Decoding the Promise and Challenges of miRNA-Based Cancer Therapies: An Essential Update on miR-21, miR-34, and miR-155.

MicroRNAs (miRNAs)-based therapies hold great promise for cancer treatment, challenges such as expression variability, off-target effects, and limited clinical effectiveness have led to the withdrawal of many clinical trials. This review investigates the setbacks in miRNA-based therapies by examining miR-21, miR-34, and miR-155, highlighting their functional complexity, off-target effects, and the challenges in delivering these therapies effectively. Moreover, It highlights recent advances in delivery methods, combination therapies, and personalized treatment approaches to overcome these challenges.

Network Medicine-Based Strategy Identifies Maprotiline as a Repurposable Drug by Inhibiting PD-L1 Expression via Targeting SPOP in Cancer.

Immune checkpoint inhibitors (ICIs) are drugs that inhibit immune checkpoint (ICP) molecules to restore the antitumor activity of immune cells and eliminate tumor cells. Due to the limitations and certain side effects of current ICIs, such as programmed death protein-1, programmed cell death-ligand 1, and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) antibodies, there is an urgent need to find new drugs with ICP inhibitory effects. In this study, a network-based computational framework called multi-network algorithm-driven drug repositioning targeting ICP (Mnet-DRI) is developed to accurately repurpose novel ICIs from ≈3000 Food and Drug Administration-approved or investigational drugs.

Lethal versus surviving sepsis phenotypes displayed a partly differential regional expression of neurotransmitters and inflammation and did not modify the blood-brain barrier permeability in female CLP mice.

Background: Septic encephalopathy is frequent but its pathophysiology is enigmatic. We studied expression of neurotransmitters, inflammation and integrity of the blood-brain barrier (BBB) in several brain regions during abdominal sepsis. We compared mice with either lethal or surviving phenotype in the first 4 sepsis days.

Painful Call About the Under-Reporting of Children's Pain During Humanitarian Crises.

Humanitarian crises often require urgent medical care to people of concern. Such medical aid includes assessing and treating acute medical needs and ongoing chronic health conditions. Among the people of concern there are children, who are often the most vulnerable population in humanitarian contexts because they often lack the experience, independence, and cognitive and verbal skills to deal with the ordeals they are facing.

Quality problems in clinical practice guidelines and guideline appraisal studies: Should we tolerate or eradicate?

Background: Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument have been widely used by scholars around the world to assess the methodological quality of clinical practice guidelines (CPGs). We sought to identify items or domains that are commonly scored low in the assessment, and to systematically review the issues that emerged when evaluators used the AGREE II tool for guideline quality assessment.

Methods: A systematic search was conducted to identify articles published in medically relevant databases from 2022 to 2023 regarding the use of the AGREE II tool for the assessment of CPGs.

Resolving and functional analysis of RNA editing sites in sheep ovaries and associations with litter size.

Sheep litter size is a critical trait in mutton production. While litter size regulation in relation to DNA transcription have been rigorously investigated, the function of RNA editing remains less explored. To elucidate the mechanisms controlling sheep fecundity at the RNA editing level and identify pivotal RNA editing sites, this study scrutinised RNA editing sites (RESs) in follicular and luteal phases of ovaries from sheep with high and low fecundity, and the functions of population-specific RESs were subsequently analysed.

Factors involved in gastroesophageal varix-related events in patients with hepatitis C virus-related compensated and decompensated cirrhosis after direct-acting antiviral therapy.

Aim: The incidence of and factors involved in gastroesophageal varix-related events in hepatitis C virus-related cirrhosis patients, including decompensated cirrhosis, after direct-acting antiviral therapy are unclear.

Methods: We conducted a multicenter study using prospective data from 478 hepatitis C virus-related cirrhosis patients treated with direct-acting antiviral therapy from February 2019 to December 2021 at 33 Japanese hospitals. Gastroesophageal varices were classified as F1 (small-caliber), F2 (moderately enlarged), or F3 (markedly enlarged) according to the Japanese criteria.

A human isolate of bovine H5N1 is transmissible and lethal in animal models.

The outbreak of clade 2.3.4.

Prediction of depressive symptoms in young adults by polygenic score and childhood maltreatment: Results from a population-based birth cohort.

Childhood maltreatment is linked with later depressive symptoms, but not every maltreated child will experience symptoms later in life. Therefore, we investigate whether genetic predisposition for depression (i.e.

vEMstitch: an algorithm for fully automatic image stitching of volume electron microscopy.

Background: As software and hardware have developed, so has the scale of research into volume electron microscopy (vEM), leading to ever-increasing resolution. Usually, data collection is followed by image stitching: the same area is subjected to high-resolution imaging with a certain overlap, and then the images are stitched together to achieve ultrastructure with large scale and high resolution simultaneously. However, there is currently no perfect method for image stitching, especially when the global feature distribution of the sample is uneven and the feature points of the overlap area cannot be matched accurately, which results in ghosting of the fusion area.

Effect of Unfractionated Heparin Dose on Complement Activation and Selected Extracellular Vesicle Populations during Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) provides critical support for patients with severe cardiopulmonary dysfunction. Unfractionated heparin (UFH) is used for anticoagulation to maintain circuit patency and avoid thrombotic complications, but it increases the risk of bleeding. Extracellular vesicles (EVs), nano-sized subcellular spheres with potential pro-coagulant properties, are released during cellular stress and may serve as potential targets for monitoring anticoagulation, particularly in thromboinflammation.

Molecular Mechanisms of Biofilm Formation in .

Background: Biofilm formation in () helps bacteria survive antibiotic exposure and supports bacterial colonization and persistence in the stomach. Most of the published articles have focused on one aspect of the biofilm. Therefore, we conducted the current study to better understand the mechanism of biofilm formation, how the biofilm contributes to antibiotic resistance, and how the biofilm modifies the medication delivery mechanism.

Fei-Yan-Qing-Hua decoction attenuates influenza virus infection by enhancing host antiviral response through microbiota-derived acetate.

Background: Fei-Yan-Qing-Hua decoction (FYQHD) is derived from the well-known Ma Xing Shi Gan decoction, which was documented in Zhang Zhong Jing's "Treatise on Exogenous Febrile Disease" during the Han Dynasty. Although FYQHD has been used in the treatment of pneumonia and has demonstrated clinical efficacy for decades, the underlying mechanism by which FYQHD protects against influenza virus infection through modulation of gut flora remains unclear. Here, we examined the regulatory impacts of FYQHD on an influenza virus-infected mouse model and explored the mechanisms involved.

Distribution and prediction of biocrusts under the canopy of typical vascular plants on the Loess Plateau, Northwest China.

Vascular plants exert significant effects on micro-environment, thereby affecting the distribution of biological soil crusts (biocrusts). The relationship between vascular plants and the spatial distribution characteristics of biocrusts is largely unknown. We investigated the distribution characteristics of biocrusts under the canopy of vascular plants in the water-wind erosion crisscross area of the Loess Plateau, where larger areas of biocrusts had been formed since the implantation of "Grain for Green" project.

The senolytic agent ABT263 ameliorates osteoporosis caused by active vitamin D insufficiency through selective clearance of senescent skeletal cells.

Background/objective: Active vitamin D insufficiency accelerates the development of osteoporosis, with senescent bone cells and the senescence-associated secretory phenotype (SASP) playing crucial roles. This study aimed to investigate whether the senolytic agent ABT263 could correct osteoporosis caused by active vitamin D insufficiency by selectively clearing senescent cells.

Methods: Bone marrow mesenchymal stem cells (BM-MSCs) from young and aged mice were treated with ABT263 in vitro, and 1,25(OH)D-insufficient (Cyp27b1) mice were administered ABT263 in vivo.

Retention time-independent strategy for screening pesticide residues in herbs based on a fingerprint database and all ion fragmentation acquisition with LC-QTOF MS.

A retention time (RT)-independent strategy for nontargeted screening of pesticide residues in herbs was exploited using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF MS). The core of this strategy is a fingerprint database coupled with a data-independent acquisition (DIA) scan mode of all ion fragmentation (AIF). In the fingerprint database, a total of 150 pesticides with quasimolecular ions and fragment ions at five-level collision energies were collected as qualified ions for screening.

Enhanced stereodivergent evolution of carboxylesterase for efficient kinetic resolution of near-symmetric esters through machine learning.

Carboxylesterases serve as potent biocatalysts in the enantioselective synthesis of chiral carboxylic acids and esters. However, naturally occurring carboxylesterases exhibit limited enantioselectivity, particularly toward ethyl 3-cyclohexene-1-carboxylate (CHCE, S1), due to its nearly symmetric structure. While machine learning effectively expedites directed evolution, the lack of models for predicting the enantioselectivity for carboxylesterases has hindered progress, primarily due to challenges in obtaining high-quality training datasets.

Emerging concepts in mucosal immunity and oral microecological control of respiratory virus infection-related inflammatory diseases.

Oral microecological imbalance is closely linked to oral mucosal inflammation and is implicated in the development of both local and systemic diseases, including those caused by viral infections. This review examines the critical role of the interleukin (IL)-17/helper T cell 17 (Th17) axis in regulating immune responses within the oral mucosa, focusing on both its protective and pathogenic roles during inflammation. We specifically highlight how the IL-17/Th17 pathway contributes to dysregulated inflammation in the context of respiratory viral infections.