Search

Abstract Background The innate immune system serves as the first line of host defense. Transforming growth factor-β–activated kinase 1 (TAK1) is a key regulator of innate immunity, cell survival, and cellular homeostasis. Because of its importance in immunity, several pathogens have evolved to carry TAK1 inhibitors. In response, hosts have evolved to sense TAK1 inhibition and induce robust lytic cell death, PANoptosis, mediated by the RIPK1-PANoptosome. PANoptosis is a unique innate immune inflammatory lytic cell death pathway initiated by an innate immune sensor and driven by caspases and RIPKs. While PANoptosis can be beneficial to clear pathogens, excess activation is linked to pathology. Therefore, understanding the molecular mechanisms regulating TAK1 inhibitor (TAK1i)-induced PANoptosis is central to our understanding of RIPK1 in health and disease. Results In this study, by analyzing results from a cell death-based CRISPR screen, we identified protein phosphatase 6 (PP6) holoenzyme components as regulators of TAK1i-induced PANoptosis. Loss of the PP6 enzymatic component, PPP6C, significantly reduced TAK1i-induced PANoptosis. Additionally, the PP6 regulatory subunits PPP6R1, PPP6R2, and PPP6R3 had redundant roles in regulating TAK1i-induced PANoptosis, and their combined depletion was required to block TAK1i-induced cell death. Mechanistically, PPP6C and its regulatory subunits promoted the pro-death S166 auto-phosphorylation of RIPK1 and led to a reduction in the pro-survival S321 phosphorylation. Conclusions Overall, our findings demonstrate a key requirement for the phosphatase PP6 complex in the activation of TAK1i-induced, RIPK1-dependent PANoptosis, suggesting this complex could be therapeutically targeted in inflammatory conditions.

Abstract Aerobic glycolysis, or the Warburg effect, is used by cancer cells for proliferation while producing lactate. Although lactate production has wide implications for cancer progression, it is not known how this effect increases cell proliferation and relates to oxidative phosphorylation. Here, we elucidate that a negative feedback loop (NFL) is responsible for the Warburg effect. Further, we show that aerobic glycolysis works as an amplifier of oxidative phosphorylation. On the other hand, quiescence is an important property of cancer stem cells. Based on the NFL, we show that both aerobic glycolysis and oxidative phosphorylation, playing a synergistic role, are required to achieve cell quiescence. Further, our results suggest that the cells in their hypoxic niche are highly proliferative yet close to attaining quiescence by increasing their NADH/NAD+ ratio through the severity of hypoxia. The findings of this study can help in a better understanding of the link among metabolism, cell cycle, carcinogenesis, and stemness.

Abstract The escalating global challenge of antimicrobial resistance demands innovative approaches. This review delves into the current status and future prospects of bioengineered metallic nanoparticles derived from natural sources as potent antimicrobial agents. The unique attributes of metallic nanoparticles and the abundance of natural resources have sparked a burgeoning field of research in combating microbial infections. A systematic review of the literature was conducted, encompassing a wide range of studies investigating the synthesis, characterization, and antimicrobial mechanisms of bioengineered metallic nanoparticles. Databases such as PubMed, Scopus, Web of Science, ScienceDirect, Springer, Taylor & Francis online and OpenAthen were extensively searched to compile a comprehensive overview of the topic. The synthesis methods, including green and sustainable approaches, were examined, as were the diverse biological sources used in nanoparticle fabrication. The amalgamation of metallic nanoparticles and natural products has yielded promising antimicrobial agents. Their multifaceted mechanisms, including membrane disruption, oxidative stress induction, and enzyme inhibition, render them effective against various pathogens, including drug-resistant strains. Moreover, the potential for targeted drug delivery systems using these nanoparticles has opened new avenues for personalized medicine. Bioengineered metallic nanoparticles derived from natural sources represent a dynamic frontier in the battle against microbial infections. The current status of research underscores their remarkable antimicrobial efficacy and multifaceted mechanisms of action. Future prospects are bright, with opportunities for scalability and cost-effectiveness through sustainable synthesis methods. However, addressing toxicity, regulatory hurdles, and environmental considerations remains crucial. In conclusion, this review highlights the evolving landscape of bioengineered metallic nanoparticles, offering valuable insights into their current status and their potential to revolutionize antimicrobial therapy in the future. Graphical Abstract

Abstract For the application of biochar in restoring pesticide-contaminated soils and minimizing the risk associated with their uptake in plants, it is crucial to understand the biochar impact on soil biological activities and dissipation and accumulation of pesticides in plant and soil systems. In this study, the effect of Mentha-distilled waste-derived biochar was investigated on chlorpyrifos and atrazine contaminated sandy loam soil. The four application rates of atrazine (2, 4, 6, and 8 mg kg−1) and chlorpyrifos (2, 4, 6, and 12 mg kg−1) and a single application rate of biochar (4%) were used in this study. The degradation of pesticides, the diversity of the bacterial community, and enzymatic activities (alkaline phosphatase, dehydrogenase, arylsulfatase, phenol oxidase, urease activity and N-acetyl glucosaminidase) were examined in soil. The uptake of two pesticides and their effect on growth and stress parameters were also investigated in plants (A. paniculata). The dissipation of chlorpyrifos and atrazine followed simple first-order kinetics with a half-life of 6.6–74.6 and 21–145 days, respectively. The presence of deisopropyl atrazine desethyl atrazine (metabolites of atrazine) and 3,5,6-trichloro-2-pyridinol (a metabolite of chlorpyrifos) was observed in soil and plant tissues. Biochar application significantly (p = 0.001) enhanced the degradation rate of chlorpyrifos and atrazine leading to the lower half-life of chlorpyrifos and atrazine in soil. A significant reduction (p = 0.001) in the uptake of chlorpyrifos and atrazine and alteration in their binding affinity and uptake rate in plant tissues was observed in biochar treatments. The incorporation of biochar improved chlorpyrifos/atrazine degrader and plant growth-promoting bacterial genera such as Balneimonas, Kaistobacter, Rubrobacter, Ammoniphilus, and Bacillus. The upregulation of functional genes associated with nucleotide, energy, carbohydrate, amino acid metabolism, xenobiotic biodegradation, and metabolism: atrazine degradation was observed in biochar treatments. The biochar amendments significantly (p = 0.001) reduced the plant’s uptake velocity (Vmax) and affinity (Km) of chlorpyrifos and atrazine. These results delineated that Mentha-distilled waste-derived biochar can potentially remediate chlorpyrifos and atrazine contaminated soils and ensure the safety of plants for consumption. Graphical Abstract

Abstract Innate immunity provides the first line of defense through multiple mechanisms, including pyrogen production and cell death. While elevated body temperature during infection is beneficial to clear pathogens, heat stress (HS) can lead to inflammation and pathology. Links between pathogen exposure, HS, cytokine release, and inflammation have been observed, but fundamental innate immune mechanisms driving pathology during pathogen exposure and HS remain unclear. Here, we use multiple genetic approaches to elucidate innate immune pathways in infection or LPS and HS models. Our results show that bacteria and LPS robustly increase inflammatory cell death during HS that is dependent on caspase-1, caspase-11, caspase-8, and RIPK3 through the PANoptosis pathway. Caspase-7 also contributes to PANoptosis in this context. Furthermore, NINJ1 is an important executioner of this cell death to release inflammatory molecules, independent of other pore-forming executioner proteins, gasdermin D, gasdermin E, and MLKL. In an in vivo HS model, mortality is reduced by deleting NINJ1 and fully rescued by deleting key PANoptosis molecules. Our findings suggest that therapeutic strategies blocking NINJ1 or its upstream regulators to prevent PANoptosis may reduce the release of inflammatory mediators and benefit patients.

Abstract Background Predictive biomarkers of immune checkpoint inhibitor (ICI) efficacy are currently lacking for non-small cell lung cancer (NSCLC). Here, we describe the results from the Anti–PD-1 Response Prediction DREAM Challenge, a crowdsourced initiative that enabled the assessment of predictive models by using data from two randomized controlled clinical trials (RCTs) of ICIs in first-line metastatic NSCLC. Methods Participants developed and trained models using public resources. These were evaluated with data from the CheckMate 026 trial (NCT02041533), according to the model-to-data paradigm to maintain patient confidentiality. The generalizability of the models with the best predictive performance was assessed using data from the CheckMate 227 trial (NCT02477826). Both trials were phase III RCTs with a chemotherapy control arm, which supported the differentiation between predictive and prognostic models. Isolated model containers were evaluated using a bespoke strategy that considered the challenges of handling transcriptome data from clinical trials. Results A total of 59 teams participated, with 417 models submitted. Multiple predictive models, as opposed to a prognostic model, were generated for predicting overall survival, progression-free survival, and progressive disease status with ICIs. Variables within the models submitted by participants included tumor mutational burden (TMB), programmed death ligand 1 (PD-L1) expression, and gene-expression–based signatures. The best-performing models showed improved predictive power over reference variables, including TMB or PD-L1. Conclusions This DREAM Challenge is the first successful attempt to use protected phase III clinical data for a crowdsourced effort towards generating predictive models for ICI clinical outcomes and could serve as a blueprint for similar efforts in other tumor types and disease states, setting a benchmark for future studies aiming to identify biomarkers predictive of ICI efficacy. Trial registration: CheckMate 026; NCT02041533, registered January 22, 2014. CheckMate 227; NCT02477826, registered June 23, 2015.

MXenes, a rapidly growing family of two-dimensional (2D) transition metal carbides, nitrides, or carbonitrides (Mn+1XnTx, where M is a transition metal, X is carbon, nitrogen, or both, and T represents surface functional groups), have captured the scientific community's interest due to their exceptional physicochemical properties and diverse technological applications. This comprehensive review explores the latest breakthroughs in MXene synthesis and characterisation, emphasising their multifaceted applications in energy storage, catalysis, sensing, and other cutting-edge domains. This review examines the most widely used MXene synthesis strategies, including selective etching and delamination, and highlight recent advancements in controlling surface terminations, composition, and morphology. The influence of these synthetic parameters on MXene properties is discussed in detail. Characterisation techniques, ranging from spectroscopic methods to electron microscopy, are essential for elucidating MXenes' structure-property relationships. Research into energy storage leverages MXenes' high electrical conductivity, large surface area, and chemical tunability. This has led to significant progress in the field. This paper presents research efforts focused on optimising MXenes for both battery and supercapacitor applications. Additionally, the catalytic prowess of MXenes, particularly in electrocatalysis and photocatalysis, is explored, emphasising their role in green energy technologies and environmental remediation. MXenes' remarkable sensitivity and selectivity make them promising candidates for sensing various gases, biomolecules, and ions, offering exciting possibilities in healthcare and environmental monitoring. Importantly, this review underscores the need for continued optimisation of MXene synthesis protocols to achieve large-scale production, enhanced stability, and precise control over properties across various fields.

Technology-mediated group toxicity polarization is a major socio-technological issue of our time. For better large-scale monitoring of polarization among social media news content, we quantify the toxicity of news video comments using a Toxicity Polarization Score. For polarizing news videos, our premise is that the comments’ toxicity approximates either an “M” or “U” shaped distribution—that is, there is unevenly balanced toxicity among the comments. We evaluate our premises through a case study using a dataset of ~180,000 YouTube comments on ~3,700 real news videos from an international online news organization. Toward polarization-mitigating information systems, we build a predictive machine learning model to score the toxicity polarization of news content even when its comments are disabled or not available, as it is a current trend among news publishers to disable comments. Findings imply that the most engaging news content is also often the most polarizing, which we associate with increasing research on clickbait content and the detrimental effect of attention-based metrics on the health of online social media communities, especially news communities.

Abstract The importance of inflammatory cell death, PANoptosis, in cancer is increasingly being recognized. PANoptosis can promote or inhibit tumorigenesis in context-dependent manners, and a computational approach leveraging transcriptomic profiling of genes involved in PANoptosis has shown that patients can be stratified into PANoptosis High and PANoptosis Low clusters that have significant differences in overall survival for low grade glioma (LGG), kidney renal cell carcinoma (KIRC) and skin cutaneous melanoma (SKCM). However, the molecular mechanisms that contribute to differential prognosis between PANoptosis clusters require further elucidation. Therefore, we performed a comprehensive comparison of genetic, genomic, tumor microenvironment, and pathway characteristics between the PANoptosis High and PANoptosis Low clusters to determine the relevance of each component in driving the differential associations with prognosis for LGG, KIRC and SKCM. Across these cancer types, we found that activation of the proliferation pathway was significantly different between PANoptosis High and Low clusters. In LGG and SKCM, we also found that aneuploidy and immune cell densities and activations contributed to differences in PANoptosis clusters. In individual cancers, we identified important roles for barrier gene pathway activation (in SKCM) and the somatic mutation profiles of driver oncogenes as well as hedgehog signaling pathway activation (in LGG). By identifying these genetic and molecular factors, we can possibly improve the prognosis for at risk-stratified patient populations based on the PANoptosis phenotype in LGG, KIRC and SKCM. This not only advances our mechanistic understanding of cancer but will allow for the selection of optimal treatment strategies.

Abstract Background A symbiotic connection between Piriformospora indica and Bacopa monnieri (L.) Wettest, obtained through co-cultivation synergism, was found to improve growth, biomass production, and bacoside content in the plants. Brahmi (B. monnieri L.), a well-known Indian plant prized for its memory-boosting properties, has a lengthy history and a premium price tag. Because of its remarkable ability to colonize a wide variety of plant species, the axenically cultivable mycorrhiza-like endophytic fungus P. indica has gained a lot of interest recently. Methods In the current study, fungal spores from recently revived cultures were added to jam bottles next to rooted Brahmi plants for in vitro co-cultivation. The control plants were left without fungal discs. Pre-rooted micro-propagated Brahmi plants were treated with agar discs containing actively growing hyphae. For a period of 3 months, both trials were conducted with a fully randomized setup. Microscopy of the treated and control plant roots verified co-cultivation. Results Microscopic examination of the roots of co-cultivated plants reveals a high degree of colonization with host plants. These endophytic fungal structures include intracellular chlamydospores, and arbuscules, an intercellular and intracellular hyphae network, and a mycelial network on the root surface. In both in vitro and in vivo co-cultivation studies, the plant extended the host plant’s lifespan in 3 months by displaying continuous regeneration; in contrast, the control plant displayed signs of senescence. With biomass exceeding the control by 1.18 times in vivo and 1.28 times in vitro. In vitro, co-cultivation circumstances also led to an increase in the rate of utilization of nutritional medium. In comparison to the control, the amount of bacoside increases to 100% in vivo after a month of co-cultivation and 33% in vitro after 3 months. Conclusions In the present investigation, in vivo co-cultivation showed a favorable interaction effect on biomass production as well as bacoside content, which can satisfy the raw material demands of Brahmi plants in pharmaceutical industries.

Traveling Wave Tubes (TWT) are most widely used in civil, defense, and space applications as power amplifiers over a wide range of frequency. When a TWT works at a higher bandwidth, it suffers from nonlinearities, which affects the overall performance of the tube and hence the required results aren't achieved. So, optimization of a TWT is required, mainly in terms of its power characteristics. Power characteristics of the TWTs are specified in terms of output power at different input drive levels, AM/PM transfer and AM/PM conversions, input, and output back-off, gain at saturation, etc. Some of the linearity factors like 3rd order inter modulation product (IMP), and the 1 dB compression point are also optimized. An exhaustive study has been made to achieve the optimum performance of a 140W TWT in Ku-Band. The result has been validated by experimental results.

Abstract This paper presents a hybrid technique‐based compact narrow band stop filter design for broadband applications. It provides the rejection of 60 dB at the centre frequency of 2.25 GHz without any stop band harmonics over the required frequency band of operation, i.e. 1–10 GHz. This filter is highly appropriated for the rejection of undesired bands for RADAR, electronic warfare, and military communications.

Background: Impact of drug wastage is a legitimate and persistent concern. Financial impact of drug waste is borne by the hospital network, patients, and healthcare systems. Measures to reduce drug wastage may have a positive impact throughout healthcare systems. Objective: This study investigated the stability and sterility of single-dose vials when repeatedly accessed with a closed system transfer device. By evaluating the sterility and stability, these results may be used to validate the extension of vial usage and lead to potential drug wastage reduction. Methods: Sterility testing was performed in accordance with US Pharmacopeia 71. A closed system transfer device was incorporated into simulated compounding tasks, utilizing growth media. Simulated compounding tasks were performed in the clinical environment, followed by incubation to stimulate growth. Stability testing was performed in accordance with US Pharmacopeia monographs at multiple timepoints post access. Test samples were comparatively tested via high-performance liquid chromatography to freshly opened vials at each timepoint. Results: No growth was observed in test samples. Control vials displayed growth, where appropriate. The drugs retained stability, when compared to freshly opened vials at 0, 24, 48, and 72 h, post access. Conclusions: This study confirms that closed system transfer devices do not contribute to microbial contamination of drug vials, following the repeated access, for up to 7 days and the tested drugs retained equivalent chemical stability for up to 72 h post access. This study may offer a manner by which a facility may assess single-dose vials’ sterility and stability, following repeated access by a closed system transfer device.

Abstract The COVID-19 pandemic, caused by the β-coronavirus (β-CoV) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to cause significant global morbidity and mortality. While vaccines have reduced the overall number of severe infections, there remains an incomplete understanding of viral entry and innate immune activation, which can drive pathology. Innate immune responses characterized by positive feedback between cell death and cytokine release can amplify the inflammatory cytokine storm during β-CoV–mediated infection to drive pathology. Therefore, there remains an unmet need to understand innate immune processes in response to β-CoV infections to identify therapeutic strategies. To address this gap, here we used an MHV model and developed a whole genome CRISPR-Cas9 screening approach to elucidate host molecules required for β-CoV infection and inflammatory cell death, PANoptosis, in macrophages, a sentinel innate immune cell. Our screen was validated through the identification of the known MHV receptor Ceacam1 as the top hit, and its deletion significantly reduced viral replication due to loss of viral entry, resulting in a downstream reduction in MHV-induced cell death. Moreover, this screen identified several other host factors required for MHV infection-induced macrophage cell death. Overall, these findings demonstrate the feasibility and power of using genome-wide PANoptosis screens in macrophage cell lines to accelerate the discovery of key host factors in innate immune processes and suggest new targets for therapeutic development to prevent β-CoV-induced pathology.

Abstract Anomalous increase in sea surface temperature and its impact on natural ecosystems greatly interests the research community. Here we investigate the causes, impacts, and trends of marine heat wave (MHW) events in the Bay of Bengal (BoB) from 1982 to 2021. A total of 107 MHW events have been isolated (> 90th percentile threshold) in this Indian Ocean region, and their variation in intensity, duration, and frequency has been investigated. Our research unveils that an average of three MHW events/year accompanied by a linearly increasing trend of 1.11 MHW events/decade has been observed over the study region. It was also found that the most intense event was observed in 2016, which continued for 69 days, and had a maximum intensity of 5.29 °C and a mean intensity of 2.03 °C (above climatology mean). Moreover, it was observed that the net heat flux, along with anticyclonic eddies, was the primary cause of MHW events. Anticyclonic eddies associated with positive sea surface height anomaly were observed (> 0.20 m) in the vicinity of the most intense MHW event. Additionally, climate change and climate modes like El Niño and Indian Ocean Dipole show a high positive influence on the MHW events. Furthermore, we have examined the MHW event recurrence patterns in various regions of the BoB. From the monthly analysis, it was found that August and November had the most occurrences of MHWs, while April and May had the most extreme MHW events.

Abstract Background Tumor invasiveness reflects numerous biological changes, including tumorigenesis, progression, and metastasis. To decipher the role of transcriptional regulators (TR) involved in tumor invasiveness, we performed a systematic network-based pan-cancer assessment of master regulators of cancer invasiveness. Materials and methods We stratified patients in The Cancer Genome Atlas (TCGA) into invasiveness high (INV-H) and low (INV-L) groups using consensus clustering based on an established robust 24-gene signature to determine the prognostic association of invasiveness with overall survival (OS) across 32 different cancers. We devise a network-based protocol to identify TRs as master regulators (MRs) unique to INV-H and INV-L phenotypes. We validated the activity of MRs coherently associated with INV-H phenotype and worse OS across cancers in TCGA on a series of additional datasets in the Prediction of Clinical Outcomes from the Genomic Profiles (PRECOG) repository. Results Based on the 24-gene signature, we defined the invasiveness score for each patient sample and stratified patients into INV-H and INV-L clusters. We observed that invasiveness was associated with worse survival outcomes in almost all cancers and had a significant association with OS in ten out of 32 cancers. Our network-based framework identified common invasiveness-associated MRs specific to INV-H and INV-L groups across the ten prognostic cancers, including COL1A1, which is also part of the 24-gene signature, thus acting as a positive control. Downstream pathway analysis of MRs specific to INV-H phenotype resulted in the identification of several enriched pathways, including Epithelial into Mesenchymal Transition, TGF-β signaling pathway, regulation of Toll-like receptors, cytokines, and inflammatory response, and selective expression of chemokine receptors during T-cell polarization. Most of these pathways have connotations of inflammatory immune response and feasibility for metastasis. Conclusion Our pan-cancer study provides a comprehensive master regulator analysis of tumor invasiveness and can suggest more precise therapeutic strategies by targeting the identified MRs and downstream enriched pathways for patients across multiple cancers. Graphical Abstract

The abnormal growth of oligodendrocyte precursor cells (OPCs) significantly contributes to the progression of glioblastoma tumors. Hence, molecules that block OPC growth may be of therapeutic importance in treating gliomas. 2-Methoxyestradiol (2ME), an endogenous tubulin-interacting metabolite of estradiol, is effective against multiple proliferative disorders. Based on its anti-carcinogenic and anti-angiogenic actions, it is undergoing phase II clinical trials. We hypothesize that 2ME may prevent glioma growth by targeting OPC growth. Here, we tested this hypothesis by assessing the impact of 2ME on the growth of an OPC line, “Oli-neu”, and dissected the underlying mechanism(s). Treatment with 2ME inhibited OPC growth in a concentration-dependent manner, accompanied by significant upregulation in the expression of p21 and p27, which are negative cell-cycle regulators. Moreover, treatment with 2ME altered OPC morphology from multi-arm processes to rounded cells. At concentrations of 1uM and greater, 2ME induced apoptosis, with increased expressions of caspase 3, PARP, and caspase-7 fragments, externalized phosphatidylserine staining/APOPercentage, and increased mitochondrial activity. Flow cytometry and microscopic analysis demonstrated that 2ME triggers endoreduplication in a concentration-dependent fashion. Importantly, 2ME induced cyclin E, JNK1/2, and p53 expression, as well as OPC fusion, which are key mechanisms driving endoreduplication and whole-genome duplication. Importantly, the inhibition of p53 with pifithrin-α rescued 2ME-induced endoreduplication. The pro-apoptotic and endoreduplication actions of 2ME were accompanied by the upregulation of survivin, cyclin A, Cyclin B, Cyclin D2, and ppRB. Similar growth inhibitory, apoptotic, and endoreduplication effects of 2ME were observed in CG4 cells. Taken together, our findings provide evidence that 2ME not only inhibits OPC growth and triggers apoptosis, but also activates OPCs into survival (fight or flight) mode, leading to endoreduplication. This inherent survival characteristic of OPCs may, in part, be responsible for drug resistance in gliomas, as observed for many tubulin-interacting drugs. Importantly, the fate of OPCs after 2ME treatment may depend on the cell-cycle status of individual cells. Combining tubulin-interfering molecules with drugs such as pifithrin-α that inhibit endoreduplication may help inhibit OPC/glioma growth and limit drug resistance.

The micro-light emitting diode (µLED) technology is poised to revolutionise display applications through the introduction of nanomaterials and Group III-nitride nanostructures. This review charts state-of-the-art in this important area of micro-LEDs by highlighting their key roles, progress and concerns. The review encompasses details from various types of nanomaterials to the complexity of gallium nitride (GaN) and III nitride nanostructures. The necessity to integrate nanomaterials with III-nitride structures to create effective displays that could disrupt industries was emphasised in this review. Commercialisation challenges and the economic enhancement of micro-LED integration into display applications using monolithic integrated devices have also been discussed. Furthermore, different approaches in micro-LED development are discussed from top-down and bottom-up approaches. The last part of the review focuses on nanomaterials employed in the production of micro-LED displays. It also highlights the combination of III-V LEDs with silicon LCDs and perovskite-based micro-LED displays. There is evidence that efficiency and performance have improved significantly since the inception of the use of nanomaterials in manufacturing these.

Background: Globally, Acne Vulgaris is a widespread, chronic inflammatory condition of the pilosebaceous follicles. Acne is not fatal, but depending on its severity, it can leave the sufferer with scars, irritation, and significant psychological effects (including depression). In the current review, we have included various factors for acne and their treatment explained. It also narrated the current medicament and the new investigation dosage forms with clinical phases information provided. Main body of the abstract: Acne's pathophysiology involves four important factors: excessive sebum production, hyperkeratinization of pilosebaceous follicles, hyperproliferation of propionibacterium acnes (P. acnes), and inflammation. Identifying both inflammatory (Papule, pustule, nodule, and cyst) and non-inflammatory (black heads, white heads) acne lesions is necessary for diagnosing and treating acne vulgaris. Short conclusion: In this review, traditional therapy approaches such as topical (i.e., retinoids and antibiotics), systemic (i.e., retinoids, antibiotics, and hormonal), and physical therapies are briefly discussed. In addition, we highlight the issues posed by P. acne's resistance to the antibiotics used in commercially available medications and the necessity for novel therapeutic techniques. Finally, we examined a few innovative acne therapies pending clinical trial approval and commercial acne medications.

The study aims to investigate the hot deformation behavior of Co–Cr–Fe–Ni–V high entropy alloy (HEA) at temperatures ranging from 1073 K to 1373 K and strain rates of 0.001, 0.01, 1, and 10 s−1, and to generate processing maps using dynamic materials modeling (DMM) to identify the optimum processing domain for industrial applications. The material's hardening and softening characteristics are also explored under various hot working conditions. Deformation twinning is observed in materials deformed at 0.1 s−1 at 1273 K and 1373 K, contributing to their observed hardening. The mean free path of dislocation defines the material's strength, and the transition point from dynamic recovery to dislocation-dislocation or dislocation-solute interaction occurs when the mean free path of dislocation reaches its lowest value. The inhomogeneity in the deformed sample is correlated with the strain field distribution using an integrated approach using finite element method (FEM) modeling and electron backscattered diffraction (EBSD) results. EBSD characterization reveals the presence of deformation bands and annealing twins at low and high temperatures, respectively. Additionally, an artificial neural network (ANN) model is proposed to predict the hot deformation behavior of Co–Cr–Fe–Ni–V HEA, with promising results, as evidenced by a correlation coefficient (R) of 0.9983 and an average absolute relative error (AARE) of 2.71% on the test dataset.

Abstract Epoxy is widely used material, but epoxy has limitations in terms of brittleness in failure, and thus researchers explore toughening and strengthening options such as adding a second phase or using electromagnetic fields to tailor toughness and strength, on demand and nearly instantaneously. Such approach falls into the category of active toughening but has not been extensively investigated. In this research, Si-BaTiO3 nanoparticles were used to modify the electro-mechanical properties of a high-performance aerospace-grade epoxy so as to study its response to electric fields, specifically low field strengths. To promote uniform dispersion and distribution, the Si-BaTiO3 nanoparticles were functionalised with silane coupling agents and mixed in the epoxy Araldite LY1564 at different content loads (1, 5, 10 wt%), which was then associated with its curing agent Aradur 3487. Real-time measurements were conducted using Raman spectroscopy while applying electric fields to the nanocomposite specimens. The Raman data showed a consistent trend of increasing intensity and peak broadening under the increasing electric field strength and Si-BaTiO3 contents. This was attributed to the BaTiO3 particles’ dipolar displacement in the high-content nanocomposites (i.e., 5 wt% and 10 wt%). The study offers valuable insights on how electric field stimulation can actively enhance the mechanical properties in epoxy composites, specifically in relatively low fields and thin, high-aspect-ratio composite layers which would require in-situ mechanical testing equipped with electric field application, an ongoing investigation of the current research.

Monkeypox virus (MPXV) was confirmed in May 2022 and designated a global health emergency by WHO in July 2022. MPX virions are big, enclosed, brick-shaped, and contain a linear, double-stranded DNA genome as well as enzymes. MPXV particles bind to the host cell membrane via a variety of viral-host protein interactions. As a result, the wrapped structure is a potential therapeutic target. DeepRepurpose, an artificial intelligence-based compound-viral proteins interaction framework, was used via a transfer learning setting to prioritize a set of FDA approved and investigational drugs which can potentially inhibit MPXV viral proteins. To filter and narrow down the lead compounds from curated collections of pharmaceutical compounds, we used a rigorous computational framework that included homology modeling, molecular docking, dynamic simulations, binding free energy calculations, and binding pose metadynamics. We identified Elvitegravir as a potential inhibitor of MPXV virus using our comprehensive pipeline.

Endothelial progenitor cells (EPCs) play a critical role in cardiovascular regeneration. Enhancement of their native properties would be highly beneficial to ensuring the proper functioning of the cardiovascular system. As androgens have a positive effect on the cardiovascular system, we hypothesized that dihydrotestosterone (DHT) could also influence EPC-mediated repair processes. To evaluate this hypothesis, we investigated the effects of DHT on cultured human EPCs’ proliferation, viability, morphology, migration, angiogenesis, gene and protein expression, and ability to integrate into cardiac tissue. The results showed that DHT at different concentrations had no cytotoxic effect on EPCs, significantly enhanced the cell proliferation and viability and induces fast, androgen-receptor-dependent formation of capillary-like structures. DHT treatment of EPCs regulated gene expression of androgen receptors and the genes and proteins involved in cell migration and angiogenesis. Importantly, DHT stimulation promoted EPC migration and the cells’ ability to adhere and integrate into murine cardiac slices, suggesting it has a role in promoting tissue regeneration. Mass spectrometry analysis further highlighted the impact of DHT on EPCs’ functioning. In conclusion, DHT increases the proliferation, migration, and androgen-receptor-dependent angiogenesis of EPCs; enhances the cells’ secretion of key factors involved in angiogenesis; and significantly potentiates cellular integration into heart tissue. The data offer support for potential therapeutic applications of DHT in cardiovascular regeneration and repair processes.

Chickpea (Cicer arietinum L.), encompassing the desi and kabuli varieties, is a beloved pulse crop globally. Its cultivation spans over fifty countries, from the Indian subcontinent and southern Europe to the Middle East, North Africa, the Americas, Australia, and China. With a rich composition of carbohydrates and protein, constituting 80% of its dry seed mass, chickpea is also touted for its numerous health benefits, earning it the title of a ‘functional food’. In the past two decades, research has extensively explored the rhizobial diversity associated with chickpea and its breeding in various countries across Europe, Asia, and Oceania, aiming to understand its impact on the sustainable yield and quality of chickpea crops. To date, four notable species of Mesorhizobium—M. ciceri, M. mediterraneum, M. muleiense, and M. wenxiniae—have been reported, originally isolated from chickpea root nodules. Other species, such as M. amorphae, M. loti, M. tianshanense, M. oportunistum, M. abyssinicae, and M. shonense, have been identified as potential symbionts of chickpea, possibly acquiring symbiotic genes through lateral gene transfer. While M. ciceri and M. mediterraneum are widely distributed and studied across chickpea-growing regions, they remain absent in China, where M. muleiense and M. wenxiniae are the sole rhizobial species associated with chickpea. The geographic distribution of chickpea rhizobia is believed to be influenced by factors such as genetic characteristics, competitiveness, evolutionary adaptation to local soil conditions, and compatibility with native soil microbes. Inoculating chickpea with suitable rhizobial strains is crucial when introducing the crop to new regions lacking indigenous chickpea rhizobia. The introduction of a novel chickpea variety, coupled with the effective use of rhizobia for inoculation, offers the potential not only to boost the yield and seed quality of chickpeas, but also to enhance crop productivity within rotation and intercropped systems involving chickpea and other crops. Consequently, this advancement holds the promise to drive forward the cause of sustainable agriculture on a global scale.

Abstract Objectives To examine the hypothesis that obesity complicated by the metabolic syndrome, compared to uncomplicated obesity, has distinct molecular signatures and metabolic pathways. Methods We analyzed a cohort of 39 participants with obesity that included 21 with metabolic syndrome, age-matched to 18 without metabolic complications. We measured in whole blood samples 754 human microRNAs (miRNAs), 704 metabolites using unbiased mass spectrometry metabolomics, and 25,682 transcripts, which include both protein coding genes (PCGs) as well as non-coding transcripts. We then identified differentially expressed miRNAs, PCGs, and metabolites and integrated them using databases such as mirDIP (mapping between miRNA-PCG network), Human Metabolome Database (mapping between metabolite-PCG network) and tools like MetaboAnalyst (mapping between metabolite-metabolic pathway network) to determine dysregulated metabolic pathways in obesity with metabolic complications. Results We identified 8 significantly enriched metabolic pathways comprising 8 metabolites, 25 protein coding genes and 9 microRNAs which are each differentially expressed between the subjects with obesity and those with obesity and metabolic syndrome. By performing unsupervised hierarchical clustering on the enrichment matrix of the 8 metabolic pathways, we could approximately segregate the uncomplicated obesity strata from that of obesity with metabolic syndrome. Conclusions The data suggest that at least 8 metabolic pathways, along with their various dysregulated elements, identified via our integrative bioinformatics pipeline, can potentially differentiate those with obesity from those with obesity and metabolic complications.

Abstract Given an arbitrary Lorentzian metric $$g_{ab}$$ g ab and a nowhere vanishing, timelike vector field $$u^a$$ u a , one can construct a class of metrics $${\widehat{g}}_{ab}$$ g ^ ab which have Euclidean signature in a specific domain, with a transition to Lorentzian regime occurring on some hypersurface $$\Sigma $$ Σ orthogonal to $$u^a$$ u a . Geometry associated with $${{{\widehat{g}}}}_{ab}$$ g ^ ab has been shown to yield some remarkable insights for classical and quantum gravity. In this work, we focus on studying the implications of this geometry for thermal effects in curved spacetimes and compare and contrast the results with those obtained through conventional Euclidean methods. We show that the expression for entropy computed using $${\widehat{g}}_{ab}$$ g ^ ab for simple field theories and Lanczos–Lovelock actions differ from Wald entropy by additional terms depending on extrinsic curvature. We also compute the holonomy associated with loops lying partially or wholly in the Euclidean regime in terms of extrinsic curvature and acceleration and compare it with the well-known expression for temperature.

Background: Childhood epilepsy is a prevalent neurological disorder. Imaging, especially MRI of the brain, plays a pivotal role in diagnosing the underlying cause. This study aimed to assess the frequency of causative factors of epilepsy detected in MRI. Materials and Methods: This hospital-based prospective observational study was conducted in the Radiology Department at Rajendra Institute of Medical Sciences (RIMS), Ranchi, Jharkhand, India from November 2021 to October 2022 in 100 children of 0 to 12 years of age referred from Pediatrics department for an MRI brain scan. MRI of the brain was performed in all cases and findings were analyzed and causes of epilepsy were assessed. Magnetic resonance spectroscopy (MRS) was also done when required for confirmation of diagnosis. Results: Positive findings in MRI were detected in 87% of children, and no abnormalities were detected in 13%. The majority of children belonged to the age group of 10-12 years (37%) and were predominantly males (66%). The most common cause of epilepsy was infections (27%) followed by hypoxic ischemic encephalopathy (22%). Tuberculoma was the most common infective cause of epilepsy in 59.3%. These were further followed by temporal lobe epilepsy and congenital malformations (11% each). The rest were other miscellaneous and idiopathic causes. Conclusion: MRI findings were specific to various conditions, helping in the localization and characterization of etiologies and playing a significant role in the evaluation of children who were newly diagnosed with epilepsy, especially those with partial seizures. Recommendation: Further research with a larger sample size and meta-analysis is recommended for more conclusive results.

Yolk-shell-based silica-coated silver nanoparticles are prominently used in the biomedical field aas well as bare silver nanoparticles for various biological applications. The present work narrates the synthesis and silica coating of metallic silver nanoparticles and investigates their antibacterial, antifungal, and anticancerous activity. Both synthesized nanoparticles were characterized by TEM, and SEM-EDX. The average size of silver nanoparticles was 50 nm, while after coating with silica, the average size of silica-coated silver nanoparticles was 80 nm. The nanoparticles' antibacterial, antifungal, and anticancer properties were comparatively examined in vitro. Agar well diffusion method was employed to explore the antibacterial activity against gram-positive bacteria (Bacillus cereus) and gram-negative bacteria (Escherichia coli) at different concentrations and antifungal activity against Candida Albicans. To understand the minimum concentration of both nanoparticles, we employed the minimum inhibitory concentration (MIC) test, against bacterial and fungal strains, which was dose dependent. We learned that bare silver nanoparticles showed high antibacterial activity, whereas silica-coated silver nanoparticles surpassed their antifungal capability over bare silver nanoparticles against Candida albicans. The anticancer activity of the as-prepared nanoparticles was executed in opposition to the prostate cancer cell (PC-3) line by MTT assay, which showed meaningful activity. Following this, flow cytometry was also effectuated to learn about the number of apoptotic and necrotic cells. The results of this study demonstrate the dynamic anti-cancerous, antibacterial, and antifungal activities of bare silver nanoparticles and silica-coated silver nanoparticles for a long-lasting period.

When a new customer enters the spectrum of the E-Commerce system, the informative records and dataset, such as about the new user, purchasing history and other browsing data become insufficient, resulting in the emergence of one serious issue such as a Cold start problem (CSP). Furthermore, when the interaction among the product items becomes limited, a new problem such as Sparsity arises to handle such problems in E-Commerce system, we have designed an extensive and hybridized methodological approach known as Cold start and sparsity aware hybridized recommendation system (CSSHRS), to reduce the Sparsity of dataset as well as to overcome the cold start problem in the recommendation framework. The proposed CSSHRS technique has been predicted by using the dataset of Last. FM, and Book-Crossing resulted in Mean absolute percentage error (MAPE) of 37%, recalls 0.07, precision 0.18, Normalized Discounted Cumulative Gain (NDCD) 0.61, and F-measure 0.1. This article proves the proposed CSSHRS technique as an effective and efficient hybrid of RS against the issue of data sparsity as well as CSP.

Background: Organization, coordination, and discipline are required to complete any intricate operation, conducting a clinical experiment is no different. There are usually many moving components, from designing a plan, to conveying changes, to calculating risk, and excellent project management which are necessary to guarantee the study works successfully. Past evidence suggested that roadblock at any level hampers the progress of the clinical research. Understanding program management challenges hence becomes the key for timely and effective completion of clinical research. Methods: A cross-sectional qualitative enquiry involving stakeholders in clinical research program management. We used problem tree-based approach wherein we documented views of various stakeholders to understand the interaction, interdependence, and related interventional needs of bottlenecks for long-term research gains using modern management methods applicable in clinical settings. The best fit approach was also explored to augment maximum benefit in limited resource settings. Results: Non-alignment with state policy aims, a lack of effective coordination and communication among members, challenging logistic management, limited use of technology, a need for training, and an inefficient monitoring mechanism were among the major issues highlighted, and solutions were proposed. Conclusion: Study concludes that an Integrated Process-cum-Timeline-Based Management strategy with multisectoral emphasis is ideal for program management of clinical projects.

Abstract Osteoarthritis (OA) is the most common type of degenerative joint disease which affects 7% of the global population and more than 500 million people worldwide. One research frontier is the development of hydrogels for OA treatment, which operate either as functional scaffolds of tissue engineering or as delivery vehicles of functional additives. Both approaches address the big challenge: establishing stable integration of such delivery systems or implants. Adhesive hydrogels provide possible solutions to this challenge. However, few studies have described the current advances in using adhesive hydrogel for OA treatment. This review summarizes the commonly used hydrogels with their adhesion mechanisms and components. Additionally, recognizing that OA is a complex disease involving different biological mechanisms, the bioactive therapeutic strategies are also presented. By presenting the adhesive hydrogels in an interdisciplinary way, including both the fields of chemistry and biology, this review will attempt to provide a comprehensive insight for designing novel bioadhesive systems for OA therapy.

Medicago sativa L. (alfalfa), a leguminous crop, is vital globally for forage, crop rotation, and soil fertility. Though, the microbiome of alfalfa grown in uncultivated land has not been studied yet. Here, we employed the high-throughput 16S rRNA and nifH gene amplicon sequencing to unravel the rhizosphere microbiome and nodules endosymbionts of alfalfa grown in poor lawn and coastal sandy soils. The root nodule of alfalfa of coastal sands and poor lawn soil, Sinorhizobia/Ensifer accounted for 80.599% and 67.727% of the total microbiome, respectively. The class Actinobacteria (except Frankiales) and order Rhizobiales, Sphingomonadales, Burkholderiales, Pseudomonas, and Cytophagia were found significantly enriched. Culturable studies displayed the dominance of Bacillus followed by Arthrobacter, Microbacterium, and Streptomyces. Hydroponics studies revealed the efficiency of cultured isolates for nodulation and plant growth attributes. Overall studies decipher the soil indigenous microbiome associated with root nodule and rhizosphere of Alfalfa grown in uncultivated coastal and sandy land.

We present a method to estimate distances to asymptotic giant branch (AGB) stars in the Galaxy, using spectral energy distributions (SEDs) in the near- and mid-infrared. By assuming that a given set of source properties (initial mass, stellar temperature, composition, and evolutionary stage) will provide a typical SED shape and brightness, sources are color matched to a distance-calibrated template and thereafter scaled to extract the distance. The method is tested by comparing the distances obtained to those estimated from very long baseline interferometry or Gaia parallax measurements, yielding a strong correlation in both cases. Additional templates are formed by constructing a source sample likely to be close to the Galactic center, and thus with a common, typical distance for calibration of the templates. These first results provide statistical distance estimates to a set of almost 15,000 Milky Way AGB stars belonging to the Bulge Asymmetries and Dynamical Evolution (BAaDE) survey, with typical distance errors of ±35%. With these statistical distances, a map of the intermediate-age population of stars traced by AGBs is formed, and a clear bar structure can be discerned, consistent with the previously reported inclination angle of 30° to the GC–Sun direction vector. These results motivate deeper studies of the AGB population to tease out the intermediate-age stellar distribution throughout the Galaxy, as well as determining statistical properties of the AGB population luminosity and mass-loss-rate distributions.

We present Submillimeter Array (SMA) mapping of ^12 CO J = 2 → 1, ^13 CO J = 2 → 1, and CN N = 2 → 1 emission from the ring-like planetary nebula NGC 3132, one of the subjects of JWST Early Release Observation near-infrared imaging. The ∼5″ resolution SMA data demonstrate that the Southern Ring’s main, bright, molecule-rich ring is indeed an expanding ring, as opposed to a limb-brightened shell, in terms of its intrinsic (physical) structure. This suggests that NGC 3132 is a bipolar nebula viewed more or less pole-on (inclination ∼15°–30°). The SMA data furthermore reveal that the nebula harbors a second expanding molecular ring that is aligned almost orthogonally to the main, bright molecular ring. We propose that this two-ring structure is the remnant of an ellipsoidal molecular envelope of ejecta that terminated the progenitor star’s asymptotic giant branch evolution and was subsequently disrupted by a series of misaligned fast, collimated outflows or jets resulting from interactions between the progenitor and one or more companions.

Summary: Transforming growth factor-β-activated kinase 1 (TAK1) is a central regulator of innate immunity, cell death, inflammation, and cellular homeostasis. Therefore, many pathogens carry TAK1 inhibitors (TAK1i). As a host strategy to counteract this, inhibition or deletion of TAK1 induces spontaneous inflammatory cell death, PANoptosis, through the RIPK1-PANoptosome complex, containing the NLRP3 inflammasome and caspase-8/FADD/RIPK3 as integral components; however, PANoptosis also promotes pathological inflammation. Therefore, understanding molecular mechanisms that regulate TAK1i-induced cell death is essential. Here, we report a genome-wide CRISPR screen in macrophages that identified TAK1i-induced cell death regulators, including polypyrimidine tract-binding (PTB) protein 1 (PTBP1), a known regulator of RIPK1, and a previously unknown regulator RAVER1. RAVER1 blocked alternative splicing of Ripk1, and its genetic depletion inhibited TAK1i-induced, RIPK1-mediated inflammasome activation and PANoptosis. Overall, our CRISPR screen identified several positive regulators of PANoptosis. Moreover, our study highlights the utility of genome-wide CRISPR-Cas9 screens in myeloid cells for comprehensive characterization of complex cell death pathways to discover therapeutic targets.

Summary: Background: It is critical to identify high-risk groups among children with COVID-19 from low-income and middle-income countries (LMICs) to facilitate the optimum use of health system resources. The study aims to describe the severity and mortality of different clinical phenotypes of COVID-19 in a large cohort of children admitted to tertiary care hospitals in India. Methods: Children aged 0–19 years with evidence of SARS-CoV-2 infection (real time polymerase chain reaction or rapid antigen test positive) or exposure (anti-SARS-CoV-2 antibody, or history of contact with SARS-CoV-2) were enrolled in the study, between January 2021 and March 2022 across five tertiary hospitals in India. All study participants enrolled prospectively and retrospectively were followed up for three months after discharge. COVID-19 was classified into severe (Multisystem Inflammatory Syndrome in Children (MIS-C), severe acute COVID-19, ‘unclassified’) or non-severe disease. The mortality rates were estimated in different phenotypes. Findings: Among 2468 eligible children enrolled, 2148 were hospitalised. Signs of illness were present in 1688 (79%) children with 1090 (65%) having severe disease. High mortality was reported in MIS-C (18.6%), severe acute COVID-19 (13.3%) and the unclassified severe COVID-19 disease (12.3%). Mortality remained high (17.5%) when modified MIS-C criteria was used. Non-severe COVID-19 disease had 14.1% mortality when associated with comorbidity. Interpretation: Our findings have important public health implications for low resource settings. The high mortality underscores the need for better preparedness for timely diagnosis and management of COVID-19. Children with associated comorbidity or coinfections are a vulnerable group and need special attention. MIS-C requires context specific diagnostic criteria for low resource settings. It is important to evaluate the clinical, epidemiological and health system-related risk factors associated with severe COVID-19 and mortality in children from LMICs. Funding: Department of Biotechnology, Govt of India and Department of Maternal, Child and Adolescent Health and Aging, WHO, Geneva, Switzerland.

Waste papers are used as a source of raw material to fabricate cellulose nanocrystals (CNCs), a highly valued product with a high degree of crystallinity. Rod-shaped CNCs with an average diameter of 53 ± 9 nm and an average length of 234 ± 42 nm were obtained with a crystallinity of around 78%. Polyvinylidene fluoride (PVDF) thin composite membrane was developed by adding CNCs into the PVDF matrix in different amounts (0, 0.5, 1, 1.5, 2, 3 wt%). Porous finger-like structures in the membrane increased with an increase in CNC content. The FTIR measurement and high-resolution FESEM image of the membranes verified the presence of CNCs in the composite membranes. 48% high pure water flux (PWF) was obtained for PVDF/CNC as compared to pristine PVDF membrane with the addition of 3% CNCs at a pressure of 1 kg−1cm−2. Water contact angle (WCA) also decreased from 85° to 69° with increasing the wt% of CNCs in the dope solution, which signifies improved hydrophilicity. Further, the PVDF/CNCs membrane showed a high bovine serum albumin (BSA) rejection of 93% and a flux recovery ratio (FRR) of 76.76 %, whereas the pristine PVDF membrane showed BSA rejection of 70.86% and a FRR of 40.82 %, respectively.

Although waste hair fibers are consumed in agricultural and pharmaceutical industries, etc., their use in civil engineering is very limited. Because of fibrous nature, it can be used as reinforcement material in soil for sustainable development, similar to other commercially used fibers in practice. In this study, an effort is made to improve the properties of the Delhi silt and Dhanauri clay using the human hair fiber. All the tests on Delhi silt and Dhanauri clay were performed with optimum fiber content, i.e., 2%. The results indicate that the shear strength, modulus and CBR value of soil reinforced with human hair fibers have increased considerably. And then, the suitability of human hair fibers in pavement engineering is examined by designing both rigid and flexible pavements using improved properties. Results indicate that there is a reduction in thickness of both pavements, which means that there can be saving of cost in major projects, when human hair fiber is used.

Abstract Appendiceal diverticulitis, a frequently underdiagnosed entity, differs from typical appendicitis by the presence of an inflamed appendiceal diverticulum. Appendiceal diverticulitis is a surgical emergency which has an increased risk of perforation compared to typical appendicitis. We will discuss a surgically and pathologically confirmed case of complicated appendiceal diverticulitis and its management implications.

Abstract Background Advances in our understanding of the tumor microenvironment have radically changed the cancer field, highlighting the emerging need for biomarkers of an active, favorable tumor immune phenotype to aid treatment stratification and clinical prognostication. Numerous immune-related gene signatures have been defined; however, their prognostic value is often limited to one or few cancer types. Moreover, the area of non-coding RNA as biomarkers remains largely unexplored although their number and biological roles are rapidly expanding. Methods We developed a multi-step process to identify immune-related long non-coding RNA signatures with prognostic connotation in multiple TCGA solid cancer datasets. Results Using the breast cancer dataset as a discovery cohort we found 2988 differentially expressed lncRNAs between immune favorable and unfavorable tumors, as defined by the immunologic constant of rejection (ICR) gene signature. Mapping of the lncRNAs to a coding-non-coding network identified 127 proxy protein-coding genes that are enriched in immune-related diseases and functions. Next, we defined two distinct 20-lncRNA prognostic signatures that show a stronger effect on overall survival than the ICR signature in multiple solid cancers. Furthermore, we found a 3 lncRNA signature that demonstrated prognostic significance across 5 solid cancer types with a stronger association with clinical outcome than ICR. Moreover, this 3 lncRNA signature showed additional prognostic significance in uterine corpus endometrial carcinoma and cervical squamous cell carcinoma and endocervical adenocarcinoma as compared to ICR. Conclusion We identified an immune-related 3-lncRNA signature with prognostic connotation in multiple solid cancer types which performed equally well and in some cases better than the 20-gene ICR signature, indicating that it could be used as a minimal informative signature for clinical implementation.

The issues related to global energy needs and environmental safeties as well as health crisis are some of the major challenges faced by the human, which make us to generate new pollution-free and sustainable energy sources. For that the optical functional nanostructures can be manipulated the confined light at the nanoscale level. These characteristics are emerging and leading candidate for the solar energy conversion. The combination of photonic (dielectric) and plasmonic (metallic) nanostructures are responsible for the development of better optical performance in solar cells. Here, the enhancement of light trapping within the thin active region is the primary goal. In this work, we have studied the influence of front-ITO (rectangular) and back-Ag (triangular) nanogratings were incorporated with ultrathin film amorphous silicon (a-Si) solar cell by using rigorous coupled wave analysis (RCWA) method. The improvement of light absorption, scattering (large angle), diffraction and field distributions (TE/TM) were demonstrated by the addition of single and dual nanogratings structures. Significantly, the plasmonic (noble metal) nanogratings are located at the bottom of the cell structure as a backside reflector which is helpful for the omni-directional reflection and increased the path length (life time) of the photons due to that the collection of the charge carriers were enhanced. Further, the proposed solar cell structure has optimized and compared to a back-Ag, front-ITO and dual nanogratings based ultrathin film amorphous silicon solar cell. Finally, the obtained results were evidenced for the assistance of photonic and plasmonic modes and achieved the highest current density (Jsc) of 23.82 mA/cm2(TE) and 22.75 mA/cm2 (TM) with in 50 nm thin active layers by integration of (dual) cell structures.

Mucormycosis is a life-threatening fungal infection caused by mucormycetes, fungi of the Mucorales order.1 Rhino-orbital-cerebral involvement is the most common form of invasive mucormycosis. However, gastrointestinal (GI) mucormycosis cases have increased in the last two to three decades.2 Involvement of the GI tract in invasive mucormycosis is seen in 7–13% of cases.3 Out of which, involvement of the stomach is seen in 58% of the cases, and the remaining 42% involve small and large intestines. GI mucormycosis has been mostly associated with immunocompromised patients or premature infants.2 It has also been reported in immunocompetent patients.1 Many cases of GI mucormycosis are first recognized on autopsy, owing to its acute course and rapidly fatal nature.2 According to the literature, only about 25% of cases of GI mucormycosis are clinically diagnosed.4 The endoscopic appearance of gastric mucormycosis is usually a large ulcer with necrosis, eventually presenting an adherent, thick, green exudate.3 Figures 1A typically show green exudates surrounding the lesions. Autopsy diagnosis of GI mucormycosis is mostly based on gross and histopathological examination. Grossly, numerous well-circumscribed, dark red, targetoid mucosal lesions have been described in the post-mortem diagnosis of GI mucormycosis.4 Figures 1A show the so-called ‘targetoid lesion’ in the stomach mucosa. Figure 1 A - Macroscopic view of the stomach with multiple targetoid lesions of varying size, round to oval in shape with elevated margins and necrotic base (scale bar= 5 cm); B - Section from stomach depicting the transition zone between viable and necrotic tissue, left side of the image shows viable gastric tissue with patent submucosal blood vessels, while the right side shows bland necrosis with obliterated blood vessels (H&E, 20x); C and D - Gomori methenamine silver (GMS) and Periodic acid Schiff (PAS) stains highlight the angioinvasive fungal profiles within the submucosal blood vessels (400x). These hyphae are broad, aseptate foldable with right angle branching conforming to the morphology of mucormycosis.: Clinical diagnosis of GI mucormycosis is challenging. It can present an array of nonspecific symptoms, including discomfort, diarrhea, fever, gastrointestinal bleeding, necrosis, perforation, and as a necrotizing enterocolitis in premature neonates.5 The mechanism of GI tract involvement in mucormycosis is unclear. Pre-existing peptic ulcer disease, consumption of food and water contaminated with Mucorales, and use of contaminated nasogastric tubes, tongue depressors, and wooden spatula are a few factors responsible for the involvement of the GI system in mucormycosis.5,6 Mortality rate of GI mucormycosis is reported as 40 to 78%.4,5 Perforation of necrotic ulcers and peritonitis are the leading causes of death in such cases. The reported images belong to a 48-year-old man who died from septicemia seven days after a road traffic accident. At autopsy, apart from findings of traumatic injuries, the stomach showed multiple rounds to oval lesions with sizes ranging from 0.5cm X 0.5 cm to 3cm X 2 cm, over the pylorus with elevated margins and necrotic base (Figure 1A). On the formalin-fixed specimen, they were noted as ulcers with a greenish-black base and flattened edges. The periphery of the ulcer was congested. The microscopic examination showed that the ulcers were extending to the muscularis propria. They were invading underlying arteries and veins in the submucosa, indicating angioinvasion (Figure 1B). Gomori methenamine silver (GMS) and Periodic acid Schiff (PAS) stains highlighted fungal hyphae, which were broad aseptate and foldable, confirming the morphology of mucormycosis (Figure 11D, respectively). In conclusion, gastric mucormycosis cases usually go unnoticed clinically unless it becomes symptomatic or diagnosed incidentally on endoscopy. Thus, such cases are being diagnosed at autopsy.

Abstract Background Childhood diarrhea remains a major disease burden, particularly in developing countries, and is a leading cause of death in children aged

Abstract Photobiomodulation (PBM) in the red/near-infrared (R/NIR) spectral range has become widely recognized due to its anti-inflammatory and cytoprotective potential. We aimed to assess the effects of blood PBM on platelets function and hemolysis in an in vitro setting. Porcine blood samples were separated into four aliquots for this study, one of which served as a control, while the other three were subjected to three different NIR PBM dosages. The platelet count and functions and the plasma free haemoglobin and osmotic fragility of red blood cells were measured during the experiment. The control group had a considerable drop in platelet number, but the NIR exposed samples had more minimal and strictly dose-dependent alterations. These modifications were consistent with ADP and collagen-induced platelet aggregation. Furthermore, red blood cells that had received PBM were more resistant to osmotic stress and less prone to hemolysis, as seen by a slightly lower quantity of plasma free hemoglobin. Here we showed under well-controlled in vitro conditions that PBM reversibly inhibits platelet activation in a dose-dependent manner and reduces hemolysis.

Abstract Fault current magnitude in a microgrid depends upon its mode of operation, namely, grid-connected mode or islanded mode. Depending on the type of fault in a given mode, separate protection schemes are generally employed. With the change in microgrid operating mode, the protection scheme needs to be modified which is uneconomical and time inefficient. In this paper, a novel optimal protection coordination scheme is proposed, one which enables a common optimal relay setting which is valid in both operating modes of the microgrid. In this context, a common optimal protection scheme is introduced for dual setting directional overcurrent relays (DOCRs) using a combination of various standard relay characteristics. Along with the two variables, i.e., time multiplier setting (TMS) and plug setting (PS) for conventional directional overcurrent relay, dual setting DOCRs are augmented with a third variable of relay characteristics identifier (RCI), which is responsible for selecting optimal relay characteristics from the standard relay characteristics according to the IEC-60255 standard. The relay coordination problem is formulated as a mixed-integer nonlinear programming (MINLP) problem, and the settings of relays are optimally determined using the genetic algorithm (GA) and the grey wolf optimization (GWO) algorithm. To validate the superiority of the proposed protection scheme, the distribution parts of the IEEE-14 and IEEE-30 bus benchmark systems are considered.