High-affinity chimeric antigen receptor signaling induces an inflammatory program in human regulatory T cells.

Regulatory T cells (Tregs) are promising cellular therapies to induce immune tolerance in organ transplantation and autoimmune disease. The success of chimeric antigen receptor (CAR) T cell therapy for cancer has sparked interest in using CARs to generate antigen-specific Tregs. Here, we compared CAR with endogenous T cell receptor (TCR)/CD28 activation in human Tregs.

Triptolide and its prodrug Minnelide target high-risk MYC-amplified medulloblastoma in preclinical models.

Most children with medulloblastoma (MB) achieve remission, but some face very aggressive metastatic tumors. Their dismal outcome highlights the critical need to advance therapeutic approaches that benefit such high-risk patients. Minnelide, a clinically relevant analog of the natural product triptolide, has oncostatic activity in both preclinical and early clinical settings.

Novel Spirocyclic Dimer, SpiD3, Targets Chronic Lymphocytic Leukemia Survival Pathways with Potent Preclinical Effects.

Unlabelled: Chronic lymphocytic leukemia (CLL) cell survival and growth is fueled by the induction of B-cell receptor (BCR) signaling within the tumor microenvironment (TME) driving activation of NFκB signaling and the unfolded protein response (UPR). Malignant cells have higher basal levels of UPR posing a unique therapeutic window to combat CLL cell growth using pharmacologic agents that induce accumulation of misfolded proteins. Frontline CLL therapeutics that directly target BCR signaling such as Bruton tyrosine kinase (BTK) inhibitors (e.

Design and validation of an artificial intelligence system to detect the quality of colon cleansing before colonoscopy.

Background And Aims: Patients' perception of their bowel cleansing quality may guide rescue cleansing strategies before colonoscopy. The main aim of this study was to train and validate a convolutional neural network (CNN) for classifying rectal effluent during bowel preparation intake as "adequate" or "inadequate" cleansing before colonoscopy.

Patients And Methods: Patients referred for outpatient colonoscopy were asked to provide images of their rectal effluent during the bowel preparation process.

The Impacts of Plastic Waste from Personal Protective Equipment Used during the COVID-19 Pandemic.

The period from 2019 to 2022 has been defined by the COVID-19 pandemic, resulting in an unprecedented demand for and use of Personal Protective Equipment (PPE). However, the disposal of PPE without considering its environmental impact and proper waste management practices has become a growing concern. The increased demand for PPE during the pandemic and associated waste management practices have been analyzed.

Advances in the Production of Biomaterials through Kombucha Using Food Waste: Concepts, Challenges, and Potential.

In recent years, several researchers have focused their studies on the development of sustainable biomaterials using renewable sources, including the incorporation of living biological systems. One of the best biomaterials is bacterial cellulose (BC). There are several ways to produce BC, from using a pure strain to producing the fermented drink kombucha, which has a symbiotic culture of bacteria and yeasts (SCOBY).

Immunogenicity in renal cell carcinoma: shifting focus to alternative sources of tumour-specific antigens.

Renal cell carcinoma (RCC) comprises a group of malignancies arising from the kidney with unique tumour-specific antigen (TSA) signatures that can trigger cytotoxic immunity. Two classes of TSAs are now considered potential drivers of immunogenicity in RCC: small-scale insertions and deletions (INDELs) that result in coding frameshift mutations, and activation of human endogenous retroviruses. The presence of neoantigen-specific T cells is a hallmark of solid tumours with a high mutagenic burden, which typically have abundant TSAs owing to non-synonymous single nucleotide variations within the genome.

Multiomics in primary and metastatic breast tumors from the AURORA US network finds microenvironment and epigenetic drivers of metastasis.

The AURORA US Metastasis Project was established with the goal to identify molecular features associated with metastasis. We assayed 55 females with metastatic breast cancer (51 primary cancers and 102 metastases) by RNA sequencing, tumor/germline DNA exome and low-pass whole-genome sequencing and global DNA methylation microarrays. Expression subtype changes were observed in ~30% of samples and were coincident with DNA clonality shifts, especially involving HER2.

Plastics and Microplastic in the Cosmetic Industry: Aggregating Sustainable Actions Aimed at Alignment and Interaction with UN Sustainable Development Goals.

Excessive use of petroleum derivatives in cosmetics, whether in compositions or packaging, predominating the use of plastics, parabens, microplastics and other polymers, has had negative environmental impacts. The cosmetics market has gained prominence in recent years and bioeconomy and circular economy policies are putting pressure on the market to use bio-based and biodegradable materials. In this context, the objective of this review article is to provide an overview of how the aggregation of sustainable actions in the cosmetic industry contributes to the fulfillment of the 2030 Agenda and how this can serve as a guide in building a more resilient and sustainable society.

Impacts of illegal fishing in the inland waters of the State of Santa Catarina -Brazil.

Fish stocks are being severely depleted, marine habitats are threatened and marine pollution is on the rise due to discarded fishing gear. This equipment is generally from illegal, unreported and unregulated fishing, leading to incidental fishing and sometimes ghost fishing. In this study, data obtained from reports produced by the Environmental Military Police in Santa Catarina, Brazil, on gill nets fixed in the coastal area and at the baseline limit of this state, for the period of 2019 to 2020, were analyzed.

Influence of non-thermal plasma reactor geometry and plasma gas on the inactivation of Escherichia coli in water.

The inactivation of bacteria Escherichia coli (E. coli) by non-thermal plasma (NTP) was investigated using argon, air and 1:1 mixture of air/Ar as plasma gas on five different reactors. The experiments were carried out in triplicate in each reactor, using 60 mL of distilled water pre-inoculated with E.

Ischemic stroke and purpuric dermatitis as COVID-19-related complications in a peritoneal dialysis patient.

Patients on dialysis may have an elevated risk of severe coronavirus disease 2019 (COVID-19) and its complications due to their high prevalence of comorbidities. Here we describe the case of an 80-year-old male undergoing peritoneal dialysis with a moderate SARS-CoV-2 infection who developed a purpuric dermatitis and ischemic stroke after successful recovery from his bilateral pneumonia. Erythemato-papular lesions affecting trunk and lower limbs appeared 17 days after the onset of SARS-CoV-2 symptoms.

DNA hypomethylation promotes transposable element expression and activation of immune signaling in renal cell cancer.

Recently, we reported that expression of endogenous retroviruses (ERVs) is associated with response to immune checkpoint blockade (ICB) in renal cell carcinoma (RCC). We show that decitabine, a DNA hypomethylating agent, activates transposable element (TE) expression (LINE1 and ERVs ERV3-2 and ERV4700) and antiviral signaling to potentially enhance response to ICB in kidney cancer cell lines and primary cells. KO of RIGI and MDA5 dsRNA sensors attenuated activation of antiviral signaling associated with DNA hypomethylation, and RIGI and MDA5 IPs showed increased ERV binding with decitabine treatment.

Integrative multi-omics analysis identifies a prognostic miRNA signature and a targetable miR-21-3p/TSC2/mTOR axis in metastatic pheochromocytoma/paraganglioma.

: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that present variable outcomes. To date, no effective therapies or reliable prognostic markers are available for patients who develop metastatic PPGL (mPPGL). Our aim was to discover robust prognostic markers validated through models, and define specific therapeutic options according to tumor genomic features.

Distinct Regulation of Th17 and Th1 Cell Differentiation by Glutaminase-Dependent Metabolism.

Activated T cells differentiate into functional subsets with distinct metabolic programs. Glutaminase (GLS) converts glutamine to glutamate to support the tricarboxylic acid cycle and redox and epigenetic reactions. Here, we identify a key role for GLS in T cell activation and specification.

Use of Cold Plasma To Inactivate Escherichia coli and Physicochemical Evaluation in Pumpkin Puree.

This work aimed to study the pumpkin puree processing by cold plasma corona discharge as an alternative to heat treatment to reduce Escherichia coli contamination and evaluate physicochemical alterations, using argon (Ar) as the process gas. The treatment time to verify E. coli inactivation was between 2 and 20 min, while physicochemical alterations were analyzed at 5, 10, 15, and 20 min.

Endogenous retroviral signatures predict immunotherapy response in clear cell renal cell carcinoma.

Human endogenous retroviruses (hERVs) are remnants of exogenous retroviruses that have integrated into the genome throughout evolution. We developed a computational workflow, hervQuant, which identified more than 3,000 transcriptionally active hERVs within The Cancer Genome Atlas (TCGA) pan-cancer RNA-Seq database. hERV expression was associated with clinical prognosis in several tumor types, most significantly clear cell renal cell carcinoma (ccRCC).

Endogenous retrovirus expression is associated with response to immune checkpoint blockade in clear cell renal cell carcinoma.

Although a subset of clear cell renal cell carcinoma (ccRCC) patients respond to immune checkpoint blockade (ICB), predictors of response remain uncertain. We investigated whether abnormal expression of endogenous retroviruses (ERVs) in tumors is associated with local immune checkpoint activation (ICA) and response to ICB. Twenty potentially immunogenic ERVs (πERVs) were identified in ccRCC in The Cancer Genome Atlas data set, and tumors were stratified into 3 groups based on their expression levels.

Epigenetic modifiers: activities in renal cell carcinoma.

Renal cell carcinomas (RCCs) are a diverse set of malignancies that have recently been shown to harbour mutations in a number of chromatin modifier genes - including PBRM1, SETD2, BAP1, KDM5C, KDM6A, and MLL2 - through high-throughput sequencing efforts. Current research focuses on understanding the biological activities that chromatin modifiers employ to suppress tumorigenesis and on developing clinical approaches that take advantage of this knowledge. Unsurprisingly, several common themes unify the functions of these epigenetic modifiers, particularly regulation of histone post-translational modifications and nucleosome organization.