1280 [8.1%]; age 40-64 years, 217 of 3937 [5.5%]; aged ≥65 years, 199 of 3736 [5.3%]), but the association was not statistically significant (age ≥65 years, odds ratio [OR], 1.49; 95% CI, 1.00-2.23; P = .05). Young adults were more likely to receive chemotherapy than older patients (age 40-65 years, OR, 0.52; 95% CI, 0.45-0.60; P = .001; ≥65 years, OR, 0.16; 95% CI, 0.12-0.20; P = .001). Conversely, young adults were less likely to receive radiation therapy compared with older patients (age 40-65 years, OR, 1.40; 95% CI, 1.22-1.61; P = .001; ≥65 years, OR, 1.33; 95% CI, 1.10-1.61; P = .003). Unique to younger adults, clinical stage II disease vs stage I and positive surgical margins were not associated with use of radiation therapy (stage II disease: OR, 1.25; 95% CI, 0.81-1.91; P = .31; positive surgical margins: OR, 1.43; 95% CI, 0.93-2.22; P = .11). White Hispanic young adults were less likely than non-Hispanic White young adults to receive radiation therapy (OR, 0.53; 95% CI, 0.36-0.78; P = .002)., Conclusions and Relevance: In this study, young adults with ESS were more likely to receive chemotherapy and less likely to receive radiation therapy than older adults. Further study is warranted to identify the clinical outcomes of these practice disparities.