IL-24 promotes atopic dermatitis-like inflammation through driving MRSA-induced allergic responses.

Atopic dermatitis (AD) is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching. The colonization of Staphylococcus aureus (S. aureus) is correlated with the severity of the disease, but its role in AD development remains elusive. Using single-cell RNA sequencing, we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S. aureus (MRSA). Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology. Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march. Mechanistically, IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33, which in turn aggravated type 2 immunity and AD-like skin conditions. Overall, these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.

Failure mechanisms of the Li(Ni0.6Co0.2Mn0.2)O2-Li4Ti5O12 lithium-ion batteries in long-time high-rate cycle.

With the ever-growing widespread use of lithium-ion batteries in heavy machinery and daily life, the demand for improved longevity and high-rate performance is escalating. While Li4Ti5O12 (LTO) batteries excel in safety and cycling performance, their full potential for long-term, high-rate cycling still yet remains unrealized. In this paper, we present an analysis of a pouch battery with an LTO anode system that was cycled for an extended period at high rates. We compared the performance changes and internal component properties between fresh and cycled batteries. Our results reveal that, after tens of thousands of high-rate cycles, microcracks emerged on the cathode electrode material (NCM622) particles of the battery, whereas the LTO remained largely unchanged. Additionally, we observed significant electrolyte reduction, characterized the separator surface, and measured its properties. Our findings indicate that the electrolyte reactions are the primary cause of battery failure, leading to capacity fading and impedance increase. This research provides valuable insights into the failure mechanisms of lithium-ion batteries at high rates, thus contributing to the improvement of high-rate lithium-ion batteries.

RBP-J regulates homeostasis and function of circulating Ly6Clo monocytes.

Notch-RBP-J signaling plays an essential role in the maintenance of myeloid homeostasis. However, its role in monocyte cell fate decisions is not fully understood. Here, we showed that conditional deletion of transcription factor RBP-J in myeloid cells resulted in marked accumulation of blood Ly6Clo monocytes that highly expressed chemokine receptor CCR2. Bone marrow transplantation and parabiosis experiments revealed a cell-intrinsic requirement of RBP-J for controlling blood Ly6CloCCR2hi monocytes. RBP-J-deficient Ly6Clo monocytes exhibited enhanced capacity competing with wildtype counterparts in blood circulation. In accordance with alterations of circulating monocytes, RBP-J deficiency led to markedly increased population of lung tissues with Ly6Clo monocytes and CD16.2+ interstitial macrophages. Furthermore, RBP-J deficiency-associated phenotypes could be genetically corrected by further deleting Ccr2 in myeloid cells. These results demonstrate that RBP-J functions as a crucial regulator of blood Ly6Clo monocytes and thus derived lung-resident myeloid populations, at least in part through regulation of CCR2.

Sympathetic nerve-enteroendocrine L cell communication modulates GLP-1 release, brain glucose utilization, and cognitive function.

Glucose homeostasis is controlled by brain-gut communications. Yet our understanding of the neuron-gut interface in the glucoregulatory system remains incomplete. Here, we find that sympathetic nerves elevate postprandial blood glucose but restrict brain glucose utilization by repressing the release of glucagon-like peptide-1 (GLP-1) from enteroendocrine L cells. Sympathetic nerves are in close apposition with the L cells. Importantly, sympathetic denervation or intestinal deletion of the adrenergic receptor α2 (Adra2a) augments postprandial GLP-1 secretion, leading to reduced blood glucose levels and increased brain glucose uptake. Conversely, sympathetic activation shows the opposite effects. At the cellular level, adrenergic signaling suppresses calcium flux to limit GLP-1 secretion upon sugar ingestion. Consequently, abrogation of adrenergic signal results in a significant improvement in learning and memory ability. Together, our results reveal a sympathetic nerve-enteroendocrine unit in constraining GLP-1 secretion, thus providing a therapeutic nexus of mobilizing endogenous GLP-1 for glucose management and cognitive improvement.

The Sympathetic-Immune Milieu in Metabolic Health and Diseases: Insights from Pancreas, Liver, Intestine, and Adipose Tissues.

Sympathetic innervation plays a crucial role in maintaining energy balance and contributes to metabolic pathophysiology. Recent evidence has begun to uncover the innervation landscape of sympathetic projections and sheds light on their important functions in metabolic activities. Additionally, the immune system has long been studied for its essential roles in metabolic health and diseases. In this review, the aim is to provide an overview of the current research progress on the sympathetic regulation of key metabolic organs, including the pancreas, liver, intestine, and adipose tissues. In particular, efforts are made to highlight the critical roles of the peripheral nervous system and its potential interplay with immune components. Overall, it is hoped to underscore the importance of studying metabolic organs from a comprehensive and interconnected perspective, which will provide valuable insights into the complex mechanisms underlying metabolic regulation and may lead to novel therapeutic strategies for metabolic diseases.

Enhancement of pyranoanthocyanin formation in blueberry wine with non-Saccharomyces yeasts.

The development of blueberry wine provides an alternative method for maintaining the nutritional value and extending the shelf life of blueberries. However, anthocyanin loss and off-flavor compound generation during fermentation impair blueberry wine color and quality. Hydroxycinnamate decarboxylase from yeast can catalyze the conversion of hydroxycinnamic acids to vinylphenols, which later may condense with anthocyanins to form more stable vinylphenolic pyranoanthocyanins. In this study, 10 non-Saccharomyces yeasts from Daqu that showed hydroxycinnamate decarboxylase activity were screened. Among the 10 strains, Wickerhamomyces anomalus Y5 showed the highest consumption (34.59%) of the total tested phenolic acids and almost no H2S production. Furthermore, Y5 seemed to produce four vinylphenol pyranoanthocyanins (cyanidin-3-O-galactoside/glucoside-4-vinylcatechol, cyanidin-3-O-galactoside/glucoside-4-vinylsyringol, malvidin-4-vinylguaiacol, and malvidin-4-vinylcatechol) during blueberry wine fermentation, which may improve the color stability of blueberry wine. These findings provide new insights for improving the quality of blueberry wine using non-Saccharomyces yeasts.

Single-cell landscape reveals the epithelial cell-centric pro-inflammatory immune microenvironment in dry eye development.

Dry eye disease (DED) is a prevalent chronic eye disease characterized by an aberrant inflammatory response in ocular surface mucosa. The immunological alterations underlying DED remain largely unknown. In this study, we employed single-cell transcriptome sequencing of conjunctival tissue from environment-induced DED mice to investigate multicellular ecosystem and functional changes at different DED stages. Our results revealed an epithelial subtype with fibroblastic characteristics and pro-inflammatory effects emerging in the acute phase of DED. We also found that T helper (Th)1, Th17, and regulatory T cells (Treg) were the dominant clusters of differentiation (CD)4+ T-cell types involved in regulating immune responses and identified three distinct macrophage subtypes, with the CD72+CD11c+ subtype enhancing chronic inflammation. Furthermore, bulk transcriptome analysis of video display terminal-induced DED consistently suggested the presence of the pro-inflammatory epithelial subtype in human conjunctiva. Our findings have uncovered a DED-associated pro-inflammatory microenvironment in the conjunctiva, centered around epithelial cells, involving interactions with macrophages and CD4+ T cells, which deepens our understanding of ocular surface mucosal immune responses during DED progression.

Structural basis for recruitment of TASL by SLC15A4 in human endolysosomal TLR signaling.

Toll-like receptors (TLRs) are a class of proteins that play critical roles in recognizing pathogens and initiating innate immune responses. TASL, a recently identified innate immune adaptor protein for endolysosomal TLR7/8/9 signaling, is recruited by the lysosomal proton-coupled amino-acid transporter SLC15A4, and then activates IRF5, which in turn triggers the transcription of type I interferons and cytokines. Here, we report three cryo-electron microscopy (cryo-EM) structures of human SLC15A4 in the apo monomeric and dimeric state and as a TASL-bound complex. The apo forms are in an outward-facing conformation, with the dimeric form showing an extensive interface involving four cholesterol molecules. The structure of the TASL-bound complex reveals an unprecedented interaction mode with solute carriers. During the recruitment of TASL, SLC15A4 undergoes a conformational change from an outward-facing, lysosomal lumen-exposed state to an inward-facing state to form a binding pocket, allowing the N-terminal helix of TASL to be inserted into. Our findings provide insights into the molecular basis of regulatory switch involving a human solute carrier and offers an important framework for structure-guided drug discovery targeting SLC15A4-TASL-related human autoimmune diseases.

Antiviral immunity rewired for axon regeneration.

In Neuron's January 18th issue, Wang et al.1 report that activating the immune signaling IFNγ-cGAS-STING axis promotes axon regeneration in both the peripheral and central nervous systems. Their findings uncover the coordination mechanism of neural innate immune responses for axon regeneration.

Sensing and acting: Full circle in fat.

White adipose tissue (WAT) communicates with the CNS bidirectionally. In recent studies, aided by three-dimensional imaging, Wang et al. and Frei et al. have provided the organ-wide view of the afferent somatosensory network in the inguinal WAT (iWAT) and have further delineated its critical involvement in energy balance.

Assessing the Impacts of Meteorological Factors on COVID-19 Pandemic Using Generalized Estimating Equations.

Background: Meteorological factors have been proven to affect pathogens; both the transmission routes and other intermediate. Many studies have worked on assessing how those meteorological factors would influence the transmissibility of COVID-19. In this study, we used generalized estimating equations to evaluate the impact of meteorological factors on Coronavirus disease 2019 (COVID-19) by using three outcome variables, which are transmissibility, incidence rate, and the number of reported cases. Methods: In this study, the data on the daily number of new cases and deaths of COVID-19 in 30 provinces and cities nationwide were obtained from the provincial and municipal health committees, while the data from 682 conventional weather stations in the selected provinces and cities were obtained from the website of the China Meteorological Administration. We built a Susceptible-Exposed-Symptomatic-Asymptomatic-Recovered/Removed (SEIAR) model to fit the data, then we calculated the transmissibility of COVID-19 using an indicator of the effective reproduction number (Reff ). To quantify the different impacts of meteorological factors on several outcome variables including transmissibility, incidence rate, and the number of reported cases of COVID-19, we collected panel data and used generalized estimating equations. We also explored whether there is a lag effect and the different times of meteorological factors on the three outcome variables. Results: Precipitation and wind speed had a negative effect on transmissibility, incidence rate, and the number of reported cases, while humidity had a positive effect on them. The higher the temperature, the lower the transmissibility. The temperature had a lag effect on the incidence rate, while the remaining five meteorological factors had immediate and lag effects on the incidence rate and the number of reported cases. Conclusion: Meteorological factors had similar effects on incidence rate and number of reported cases, but different effects on transmissibility. Temperature, relative humidity, precipitation, sunshine hours, and wind speed had immediate and lag effects on transmissibility, but with different lag times. An increase in temperature may first cause a decrease in virus transmissibility and then lead to a decrease in incidence rate. Also, the mechanism of the role of meteorological factors in the process of transmissibility to incidence rate needs to be further explored.

Leptin receptor signaling sustains metabolic fitness of alveolar macrophages to attenuate pulmonary inflammation.

Alveolar macrophages (AMs) are critical mediators of pulmonary inflammation. Given the unique lung tissue environment, whether there exist AM-specific mechanisms that control inflammation is not known. Here, we found that among various tissue-resident macrophage populations, AMs specifically expressed Lepr, encoding receptor for a key metabolic hormone leptin. AM-intrinsic Lepr signaling attenuated pulmonary inflammation in vivo, manifested as subdued acute lung injury yet compromised host defense against Streptococcus pneumoniae infection. Lepr signaling protected AMs from necroptosis and thus constrained neutrophil recruitment and tissue damage secondary to release of proinflammatory cytokine interleukin-1α. Mechanistically, Lepr signaling sustained activation of adenosine monophosphate-activated protein kinase in a Ca2+ influx-dependent manner and rewired cellular metabolism, thus preventing excessive lipid droplet formation and overloaded metabolic stress in a lipid-rich alveolar microenvironment. In conclusion, our results defined AM-expressed Lepr as a metabolic checkpoint of pulmonary inflammation and exemplified a macrophage tissue adaptation strategy for maintenance of immune homeostasis.

Interactions between central nervous system and peripheral metabolic organs.

According to Descartes, minds and bodies are distinct kinds of "substance", and they cannot have causal interactions. However, in neuroscience, the two-way interaction between the brain and peripheral organs is an emerging field of research. Several lines of evidence highlight the importance of such interactions. For example, the peripheral metabolic systems are overwhelmingly regulated by the mind (brain), and anxiety and depression greatly affect the functioning of these systems. Also, psychological stress can cause a variety of physical symptoms, such as bone loss. Moreover, the gut microbiota appears to play a key role in neuropsychiatric and neurodegenerative diseases. Mechanistically, as the command center of the body, the brain can regulate our internal organs and glands through the autonomic nervous system and neuroendocrine system, although it is generally considered to be outside the realm of voluntary control. The autonomic nervous system itself can be further subdivided into the sympathetic and parasympathetic systems. The sympathetic division functions a bit like the accelerator pedal on a car, and the parasympathetic division functions as the brake. The high center of the autonomic nervous system and the neuroendocrine system is the hypothalamus, which contains several subnuclei that control several basic physiological functions, such as the digestion of food and regulation of body temperature. Also, numerous peripheral signals contribute to the regulation of brain functions. Gastrointestinal (GI) hormones, insulin, and leptin are transported into the brain, where they regulate innate behaviors such as feeding, and they are also involved in emotional and cognitive functions. The brain can recognize peripheral inflammatory cytokines and induce a transient syndrome called sick behavior (SB), characterized by fatigue, reduced physical and social activity, and cognitive impairment. In summary, knowledge of the biological basis of the interactions between the central nervous system and peripheral organs will promote the full understanding of how our body works and the rational treatment of disorders. Thus, we summarize current development in our understanding of five types of central-peripheral interactions, including neural control of adipose tissues, energy expenditure, bone metabolism, feeding involving the brain-gut axis and gut microbiota. These interactions are essential for maintaining vital bodily functions, which result in homeostasis, i.e., a natural balance in the body's systems.

Facile synthesis of carbon and oxygen vacancy co-modified TiNb6O17 as an anode material for lithium-ion batteries.

Titanium niobium oxides (TNOs), benefitting from their large specific capacity and Wadsley-Roth shear structure, are competitive anode materials for high-energy density and high-rate lithium-ion batteries. Herein, carbon and oxygen vacancy co-modified TiNb6O17 (A-TNO) was synthesized through a facile sol-gel reaction with subsequent heat treatment and ball-milling. Characterizations indicated that A-TNO is composed of nanosized primary particles, and the carbon content is about 0.7 wt%. The nanoparticles increase the contact area of the electrode and electrolyte and shorten the lithium-ion diffusion distance. The carbon and oxygen vacancies decrease the charge transfer resistance and enhance the Li-ion diffusion coefficient of the obtained anode material. As a result of these advantages, A-TNO exhibits excellent rate performance (208 and 177 mA h g-1 at 10C and 20C, respectively). This work reveals that A-TNO possesses good electrochemical performance and has a facile preparation process, thus A-TNO is believed to be a potential anode material for large-scale applications.

TiO2(B) nanosheets modified Li4Ti5O12microsphere anode for high-rate lithium-ion batteries.

With the increasing applications of Lithium-ion batteries in heavy equipment and engineering machinery, the requirements of rate capability are continuously growing. The high-rate performance of Li4Ti5O12(LTO) needs to be further improved. In this paper, we synthesized LTO microsphere-TiO2(B) nanosheets (LTO-TOB) composite by using a solvothermal method and subsequent calcination. LTO-TOB composite combines the merits of TiO2(B) and LTO, resulting in excellent high-rate capability (144.8, 139.3 and 124.4 mAh g-1at 20 C, 30 C and 50 C) and superior cycling stability (98.9% capability retention after 500 cycles at 5 C). Its excellent electrochemical properties root in the large surface area, high grain-boundary density and pseudocapacitive effect of LTO-TOB. This work reveals that LTO-TOB composite can be a potential anode for high power and energy density lithium-ion batteries.

An immune-sympathetic neuron communication axis guides adipose tissue browning in cancer-associated cachexia.

Cancer-associated cachexia (CAC) is a hypermetabolic syndrome characterized by unintended weight loss due to the atrophy of adipose tissue and skeletal muscle. A phenotypic switch from white to beige adipocytes, a phenomenon called browning, accelerates CAC by increasing the dissipation of energy as heat. Addressing the mechanisms of white adipose tissue (WAT) browning in CAC, we now show that cachexigenic tumors activate type 2 immunity in cachectic WAT, generating a neuroprotective environment that increases peripheral sympathetic activity. Increased sympathetic activation, in turn, results in increased neuronal catecholamine synthesis and secretion, ß-adrenergic activation of adipocytes, and induction of WAT browning. Two genetic mouse models validated this progression of events. 1) Interleukin-4 receptor deficiency impeded the alternative activation of macrophages, reduced sympathetic activity, and restrained WAT browning, and 2) reduced catecholamine synthesis in peripheral dopamine ß-hydroxylase (DBH)-deficient mice prevented cancer-induced WAT browning and adipose atrophy. Targeting the intraadipose macrophage-sympathetic neuron cross-talk represents a promising therapeutic approach to ameliorate cachexia in cancer patients.

Eosinophils regulate intra-adipose axonal plasticity.

Sympathetic innervation regulates energy balance, and the nerve density in the adipose tissues changes under various metabolic states, resulting in altered neuronal control and conferring resilience to metabolic challenges. However, the impact of the immune milieu on neuronal innervation is not known. Here, we examined the regulatory role on nerve plasticity by eosinophils and found they increased cell abundance in response to cold and produced nerve growth factor (NGF) in the white adipose tissues (WAT). Deletion of Ngf from eosinophils or depletion of eosinophils impairs cold-induced axonal outgrowth and beiging process. The spatial proximity between sympathetic nerves, IL-33-expressing stromal cells, and eosinophils was visualized in both human and mouse adipose tissues. At the cellular level, the sympathetic adrenergic signal induced calcium flux in the stromal cells and subsequent release of IL-33, which drove the up-regulation of IL-5 from group 2 innate lymphoid cells (ILC2s), leading to eosinophil accretion. We propose a feed-forward loop between sympathetic activity and type 2 immunity that coordinately enhances sympathetic innervation and promotes energy expenditure.

Neuroimmune regulation of white adipose tissues.

The white adipose tissues (WAT) are located in distinct depots throughout the body. They serve as an energy reserve, providing fatty acids for other tissues via lipolysis when needed, and function as an endocrine organ to regulate systemic metabolism. Their activities are coordinated through intercellular communications among adipocytes and other cell types such as residential and infiltrating immune cells, which are collectively under neuronal control. The adipocytes and immune subtypes including macrophages/monocytes, eosinophils, neutrophils, group 2 innate lymphoid cells (ILC2s), T and B cells, dendritic cells (DCs), and natural killer (NK) cells display cellular and functional diversity in response to the energy states and contribute to metabolic homeostasis and pathological conditions. Accumulating evidence reveals that neuronal innervations control lipid deposition and mobilization via regulating lipolysis, adipocyte size, and cellularity. Vice versa, the neuronal innervations and activity are influenced by cellular factors in the WAT. Though the literature describing adipose tissue cells is too extensive to cover in detail, we strive to highlight a selected list of neuronal and immune components in this review. The cell-to-cell communications and the perspective of neuroimmune regulation are emphasized to enlighten the potential therapeutic opportunities for treating metabolic disorders.

The Risk Monitoring of Aflatoxins and Ochratoxin A in Critical Control Point of Soy Sauce Aroma-Type Baijiu Production.

Soy sauce aroma-type baijiu-producing regions are mostly in southwest China (Guizhou and Sichuan province) with a hot and humid subtropical monsoon climate, which is conducive to the propagation of toxigenic fungi. This suggests that there is a risk of potential contamination by mycotoxins in the soy sauce aroma-type baijiu production process, which poses significant food safety risks. Few studies on the safety of mycotoxins in soy sauce aroma-type baijiu production exist. Aiming to evaluate the safety of mycotoxins in soy sauce aroma-type baijiu during its production, this study screened and analyzed mycotoxic risk at critical points throughout the production process, investigated from raw materials, daqu, alcoholic fermentative grains, crude baijiu and microbial communities in different stages of the production process. The aflatoxins (AFs) and ochratoxin A (OTA) contents in wheat, daqu, alcoholic fermentative grains and crude baijiu samples were detected by ultra-performance liquid chromatography with tandem mass spectrometry. Mycotoxins were detected in wheat, daqu and alcoholic fermentative grains. The AFs and OTA detection rates, as well as their contents in the daqu samples, were relatively higher compared to those observed in the wheat and alcoholic fermentative grains. AFs were detected in 30% of the daqu samples, while OTA was detected in 20% of the daqu samples, though the contents of both AFs and OTA were under the maximum limit of the Chinese national standard. Furthermore, the fungi contained in daqu samples were isolated and identified, and the results showed that no fungi in the separated bacterial strains were producers of mycotoxins. According to the assessment results, the safety of soy sauce aroma-type baijiu production process in terms of AFs and OTA is confirmed.