Mainstream medicine commonly categorizes acupuncture as “alternative and complementary,” a designation that reflects conceptual gaps in existing treatment classification systems. Integrating complementary medicine into the mainstream medical system requires a conceptual adjustment. Here, I propose a mechanism-based 5R classification—Removing, Repairing, Replacing, Replenishing, Regulating—to systematically categorize therapies. Based on this classification, acupuncture and its related interventions fall under functional regulation therapy. This framework offers a unified, functional perspective that facilitates the integration of complementary medicine into mainstream medical taxonomy.

In the dynamic landscape of scientific research, imaging core facilities are vital hubs propelling collaboration and innovation at the technology development and dissemination frontier. Here, we present a collaborative effort led by Global BioImaging (GBI), introducing international recommendations geared towards elevating the careers of Imaging Scientists in core facilities. Despite the critical role of Imaging Scientists in modern research ecosystems, challenges persist in recognising their value, aligning performance metrics and providing avenues for career progression and job security. The challenges encompass a mismatch between classic academic career paths and service-oriented roles, resulting in a lack of understanding regarding the value and impact of Imaging Scientists and core facilities and how to evaluate them properly. They further include challenges around sustainability, dedicated training opportunities and the recruitment and retention of talent. Structured across these interrelated sections, the recommendations within this publication aim to propose globally applicable solutions to navigate these challenges. These recommendations apply equally to colleagues working in other core facilities and research institutions through which access to technologies is facilitated and supported. This publication emphasises the pivotal role of Imaging Scientists in advancing research programs and presents a blueprint for fostering their career progression within institutions all around the world.

Peer review is an important part of the scientific process, but traditional peer review at journals is coming under increased scrutiny for its inefficiency and lack of transparency. As preprints become more widely used and accepted, they raise the possibility of rethinking the peer-review process. Preprints are enabling new forms of peer review that have the potential to be more thorough, inclusive, and collegial than traditional journal peer review, and to thus fundamentally shift the culture of peer review toward constructive collaboration. In this Consensus View, we make a call to action to stakeholders in the community to accelerate the growing momentum of preprint sharing and provide recommendations to empower researchers to provide open and constructive peer review for preprints.

The evolution of behavior seems inconsistent with the deep homology of neuromodulatory signaling. G protein coupled receptors (GPCRs) evolved slowly from a common ancestor through a process involving gene duplication, neofunctionalization, and loss. Neuropeptides co-evolved with their receptors and exhibit many conserved functions. Furthermore, brain areas are highly conserved with suggestions of deep anatomical homology between arthropods and vertebrates. Yet, behavior evolved more rapidly; even members of the same genus or species can differ in heritable behavior. The solution to the paradox involves changes in the compartmentalization, or subfunctionalization, of neuromodulation; neurons shift their expression of GPCRs and the content of monoamines and neuropeptides. Furthermore, parallel evolution of neuromodulatory signaling systems suggests a route for repeated evolution of similar behaviors.

Mammalian development takes place inside the maternal uterus, creating technological constraints that make difficult the study of embryogenesis in live developing embryos. A central challenge for understanding the role of metabolism in mammalian development is discriminating placental and uterine-regulated signals from embryo-intrinsic processes independent of maternal influence, a process that until now has remained inseparable during gastrulation and organogenesis1–3. Ex utero culture systems allowing continuous growth of embryos during pre-gastrulation to organogenesis4,5 offer a promising solution to this challenge. Here, we present optimized ex utero culture platforms that support faithful development of mouse embryos from gastrulation (embryonic day 6.5/7.5) through the fetal period (embryonic day \~12.5) and harnessed these platforms for dissecting metabolic transitions in vivo during embryogenesis independently of uterus and placenta. We characterized the metabolome of in utero and ex utero whole embryos, fetal organs and culture medium between embryonic days E6.5 and E12.5 by liquid chromatography mass-spectrometry (LC-MS) metabolomics, isotope tracing, and single cell transcriptomics. These datasets present a comprehensive overview of the dynamic embryonic metabolism during gastrulation and organogenesis in utero and ex utero. This analysis revealed that the midgestational metabolic switch occurring at E10.5-E11.5 is faithfully recapitulated ex utero, indicating that this transition is intrinsically programmed in embryonic tissues and does not require direct maternal or placental cues. Notably, oxygen availability modulated the extent of this transition, but elevated oxygen was insufficient to induce it prematurely, demonstrating that the switch is developmentally timed and only partially environmental-responsive. We further harnessed the ex utero platform for identifying and perturbing a mitochondrial redox shift at E7.5-E8.5 that is critical for developmental progress after gastrulation. These findings uncover the remarkable metabolic plasticity of the mammalian embryo, demonstrating its capacity to sustain growth independently of maternal inputs from the establishment of the body plan through the onset of the fetal period. Moreover, they highlight the use of long-term ex utero culture as a unique framework for dissecting the mechanisms that shape embryogenesis under physiological and experimentally perturbed conditions, while functionally uncoupling embryonic programs from maternal and placental influences.

Maintaining physiological homeostasis requires a complex interplay among endocrine organs, peripheral tissues, and distributed neuroendocrine control circuits, all of which are coupled through feedback loops that operate over minutes to hours. Although many physiological needs are broadcast through hormones, metabolites, and other chemical compounds circulating in the bloodstream, we rarely observe more than a few of these messengers together and at high cadence during behavior. To address this, we developed a minimally disruptive workflow to measure the free fraction of hundreds of amines and small peptides at a 7.5-minute cadence for \~8 hrs in freely moving mice using chronic jugular microdialysis implants and chemical isotope labeling Liquid Chromatography-Mass Spectrometry. Single-compound profiles behave according to known physiology, such as purine turnover correlating with movement, delayed histamine/5-HIAA changes, and coordinated amino-acid dynamics. Our multiplexed measures enable high-dimensional analyses that uncover properties of the underlying dynamics. For example, systems-level analyses show that 10 dimensions explain over 70% of the variance in hormone/metabolite covariation, consistent with a low rank description of the physiological state space, with projections aligned to locomotion state transitions. Our work opens avenues for the discovery of hormonal dynamics, compound interactions, and their effects on behavior.

Novel approaches to bio-imaging and automated computational image processing allow the design of truly quantitative studies in developmental biology. Cell behavior, cell fate decisions, cell interactions during tissue morphogenesis, and gene expression dynamics can be analyzed in vivo for entire complex organisms and throughout embryonic development. We review state-of-the-art technology for live imaging, focusing on fluorescence light microscopy techniques for system-level investigations of animal development and discuss computational approaches to image segmentation, cell tracking, automated data annotation, and biophysical modeling. We argue that the substantial increase in data complexity and size requires sophisticated new strategies to data analysis to exploit the enormous potential of these new resources.

Neuronal cell types are the nodes of neural circuits that determine the flow of information within the brain. Neuronal morphology, especially the shape of the axonal arbor, provides an essential descriptor of cell type and reveals how individual neurons route their output across the brain. Despite the importance of morphology, few projection neurons in the mouse brain have been reconstructed in their entirety. Here we present a robust and efficient platform for imaging and reconstructing complete neuronal morphologies, including axonal arbors that span substantial portions of the brain. We used this platform to reconstruct more than 1,000 projection neurons in the motor cortex, thalamus, subiculum, and hypothalamus. Together, the reconstructed neurons constitute more than 85 meters of axonal length and are available in a searchable online database. Axonal shapes revealed previously unknown subtypes of projection neurons and suggest organizational principles of long-range connectivity.

Many animals use coordinated limb movements to interact with and navigate through the environment. To investigate circuit mechanisms underlying locomotor behavior, we used serial-section electron microscopy (EM) to map synaptic connectivity within a neuronal network that controls limb movements. We present a synapse-resolution EM dataset containing the ventral nerve cord (VNC) of an adult female Drosophila melanogaster. To generate this dataset, we developed GridTape, a technology that combines automated serial-section collection with automated high-throughput transmission EM. Using this dataset, we reconstructed 507 motor neurons, including all those that control the legs and wings. We show that a specific class of leg sensory neurons directly synapse onto the largest-caliber motor neuron axons on both sides of the body, representing a unique feedback pathway for fast limb control. We provide open access to the dataset and reconstructions registered to a standard atlas to permit matching of cells between EM and light microscopy data. We also provide GridTape instrumentation designs and software to make large-scale EM data acquisition more accessible and affordable to the scientific community.

One of the central problems in neuroscience is reconstructing synaptic connectivity in neural circuits. Synapses onto a neuron can be probed by sequentially stimulating potentially pre-synaptic neurons while monitoring the membrane voltage of the post-synaptic neuron. Reconstructing a large neural circuit using such a "brute force" approach is rather time-consuming and inefficient because the connectivity in neural circuits is sparse. Instead, we propose to measure a post-synaptic neuron's voltage while stimulating sequentially random subsets of multiple potentially pre-synaptic neurons. To reconstruct these synaptic connections from the recorded voltage we apply a decoding algorithm recently developed for compressive sensing. Compared to the brute force approach, our method promises significant time savings that grow with the size of the circuit. We use computer simulations to find optimal stimulation parameters and explore the feasibility of our reconstruction method under realistic experimental conditions including noise and non-linear synaptic integration. Multineuronal stimulation allows reconstructing synaptic connectivity just from the spiking activity of post-synaptic neurons, even when sub-threshold voltage is unavailable. By using calcium indicators, voltage-sensitive dyes, or multi-electrode arrays one could monitor activity of multiple postsynaptic neurons simultaneously, thus mapping their synaptic inputs in parallel, potentially reconstructing a complete neural circuit.