Ultrasound Assessment of Cerebral Blood Flow Changes Upon Rapid Exposure to Hypoxic High-Altitude Environment.

Objectives: To investigate cerebral blood flow (CBF) regulation and cerebrovascular reactivity (CVR) in response to rapid high-altitude exposure and identify hemodynamic characteristics of CVR impairment.

Methods: Transcranial color-coded duplex sonography (TCCD) and breath-holding tests were used to assess CBF in rapid high-altitude entrants (n = 64, 26 ± 6 years) and long-term residents (n = 66, 25 ± 4 years). The breath-holding test can alter CBF through the dilation of intracranial small vessels, and the breath-holding index (BHI) can be utilized to quantify the changes in CBF associated with vasodilation.

Loop Site Mutation-Enhanced Sensing Performance of G-Triplex Probe: Preliminary Exploration on Its Stability and "Structure-Efficiency" Relationship.

G-triplex is a unique topological structure formed by G-rich nucleic acid sequences with three G-tracts. It can bind to small ligands and function as a label-free sensing probe. However, the number of discovered G-triplex/small ligands with stable structures and excellent performance is still limited, requiring deeper insight on their "structure-efficiency" relationships.

Engineering of photo-inducible binary interaction tools for biomedical applications.

The ssrA-sspB dimerization system, derived from the bacterial degradation machinery, comprises a 7-residue ssrA peptide and its binding partner sspB. The compact size of ssrA makes it ideal for insertion into proteins of interest to manipulate host protein function by engineered light-responsive sspB. In contrast to the LOV2 caging strategy employed to develop optical dimerizers, we present herein two distinct photo-inducible binary interaction tools (PhoBITs) systems: PhoBIT1, a light-OFF switch generated by integrating LOV2 into sspB, and PhoBIT2, a light-ON switch building upon an evolved ssrA/CRY2-sspB pair with minimal basal interaction.

Recent Advances in Fluorescence Resonance Energy Transfer (FRET) Biosensors for Exosomes.

Cancer is a significant global health challenge, where early diagnosis is crucial for enhancing patient survival and mitigating the treatment burden on patients. Exosomes are extracellular vesicles released through the fusion of multivesicular bodies with cell membranes, carrying disease-associated information from donor cells. This makes exosomes a key biomarker in liquid biopsy analysis, particularly for early cancer detection.

Assessment of flight fatigue using heart rate variability and machine learning approaches.

The accurate identification of flight fatigue is crucial for managing pilot training intensity and preventing aviation accidents. However, as a subjective perception, flight fatigue is often difficult to evaluate objectively. Heart rate variability (HRV), derived from electrocardiogram signals and regulated by the autonomic nervous system, is recognized as an effective biomarker for assessing fatigue status.

Optogenetic control of T cells for immunomodulation.

Cellular immunotherapy has transformed cancer treatment by harnessing T cells to target malignant cells. However, its broader adoption is hindered by challenges such as efficacy loss, limited persistence, tumor heterogeneity, an immunosuppressive tumor microenvironment (TME), and safety concerns related to systemic adverse effects. Optogenetics, a technology that uses light-sensitive proteins to regulate cellular functions with high spatial and temporal accuracy, offers a potential solution to overcome these issues.

Repurposing salicylic acid as a versatile inducer of proximity.

Chemically induced proximity (CIP) has remarkably advanced the development of molecular and cellular therapeutics. To maximize therapeutic potential, there is a pressing need to expand the repertoire of CIP systems of translational values, favoring chemical ligands that are cost-effective, structurally simple, biocompatible, reversible and have minimal side effects. Here, we present a salicylic acid (SA)-mediated binary association system (SAMBA), evolved from a tobacco SA receptor, that enables rapid protein-protein heterodimerization in response to SA or aspirin after hydrolysis.

Optogenetic engineering for precision cancer immunotherapy.

Cancer immunotherapy has revolutionized oncology, but its full potential remains constrained by treatment resistance, limited durability, immune evasion, and systemic toxicity. Overcoming these obstacles requires innovative strategies for remote and targeted immunomodulation. Opsin-free optogenetics has emerged as a powerful tool in cancer immunotherapy because its versatility and photoactivation kinetics align with the timescale of immune cell signaling, and it has given rise to the subfield of optogenetic immunoengineering.

Self-Powered Switchable Gas-Humidity Difunctional Flexible Chemosensors Based on Smart Adaptable Hydrogel.

The development of self-powered, flexible, and multi-function sensors is highly anticipated in wearable electronics, however, it remains a daunting challenge to identify different signals based on a single device with singular sensing material without algorithmic support. Here, a smart adaptable hydrogel is developed by co-introducing two ions with vastly different hydrophilicity for the construction of an electrochemically self-powered, flexible, and reversibly switchable difunctional chemosensor with a metal-air battery structure. The prepared hydrogel can readily switch between water-rich and water-deficient states for crosstalk-free detection of oxygen and humidity respectively, since O gas and water molecules can directly participate in the oxygen reduction reaction in the device and act alone as limiting reactants and catalysts to affect the reaction rate under different hydrogel states.

Cross language transformation of free text into structured lobectomy surgical records from a multi center study.

In a recent study, the effectiveness of GPT-4 Omni in transforming lobectomy surgical records into structured data across multiple languages was explored. The aim was to improve both efficiency and accuracy in documenting thoracic surgical oncology procedures. Involving 466 records from seven specialized hospitals, the process started with OCR and text normalization.

Activation of the γ-Aminobutyric Acid Receptor Type B Suppresses the Proliferation of Lung Adenocarcinoma Cells.

Background/aim: The roles of γ-aminobutyric acid (GABA) and its receptors in lung cancer development and progression remain controversial. This study aimed to investigate the effects of activating GABA receptor type B (GABA-B receptor) using baclofen, a GABA-B receptor agonist, on the proliferation of lung adenocarcinoma cells and its underlying mechanisms.

Materials And Methods: Differential expression of GABA-B receptors was analyzed using the online Gene Expression Profiling Interactive Analysis tool.

Modulating ion channels with nanobodies.

Ion channels play instrumental roles in regulating membrane potential and cross-membrane signal transduction, thus making them attractive targets for understanding various physiological processes and associated diseases. Gaining a deeper understanding of their structural and functional properties has significant implications for developing therapeutic interventions. In recent years, nanobodies, single-domain antibody fragments derived from camelids, have emerged as powerful tools in ion channel and synthetic biology research.

Optogenetic engineering for ion channel modulation.

Optogenetics, which integrates photonics and genetic engineering to control protein activity and cellular processes, has transformed biomedical research. Its precise spatiotemporal control, minimal invasiveness, and tunable reversibility have spurred its widespread adoption in both basic and clinical research. Optogenetic techniques have been applied to partially restore vision in blind patients and are being actively explored as innovative treatments for neurological, psychiatric, cardiac, and immunological disorders.

Efficacy and safety of immunotherapy in locally advanced or metastatic pulmonary lymphoepithelioma-like carcinoma: a multicenter retrospective study.

Background: Pulmonary lymphoepithelioma-like carcinoma (pLELC) is a rare subtype of non-small-cell lung cancer that predominantly affects younger, non-smoking individuals in southern and southeast Asia, where Epstein-Barr virus (EBV) prevalence is high. The efficacy and safety of immunotherapy in pLELC, especially in second-line settings, remain inadequately explored.

Objectives: This study aimed to evaluate the efficacy of immunotherapy, either alone or in combination with chemotherapy, in improving progression-free survival (PFS) and overall survival (OS) in patients with advanced pLELC.

A Chemogenetic Toolkit for Inducible, Cell Type-Specific Actin Disassembly.

The actin cytoskeleton and its nanoscale organization are central to all eukaryotic cells-powering diverse cellular functions including morphology, motility, and cell division-and is dysregulated in multiple diseases. Historically studied largely with purified proteins or in isolated cells, tools to study cell type-specific roles of actin in multicellular contexts are greatly needed. DeActs are recently created, first-in-class genetic tools for perturbing actin nanostructures and dynamics in specific cell types across diverse eukaryotic model organisms.

STIM1 and lipid interactions at ER-PM contact sites.

Store-operated calcium (Ca) entry (SOCE) represents a major route of Ca permeation across the plasma membrane (PM) in nonexcitable cells, which plays an indispensable role in maintaining intracellular Ca homeostasis. This process is orchestrated through the dynamic coupling between the endoplasmic reticulum (ER)-localized Ca sensor stromal interaction molecule 1 (STIM1) and the PM-resident ORAI1 channel. Upon depletion of ER Ca stores, STIM1 undergoes conformational rearrangements and oligomerization, leading to the translocation of activated STIM1 toward the PM.

GA-BP-Based Low-Noise FBG Hydroacoustic Monitoring System with Reference Sensor.

To address the issue of harsh marine background noise impacting the monitoring signal of fiber-optic hydrophones, we propose a low-noise fiber Bragg grating (FBG) hydroacoustic monitoring system with a reference sensor based on genetic algorithm backpropagation (GA-BP). Through theoretical analysis, we deduce the noise suppression steps of the GA-BP algorithm based on the reference sensor and construct train and test sets based on the data from the reference sensor and monitoring sensor at different times, optimizing the GA-BP algorithm to find the best fitting results and thereby obtaining the low-noise monitoring signal. Experimental results from the anechoic tank show that the proposed method can suppress background noise interference on effective signals and that the suppression effect improves as the background noise increases.

Perturbing TET2 condensation promotes aberrant genome-wide DNA methylation and curtails leukaemia cell growth.

The ten-eleven translocation (TET) family of dioxygenases maintain stable local DNA demethylation during cell division and lineage specification. As the major catalytic product of TET enzymes, 5-hydroxymethylcytosine is selectively enriched at specific genomic regions, such as enhancers, in a tissue-dependent manner. However, the mechanisms underlying this selectivity remain unresolved.

Hydrogel Loaded with Extracellular Vesicles: An Emerging Strategy for Wound Healing.

An increasing number of novel biomaterials have been applied in wound healing therapy. Creating beneficial environments and containing various bioactive molecules, hydrogel- and extracellular vesicle (EV)-based therapies have respectively emerged as effective approaches for wound healing. Moreover, the synergistic combination of these two components demonstrates more favorable outcomes in both chronic and acute wound healing.

Differential Lipid Binding Specificities of RAP1A and RAP1B are Encoded by the Amino Acid Sequence of the Membrane Anchors.

RAP1 proteins belong to the RAS family of small GTPases that operate as molecular switches by cycling between GDP-bound inactive and GTP-bound active states. The C-terminal anchors of RAP1 proteins are known to direct membrane localization, but how these anchors organize RAP1 on the plasma membrane (PM) has not been investigated. Using high-resolution imaging, we show that RAP1A and RAP1B form spatially segregated nanoclusters on the inner leaflet of the PM, with further lateral segregation between GDP-bound and GTP-bound proteins.

Ion channel signalling mechanisms in physiology and disease.

The 19 FASEB Science Research Conference on “Calcium and Cell Function” was organized in Malahide, Ireland, on June 25–30, 2023. Co-chaired by Mohamed Trebak (University of Pittsburgh) and Yubin Zhou (Texas A&M University), with Jen Liou and Ilya Bezprozvanny (University of Texas Southwestern) as co-vice chairs. The conference, which was attended by over 125 scientists from North America, Europe, and Asia was partially supported by .