School of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China # These authors contributed equally to this work. Email: andrewxiao@bupt.edu.cn;liuliqing@ibp.ac.cn;huj@ibp.ac.cn; feisun@ibp.ac.cn; yangge@ucas.edu.cn;xutao@ibp.ac.cn ABSTRACT Recent advances in 2D large - scale and 3D volume electron microscopy have stimulated the rapid development of nanoscale functional analysis at the tissue and organ levels. To meet the requirements of characterizing intracellular organelle s and their interactions within defined cellular cohorts at tissue level, we have developed DeepOrganelle. It adopts a lightweighted Mask2Former frameworks as a universal segmentor and is capable of segmenting and extracting organelles within different cell types, performing statistical quantitative analysis, as well as visualizing and quantifying the spatial distribution of organelle morphologies and interactions across different cell types at tissue scales. Using DeepOrganelle, we systemically perform cross - scale quantification of membrane contact sites( MCSs) dynamics across the progression of the seminiferous epithelial cycle, covering 12 distinct developmental stages and 24 statuses of germ cells . Noticeably, it discovers a waved pattern of mitochondria(Mito) - endoplasmic reticulum(ER) contact with a significant increase specifically at Stage X pachytene preceding the transition to diplotene, which aligns well with a newly reported experiment that mitochondrial metabolic proteins like PDHA2 are essential for this transition by maintaining ATP supply for double - strand break (DSB) repair.

The significant morphological and distributional variability among subcellular components poses a long-standing challenge for learning-based organelle segmentation models, significantly increasing the risk of biased feature learning. Existing methods often rely on single mapping relationships, overlooking feature diversity and thereby inducing biased training. Although the Segment Anything Model (SAM) provides rich feature representations, its application to subcellular scenarios is hindered by two key challenges: (1) The variability in subcellular morphology and distribution creates gaps in the label space, leading the model to learn spurious or biased features. (2) SAM focuses on global contextual understanding and often ignores fine-grained spatial details, making it challenging to capture subtle structural alterations and cope with skewed data distributions. To address these challenges, we introduce ScSAM, a method that enhances feature robustness by fusing pre-trained SAM with Masked Autoencoder (MAE)-guided cellular prior knowledge to alleviate training bias from data imbalance. Specifically, we design a feature alignment and fusion module to align pre-trained embeddings to the same feature space and efficiently combine different representations. Moreover, we present a cosine similarity matrix-based class prompt encoder to activate class-specific features to recognize subcellular categories. Extensive experiments on diverse subcellular image datasets demonstrate that ScSAM outperforms state-of-the-art methods.

The colonization of Mars presents extraordinary challenges, including radiation exposure, low atmospheric pressure, and toxic regolith. Recent advancements in synthetic biology and genetic engineering offer unprecedented opportunities to address these obstacles by utilizing terrestrial extremophiles and engineered organisms. This paper examines the potential for creating symbiotic relationships between terrestrial microbes and hypothetical Martian life forms, should they exist, to support a sustainable human presence on Mars. Inspired by natural examples of endosymbiosis, such as mitochondria and chloroplasts, we propose methods to engineer life forms capable of enduring Martian conditions. Key components include experimental designs, laboratory simulations, and bioengineering approaches essential to this endeavor. The ethical, political, and technological challenges of introducing engineered life to Mars are critically evaluated, with an emphasis on international collaboration and robust planetary protection policies. This research underscores engineered symbiosis as a transformative strategy for enabling life to adapt and thrive on Mars while advancing humanity's aspirations for interplanetary habitation and exploration. By addressing these challenges, this work highlights a path toward sustainable life on Mars, reflecting both scientific ingenuity and ethical stewardship.

Automatic prediction of fluorescently labeled organelles from label-free transmitted light input images is an important, yet difficult task. The traditional way to obtain fluorescence images is related to performing biochemical labeling which is time-consuming and costly. Therefore, an automatic algorithm to perform the task based on the label-free transmitted light microscopy could be strongly beneficial. The importance of the task motivated researchers from the France-BioImaging to organize the LightMyCells challenge where the goal is to propose an algorithm that automatically predicts the fluorescently labeled nucleus, mitochondria, tubulin, and actin, based on the input consisting of bright field, phase contrast, or differential interference contrast microscopic images. In this work, we present the contribution of the AGHSSO team based on a carefully prepared and trained encoder-decoder deep neural network that achieves a considerable score in the challenge, being placed among the best-performing teams.

Online learning has soared in popularity in the educational landscape of COVID-19 and carries the benefits of increased flexibility and access to far-away training resources. However, it also restricts communication between peers and teachers, limits physical interactions and confines learning to the computer screen and keyboard. In this project, we designed a novel way to engage students in collaborative online learning by using haptic-enabled tangible robots, Cellulo. We built a library which connects two robots remotely for a learning activity based around the structure of a biological cell. To discover how separate modes of haptic feedback might differentially affect collaboration, two modes of haptic force-feedback were implemented (haptic co-location and haptic consensus). With a case study, we found that the haptic co-location mode seemed to stimulate collectivist behaviour to a greater extent than the haptic consensus mode, which was associated with individualism and less interaction. While the haptic co-location mode seemed to encourage information pooling, participants using the haptic consensus mode tended to focus more on technical co-ordination. This work introduces a novel system that can provide interesting insights on how to integrate haptic feedback into collaborative remote learning activities in future.

The analysis of dynamic organelles remains a formidable challenge, though key to understanding biological processes. We introduce Nellie, an automated and unbiased pipeline for segmentation, tracking, and feature extraction of diverse intracellular structures. Nellie adapts to image metadata, eliminating user input. Nellie's preprocessing pipeline enhances structural contrast on multiple intracellular scales allowing for robust hierarchical segmentation of sub-organellar regions. Internal motion capture markers are generated and tracked via a radius-adaptive pattern matching scheme, and used as guides for sub-voxel flow interpolation. Nellie extracts a plethora of features at multiple hierarchical levels for deep and customizable analysis. Nellie features a Napari-based GUI that allows for code-free operation and visualization, while its modular open-source codebase invites customization by experienced users. We demonstrate Nellie's wide variety of use cases with two examples: unmixing multiple organelles from a single channel using feature-based classification and training an unsupervised graph autoencoder on mitochondrial multi-mesh graphs to quantify latent space embedding changes following ionomycin treatment.

Virtually all cells use energy and ion-specific membrane pumps to maintain large transmembrane gradients of Na$^+$, K$^+$, Cl$^-$, Mg$^{++}$, and Ca$^{++}$. Although they consume up to 1/3 of a cell's energy budget, the corresponding evolutionary benefit of transmembrane ion gradients remain unclear. Here, we propose that ion gradients enable a dynamic and versatile biological system that acquires, analyzes, and responds to environmental information. We hypothesize environmental signals are transmitted into the cell by ion fluxes along pre-existing gradients through gated ion-specific membrane channels. The consequent changes of cytoplasmic ion concentration can generate a local response and orchestrate global or regional responses through wire-like ion fluxes along pre-existing and self-assembling cytoskeleton to engage the endoplasmic reticulum, mitochondria, and nucleus. Here, we frame our hypothesis through a quasi-physical (Cell-Reservoir) model that treats intra-cellular ion-based information dynamics as a sub-cellular process permitting spatiotemporally resolved cellular response that is also capable of learning complex nonlinear dynamical cellular behavior. We demonstrate the proposed ion dynamics permits rapid dissemination of response to information extrinsic perturbations that is consistent with experimental observations.

Volume electron microscopy is the method of choice for the in-situ interrogation of cellular ultrastructure at the nanometer scale. Recent technical advances have led to a rapid increase in large raw image datasets that require computational strategies for segmentation and spatial analysis. In this protocol, we describe a practical and annotation-efficient pipeline for organelle-specific segmentation, spatial analysis, and visualization of large volume electron microscopy datasets using freely available, user-friendly software tools that can be run on a single standard workstation. We specifically target researchers in the life sciences with limited computational expertise, who face the following tasks within their volume electron microscopy projects: i) How to generate 3D segmentation labels for different types of cell organelles while minimizing manual annotation efforts, ii) how to analyze the spatial interactions between organelle instances, and iii) how to best visualize the 3D segmentation results. To meet these demands we give detailed guidelines for choosing the most efficient segmentation tools for the specific cell organelle. We furthermore provide easily executable components for spatial analysis and 3D rendering and bridge compatibility issues between freely available open-source tools, such that others can replicate our full pipeline starting from a raw dataset up to the final plots and rendered images. We believe that our detailed description can serve as a valuable reference for similar projects requiring special strategies for single- or multiple organelle analysis which can be achieved with computational resources commonly available to single-user setups.

If you follow me, you've seen I'm fascinated with GPT-3 both as a tool for productivity and as a tool for information retrieval through natural questions. You've also seen that GPT-3 often provides correct answers to a question, but sometimes it does not and it can even be misleading or confusing because its answer appears confident despite being wrong. In some cases, but not always, when it cannot find a reasonable completion (i.e. it "doesn't know" the answer) it tells you so, or it just doesn't provide any answer. I showed you that factual accuracy can be improved by fine-tuning the model, or more easily, by few-shot learning. But it isn't easy to decide what information to use in these procedures, let alone how to apply it.

Author Summary Recently, quantitative-phase imaging (QPI) has demonstrated the ability to elucidate novel parameters of cellular physiology and metabolism without the need for fluorescent staining. Here, we apply label-free, low photo-toxicity QPI to yeast cells in order to identify lipid droplets (LDs), an important organelle with key implications in human health and biofuel development. Because QPI yields low specificity, we explore the use of modern machine learning methods to rapidly identify intracellular LDs with high discriminatory power and accuracy. In recent years, machine learning has demonstrated exceptional abilities to recognize and segment objects in biomedical imaging, remote sensing, and other areas. Trained machine learning classifiers can be combined with QPI within high-throughput analysis pipelines, allowing for efficient and accurate identification and quantification of cellular components.