Diagnosis of Fibrotic Interstitial Lung Diseases Based on the Combination of Label-Free Quantitative Multiphoton Fiber Histology and Machine Learning.

Interstitial lung disease (ILD), characterized by inflammation and fibrosis, often suffers from low diagnostic accuracy and consistency. Traditional hematoxylin and eosin (H&E) staining primarily reveals cellular inflammation with limited detail on fibrosis. To address these issues, we introduce a pioneering label-free quantitative multiphoton fiber histology (MPFH) technique that delineates the intricate characteristics of collagen and elastin fibers for ILD diagnosis.

π-HuB: the proteomic navigator of the human body.

The human body contains trillions of cells, classified into specific cell types, with diverse morphologies and functions. In addition, cells of the same type can assume different states within an individual's body during their lifetime. Understanding the complexities of the proteome in the context of a human organism and its many potential states is a necessary requirement to understanding human biology, but these complexities can neither be predicted from the genome, nor have they been systematically measurable with available technologies.

Thirty years of Ca spark research: digital principle of cell signaling unveiled.

Calcium ions (Ca) are an archetypical and most versatile second messenger in virtually all cell types. Inspired by the discovery of Ca sparks in the 1990s, vibrant research over the last three decades has unveiled a constellation of Ca microdomains as elementary events of Ca signaling and, more importantly, a digital-analog dualism as the system design principle of Ca signaling. In this brief review, we present a sketchy summary on advances in the field of sparkology, and discuss how the digital subsystem can fulfill physiological roles otherwise impossible for any analog system.

System-level time computation and representation in the suprachiasmatic nucleus revealed by large-scale calcium imaging and machine learning.

The suprachiasmatic nucleus (SCN) is the mammalian central circadian pacemaker with heterogeneous neurons acting in concert while each neuron harbors a self-sustained molecular clockwork. Nevertheless, how system-level SCN signals encode time of the day remains enigmatic. Here we show that population-level Ca signals predict hourly time, via a group decision-making mechanism coupled with a spatially modular time feature representation in the SCN.

Enhanced interfacial effect via acid theory with boosted photocatalytic performance of nitenpyram removal.

Surface reaction is a prominent aspect that affects the efficiency of photocatalysis. In this work, acid theory was employed to facilitate the reaction dynamics and enhance the interfacial effect between photocatalysts and target molecules. The photocatalytic removal efficiency of NTP was 66 % for bare CdS in 50 min with apparent rate constants of 0.

Programmable ultrasound imaging guided theranostic nanodroplet destruction for precision therapy of breast cancer.

Ultrasound-stimulated contrast agents have gained significant attention in the field of tumor treatment as drug delivery systems. However, their limited drug-loading efficiency and the issue of bulky, imprecise release have resulted in inadequate drug concentrations at targeted tissues. Herein, we developed a highly efficient approach for doxorubicin (DOX) precise release at tumor site and real-time feedback via an integrated strategy of "programmable ultrasonic imaging guided accurate nanodroplet destruction for drug release" (PND).

Pattern recognition of microcirculation with super-resolution ultrasound imaging provides markers for early tumor response to anti-angiogenic therapy.

Cancer treatment outcome is traditionally evaluated by tumor volume change in clinics, while tumor microvascular heterogeneity reflecting tumor response has not been fully explored due to technical limitations. We introduce a new paradigm in super-resolution ultrasound imaging, termed pattern recognition of microcirculation (PARM), which identifies both hemodynamic and morphological patterns of tumor microcirculation hidden in spatio-temporal space trajectories of microbubbles. PARM demonstrates the ability to distinguish different local blood flow velocities separated by a distance of 24 μm.

Imaging microglia surveillance during sleep-wake cycles in freely behaving mice.

Microglia surveillance manifests itself as dynamic changes in cell morphology and functional remodeling. Whether and how microglia surveillance is coupled to brain state switches during natural sleep-wake cycles remains unclear. To address this question, we used miniature two-photon microscopy (mTPM) to acquire time-lapse high-resolution microglia images of the somatosensory cortex, along with EEG/EMG recordings and behavioral video, in freely-behaving mice.

Millimeter field-of-view miniature two-photon microscopy for brain imaging in freely moving mice.

Development of miniature two-photon microscopy (m2PM) has made it possible to observe fine structure and activity of neurons in the brain of freely moving animals. However, the imaging field-of-view of existing m2PM is still significantly smaller than that of miniature single-photon microscopy. Here we report that, through the design of low-magnification objective, large field-of-view scan lens and small tilt angle microscanner, a 2.

Succinate dehydrogenase is essential for epigenetic and metabolic homeostasis in hearts.

A hallmark of heart failure is a metabolic switch away from fatty acids β-oxidation (FAO) to glycolysis. Here, we show that succinate dehydrogenase (SDH) is required for maintenance of myocardial homeostasis of FAO/glycolysis. Mice with cardiomyocyte-restricted deletion of subunit b or c of SDH developed a dilated cardiomyopathy and heart failure.

C17orf80 binds the mitochondrial genome to promote its replication.

Serving as the power plant and signaling hub of a cell, mitochondria contain their own genome which encodes proteins essential for energy metabolism and forms DNA-protein assemblies called nucleoids. Mitochondrial DNA (mtDNA) exists in multiple copies within each cell ranging from hundreds to tens of thousands. Maintaining mtDNA homeostasis is vital for healthy cells, and its dysregulation causes multiple human diseases.

A neural circuit for regulating a behavioral switch in response to prolonged uncontrollability in mice.

Persistence in the face of failure helps to overcome challenges. But the ability to adjust behavior or even give up when the task is uncontrollable has advantages. How the mammalian brain switches behavior when facing uncontrollability remains an open question.

Miniature three-photon microscopy maximized for scattered fluorescence collection.

In deep-tissue multiphoton microscopy, diffusion and scattering of fluorescent photons, rather than ballistic emanation from the focal point, have been a confounding factor. Here we report on a 2.17-g miniature three-photon microscope (m3PM) with a configuration that maximizes fluorescence collection when imaging in highly scattering regimes.

New imaging instrument in animal models: Two-photon miniature microscope and large field of view miniature microscope for freely behaving animals.

Over the past decade, novel optical imaging tools have been developed for imaging neuronal activities along with the evolution of fluorescence indicators with brighter expression and higher sensitivity. Miniature microscopes, as revolutionary approaches, enable the imaging of large populations of neuron ensembles in freely behaving rodents and mammals, which allows exploring the neural basis of behaviors. Recent progress in two-photon miniature microscopes and mesoscale single-photon miniature microscopes further expand those affordable methods to navigate neural activities during naturalistic behaviors.

Encoding of social novelty by sparse GABAergic neural ensembles in the prelimbic cortex.

Although the prelimbic (PrL) area is associated with social behaviors, the neural ensembles that regulate social preference toward novelty or familiarity remain unknown. Using miniature two-photon microscopy (mTPM) to visualize social behavior-associated neuronal activity within the PrL in freely behaving mice, we found that the Ca transients of GABAergic neurons were more highly correlated with social behaviors than those of glutamatergic neurons. Chemogenetic suppression of social behavior-activated GABAergic neurons in the PrL disrupts social novelty behaviors.

Non-Invasive Skin Imaging Assessment of Human Stress During Head-Down Bed Rest Using a Portable Handheld Two-Photon Microscope.

Spaceflight presents a series of physiological and pathological challenges to astronauts resulting from ionizing radiation, microgravity, isolation, and other spaceflight hazards. These risks cause a series of aging-related diseases associated with increased oxidative stress and mitochondria dysfunction. The skin contains many autofluorescent substances, such as nicotinamide adenine dinucleotide phosphate (NAD(P)H), keratin, melanin, elastin, and collagen, which reflect physiological and pathological changes .

CMYA5 establishes cardiac dyad architecture and positioning.

Cardiac excitation-contraction coupling requires dyads, the nanoscopic microdomains formed adjacent to Z-lines by apposition of transverse tubules and junctional sarcoplasmic reticulum. Disruption of dyad architecture and function are common features of diseased cardiomyocytes. However, little is known about the mechanisms that modulate dyad organization during cardiac development, homeostasis, and disease.

Functional network topography of the medial entorhinal cortex.

The medial entorhinal cortex (MEC) creates a map of local space, based on the firing patterns of grid, head-direction (HD), border, and object-vector (OV) cells. How these cell types are organized anatomically is debated. In-depth analysis of this question requires collection of precise anatomical and activity data across large populations of neurons during unrestrained behavior, which neither electrophysiological nor previous imaging methods fully afford.

Arterial Labeling Ultrasound Subtraction Angiography (ALUSA) Based on Acoustic Phase-Change Nanodroplets.

Biomedical imaging technology (like digital subtraction angiography (DSA)) based on contrast agents has been widely employed in the diagnosis of vascular-related diseases. While the DSA achieves the high-resolution observation of specified vessels and their downstream perfusion at the cost of invasive, radioactive operation and hepatorenal toxicity. To address those problems, this study develops arterial labeling ultrasound (US) subtraction angiography (ALUSA) based on a new perfluorobutane (PFB) nanodroplets with a lower vaporization threshold through spontaneous nucleation.

Isobaric Tags for Relative and Absolute Quantification-Based Proteomics Reveals Candidate Proteins of Fat Deposition in Chinese Indigenous Sheep With Morphologically Different Tails.

Chinese indigenous sheep can be classified into two types according to their tail morphology: fat-rumped and thin-tailed sheep, of which the typical breeds are Altay sheep and Tibetan sheep, respectively. To identify the differentially expressed proteins (DEPs) underlying the phenotypic differences between tail types, we used isobaric tags for relative and absolute quantification (iTRAQ) combined with multi-dimensional liquid chromatography tandem-mass spectrometry (LC-MS/MS) technology to detect candidate proteins. We then subjected these to a database search and identified the DEPs.

Spatiotemporal regulation of store-operated calcium entry in cancer metastasis.

The store-operated calcium (Ca2+) entry (SOCE) is the Ca2+ entry mechanism used by cells to replenish depleted Ca2+ store. The dysregulation of SOCE has been reported in metastatic cancer. It is believed that SOCE promotes migration and invasion by remodeling the actin cytoskeleton and cell adhesion dynamics.

Dynamics of a disinhibitory prefrontal microcircuit in controlling social competition.

Social competition plays a pivotal role in determining individuals' social status. While the dorsomedial prefrontal cortex (dmPFC) is essential in regulating social competition, it remains unclear how information is processed within its local networks. Here, by applying optogenetic and chemogenetic manipulations in a dominance tube test, we reveal that, in accordance with pyramidal (PYR) neuron activation, excitation of the vasoactive intestinal polypeptide (VIP) or inhibition of the parvalbumin (PV) interneurons induces winning.