UNASSIGNED: Osteocytes are the main stress-sensing cells in bone. The substances secreted by osteocytes under mechanical loading play a crucial role in maintaining body homeostasis. Osteocytes have recently been found to release exosomes into the circulation, but whether they are affected by mechanical loading or participate in the regulation of systemic homeostasis remains unclear.
UNASSIGNED: We used a tail-suspension model to achieve mechanical unloading on osteocytes. Osteocyte-specific CD63 reporter mice were used for osteocyte exosome tracing. Exosome detection and inhibitor treatment were performed to confirm the effect of mechanical loading on exosome secretion by osteocytes. Co-culture, GW4869 and exosome treatment were used to investigate the biological functions of osteocyte-derived exosomes on brown adipose tissue (BAT) and primary brown adipocytes. Osteocyte-specific Dicer KO mice were used to screen for loading-sensitive miRNAs. Dual luciferase assay was performed to validate the selected target gene.
UNASSIGNED: Firstly, we found the thermogenic activity was increased in BAT of mice subjected to tail suspension, which is due to the effect of unloaded bone on circulating exosomes. Further, we showed that the secretion of exosomes from osteocytes is regulated by mechanical loading, and osteocyte-derived exosomes can reach BAT and affect thermogenic activity. More importantly, we confirmed the effect of osteocyte exosomes on BAT both in vivo and in vitro. Finally, we discovered that let-7e-5p contained in exosomes is under regulation of mechanical loading and regulates thermogenic activity of BAT by targeting Ppargc1a.
UNASSIGNED: Exosomes derived from osteocytes are loading-sensitive, and play a vital role in regulation on BAT, suggesting that regulation of exosomes secretion can restore homeostasis.
UNASSIGNED: This study provides a biological rationale for using osteocyte exosomes as potential agents to modulate BAT and even whole-body homeostasis. It also provides a new pathological basis and a new treatment approach for mechanical unloading conditions such as spaceflight.

Bats are important reservoirs and spreaders of pathogens. Giardia duodenalis is a globally important protozoan that infects humans and other mammals with considerable public health burden, particularly on the child development. Based on genetic variation and host specificity, G. duodenalis is categorized into eight genotypes/assemblages A-H. Assemblages A and B are widespread globally and are associated with human and animal disease. There is evidence of Giardia in the bat feces from diverse geographic regions, but the G. duodenalis assemblages are unknown, which is a key point for the One Health view. Here, we successfully amplified the BG/GDH/DIS3/HCMP2/HCMP3 targets of G. duodenalis from five bat species captured in the Brazilian Amazon biome revealing the presence of zoonotic G. duodenalis assemblages A and B in the feces of these flying mammals. Our study reveals that bats may play a role in transmission of zoonotic G. duodenalis, at least in this biome.

Obesity, a global pandemic, poses a major threat to healthcare systems worldwide. Adipose tissue, the energy-storing organ during excessive energy intake, functions as a thermoregulator, interacting with other tissues to regulate systemic metabolism. Specifically, brown adipose tissue (BAT) is positively associated with an increased resistance to obesity, due to its thermogenic function in the presence of uncoupled protein 1 (UCP1). Recently, studies on climate change and the influence of environmental pollutants on energy homeostasis and obesity have drawn increasing attention. The reciprocal relationship between increasing adiposity and increasing temperatures results in reduced adaptive thermogenesis, decreased physical activity, and increased carbon footprint production. In addition, the impact of climate change makes obese individuals more prone to developing type 2 diabetes mellitus (T2DM). An impaired response to heat stress, compromised vasodilation, and sweating increase the risk of diabetes-related comorbidities. This comprehensive review provides information about the effects of climate change on obesity and adipose tissue, the risk of T2DM development, and insights into the environmental pollutants causing adipose tissue dysfunction and obesity. The effects of altered dietary patterns on adiposity and adaptation strategies to mitigate the detrimental effects of climate change are also discussed.

Heavy metal residues in natural ecosystems have emerged as a significant global environmental problem requiring urgent resolution. Because these elements are non-biodegradable, organisms can accumulate excessive levels of heavy metal elements into their tissues. Previous studies suggest that prolonged exposure to heavy metal enrichment poses comprehensive toxicity to various organs in vertebrates. However, few studies have focused on elucidating the molecular mechanism underlying the hepatotoxic effects of heavy metal enrichment in Chiroptera. In this study, 10 Hipposideros armiger individuals were dissected from Yingde City (YD, relatively pollution-free) and Chunwan City (CW, excessive heavy metals emission). Environmental samples were also obtained. To investigate the mechanism of heavy metal toxicity in bat livers, we employed a combination of multi-omics, pathology, and molecular biology methods. Our results revealed significant enrichment of Cd and Pb in the bat livers and food sources in the CW group (P<0.05). Furthermore, prolonged accumulation of heavy metals disrupted hepatic transcription profiles associated with the solute carriers family, the ribosome pathway, ATP usage, and heat shock proteins. Excessive heavy metal enrichment also altered the relative abundance of typical gut microbe taxa significantly (P<0.05), inhibiting tight-junction protein expression. We observed a significant decrease in the levels of superoxide dismutase, glutathione peroxidase, and glutathione (P<0.05), along with elevated reactive oxygen species (ROS) density and malondialdehyde content following excessive heavy metal enrichment. Additionally, hepatic fat accumulation and inflammation injuries were present under conditions of excessive heavy metal enrichment, while the contents of metabolism biomarkers significantly decreased (P<0.05). Consequently, prolonged heavy metal enrichment can induce hepatotoxicity by disturbing the microbes-gut-liver axis and hepatic transcription modes, leading to a decrease in overall metabolic activity in bats. Our study offers strategies for biodiversity conservation and highlights the importance of addressing environmental pollution to raise public awareness.

Bats, notable as the only flying mammals, serve as natural reservoir hosts for various highly pathogenic viruses in humans (e.g., SARS-CoV and Ebola virus). Furthermore, bats exhibit an unparalleled longevity among mammals relative to their size, particularly the Myotis bats, which can live up to 40 years. However, the mechanisms underlying these distinctive traits remain incompletely understood. In our prior research, we demonstrated that bats exhibit dampened STING-interferon activation, potentially conferring upon them the capacity to mitigate virus- or aging-induced inflammation. To substantiate this hypothesis, we established the first in vivo bat-mouse model for aging studies by integrating Myotis davidii bat STING ( MdSTING) into the mouse genome. We monitored the genotypes of these mice and performed a longitudinal comparative transcriptomic analysis on MdSTING and wild-type mice over a 3-year aging process. Blood transcriptomic analysis indicated a reduction in aging-related inflammation in female MdSTING mice, as evidenced by significantly lower levels of pro-inflammatory cytokines and chemokines, immunopathology, and neutrophil recruitment in aged female MdSTING mice compared to aged wild-type mice in vivo. These results indicated that MdSTING knock-in attenuates the aging-related inflammatory response and may also improve the healthspan in mice in a sex-dependent manner. Although the underlying mechanism awaits further study, this research has critical implications for bat longevity research, potentially contributing to our comprehension of healthy aging in humans.
蝙蝠作为唯一能够飞行的哺乳动物，是各种对人类具有高致病性的病毒的天然宿主（如SARS-CoV和埃博拉病毒）。此外，相对于其体型，蝙蝠展现出了哺乳动物中引人瞩目的长寿特性，尤其是大鼠耳蝙蝠，其寿命可长达40年。然而，这些独特特征背后的机制尚未完全揭开。在先前的研究中，我们证明了蝙蝠表现出弱化的STING-干扰素激活，这可能赋予它们减轻病毒或衰老引起的炎症的能力。为了证实这一假设，我们将大卫鼠耳蝠（ Myotis davidii）STING（ MdSTING）整合到小鼠基因组中，建立了用于衰老研究的第一个蝙蝠-小鼠模型。我们监测了这些小鼠的基因型，并在为期3年的自然衰老过程中对 MdSTING小鼠和野生型小鼠进行了纵向比较转录组学分析。血液转录组学分析显示，与老龄野生型小鼠相比，老龄雌性 MdSTING小鼠在体内显示出衰老相关炎症的降低，表现为明显较低水平的促炎细胞因子和趋化因子、免疫病理学以及衰老中后期的中性粒细胞聚集。这些结果表明， MdSTING敲入会减轻与衰老相关的炎症反应，并且可能以性别相关的方式改善小鼠的健康寿命。尽管具体机制仍有待进一步研究，但这项研究对蝙蝠长寿研究具有重要意义，可能有助于我们理解人类健康衰老的过程。.

Adipose tissue is a crucial metabolic organ in the human body. It stores and exerts distinct physiological functions in different body regions. Fat not only serves as a cushion and insulator but also stores energy and conveys endocrine signals within the body. There is a growing recognition that adipose tissue is an organ that is misunderstood and underestimated in contribution to human health and disease progression by regulating its size and functionality. In mammals, the adipose tissue reservoir consists of three functionally distinct types of fat: white adipose tissue (WAT), brown adipose tissue (BAT), and beige or inducible brown adipose tissue (iWAT), which exhibits thermogenic capabilities intermediate between the other two. Fat in different depots exhibits considerable differences in origin, characteristics, and functions. They vary not only in adipocyte lineage, properties, thermogenesis, and endocrine functions but also in their immunological functions. In a recent study published in Nature Metabolism, Zhang et al. investigated the role of JunB in the thermogenic capacity of adipocytes and its significance in obesity and metabolic disorders. The study revealed that JunB expression in BAT coexists with both low and high thermogenic adipocytes, indicating a fundamental feature of heterogeneity and plasticity within BAT. In summary, this article demonstrates that research targeting JunB holds promise for improving diet-induced obesity and insulin resistance, offering new avenues for treating metabolic disorders.

OBJECTIVE: In the last decade, an increasing trend towards a supposedly healthier vegan diet could be observed. However, recently, more cases of allergic reactions to plants and plant-based products such as meat-substitution products, which are often prepared with legumes, were reported. Here, we provide the current knowledge on legume allergen sources and the respective single allergens. We answer the question of which legumes beside the well-known food allergen sources peanut and soybean should be considered for diagnostic and therapeutic measures.
RESULTS: These \"non-priority\" legumes, including beans, pea, lentils, chickpea, lupine, cowpea, pigeon pea, and fenugreek, are potentially new important allergen sources, causing mild-to-severe allergic reactions. Severe reactions have been described particularly for peas and lupine. An interesting aspect is the connection between anaphylactic reactions and exercise (food-dependent exercise-induced anaphylaxis), which has only recently been highlighted for legumes such as soybean, lentils and chickpea. Most allergic reactions derive from IgE cross-reactions to homologous proteins, for example between peanut and lupine, which is of particular importance for peanut-allergic individuals ignorant to these cross-reactions. From our findings we conclude that there is a need for large-scale studies that are geographically distinctive because most studies are case reports, and geographic differences of allergic diseases towards these legumes have already been discovered for well-known \"Big 9\" allergen sources such as peanut and soybean. Furthermore, the review illustrates the need for a better molecular diagnostic for these emerging non-priority allergen sources to evaluate IgE cross-reactivities to known allergens and identify true allergic reactions.

Torpor is widespread among bats presumably because most species are small, and torpor greatly reduces their high mass-specific resting energy expenditure, especially in the cold. Torpor has not been recorded in any bat species larger than 50 g, yet in theory could be beneficial even in the world\'s largest bats (flying-foxes; Pteropus spp.) that are exposed to adverse environmental conditions causing energy bottlenecks. We used temperature telemetry to measure body temperature in wild-living adult male grey-headed flying-foxes (P. poliocephalus; 799 g) during winter in southern Australia. We found that all individuals used torpor while day-roosting, with minimum body temperature reaching 27°C. Torpor was recorded following a period of cool, wet and windy weather, and on a day with the coldest maximum air temperature, suggesting it is an adaptation to reduce energy expenditure during periods of increased thermoregulatory costs and depleted body energy stores. A capacity for torpor among flying-foxes has implications for understanding their distribution, behavioural ecology and life history. Furthermore, our discovery increases the body mass of bats known to use torpor by more than tenfold and extends the documented use of this energy-saving strategy under wild conditions to all bat superfamilies, with implications for the evolutionary maintenance of torpor among bats and other mammals.

With the successful control of rabies transmitted by dogs in Brazil, wild animals have played a relevant epidemiological role in the transmission of rabies virus (RABV). Bats, non-human primates and wild canines are the main wild animals that transmit RABV in the country. It is worth highlighting the possibility of synanthropic action of these species, when they become adapted to urban areas, causing infections in domestic animals and eventually in humans. This work aimed to evaluate the circulation of RABV in the Pedra Branca Forest, an Atlantic Forest area, located in the state of Rio de Janeiro, Southeast Brazil. Saliva and blood samples were obtained from 60 individuals of eight species of bats, captured with mist nets, and 13 individuals of callitrichid primates, captured with tomahawk traps. Saliva samples were subjected to Reverse Transcription Polymerase Chain Reaction (RT-PCR), targeting the RABV N gene, with all samples being negative. Blood samples of all animals were submitted to the Rapid Fluorescent Focus Inhibition Test (RFFIT) to detect neutralizing antibodies (Ab) for RABV. Six bat samples (8%) were seropositive for RABV with antibody titers greater than or equal to 0.1 IU/mL. The detection of Ab but not viral RNA indicates exposure rather than current RABV transmission in the analyzed populations. The results presented here reinforce the importance of serological studies in wildlife to access RABV circulation in a region.

Bats are the natural reservoir hosts for SARS-related coronavirus (SARSr-CoV) and other highly pathogenic microorganisms. Therefore, it is conceivable that an individual bat may harbor multiple microbes. However, there is limited knowledge on the overall co-circulation of microorganisms in bats. Here, we conducted a 16-year monitoring of bat viruses in south and central China and identified 238 SARSr-CoV positive samples across nine bat species from ten provinces or administrative districts. Among these, 76 individual samples were selected for further metagenomics analysis. We found a complex microenvironment characterized by the general co-circulation of microbes from two different sources: mammal-associated viruses or environment-associated microbes. The later includes commensal bacteria, enterobacteria-related phages, and insect or fungal viruses of food origin. Results showed that 25% (19/76) of the samples contained at least one another mammal-associated virus, notably alphacoronaviruses (13/76) such as AlphaCoV/YN2012, HKU2-related CoV and AlphaCoV/Rf-HuB2013, along with viruses from other families. Notably, we observed three viruses co-circulating within a single bat, comprising two coronavirus species and one picornavirus. Our analysis also revealed the potential presence of pathogenic bacteria or fungi in bats. Furthermore, we obtained 25 viral genomes from the 76 bat SARSr-CoV positive samples, some of which formed new evolutionary lineages. Collectively, our study reveals the complex microenvironment of bat microbiome, facilitating deeper investigations into their pathogenic potential and the likelihood of cross-species transmission.