Exploring the mechanism of contact-dependent cell-cell communication on chemosensitivity based on single-cell high-throughput drug screening platform.

High-throughput drug screening (HTDS) has significantly reduced the time and cost of new drug development. Nonetheless, contact-dependent cell-cell communication (CDCCC) may impact the chemosensitivity of tumour cells. There is a pressing need for low-cost single-cell HTDS platforms, alongside a deep comprehension of the mechanisms by which CDCCC affects drug efficacy, to fully unveil the efficacy of anticancer drugs. In this study, we develop a microfluidic chip for single-cell HTDS and evaluate the molecular mechanisms impacted by CDCCC using quantitative mass spectrometry-based proteomics. The chip achieves high-quality drug mixing and single-cell capture, with single-cell drug screening results on the chip showing consistency with those on the 96-well plates under varying concentration gradients. Through quantitative proteomic analysis, we deduce that the absence of CDCCC in single tumour cells can enhance their chemoresistance potential, but simultaneously subject them to stronger proliferation inhibition. Additionally, pathway enrichment analysis suggests that CDCCC could impact several signalling pathways in tumour single cells that regulate vital biological processes such as tumour proliferation, adhesion, and invasion. These results offer valuable insights into the potential connection between CDCCC and the chemosensitivity of tumour cells. This research paves the way for the development of single-cell HTDC platforms and holds the promise of advancing tumour personalized treatment strategies.

Bioactive compounds and biological functions of medicinal plant-derived extracellular vesicles.

Extracellular vesicles (EVs) are tiny lipid bilayer-enclosed membrane particles released from a variety of cell types into the surrounding environment. These EVs have massive participated in cell-to-cell communication and interspecies communication. In recent years, plant-derived extracellular vesicles (PDEVs) and "exosome-like" EVs populations found in distinct plants have attracted widespread attention. Especially, research on medicinal plant-derived extracellular vesicles (MPDEVs) are increasing, which are considered a kind of promising natural compound. This review summarizes current knowledge on MPDEVs in terms of bioactive compounds, including small RNA, protein, lipid, and metabolite, have been found on the surface and/or in the lumen of MPDEVs. Moreover, both in vitro and in vivo experiments have shown that MPDEVs exert broad biomedical functions, such as anti-inflammatory, anticancer, antioxidant, modulate microbiota, etc. MPDEVs may be a better substitute than animal-derived extracellular vesicles (ADEVs) because of safety and biocompatibility in the future.

Adherens junctions as molecular regulators of emergent tissue mechanics.

Tissue and organ development during embryogenesis relies on the collective and coordinated action of many cells. Recent studies have revealed that tissue material properties, including transitions between fluid and solid tissue states, are controlled in space and time to shape embryonic structures and regulate cell behaviours. Although the collective cellular flows that sculpt tissues are guided by tissue-level physical changes, these ultimately emerge from cellular-level and subcellular-level molecular mechanisms. Adherens junctions are key subcellular structures, built from clusters of classical cadherin receptors. They mediate physical interactions between cells and connect biochemical signalling to the physical characteristics of cell contacts, hence playing a fundamental role in tissue morphogenesis. In this Review, we take advantage of the results of recent, quantitative measurements of tissue mechanics to relate the molecular and cellular characteristics of adherens junctions, including adhesion strength, tension and dynamics, to the emergent physical state of embryonic tissues. We focus on systems in which cell-cell interactions are the primary contributor to morphogenesis, without significant contribution from cell-matrix interactions. We suggest that emergent tissue mechanics is an important direction for future research, bridging cell biology, developmental biology and mechanobiology to provide a holistic understanding of morphogenesis in health and disease.

Jiawei Buzhong Yiqi decoction ameliorates polycystic ovary syndrome via oocyte-granulosa cell communication.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei Buzhong Yiqi Decoction (JWBZYQ), from records of FuqingzhuNvke, is a classical formula for treating obese women related infertility. JWBZYQ has been shown to be effective in treating polycystic ovary syndrome (PCOS) in both clinical studies and practical practice, with the pharmacological mechanism remaining unknown. AIM OF THE STUDY: To explore the potential therapeutic effects and mechanistic insights of JWBZYQ in PCOS. MATERIALS AND METHODS: An overweight PCOS rat model was established via testosterone propionate (TP) injection and 45% high-fat diet (HFD). Then they were categorized into five distinct groups: Control group, Model group, low-dose of JWBZYQ (JWBZYQ1) group, high-dose of JWBZYQ (JWBZYQ2) group, and metformin (Met) group. Body weight, estrous cycle, and sex hormone levels were observed. Hematoxylin-Eosin staining was employed to investigate the histological characteristics of the ovaries. To identify the pathways that changed significantly, transcriptome analysis was performed. The protein and mRNA levels of key molecules in ovarian zona pellucida (ZP) organization, transzonal projections (TZPs) assembly, steroid hormone receptors, and steroidogenesis were assessed using phalloidin staining, immunohistochemistry, Western blot, and polymerase chain reaction. RESULTS: RNA-seq analysis demonstrated that regulation of hormone secretion, cilium assembly, cell projection assembly, and ZP production may all have crucial impact on the etiology of PCOS and therapeutic effect of JWBZYQ. In particular, PCOS rats exhibited elevated expressions of ZP1-3, which can be reversed by JWBZYQ2 particularly. Simultaneously, TZPs assembly was totally disrupted in PCOS rats, evidenced by the phalloidin staining, upregulated calcium-/calmodulin-dependent protein kinase II beta (CaMKIIß), and deficient p-CaMKIIß, myosin X (MYO10), proline-rich tyrosine kinase 2 (PTK2), and Fascin. Nonetheless, JWBZYQ or metformin treatment revived the disturbance, repairing the oocyte-granulosa cell communication, regulating steroidogenesis in PCOS rats. In this way, JWBZYQ and metformin exerted remarkable effects in alleviating altered ovarian morphology and function in PCOS rats, with JWBZYQ2 revealing the best effect. CONCLUSIONS: JWBZYQ restored the altered ovarian morphology and function by regulating the oocyte-granulosa cell communication, which was related with ZP organization and TZPs assembly in the ovary.

Plant-Derived Exosome-Like Nanovesicles: Current Progress and Prospects.

Exosomes are small extracellular vesicles, ranging in size from 30-150nm, which can be derived from various types of cells. In recent years, mammalian-derived exosomes have been extensively studied and found to play a crucial role in regulating intercellular communication, thereby influencing the development and progression of numerous diseases. Traditional Chinese medicine has employed plant-based remedies for thousands of years, and an increasing body of evidence suggests that plant-derived exosome-like nanovesicles (PELNs) share similarities with mammalian-derived exosomes in terms of their structure and function. In this review, we provide an overview of recent advances in the study of PELNs and their potential implications for human health. Specifically, we summarize the roles of PELNs in respiratory, digestive, circulatory, and other diseases. Furthermore, we have extensively investigated the potential shortcomings and challenges in current research regarding the mechanism of action, safety, administration routes, isolation and extraction methods, characterization and identification techniques, as well as drug-loading capabilities. Based on these considerations, we propose recommendations for future research directions. Overall, our review highlights the potential of PELNs as a promising area of research, with broad implications for the treatment of human diseases. We anticipate continued interest in this area and hope that our summary of recent findings will stimulate further exploration into the implications of PELNs for human health.

Extracellular vesicles as a novel mediator of interkingdom communication.

Extracellular vesicles (EVs) are nanosized lipid bilayer-delimited particles secreted from almost all types of cells including bacteria, mammals and plants, and are presumed to be mediators of intercellular communication. Bacterial extracellular vesicles (BEVs) are nanoparticles with diverse diameters, ranging from 20 to 400 nm. BEVs are composed of soluble microbial metabolites, including nucleic acid, proteins, lipoglycans, and short-chain fatty acids (SCFAs). In addition, EVs may contain quorum sensing peptides that are endowed with the ability to protect bacteria against bacteriophages, form and maintain bacterial communities, and modulate the host immune system. BEVs are potentially promising therapeutic modalities for use in vaccine development, cancer immunotherapy regimens, and drug delivery cargos. Plant-derived EVs (PEVs), such as EVs derived from herbal medicines, can be absorbed by the gut microbiota and influence the composition and homeostasis of gut microbiota. This review highlights the roles of BEVs and PEVs in bacterial and plant physiology and discusses crosstalk among gut bacteria, host metabolism and herbal medicine. In summary, EVs represent crucial communication messengers in the gut microbiota, with potential therapeutic value in the delivery of herbal medicines.

SD-RLK28 positively regulates pollen hydration on stigmas as a PCP-Bß receptor in Arabidopsis thaliana.

Pollen hydration on dry stigmas is strictly regulated by pollen-stigma interactions in Brassicaceae. Although several related molecular events have been described, the molecular mechanism underlying pollen hydration remains elusive. Multiple B-class pollen coat proteins (PCP-Bs) are involved in pollen hydration. Here, by analyzing the interactions of two PCP-Bs with three Arabidopsis thaliana stigmas strongly expressing S-domain receptor kinase (SD-RLK), we determined that SD-RLK28 directly interacts with PCP-Bß. We investigated pollen hydration, pollen germination, pollen tube growth, and stigma receptivity in the sd-rlk28 and pcp-bß mutants. PCP-Bß acts in the pollen to regulate pollen hydration on stigmas. Loss of SD-RLK28 had no effect on pollen viability, and sd-rlk28 plants had normal life cycles without obvious defects. However, pollen hydration on sd-rlk28 stigmas was impaired and pollen tube growth in sd-rlk28 pistils was delayed. The defect in pollen hydration on sd-rlk28 stigmas was independent of changes in reactive oxygen species levels in stigmas. These results indicate that SD-RLK28 functions in the stigma as a PCP-Bß receptor to positively regulate pollen hydration on dry stigmas.

Novel Insights into the Physiology of Nutrient Sensing and Gut-Brain Communication in Surgical and Experimental Obesity Therapy.

Despite standardized surgical technique and peri-operative care, metabolic outcomes of bariatric surgery are not uniform. Adaptive changes in brain function may play a crucial role in achieving optimal postbariatric weight loss. This review follows the anatomic-physiologic structure of the postbariatric nutrient-gut-brain communication chain through its key stations and provides a concise summary of recent findings in bariatric physiology, with a special focus on the composition of the intestinal milieu, intestinal nutrient sensing, vagal nerve-mediated gastrointestinal satiation signals, circulating hormones and nutrients, as well as descending neural signals from the forebrain. The results of interventional studies using brain or vagal nerve stimulation to induce weight loss are also summarized. Ultimately, suggestions are made for future diagnostic and therapeutic research for the treatment of obesity.

The evolution of early hominin food production and sharing.

How did humans evolve from individualistic to collective foraging with sex differences in production and widespread sharing of plant and animal foods? While current evolutionary scenarios focus on meat, cooking, or grandparental subsidies, considerations of the economics of foraging for extracted plant foods (e.g., roots, tubers), inferred to be important for early hominins (∼6 to 2.5 mya), suggest that early hominins shared such foods with offspring and others. Here, we present a conceptual and mathematical model of early hominin food production and sharing, prior to the emergence of frequent hunting, cooking, and increased lifespan. We hypothesize that extracted plant foods were vulnerable to theft, and that male mate guarding protected females from food theft. We identify conditions favoring extractive foraging and food sharing across mating systems (i.e., monogamy, polygyny, promiscuity), and we assess which system maximizes female fitness with changes in the profitability of extractive foraging. Females extract foods and share them with males only when: i) extracting rather than collecting plant foods pays off energetically; and ii) males guard females. Males extract foods when they are sufficiently high in value, but share with females only under promiscuous mating and/or no mate guarding. These results suggest that if early hominins had mating systems with pair-bonds (monogamous or polygynous), then food sharing by adult females with unrelated adult males occurred before hunting, cooking, and extensive grandparenting. Such cooperation may have enabled early hominins to expand into more open, seasonal habitats, and provided a foundation for the subsequent evolution of human life histories.

Targeting tumor-derived exosome-mediated premetastatic niche formation: The metastasis-preventive value of traditional Chinese medicine.

Tumor-derived exosome (TDE)-mediated premetastatic niche (PMN) formation is a potential mechanism underlying the organotropic metastasis of primary tumors. Traditional Chinese medicine (TCM) has shown considerable success in preventing and treating tumor metastasis. However, the underlying mechanisms remain elusive. In this review, we discussed PMN formation from the perspectives of TDE biogenesis, cargo sorting, and TDE recipient cell alterations, which are critical for metastatic outgrowth. We also reviewed the metastasis-preventive effects of TCM, which act by targeting the physicochemical materials and functional mediators of TDE biogenesis, regulating the cargo sorting machinery and secretory molecules in TDEs, and targeting the TDE-recipient cells involved in PMN formation.

Extracellular vesicles: A new communication paradigm of complement in neurological diseases.

The complement system is crucial to the innate immune system. It has the function of destroying pathogens by activating the classical, alternative, and lectin pathways. The complement system is important in nervous system diseases such as cerebrovascular and neurodegenerative diseases. Activation of the complement system involves a series of intercellular signaling and cascade reactions. However, research on the source and transport mechanisms of the complement system in neurological diseases is still in its infancy. Studies have increasingly found that extracellular vesicles (EVs), a classic intercellular communication paradigm, may play a role in complement signaling disorders. Here, we systematically review the EV-mediated activation of complement pathways in different neurological diseases. We also discuss the prospect of EVs as future immunotherapy targets.

Inhibiting leukocyte-endothelial cell interactions by Chinese medicine Tongxinluo capsule alleviates no-reflow after arterial recanalization in ischemic stroke.

AIMS: Despite successful vascular recanalization in stroke, one-fourth of patients have an unfavorable outcome due to no-reflow. The pathogenesis of no-reflow is fully unclear, and therapeutic strategies are lacking. Upon traditional Chinese medicine, Tongxinluo capsule (TXL) is a potential therapeutic agent for no-reflow. Thus, this study is aimed to investigate the pathogenesis of no-reflow in stroke, and whether TXL could alleviate no-reflow as well as its potential mechanisms of action. METHODS: Mice were orally administered with TXL (3.0 g/kg/d) after transient middle cerebral artery occlusion. We examined the following parameters: neurological function, no-reflow, leukocyte-endothelial cell interactions, HE staining, leukocyte subtypes, adhesion molecules, and chemokines. RESULTS: Our results showed stroke caused neurological deficits, neuron death, and no-reflow. Adherent and aggregated leukocytes obstructed microvessels as well as leukocyte infiltration in ischemic brain. Leukocyte subtypes changed after stroke mainly including neutrophils, lymphocytes, regulatory T cells, suppressor T cells, helper T type 1 (Th1) cells, Th2 cells, B cells, macrophages, natural killer cells, and dendritic cells. Stroke resulted in upregulated expression of adhesion molecules (P-selectin, E-selectin, and ICAM-1) and chemokines (CC-chemokine ligand (CCL)-2, CCL-3, CCL-4, CCL-5, and chemokine C-X-C ligand 1 (CXCL-1)). Notably, TXL improved neurological deficits, protected neurons, alleviated no-reflow and leukocyte-endothelial cell interactions, regulated multiple leukocyte subtypes, and inhibited the expression of various inflammatory mediators. CONCLUSION: Leukocyte-endothelial cell interactions mediated by multiple inflammatory factors are an important cause of no-reflow in stroke. Accordingly, TXL could alleviate no-reflow via suppressing the interactions through modulating various leukocyte subtypes and inhibiting the expression of multiple inflammatory mediators.

Role of Lipids in Regulation of Neuroglial Interactions.

Lipids comprise an extremely heterogeneous group of compounds that perform a wide variety of biological functions. Traditional view of lipids as important structural components of the cell and compounds playing a trophic role is currently being supplemented by information on the possible participation of lipids in signaling, not only intracellular, but also intercellular. The review article discusses current data on the role of lipids and their metabolites formed in glial cells (astrocytes, oligodendrocytes, microglia) in communication of these cells with neurons. In addition to metabolic transformations of lipids in each type of glial cells, special attention is paid to the lipid signal molecules (phosphatidic acid, arachidonic acid and its metabolites, cholesterol, etc.) and the possibility of their participation in realization of synaptic plasticity, as well as in other possible mechanisms associated with neuroplasticity. All these new data can significantly expand our knowledge about the regulatory functions of lipids in neuroglial relationships.

Peptide signaling in anther development and pollen-stigma interactions.

Polypeptides play irreplaceable roles in cell-cell communication by binding to receptor-like kinases. Various types of peptide-receptor-like kinase-mediated signaling have been identified in anther development and male-female interactions in flowering plants. Here, we provide a comprehensive summary of the biological functions and signaling pathways of peptides and receptors involved in anther development, self-incompatibility, pollen tube growth and pollen tube guidance.

Chloroplast redox state changes mark cell-to-cell signaling in the hypersensitive response.

Hypersensitive response (HR)-conferred resistance is associated with induction of programmed cell death and pathogen spread restriction in its proximity. The exact role of chloroplastic reactive oxygen species and its link with salicylic acid (SA) signaling in HR remain unexplained. To unravel this, we performed a detailed spatiotemporal analysis of chloroplast redox response in palisade mesophyll and upper epidermis to potato virus Y (PVY) infection in a resistant potato genotype and its transgenic counterpart with impaired SA accumulation and compromised resistance. Besides the cells close to the cell death zone, we detected individual cells with oxidized chloroplasts further from the cell death zone. These are rare in SA-deficient plants, suggesting their role in signaling for resistance. We confirmed that chloroplast redox changes play important roles in signaling for resistance, as blocking chloroplast redox changes affected spatial responses at the transcriptional level. Through spatiotemporal study of stromule induction after PVY infection, we show that stromules are induced by cell death and also as a response to PVY multiplication at the front of infection. Overall induction of stromules is attenuated in SA-deficient plants.

Profiling of Secreted Proteins in Serum-Containing Media Using BONCAT and Pulsed SILAC.

Secreted proteins play pivotal roles in signal transduction and cell-to-cell communication. Despite increasing interest in secretome analysis over the past decade, most studies on this topic have utilized serum-free medium (SFM). However, fetal bovine serum (FBS) is the most widely used serum supplement for cell culture, and secretome analysis using serum-containing medium (SCM) is important to identify proteins secreted under realistic conditions and to understand their physiological roles. In this chapter, we describe a simple and robust protocol based on bioorthogonal non-canonical amino acid tagging (BONCAT) and pulsed stable isotope labeling by amino acids in cell culture (pSILAC), for identification and quantitation of the cell secretome in SCM. In this protocol, the secretome of SFM is compared with that of SCM to confirm the effect of FBS. Additionally, for mass spectrometric data processing, we provide parameters that increase true positives and decrease both false positives and false negatives.

A invenção de um setting on-line para atendimento psicológico remoto / The invention of an online environment for remote psychological care / La invención de un entorno en línea para la atención psicológica remota

Com o advento da covid-19, foi declarado estado de emergência de saúde pública e decretadas medidas de isolamento e distanciamento social para conter a propagação da doença. O Conselho Federal de Psicologia, considerando a importância do acolhimento seguro durante a pandemia, publicou a Resolução CFP nº 4/2020, permitindo que serviços psicológicos aconteçam de maneira remota. O presente estudo visa, através do Método da Cartografia, apresentar a construção de um setting on-line para intervenções grupais e os desafios na oferta de acolhimento e atendimento remoto. Foram ofertados grupos terapêuticos, por meio da plataforma Google Meet, para estudantes da Universidade Federal Rural do Rio de Janeiro. Um diário de bordo foi produzido para acompanhar as forças que atravessavam e constituíam o território e a experiência grupal remota. Compreendemos que o território-espaço-grupal-on-line era composto pelo espaço virtual em que nos reuníamos, pelos espaços individuais de cada integrante e pelas forças que os atravessavam. Observamos que nem sempre os participantes dispunham de um lugar privado, mas estiveram presentes no encontro com câmeras e áudios abertos e/ou fechados e/ou através do chat da videochamada. A participação no grupo funcionou como alternativa no momento de distanciamento social, sendo uma possibilidade para o atendimento psicológico em situações de dificuldade de encontros presenciais; entretanto, se mostrou dificultada em diversos momentos, pela falta de equipamentos adequados e instabilidade na internet, fatores que interferiram nas reuniões e impactaram na possibilidade de falar e escutar o que era desejado.(AU)

With the advent of COVID-19, a state of public health was declared, and measures of isolation and social distance to contain the spread of the disease was decreed. The Federal Council of Psychology, considering the importance of safe reception during the pandemic, published CFP Resolution No. 4/2020, allowing psychological services to happen remotely. This study narrates, via the Cartography Method, the experience of inventing an Online Setting for group reception. Therapeutic groups were offered, via Google Meet Platform, to students at the Federal Rural University of Rio de Janeiro. A logbook was produced to accompany the forces that crossed and constituted the territory and the remote group experience. We understand that the territoryspace-group-online was composed by the virtual-space that we gathered, by the individualspaces of each member and by the forces that crossed them. We observed that the participants did not always have a private place, but they were present at the meeting with open and/or closed cameras and audio and/or through the video call chat. Participation in the group worked as an alternative at the time of social distancing, being a possibility for psychological care in situations of difficulty in face-to-face meetings, however, it proved to be difficult at various times, due to the lack of adequate equipment and instability on the internet, factors that interfered in meetings and impacted the possibility of speaking and listening to what was desired.(AU)

La llegada de la COVID-19 produjo un estado de emergencia de salud pública, en el que se decretaron medidas de confinamiento y distanciamiento físico para contener la propagación de la enfermedad. El Consejo Federal de Psicología, considerando la importancia de la acogida segura durante la pandemia, publicó la Resolución CFP nº 4/2020, por la que se permite la atención psicológica remota. Este estudio tiene por objetivo presentar, mediante el método de la Cartografía, la elaboración de un escenario en línea para la intervención grupal y los desafíos en la oferta de acogida y atención remota. Grupos terapéuticos se ofrecieron, en la plataforma Google Meet, a estudiantes de la Universidad Federal Rural de Río de Janeiro. Se elaboró un diario para acompañar a las fuerzas que atravesaron y constituyeron el territorio y la experiencia remota del grupo. Entendemos que el territorio-espacio-grupo-en línea estaba compuesto por el espacio-virtual que reunimos, por los espacios individuales de cada integrante y por las fuerzas que los atravesaban. Observamos que los participantes no siempre tenían un lugar privado y que estaban presentes en la reunión con cámaras y audio abiertos y/o cerrados y/o por el chat de la videollamada. La participación en el grupo funcionó como una alternativa en el momento del distanciamiento físico y revela ser una posibilidad de atención psicológica en situaciones de dificultad en los encuentros presenciales, sin embargo, se mostró difícil en varios momentos, ya sea por la falta de medios adecuados o por inestabilidad en Internet, factores que interferían en las reuniones e impactaban en la posibilidad de hablar y escuchar lo que se deseaba.(AU)

Exosomes as Novel Delivery Systems for Application in Traditional Chinese Medicine.

Exosomes, as gifts of nature derived from various cell types with a size range from ~40 to 160 nm in diameter, have gained attention recently. They are composed of a lipid membrane bilayer structure containing different constituents, such as surface ligands and receptors, from the parental cells. Originating from a variety of sources, exosomes have the ability to participate in a diverse range of biological processes, including the regulation of cellular communication. On account of their ideal native structure and characteristics, exosomes are taken into account as drug delivery systems (DDSs). They can provide profound effects on conveying therapeutic agents with great advantages, including specific targeting, high biocompatibility, and non-toxicity. Further, they can also be considered to ameliorate natural compounds, the main constituents of traditional Chinese medicine (TCM), which are usually ignored due to the complexity of their structures, poor stability, and unclear mechanisms of action. This review summarizes the classification of exosomes as well as the research progress on exosome-based DDSs for the treatment of different diseases in TCM. Furthermore, this review discusses the advantages and challenges faced by exosomes to contribute to their further investigation and application.

Exceptional Properties of Lepidium sativum L. Extract and Its Impact on Cell Viability, Ros Production, Steroidogenesis, and Intracellular Communication in Mice Leydig Cells In Vitro.

The prevalence of reproductive dysfunction in males has risen in the last few years, and alternative therapies are gradually gaining in popularity. Our in vitro study aimed to evaluate the potential impact of Lepidium sativum L. on mice TM3 Leydig cells, concerning basal parameters such as cell viability, cell membrane integrity, and lysosomal activity, after 24 h and 48 h exposure. Moreover, reactive oxygens species generation, sex-steroid hormone secretion, and intercellular communication were quantified. In the present study, the microgreen extract from Lepidium was rich in ferulic acid, 4-OH benzoic acid, and resveratrol, with a significant antioxidant activity. The results showed that lower experimental doses (62.5-250 µg/mL) could positively affect the observed parameters, with significant differences at 250 µg/mL after 24 h and 48 h, respectively. Potential risks could be associated with higher concentrations, starting at 500 µg/mL, 1000 µg/mL, and 2000 µg/mL of Lepidium. Nevertheless, biochemical quantification indicated a significant antioxidant potential and a rich content of biologically active molecules at the applied doses, and time determined the intracellular response of the cultured model.

A developmental switch between electrical and neuropeptide communication in the ventromedial hypothalamus.

Dissecting neural connectivity patterns within local brain regions is an essential step to understanding the function of the brain.1 Neural microcircuits in brain regions, such as the neocortex and the hippocampus, have been extensively studied.2 By contrast, the microcircuit in the hypothalamus remains largely uncharacterized. The hypothalamus is crucial for animals' survival and reproduction.3 Knowledge of how different hypothalamic nuclei coordinate with each other and outside brain regions for hypothalamus-related functions has been significantly advanced.4-9 Although there are limited studies on the neural microcircuit in the lateral hypothalamus (LHA)10,11 and the suprachiasmatic nucleus (SCN),12,13 the patterns of neural microcircuits in most of the given hypothalamic nuclei remain largely unknown. This study applied combinatory approaches to address the local neural circuit pattern in the ventromedial hypothalamus (VMH) and other hypothalamic nuclei. We discovered a unique neural circuit design in the VMH. Neurons in the VMH were electrically coupled at the early postnatal stage like ones in the neocortex.14 However, unlike neocortical neurons,14,15 they developed very few chemical synapses after the disappearance of electrical synapses. Instead, VMH neurons communicated with neuropeptides. The similar scarceness of synaptic connectivity found in other hypothalamic nuclei further indicated that the lack of synaptic connections is a unique feature for local neural circuits in most adult hypothalamic nuclei. Thus, our findings provide a solid synaptic basis at the cellular level to understand hypothalamic functions better.