Staggered immunization with mRNA vaccines encoding SARS-CoV-2 polymerase or spike antigens broadens the T cell epitope repertoire.

Combining a T cell-targeting mRNA vaccine encoding the conserved SARS-CoV-2 RNA-dependent RNA polymerase, RdRp, with a Spike-encoding mRNA vaccine may offer an additional pathway toward COVID-19 protection. Here, we show that a nucleoside-modified RdRp mRNA vaccine raises robust and durable CD8+ T cell responses in mice. Immunization drives a CD8+ T cell response enriched toward a specific RdRp epitope.

Effect of SGLT2 inhibitors on kidney function of type 2 diabetes patients during Ramadan: A systematic review.

Background: SGLT2 inhibitors are known for their osmotic diuretic effect, and their use by Muslim patients with type 2 diabetes during the fasting month of Ramadan may pose an increased risk of volume depletion, potentially impacting renal function.

Methods: We conducted a systematic review registered on PROSPERO (registration number CRD42020204582) of studies published between 2013 and January 2023, sourced from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. The study selection criteria included controlled studies that reported the use of SGLT2 inhibitors (SGLT2i) by fasting adult type 2 diabetes patients and provided data on creatinine or estimated glomerular filtration rate (eGFR) as outcomes.

Endolysosomal trapping of therapeutics and endosomal escape strategies.

Internalizing therapeutic molecules or genes into cells and safely delivering them to the target tissue where they can perform the intended tasks is one of the key characteristics of the smart gene/drug delivery vector. Despite much research in this field, endosomal escape continues to be a significant obstacle to the development of effective gene/drug delivery systems. In this review, we discuss in depth the several types of endocytic pathways involved in the endolysosomal trapping of therapeutic agents.

Effect of SGLT2 inhibitors on kidney function of type 2 diabetes patients during Ramadan: A systematic review.

Background: SGLT2 inhibitors are known for their osmotic diuretic effect, and their use by Muslim patients with type 2 diabetes during the fasting month of Ramadan may pose an increased risk of volume depletion, potentially impacting renal function.

Methods: We conducted a systematic review registered on PROSPERO (registration number CRD42020204582) of studies published between 2013 and January 2023, sourced from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. The study selection criteria included controlled studies that reported the use of SGLT2 inhibitors (SGLT2i) by fasting adult type 2 diabetes patients and provided data on creatinine or estimated glomerular filtration rate (eGFR) as outcomes.

Exploiting transcription factors to target EMT and cancer stem cells for tumor modulation and therapy.

Transcription factors (TFs) are essential in controlling gene regulatory networks that determine cellular fate during embryogenesis and tumor development. TFs are the major players in promoting cancer stemness by regulating the function of cancer stem cells (CSCs). Understanding how TFs interact with their downstream targets for determining cell fate during embryogenesis and tumor development is a critical area of research.

Long COVID-19 Syndrome: Insights From a Major Tertiary Center in the UK on Who Is at Greater Risk.

Introduction: The COVID-19 pandemic triggered the unprecedented 'long COVID' crisis, with persistent symptoms beyond two months post-infection. This study explores the nexus between long COVID symptoms, patient demographics such as age, gender, and smoking, and clinical factors like vaccination, disease severity, and comorbidities.

Methods: A retrospective analysis of records was conducted between September 2021 and December 2022.

Novel partially cross-linked nanoparticles graft co-polymer as pore former for polyethersulfone membranes for dyes removal.

A newly developed water-soluble polymeric nano-additive termed "partially cross-linked nanoparticles graft copolymer (PCLNPG)" has been successfully synthesized and harnessed as a pore former for modifying a polyethersulfone ultrafiltration membrane for dyes removal. The PCLNPG content was varied in the PES polymeric matrix aiming to scrutinize its impact on membrane surface characteristics, morphological structure, and overall performance. Proposed interaction mechanism between methylene blue (MB), methyle orange (MO), and malachite green (MG) dyes with PES membrane was presented as well.

Genome-wide association studies using multi-models and multi-SNP datasets provide new insights into pasmo resistance in flax.

Introduction: Flax ( L.) is an economically important crop due to its oil and fiber. However, it is prone to various diseases, including pasmo caused by the fungus .

Unforeseen complications: a case of dengue shock syndrome presenting with multi-organ dysfunction in a subtropical region.

Overview: Dengue fever, a viral illness transmitted by the Aedes mosquito, is capable of causing a range of serious complications, including fulminant hepatic failure, renal dysfunction, encephalitis, encephalopathy, neuromuscular and ophthalmic disorders, seizures, and cardiomyopathy.

Case Description: This report details the case of a 30-year-old lactating woman with no notable medical history who presented to the emergency department with symptoms of high-grade fever, altered mental status, and seizures. Upon imaging, bilateral infarcts in the thalami and cerebellar hemispheres were observed, consistent with cerebellitis and dengue encephalitis.

MEK Inhibition Sensitizes Pancreatic Cancer to STING Agonism by Tumor Cell-intrinsic Amplification of Type I IFN Signaling.

Purpose: Stimulator of interferon genes (STING) agonists are currently in development for treatment of solid tumors, including pancreatic ductal adenocarcinoma (PDAC). Response rates to STING agonists alone have been promising yet modest, and combination therapies will likely be required to elicit their full potency. We sought to identify combination therapies and mechanisms that augment the tumor cell-intrinsic effect of therapeutically relevant STING agonists apart from their known effects on tumor immunity.

Insight into the transcription factors regulating Ischemic stroke and glioma in response to shared stimuli.

Cerebral ischemic stroke and glioma are the two leading causes of patient mortality globally. Despite physiological variations, 1 in 10 people who have an ischemic stroke go on to develop brain cancer, most notably gliomas. In addition, glioma treatments have also been shown to increase the risk of ischemic strokes.

Cancer stem cell-derived exosome-induced metastatic cancer: An orchestra within the tumor microenvironment.

Although the mechanisms as well as pathways associated with cancer stem cell (CSC) maintenance, expansion, and tumorigenicity have been extensively studied and the role of tumor cell (TC)-derived exosomes in this process is well understood, there is a paucity of research focusing specifically on the functional mechanisms of CSC-derived exosomes (CSC-Exo)/-exosomal-ncRNAs and their impact on malignancy. This shortcoming needs to be addressed, given that these vesicular and molecular components of CSCs could have a great impact on the cancer initiation, progression, and recurrence through their interaction with other key tumor microenvironment (TME) components, such as MSCs/MSC-Exo and CAFs/CAF-Exo. In particular, understanding CSCs/CSC-Exo and its crosstalk with MSCs/MSC-Exo or CAFs/CAF-Exo that are associated with the proliferation, migration, differentiation, angiogenesis, and metastasis through an enhanced process of self-renewal, chemotherapy as well as radiotherapy resistance may aid cancer treatment.

Novel MXene-Modified Polyphenyl Sulfone Membranes for Functional Nanofiltration of Heavy Metals-Containing Wastewater.

In this work, MXene as a hydrophilic 2D nanosheet has been suggested to tailor the polyphenylsulfone (PPSU) flat sheet membrane characteristics via bulk modification. The amount of MXene varied in the PPSU casting solution from 0-1.5 wt.

Generation of liver metastases in a mouse model using ultrasound-guided intravenous injection.

Here, we present a protocol to generate a murine model of liver metastasis by directly injecting tumor cells into the portal vein under ultrasound guidance. We describe steps for animal and cell preparation and two techniques for injecting tumor cells. One technique is freehand, while the other technique is device-assisted using a 3D-printed prototype device.

Recent progress and future directions of membranes green polymers for oily wastewater treatment.

The preparation, modification and application of green polymers such as poly-lactic acid (PLA), chitosan (CS), and cellulose acetate (CA) for oily wastewater treatment is summed up in this review. Due to the low environmental pollution, good chemical resistivity, high hydrophobicity, and good capacity for water-oil emulsion separation of the presented polymers, it then highlights the various membrane production methods and their role in producing effective membranes, with a focus on recent advances in improving membrane properties through the addition of various Nano materials. As a result, the hydrophilic/hydrophobic properties that are critical in the oil separation mechanism are highlighted.

Pneumomediastinum in association with Covid-19: A less commonly considered differential diagnosis for worsening respiratory failure.

We have reported here two cases of coronavirus disease-2019 (COVID-19) patients aged 29 and 68 years who were diagnosed with pneumomediastinum (PM). PM is a rare complication that is being reported in association with COVID-19. Patients with COVID-19 can present with a variety of etiologies that make them vulnerable to PM.

Evaluation of the effectiveness of bioactive glass fillers against to PMMA denture base materials: An in vitro study.

Background: Dentures with antimicrobial properties are desirable for preventing adhesion. This study was to assess the effectiveness of bioactive glass (BAG) on adhesion, surface roughness, and hardness of denture base materials.

Methods: Heat-polymerized (HP) and autopolymerized (AP) acrylic resins were used to fabricate 240 disk specimens 120/material, 60/, 60/surface roughness and hardness).

The STAT family: Key transcription factors mediating crosstalk between cancer stem cells and tumor immune microenvironment.

Signal transducer and activator of transcription (STAT) proteins compose a family of transcription factors critical for cancer stem cells (CSCs), and they are involved in maintaining stemness properties, enhancing cell proliferation, and promoting metastasis. Recent studies suggest that STAT proteins engage in reciprocal communication between CSCs and infiltrate immune cell populations in the tumor microenvironment (TME). Emerging evidence has substantiated the influence of immune cells, including macrophages, myeloid-derived suppressor cells, and T cells, on CSC survival through the regulation of STAT signaling.

F-FDG PET Visualizes Systemic STING Agonist-Induced Lymphocyte Activation in Preclinical Models.

Stimulator of interferon genes (STING) is a mediator of immune recognition of cytosolic DNA, which plays important roles in cancer, cytotoxic therapies, and infections with certain pathogens. Although pharmacologic STING activation stimulates potent antitumor immune responses in animal models, clinically applicable pharmacodynamic biomarkers that inform of the magnitude, duration, and location of immune activation elicited by systemic STING agonists are yet to be described. We investigated whether systemic STING activation induces metabolic alterations in immune cells that can be visualized by PET imaging.

Role of anticoagulation in lowering the mortality in hospitalized covid-19 patients: Meta-analysis of available literature.

Objectives: To reducing the risk of venous thromboembolic (VTE) events and subsequent mortality in covid-19 patients is still a matter of research. This systematic review and meta-analysis serve the purpose of comparing the mortality associated with the intensity of anticoagulation in patients admitted with covid-19.

Methods: A total of 7120 patients were recruited in 11 studies comparing using prophylactic anticoagulants against therapeutic anticoagulants.

Purine nucleoside phosphorylase enables dual metabolic checkpoints that prevent T cell immunodeficiency and TLR7-associated autoimmunity.

Purine nucleoside phosphorylase (PNP) enables the breakdown and recycling of guanine nucleosides. PNP insufficiency in humans is paradoxically associated with both immunodeficiency and autoimmunity, but the mechanistic basis for these outcomes is incompletely understood. Here, we identify two immune lineage-dependent consequences of PNP inactivation dictated by distinct gene interactions.

Insights into the Genetic Architecture and Genomic Prediction of Powdery Mildew Resistance in Flax ( L.).

Powdery mildew (PM), caused by the fungus in flax, can cause defoliation and reduce seed yield and quality. To date, one major dominant gene () and three quantitative trait loci (QTL) on chromosomes 1, 7 and 9 have been reported for PM resistance. To fully dissect the genetic architecture of PM resistance and identify QTL, a diverse flax core collection of 372 accessions augmented with an additional 75 breeding lines were sequenced, and PM resistance was evaluated in the field for eight years (2010-2017) in Morden, Manitoba, Canada.

Impact of staffing levels and resources of intensive care units on compliance to standard mechanical ventilator guidelines: A city-wide study in times of COVID-19 pandemic.

Background: The COVID-19 pandemic has affected millions and resulted in a considerable strain on healthcare systems around the world. Intensive care units (ICUs) are reported to be affected the most because significant percentage of ICU patients requires respiratory support through mechanical ventilation (MV).

Aim: This study aims to examine the staffing levels and compliance with a ventilator care bundle in a single city in Pakistan.

Reprogramming of nucleotide metabolism by interferon confers dependence on the replication stress response pathway in pancreatic cancer cells.

We determine that type I interferon (IFN) response biomarkers are enriched in a subset of pancreatic ductal adenocarcinoma (PDAC) tumors; however, actionable vulnerabilities associated with IFN signaling have not been systematically defined. Integration of a phosphoproteomic analysis and a chemical genomics synergy screen reveals that IFN activates the replication stress response kinase ataxia telangiectasia and Rad3-related protein (ATR) in PDAC cells and sensitizes them to ATR inhibitors. IFN triggers cell-cycle arrest in S-phase, which is accompanied by nucleotide pool insufficiency and nucleoside efflux.