Feed-forward loop improves the transient dynamics of an antithetic biological controller.

Integral controller is widely used in industry for its capability of endowing perfect adaptation to disturbances. To harness such capability for precise gene expression regulation, synthetic biologists have endeavoured in building biomolecular (quasi-)integral controllers, such as the antithetic integral controller. Despite demonstrated successes, challenges remain with designing the controller for improved transient dynamics and adaptation.

Buzz pollination: investigations of pollen expulsion using the discrete element method.

Buzz pollination involves the release of pollen from, primarily, poricidal anthers through vibrations generated by certain bee species. Despite previous experimental and numerical studies, the intricacies of pollen dynamics within vibrating anthers remain elusive due to the challenges in observing these small-scale, opaque systems. This research employs the discrete element method to simulate the pollen expulsion process in vibrating anthers.

Autonomous learning of generative models with chemical reaction network ensembles.

Can a micron-sized sack of interacting molecules autonomously learn an internal model of a complex and fluctuating environment? We draw insights from control theory, machine learning theory, chemical reaction network theory and statistical physics to develop a general architecture whereby a broad class of chemical systems can autonomously learn complex distributions. Our construction takes the form of a chemical implementation of machine learning's optimization workhorse: gradient descent on the relative entropy cost function, which we demonstrate can be viewed as a form of integral feedback control. We show how this method can be applied to optimize any detailed balanced chemical reaction network and that the construction is capable of using hidden units to learn complex distributions.

Enhanced Ovarian FKBP51 Expression is Associated with Ovarian Aging: A Molecular Insight for Age-Related Fertility in Women.

Objective: To study the relationship between FK506-binding protein 51 (FKBP51) and ovarian aging and/or diminished ovarian reserve (DOR) in human ovaries by comparing FKBP51 levels in granulosa (GC) and cumulus cells (CC), collected during controlled ovarian stimulation (COS) from women of advanced reproductive age and/or with a diagnosis of DOR with that of young women with normal ovarian reserve. To explore the association between increased FKBP51 expression and human ovarian aging further, expression of FKBP51 was compared in ovarian stroma of post-menopausal versus pre-menopausal women. Lastly, this relation was further queried by comparing ovarian expression of several collagen genes as markers of ovarian fibrosis in 14-month-old wild type (Fkbp5) and Fkbp5 knockout (Fkbp5) mice.

Techniques and analytic workflow for spatial transcriptomics and its application to allergy and inflammation.

Spatial profiling, through single-cell gene level expression data paired with cell localization, offers unprecedented biological insights within the intact spatial context of cells in healthy and diseased tissue, adding a novel dimension to data interpretation. This review summarizes recent developments in this field, its application to allergy and inflammation, and recent single-cell resolution platforms designed for spatial transcriptomics with a focus on data processing and analyses for efficient biological interpretation of data. By preserving spatial context, these technologies provide critical insights into tissue architecture and cellular interactions unattainable with traditional transcriptomics methods, such as revealing localized inflammatory cell network in atopic dermatitis, and T-cell interactions in the lung in chronic obstructive pulmonary disease.

Vagus nerve stimulation rescues impaired fear extinction and social interaction in a rat model of autism spectrum disorder.

Clinical diagnosis of anxiety disorders is highly prevalent in autism spectrum disorders (ASD). Available treatments for anxiety offer limited efficacy in the ASD population. Vagus nerve stimulation (VNS) has an anxiolytic effect in rats and, when coupled with fear extinction training, VNS enhances extinction of fear in healthy rats.

An in-depth review of AI-powered advancements in cancer drug discovery.

The convergence of artificial intelligence (AI) and genomics is redefining cancer drug discovery by facilitating the development of personalized and effective therapies. This review examines the transformative role of AI technologies, including deep learning and advanced data analytics, in accelerating key stages of the drug discovery process: target identification, drug design, clinical trial optimization, and drug response prediction. Cutting-edge tools such as DrugnomeAI and PandaOmics have made substantial contributions to therapeutic target identification, while AI's predictive capabilities are driving personalized treatment strategies.

High Normocapnia and Better Functional Outcome in Patients Undergoing Veno-Arterial Extracorporeal Membrane Oxygenation After Out-of-Hospital Cardiac Arrest.

Background: The optimal target for partial pressure of arterial carbon dioxide (PaCO₂) remains uncertain in patients undergoing veno-arterial extracorporeal membrane oxygenation (VA-ECMO) following out-of-hospital cardiac arrest (OHCA).

Research Question: Are PaCO₂ levels associated with functional outcomes in patients receiving VA-ECMO after OHCA?

Study Design: and Methods: This multicenter, registry-based observational study, conducted from 2014 to 2020, included non-traumatic adult OHCA patients on VA-ECMO with PaCO₂ levels measured within six hours of initiation (initial PaCO₂ set) and at 18-30 hours post-initiation (24-hour PaCO₂ set). PaCO₂ levels were categorized into five groups: hypocapnia (<30 mmHg), low normocapnia (30-<40 mmHg), high normocapnia (40-<50 mmHg), mild hypercapnia (50-<60 mmHg), and moderate to severe hypercapnia (≥60 mmHg).

Some properties and applications of the tabletability equation.

A recently derived tabletability equation mathematically describes tablet tensile strength as a function of compaction pressure. In this work, further analysis of the tabletability equation reveals that the normalized slope at the inflection point correlates well with powder plasticity, indicating its potential use as a powder plasticity parameter. Additionally, we explore applications of the tabletability equation in quantifying errors caused by a tensile strength measurement method that disregards out-of-die elastic recovery for assessing tabletability.

The levels of the long non-coding RNA MALAT1 affect cell viability and modulate TDP-43 binding to mRNA in the nucleus.

TAR DNA-binding protein (TDP-43) and Metastasis Associated Lung Adenocarcinoma Transcript (MALAT1) RNA are both abundantly expressed in the human cell nucleus. Increased interaction of TDP-43 and MALAT1, as well as dysregulation of TDP-43 function, was previously identified in brain samples from patients with neurodegenerative disease compared to healthy brain tissues. We hypothesized that TDP-43 function may depend in part on MALAT1 expression levels.

Sialidase fusion protein protects against influenza infection in a cigarette smoke-induced model of COPD.

First- and secondhand smokers are at an increased risk for influenza virus (IFV)-related respiratory failure and death. Despite approved influenza antiviral treatments, there is an unmet need for treatments that can improve outcomes in populations at risk for respiratory failure, including tobacco users with Chronic Obstructive Pulmonary Disease (COPD). Here we show that the sialidase fusion protein, DAS181, reduced viral burden, mitigated inflammation, and attenuated lung function loss, consistent with broad-spectrum anti-influenza responses in a mouse model of COPD and IFV-A infection.

Genetic variants and breast carcinoma susceptibility: Unveiling the role of MTHFR (rs1801131, rs1801133) and TP53 (rs1042522).

Background: The contribution of MTHFR and TP53 genetic variants to breast carcinoma (BC) susceptibility has been examined, but their findings have been inconclusive. This work is designed to explore the potential roles of the MTHFR (rs1801131, rs1801133) and TP53 (rs1042522) variants with increased risk of BC using genetic and bioinformatic approaches.

Methods: This work included a total of 242 female participants [142 BCE patients and 100 healthy controls].

The effects of bilateral M1 anodal tDCS on corticomotor excitability and acquisition the of a bimanual videogame skill.

Most activities of daily life involve some degree of coordinated, bimanual activity from the upper limbs. However, compared to single-handed movements, bimanual movements are processed, learned, and controlled from both hemispheres of the brain. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that enhances motor learning by modulating the activity of movement-associated brain regions.

Unraveling the genetic links between depression and type 2 diabetes.

Background: Type 2 diabetes (T2D) is a chronic metabolic disorder that has high comorbidity with mental disorders. The genetic relationships between T2D and depression are far from being well understood.

Methods: We performed genetic correlation, polygenic overlap, Mendelian randomization (MR) analyses, cross-trait meta-analysis, and Bayesian colocalization analysis to assess genetic relationships between T2D and depression, in the forms of major depressive disorder (MDD) and depressed affect (DAF).

Thirty-day stroke/mortality of carotid revascularization in asymptomatic patients with newly diagnosed and/or decompensated heart failure exceeds the Society for Vascular Society guideline risks.

Background: According to the latest Society for Vascular Surgery (SVS) guidelines, carotid revascularization for asymptomatic individuals should be offered if the perioperative stroke/death rate does not exceed 3%. Heart failure (HF) has been associated with reduced survival rates following carotid revascularization, which may significantly impact the risk-benefit decision of treating asymptomatic patients with HF. This study aimed to evaluate the 30-day postoperative risks in asymptomatic patients with newly diagnosed and/or decompensated HF undergoing carotid endarterectomy (CEA) and carotid artery stenting (CAS).

Developmental and conditional regulation of DAF-2/INSR ubiquitination in Caenorhabditis elegans.

Insulin/IGF signaling (IIS) regulates developmental and metabolic plasticity. Conditional regulation of insulin-like peptide expression and secretion promotes different phenotypes in different environments. However, IIS can also be regulated by other, less-understood mechanisms.

Flow cytometric measurement of CFTR-mediated chloride transport in human neutrophils.

Immune cells express a variety of ion channels and transporters in the plasma membrane and intracellular organelles, responsible of the transference of charged ions across hydrophobic lipid membrane barriers. The correct regulation of ion transport ensures proper immune cell function, activation, proliferation, and cell death. Cystic fibrosis (CF) is a genetic disease in which the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) chloride channel gene is defective, consequently, the CFTR protein is dysfunctional, and the chloride efflux in CF cells is markedly impaired.

Tuberculosis screening in hidradenitis suppurativa patients on tumor necrosis factor inhibitors: a retrospective chart review.

Hidradenitis suppurativa (HS) patients treated with tumor necrosis factor (TNF) inhibitors are at an increased risk for tuberculosis (TB) reactivation, necessitating baseline latent TB infection (LTBI) screening. However, evidence regarding the value of periodic LTBI screening in this population is limited. In this single-center retrospective chart review, we investigated the LTBI rate in HS patients treated with adalimumab or infliximab.

Protein quality control is a master modulator of molecular evolution in bacteria.

The bacterial protein quality control (PQC) network comprises a set of genes that promote proteostasis (proteome homeostasis) through proper protein folding and function via chaperones, proteases, and a protein translational machinery. It participates in vital cellular processes and influences organismal development and evolution. In this review, we examine the mechanistic bases for how the bacterial PQC network influences molecular evolution.

Engineered allogeneic stem cells orchestrate T lymphocyte driven immunotherapy in immunosuppressive leptomeningeal brain metastasis.

Background: Immune-checkpoint inhibitors have shown clinical benefit in non-small cell lung cancer (NSCLC) derived brain metastasis (BM), however, their efficacy in lung to leptomeningeal brain metastasis (LLBM) remains poor.

Methods: A paired matched RNA expression dataset of patients with NSCLCs and BMs was analyzed to idenfiy BM specific suppressive tumor microenvironment (TME) features. Next, we created immune-competent LLBM mouse models that mimic clinical LLBM.

Structure-guided insights into TIR-mediated bacterial and eukaryotic immunity.

Within the course of evolution, TIR (Toll/interleukin-1 receptor) domains acquired a myriad of functional specificities. This has significantly added to their well-established roles in innate immune signaling. These additional functions include nicotinamide adenine dinucleotide (NAD)(P) hydrolase, RNA/DNA nuclease (in plants), CN (cyclic nucleotide) cyclase, and base exchanger activities.