Search Results (61)

T follicular helper (Tfh) and T follicular regulatory cells (Tfr) are required for antibody production and are dysregulated in SLE. Genetic variants within or near interferon regulatory factor 5 (IRF5) are associated with SLE risk. We previously reported higher plasma cells and autoantibodies in healthy IRF5-SLE homozygous risk carriers. Here, we report the dysregulation of circulating Tfh and Tfr in both SLE patients and presymptomatic IRF5-SLE homozygous risk carriers. Full article

A virtual power plant (VPP) is a potential alternative that aggregates the distributed energy resources (DERs) and addresses the prosumer’s power availability, quality, and reliability requirements. This paper reports the optimized scheduling of an interconnected VPP in a multi-area framework established through a tie-line connection comprising multiple renewable resources. The scheduling was initially performed on a day ahead (hourly basis) interval, followed by an hour ahead interval (intra-hour and real time), i.e., a 15 min and 5 min time interval for the developed VPP in a multi-area context. The target objective functions for the selected problem were two-fold, i.e., net profit and emission, for which maximization was performed for the former and reduction for the later, respectively. Since renewables are involved in the energy mix and the developed problem was complex in nature, the proposed multi-area-based VPP was tested with an advanced nature-inspired metaheuristic technique. Moreover, the proposed formulation was extended to a multi-objective context, and multiple scheduling strategies were performed to reduce the generated emissions and capitalize on the cumulative profit associated with the system by improving the profit margin simultaneously. Furthermore, a comprehensive numeric evaluation was performed with different optimization intervals, which revealed the rapid convergence in minimal computational time to reach the desired solution. Full article

Malignant growth is expected to surpass other significant causes of death as one of the top reasons for dismalness and mortality worldwide. According to a World Health Organization (WHO) study, this illness causes approximately between 9 and 10 million instances of deaths annually. Chemotherapy, radiation, and surgery are the three main methods of treating cancer. These methods seek to completely eradicate all cancer cells while having the fewest possible unintended impacts on healthy cell types. Owing to the lack of target selectivity, the majority of medications have substantial side effects. On the other hand, nanomaterials have transformed the identification, diagnosis, and management of cancer. Nanostructures with biomimetic properties have been grown as of late, fully intent on observing and treating the sickness. These nanostructures are expected to be consumed by growth in areas with profound disease. Furthermore, because of their extraordinary physicochemical properties, which incorporate nanoscale aspects, a more prominent surface region, explicit geometrical features, and the ability to embody different substances within or on their outside surfaces, nanostructures are remarkable nano-vehicles for conveying restorative specialists to their designated regions. This review discusses recent developments in nanostructured materials such as graphene, dendrimers, cell-penetrating peptide nanoparticles, nanoliposomes, lipid nanoparticles, magnetic nanoparticles, and nano-omics in the diagnosis and management of cancer. Full article

Background: Targeted therapies have been largely ineffective against glioblastoma (GBM) owing to the tumor’s heterogeneity and intrinsic and adaptive treatment resistance. Targeting multiple pro-survival pathways simultaneously may overcome these limitations and yield effective treatments. Heat shock protein 90 (HSP90), an essential component of the epichaperome complex, is critical for the proper folding and activation of several pro-survival oncogenic proteins that drive GBM biology. Methods: Using a panel of biochemical and biological assays, we assessed the expression of HSP90 and its downstream targets and the effects of PU-H71, a highly specific and potent HSP90 inhibitor, on target modulation, downstream biochemical alterations, cell cycle progression, proliferation, migration, and apoptosis in patient-derived glioma stem-like cells (GSCs) with molecular profiles characteristic of GBM, as well as commercial glioma cell lines and normal human astrocytes (NHAs). Results: HSP90 inhibition by PU-H71 in GSCs significantly reduced cell proliferation, colony formation, wound healing, migration, and angiogenesis. In glioma cells, but not NHAs, potent PU-H71-mediated HSP90 inhibition resulted in the downregulation of pro-survival client proteins such as EGFR, MAPK, AKT, and S6. This reduction in pro-survival signals increased glioma cells’ sensitivity to temozolomide, a monofunctional alkylator, and the combination of PU-H71 and temozolomide had greater anticancer efficacy than either agent alone. Conclusions: These results confirm that HSP90 is a strong pro-survival factor in molecularly heterogeneous gliomas and suggest that epichaperome inhibition with HSP90 inhibitors warrants further investigation for the treatment of gliomas. Full article

Background and Objectives: Hepatic resection offers promising outcomes for patients with hepatocellular carcinoma (HCC) but can be constrained by factors like patient suitability. Continuous advancements in laparoscopic and robotic technologies have made minimally invasive hepatectomies (MIHs) a viable alternative to open hepatectomies with benefits in terms of recovery and complications. Materials and Methods: We completed a retrospective review on 138 HCC patients who underwent OH or MIH between 2010 and 2020 at the Hume-Lee Transplant Center. Univariate and multivariate analyses were completed on demographic, clinical, and tumor-specific data to assess the impact of these variables on overall and disease-free survival at 1, 3, and 5 years. Preoperative metrics like length of hospital stay (LOS) and operation duration were also evaluated. Results: Of the 109 OH and 29 MIH patients, MIH patients demonstrated shorter LOS and operative times. However, overall survival (OS) and disease-free survival (DFS) were similar between groups, with no significant variations in 1-, 3-, and 5-year survival rates. Age > 60 years and a lack of preoperative transcatheter arterial chemoembolization (TACE) were significant predictors of inferior OS and DFS in multivariate analyses. Conclusions: MIH is an efficient substitute for OH with comparable survival, even in older patients. The reduced LOS and operation time enhance its feasibility, and older patients previously denied for curative resection may qualify for MIH. Preoperative TACE also enhances survival outcomes, emphasizing its general role in managing resectable HCCs. Both robotic and laparoscopic hepatectomies offer acceptable short- and long-term clinical outcomes, highlighting MIH as the standard choice for HCC patients. Full article

Liver transplantation is the most effective treatment for end-stage liver disease. Despite improvements in surgical techniques, transplant rejection remains a significant concern. The liver is considered an immune-privileged organ due to its unique microenvironment and complex interactions among various cell types. Alloimmune responses mediated by T cells and antigen-presenting cells (APCs) play crucial roles in transplant rejection. The liver’s dual blood supply and unique composition of its sinusoidal endothelial cells (LSECs), Kupffer cells (KCs), hepatocytes, and hepatic stellate cells (HSCs) contribute to its immune privilege. Alloantigen recognition by T cells occurs through direct, indirect, and semidirect pathways, leading to acute cellular rejection (ACR) and chronic rejection. ACR is a T cell-mediated process that typically occurs within the first few weeks to months after transplantation. Chronic rejection, on the other hand, is a gradual process characterized by progressive fibrosis and graft dysfunction, often leading to graft loss. Acute antibody-mediated rejection (AMR) is less common following surgery compared to other solid organ transplants due to the liver’s unique anatomy and immune privilege. However, when it does occur, AMR can be aggressive and lead to rapid graft dysfunction. Despite improvements in immunosuppression, rejection remains a challenge, particularly chronic rejection. Understanding the mechanisms of rejection and immune tolerance, including the roles of regulatory T cells (Tregs) and hepatic dendritic cells (DCs), is crucial for improving transplant outcomes. Strategies to induce immune tolerance, such as modulating DC function or promoting Treg activity, hold promise for reducing rejection and improving long-term graft survival. This review focuses on the liver’s unique predisposition to rejection and tolerance, highlighting the roles of individual cell types in these processes. Continued research into the mechanisms of alloimmune responses and immune tolerance in liver transplantation is essential for developing more effective therapies and improving long-term outcomes for patients with end-stage liver disease. Full article

Peanuts (Arachis hypogaea L.) are important high-protein and oil-containing legume crops adapted to arid to semi-arid regions. The yield and quality of peanuts are complex quantitative traits that show high environmental influence. In this study, a recombinant inbred line population (RIL) (Valencia-C × JUG-03) was developed and phenotyped for nine traits under two environments. A genetic map was constructed using 1323 SNP markers spanning a map distance of 2003.13 cM. Quantitative trait loci (QTL) analysis using this genetic map and phenotyping data identified seventeen QTLs for nine traits. Intriguingly, a total of four QTLs, two each for 100-seed weight (HSW) and shelling percentage (SP), showed major and consistent effects, explaining 10.98% to 14.65% phenotypic variation. The major QTLs for HSW and SP harbored genes associated with seed and pod development such as the seed maturation protein-encoding gene, serine-threonine phosphatase gene, TIR-NBS-LRR gene, protein kinase superfamily gene, bHLH transcription factor-encoding gene, isopentyl transferase gene, ethylene-responsive transcription factor-encoding gene and cytochrome P450 superfamily gene. Additionally, the identification of 76 major epistatic QTLs, with PVE ranging from 11.63% to 72.61%, highlighted their significant role in determining the yield- and quality-related traits. The significant G × E interaction revealed the existence of the major role of the environment in determining the phenotype of yield-attributing traits. Notably, the seed maturation protein-coding gene in the vicinity of major QTLs for HSW can be further investigated to develop a diagnostic marker for HSW in peanut breeding. This study provides understanding of the genetic factor governing peanut traits and valuable insights for future breeding efforts aimed at improving yield and quality. Full article

Domestication and extensive selection in the development of modern, high-yielding commercial groundnut cultivars have resulted in the selection of an undesirable trait known as in situ germination, which is also referred to as the pre-harvest sprouting of seeds. This is particularly prevalent in regions where humid weather coincides with the harvest season. Delayed harvesting and pre-sprouting can cause production losses and increase the chances of aflatoxin contamination, thereby impeding the quality and kernel yield. Breeding early maturing groundnut cultivars with 2–3 weeks of fresh seed dormancy, particularly in Spanish-type cultivars, enhances the sustainability of agriculture. In this context, we conducted a comprehensive evaluation of a groundnut mini-core collection, a major resource for genetic diversity, for fresh seed dormancy using an in vitro germination assay for two seasons, viz., rainy 2022 and post-rainy 2022–2023 at ICRISAT (Hyderabad). To enhance the effectiveness and accuracy of traditional breeding methods via the use of markers for marker-assisted selection, we performed molecular screening of the mini-core accessions using two allele-specific markers. The GMFSD1 marker was successfully validated by effectively differentiating dormant and non-dormant genotypes. By employing phenotypic and marker data, we identified a set of accessions, viz., ICG 5827 (Virginia Runner), ICG 11457 (Virginia Runner), ICG 7000 (Virginia Bunch), and ICG 11322 (Virginia Bunch) of sub spp. hypogaea var. hypogaea and ICG 9809 (Spanish Bunch) of sub spp. fastigiata var. vulgaris that exhibited a fresh seed dormancy period ranging from 2 to 3 weeks. These identified accessions hold potential as donors in breeding programs that are designed to address the groundnut production needs in various cropping systems across different countries. The validated marker, particularly GMFSD1, demonstrated considerable potential for facilitating faster breeding of groundnut cultivars with the desired dormancy using marker-assisted selection. This research provides a foundation to expediting groundnut breeding programs and offers opportunities to mitigate pre-harvest sprouting, ultimately improving seed quality and productivity in groundnut-producing regions. Full article

Despite improvements in short-term and long-term outcomes of liver transplant patients, the discrepancy between the number of available livers and transplant candidates continues to increase. The use of expanded criteria donors is one strategy that can be used to address donor shortages. In recent years, preservation strategies such as normothermic machine perfusion (NMP) have been explored to improve the preservation of organs and test their viability before transplantation. We reviewed the recent literature and trials assessing the use of NMP in the setting of liver transplantation. Multiple feasibility trials have demonstrated the clinical prospect of NMP and proved its numerous advantages compared to conventional static cold storage. These advantages include preservation and viability assessment of high-risk donor allografts and grafts that would have otherwise been discarded. This review aims to address the topic of liver NMP in the setting of current and future applications in the setting of extended criteria donor grafts. Full article

In the past decade, a sudden increase in the number and kind of emerging water contaminants has been observed. The emerging contaminants can be categorized as organic or inorganic. Organic contaminants have been known for years, and techniques for their detection and remediation have been developed. However, inorganic pollutants are much more common. This is because they are detected in very low or negligible concentrations and are equally toxic as organic pollutants at higher concentrations. To boost the research on inorganic pollutant contamination, advancements in detection and quantification techniques are required. The presented paper discusses major inorganic pollutants such as metals and their salts, inorganic fertilizers, sulfides, acids and bases, and ammonia and oxides of nitrogen. In addition, it discusses the inorganic toxicants’ toxicity to organisms and the environment, upgraded quantification methods, and advancements in inorganic toxicant mitigation. Moreover, the major bottlenecks in the quantification and removal of inorganic pollutants are discussed at the end. Full article

An agency problem is defined as a conflict of interest arising due to a misalignment of interests among the managers and other stakeholders of the company. This article aims to review the articles addressing the agency problem and their impact on business performance. This article reviews the contributions of prominent theorists on agency problems and agency costs. Using bibliometric attributes of 740 articles from the Scopus database, this study highlights the publishing trend and outlets, along with leading contributors and collaborators in terms of authors, institutions, and countries. This study identifies the clusters through the bibliographic coupling technique and a trend topics analysis. Most researchers have focused on corporate governance and expressed the agency problem as one of the impact areas. This study is unique as no study to date specifically focuses solely on agency theory or the agency problem through the lens of bibliometric analysis. Future research directions on agency problems and their solutions conclude this study. Full article

Sugar Efflux transporters (SWEET) are involved in diverse biological processes of plants. Pathogens have exploited them for nutritional gain and subsequently promote disease progression. Recent studies have implied the involvement of potato SWEET genes in the most devastating late blight disease caused by Phytophthora infestans. Here, we identified and designated 37 putative SWEET genes as StSWEET in potato. We performed detailed in silico analysis, including gene structure, conserved domains, and phylogenetic relationship. Publicly available RNA-seq data was harnessed to retrieve the expression profiles of SWEET genes. The late blight-responsive SWEET genes were identified from the RNA-seq data and then validated using quantitative real-time PCR. The SWEET gene expression was studied along with the biotrophic (SNE1) and necrotrophic (PiNPP1) marker genes of P. infestans. Furthermore, we explored the co-localization of P. infestans resistance loci and SWEET genes. The results indicated that nine transporter genes were responsive to the P. infestans in potato. Among these, six transporters, namely StSWEET10, 12, 18, 27, 29, and 31, showed increased expression after P. infestans inoculation. Interestingly, the observed expression levels aligned with the life cycle of P. infestans, wherein expression of these genes remained upregulated during the biotrophic phase and decreased later on. In contrast, StSWEET13, 14, and 32 didn’t show upregulation in inoculated samples suggesting non-targeting by pathogens. This study underscores these transporters as prime P. infestans targets in potato late blight, pivotal in disease progression, and potential candidates for engineering blight-resistant potato genotypes. Full article

Neuroendocrine neoplasms (NENs), also called neuroendocrine tumors (NETs), are relatively uncommon, heterogenous tumors primarily originating in the gastrointestinal tract. With the improvement in technology and increasing use of cross-sectional imaging and endoscopy, they are being discovered with increasing frequency. Although traditionally considered indolent tumors with good prognoses, some NENs exhibit aggressive behavior. Timely diagnosis, risk stratification, and management can often be a challenge. In general, small NENs without local invasion or lymphovascular involvement can often be managed using minimally invasive advanced endoscopic techniques, while larger lesions and those with evidence of lymphovascular invasion require surgery, systemic therapy, or a combination thereof. Ideal management requires a comprehensive and accurate understanding of the stage and grade of the tumor. With the recent advancements, a therapeutic advanced endoscopist can play a pivotal role in diagnosing, staging, and managing this rare condition. High-definition white light imaging and digital image enhancing technologies like narrow band imaging (NBI) in the newer endoscopes have improved the diagnostic accuracy of traditional endoscopy. The refinement of endoscopic ultrasound (EUS) over the past decade has revolutionized the role of endoscopy in diagnosing and managing various pathologies, including NENs. In addition to EUS-directed diagnostic biopsies, it also offers the ability to precisely assess the depth of invasion and lymphovascular involvement and thus stage NENs accurately. EUS-directed locoregional ablative therapies are increasingly recognized as highly effective, minimally invasive treatment modalities for NENs, particularly pancreatic NENs. Advanced endoscopic resection techniques like endoscopic submucosal dissection (ESD), endoscopic submucosal resection (EMR), and endoscopic full-thickness resection (EFTR) have been increasingly used over the past decade with excellent results in achieving curative resection of various early-stage gastrointestinal luminal lesions including NENs. In this article, we aim to delineate NENs of the different segments of the gastrointestinal (GI) tract (esophagus, gastric, pancreatic, and small and large intestine) and their management with emphasis on the endoscopic management of these tumors. Full article

The aim of the present study was to assess the effects of inoculation of Trichoderma harzianum, Eisenia fetida and cow dung on the physicochemical quality of paddy straw composting which was carried out for 90 days. The different treatment groups were Paddy straw (T₀), Paddy straw + Cow dung (T₁), Paddy straw + Cow dung + Eisenia fetida (T₂), Paddy straw + Cow dung + Trichoderma harzianum (T₃), Paddy straw + Cow dung + Eisenia fetida + Trichoderma harzianum (T₄). The ratio of cow dung and paddy straw was 2:1. Among all treatments, T₄ was identified as the best treatment for decomposing the paddy straw as it recovered the nutrients within the recommended levels of a high-quality product. The consortium of Trichoderma harzianum, Eisenia fetida and cow dung lowered the total organic carbon (TOC) and C:N ratio by 28.8% and 33.1%, respectively, at pH 6.5. The increase in N (0.87%), P (0.47%), K (2.66%), Ca (0.033%), Mg (0.056%) and Na (0.42%) was significant in T₄ treatment. The micronutrients, namely Cu (47.9 ppm), Fe (1128 ppm) and Zn (500 ppm), also showed a significant increase in this treatment, i.e., T₄. Therefore, results suggested that combinatorial composting by Trichoderma harzianum, Eisenia fetida and cow dung is quite promising in the decomposition of paddy straw to obtain quality compost in a short time. Furthermore, this study will help in the sustainable management of paddy straw with concomitant reduction inenvironmental pollution caused by the open burning of paddy straw. Full article