Immune regulation of the gut-brain axis and lung-brain axis involved in ischemic stroke.

Local ischemia often causes a series of inflammatory reactions when both brain immune cells and the peripheral immune response are activated. In the human body, the gut and lung are regarded as the key reactional targets that are initiated by brain ischemic attacks. Mucosal microorganisms play an important role in immune regulation and metabolism and affect blood-brain barrier permeability. In addition to the relationship between peripheral organs and central areas and the intestine and lung also interact among each other. Here, we review the molecular and cellular immune mechanisms involved in the pathways of inflammation across the gut-brain axis and lung-brain axis. We found that abnormal intestinal flora, the intestinal microenvironment, lung infection, chronic diseases, and mechanical ventilation can worsen the outcome of ischemic stroke. This review also introduces the influence of the brain on the gut and lungs after stroke, highlighting the bidirectional feedback effect among the gut, lungs, and brain.

Fluorescence determination of the total amount of tetracyclines by a flavonol-based supramolecular sensor.

Tetracyclines (TCs) are a group of broad-spectrum antibiotics against multiplying microorganisms yet with several adverse effects on humans. Since all types of TCs have the similar chemical skeleton and mechanism of action, quantification of total amount of TCs in the environment was of particular importance. To date, dozens of fluorescent probes have been reported for TCs detection, but only very few of them enabled detection of total TCs. In this study, we report a novel supramolecular sensor constructed by human serum albumin as the recognition moiety and a flavonol fluorophore as the indicator. Under the 370 nm UV excitation, this sensor exhibits the rapid response (5 s), acceptable sensitivity (limit of detection âˆ¼ 0.58 µM), long dynamic detection range (0-20 µM), prominent specificity, and excellent anti-interference properties for analysis of total TCs. The mechanism was carefully validated using 1H NMR, fluorescence titration experiments, molecular docking, and mass spectrometry. We expect this work can inspire more sensor design for TCs quantification.

Yiqi Jiedu decoction attenuates radiation injury of spermatogenic cells via suppressing IκBα/NF-κB pathway-induced excessive autophagy and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: The prescription of Yiqi Jiedu decoction (YQJD) originated from the classic Chinese herbal prescriptions of Danggui Buxue Decoction and Wuzi Yanzong Pill. A previous study has shown that 4 Gy irradiation induced the apoptosis of spermatocytes and revealed autophagosomes in cells exposed to radiation. YQJD decoction has the effect of preventing radiation injury. AIM OF THE STUDY: We used spermatocytes (GC-2spd cell line) to investigate the relationship between autophagy and apoptosis of spermatogenic cells after radiation, and the mechanisms of YQJD decoction. MATERIALS AND METHODS: Establish an in vitro radiation injury model by irradiating GC-2spd cells with 60Co γ-rays (4 Gy or 8 Gy). Autophagy agonists, autophagy inhibitors and YQJD were used to intervene cells. Cell apoptosis and inflammatory factors were measured. NF-κB localization was observed by immunofluorescence. Autophagy and apoptosis-related proteins and IκBα/NF-κB pathway factors were detected. RESULTS: Ionizing radiation promoted the growth of spermatogenic autophagosomes. After radiation, NF-κB was translocated to the nucleus, inflammatory factors were secreted, and IκBα/NF-κB pathway was activated, which promoted autophagy and apoptosis. YQJD decoction can inhibit the phosphorylation of IκBα/NF-κB pathway related factors, regulate the expression of Beclin-1 and Bcl-2 proteins, and inhibit the occurrence of autophagy and apoptosis of irradiated spermatocyte. CONCLUSIONS: The research results indicate that ionizing radiation can activate the IκBα/NF-κB signaling pathway in spermatocytes, promote cell autophagy and apoptosis by regulating the expression of Beclin-1 and Bcl-2 factors. The YQJD decoction inhibits the IκBα/NF-κB signaling pathway so as to regulate Beclin-1 and Bcl-2.

Vitro UPLC analysis and mass method identification, and in vivo or cellular immune anti-inflammatory function of Sanhuang Xiexin Decoction (SHXD).

ETHNOPHARMACOLOGICAL RELEVANCE: Sanhuang Xiexin Decoction (SHXD), consisting of Coptis chinensis Franch., Scutellaria baicalensis Georgi and Rheum palmatum L., is traditionally used for relieving fever, purging fire for removing toxins, eliminating phlegm and haemostasis, eliminating the wetness-evil from the upper warmer, clearing away the heat-evil and expelling superficial evils. Each of the three herbs contained in SHXD has been indicated to have anti-inflammatory effects in vivo, but its effects on rat NK-cell phenotypes remain unexplored, and the comprehensive mechanism of this compound SHXD in curing the inflammation induced by lipopolysaccharides (LPS) remains to be revealed. AIM OF THE STUDY: The study aim was to assess the effect of SHXD on LPS-induced fever and inflammation in a rat model, reduce NLRP3 activation in NK cells expressing specific cell phenotype antibodies and determine the therapeutic value of this approach in vivo. MATERIALS AND METHODS: SHXD extract was prepared and analysed by the developed ultra-performance liquid chromatography (UPLC) method for the simultaneous detection of 14 compounds. The main peaks were firstly identified on an Orbitrap via high resolution tandem mass spectrometry (MS). Then, the extract was used in the rat model of LPS-induced inflammation and fever for pharmacologically study the effects of drug treatment. Peripheral blood lymphocyte cells were isolated from the animals, including those subjected to the SHXD extract treatment, and the cell phenotype was determined prior to cell culture and after treating the cell cultures with the extract. The phenotypes of cells harvested using CD3, CD4, CD8a, CD81, CD161 and CD86 antibodies were used to verify the enhanced memory of the peripheral blood lymphocytes cells (PBMC) that were induced into nature killer (NK) cells. RESULTS: The SHXD extract was prepared, analysed and identified via quality control equipment and was observed to have pharmacological effects that reduced NLRP3 activation and fever in rats. The production of NK cells and peripheral blood lymphocytes was induced by the SHXD extract, which manifested as increased levels of CD4+, CD8a+, CD81+, CD161+ and CD86+ cells. The levels of CD3+ cells were significantly different between the model group and the drug-treated or control groups (p < 0.01) with dose independence, while the levels of CD4+ cells were not significantly different between the drug-treated and control groups, with a trend towards lower levels in the model group with dose independence. The levels of CD4+ cells was significantly different between the drug-treated group and the model groups with dose independence (p < 0.05). The levels of CD86+ cells were not significantly different between the drug-treated group and the model and control groups. The levels of CD8a + cells was significantly different between the model group and the drug and control groups (p < 0.05, dose 2.0 µg/ml), with higher levels in the drug-treated group. The levels of CD3+, CD4+, CD8a + cells in the drug treated group have dose dependence with SHXD. CONCLUSIONS: This experiment revealed that SHXD reduced NLRP3 activation in the blood of LPS-treated rats, which occurred through the activation of NK cells that expressed CD3, CD8a and CD161. SHXD may possess anti-inflammatory effect via activacting the one of major pharmacology effcet of NK cells that expressed CD3, CD8a and CD161 phenotypes expression. This result demonstrates that SHXD may possess ability to enhance the memory of peripheral blood lymphocytes and natural killer cells.

Pathogenic bacteria exploit transferrin receptor transcytosis to penetrate the blood-brain barrier.

The human blood-brain barrier (BBB) comprises a single layer of brain microvascular endothelial cells (HBMECs) protecting the brain from bloodborne pathogens. Meningitis is among the most serious diseases, but the mechanisms by which major meningitis-causing bacterial pathogens cross the BBB to reach the brain remain poorly understood. We found that Streptococcus pneumoniae, group B Streptococcus, and neonatal meningitis Escherichia coli commonly exploit a unique vesicle fusion mechanism to hitchhike on transferrin receptor (TfR) transcytosis to cross the BBB and illustrated the details of this process in human BBB model in vitro and mouse model. Toll-like receptor signals emanating from bacteria-containing vesicles (BCVs) trigger K33-linked polyubiquitination at Lys168 and Lys181 of the innate immune regulator TRAF3 and then activate the formation of a protein complex containing the guanine nucleotide exchange factor RCC2, the small GTPase RalA and exocyst subcomplex I (SC I) on BCVs. The distinct function of SEC6 in SC I, interacting directly with RalA on BCVs and the SNARE protein SNAP23 on TfR vesicles, tethers these two vesicles and initiates the fusion. Our results reveal that innate immunity triggers a unique modification of TRAF3 and the formation of the HBMEC-specific protein complex on BCVs to authenticate the precise recognition and selection of TfR vesicles to fuse with and facilitate bacterial penetration of the BBB.

Effect of robotic-assisted gait training on gait and motor function in spinal cord injury: a protocol of a systematic review with meta-analysis.

INTRODUCTION: Robotic-assisted gait training (RAGT) has been reported to be effective in rehabilitating patients with spinal cord injury (SCI). However, studies on RAGT showed different results due to a varied number of samples. Thus, summarising studies based on robotic-related factors is critical for the accurate estimation of the effects of RAGT on SCI. This work aims to search for strong evidence showing that using RAGT is effective in treating SCI and analyse the deficiencies of current studies. METHODS AND ANALYSIS: The following publication databases were electronically searched in December 2022 without restrictions on publication year: MEDLINE, Cochrane Library, Web of Science, Embase, PubMed, the Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure. Various combinations of keywords, including 'motor disorders', 'robotics', 'robotic-assisted gait training', 'Spinal Cord Injuries', 'SCI' and 'gait analysis' were used as search terms. All articles on randomised controlled trials (excluding retrospective trials) using RAGT to treat SCI that were published in English and Chinese and met the inclusion criteria were included. Outcomes included motor function, and gait parameters included those assessed by using the instrumented gait assessment, the Berg Balance Scale, the 10-m walk speed test, the 6-min walk endurance test, the functional ambulation category scale, the Walking index of SCI and the American Spinal Injury Association assessment scale. Research selection, data extraction and quality assessment were conducted independently by two reviewers to ensure that all relevant studies were free from personal bias. In addition, the Cochrane risk-of-bias assessment tool was used to assess the risk of bias. Review Manager V.5.3 software was used to produce deviation risk maps and perform paired meta-analyses. ETHICS AND DISSEMINATION: Ethics approval is not required for systematic reviews and network meta-analyses. The results will be submitted to a peer-reviewed journal or presented at a conference. PROSPERO REGISTRATION NUMBER: CRD42022319555.

Self-standing boron nitride bulks enabled by liquid metals for thermal management.

Thermally conductive materials (TCMs) are highly desirable for thermal management applications to tackle the "overheating" concerns in the electronics industry. Despite recent progress, the development of high performance TCMs integrated with an in-plane thermal conductivity (TC) higher than 50.0 W (m K)-1 and a through-plane TC greater than 10.0 W (m K)-1 is still challenging. Herein, self-standing liquid metal@boron nitride (LM@BN) bulks with ultrahigh in-plane TC and through-plane TC were reported for the first time. In the LM@BN bulks, LM could serve as a bonding and thermal linker among the oriented BN platelets, thus remarkably accelerating heat transfer across the whole system. Benefiting from the formation of a unique structure, the LM@BN bulk achieved an ultrahigh in-plane TC of 82.2 W (m K)-1 and a through-plane TC of 20.6 W (m K)-1, which were among the highest values ever reported for TCMs. Furthermore, the LM@BN bulks exhibited superior compressive and leakage-free performances, with a high compressive strength (5.2 MPa) and without any LM leakage even after being crushed. It was also demonstrated that the excellent TCs of the LM@BN bulks made them effectively cool high-power light emitting diode modules. This work opens up one promising pathway for the development of high-performance TCMs for thermal management in the electronics industry.

General requirements for the production of extracellular vesicles derived from human stem cells.

'General requirements for the production of extracellular vesicles derived from human stem cells' is the first guideline for stem cells derived extracellular vesicles in China, jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research. This standard specifies the general requirements, process requirements, packaging and labelling requirements and storage requirements for preparing extracellular vesicles derived from human stem cells, which is applicable to the research and production of extracellular vesicles derived from stem cells. It was originally released by the China Society for Cell Biology on 30 August 2022. We hope that the publication of this guideline will promote institutional establishment, acceptance and execution of proper protocols, and accelerate the international standardisation of extracellular vesicles derived from human stem cells.

Tracing the evolving dynamics and research hotspots of microbiota and immune microenvironment from the past to the new era.

Gut microbiota can regulate many physiological processes within gastrointestinal tract and other distal sites. Dysbiosis may not only influence chronic diseases like the inflammatory bowel disease (IBD), metabolic disease, tumor and its therapeutic efficacy, but also deteriorate acute injuries. This article aims to review the documents in this field and summarize the research hotspots as well as developing processes. Gut microbiota and immune microenvironment-related documents from 1976 to 2022 were obtained from the Web of Science Core Collection database. Bibliometrics was used to assess the core authors and journals, most contributive countries and affiliations together with hotspots in this field and keyword co-occurrence analysis. Data were visualized to help comprehension. Nine hundred and twelve documents about gut microbiota and immune microenvironment were retrieved, and the annual publications increased gradually. The most productive author, country, and affiliation were "Zitvogel L," USA and "UNIV TEXAS MD ANDERSON CANC CTR," respectively. FRONTIERS IN IMMUNOLOGY, CANCERS, and INTERNATIONAL JOURNAL OF MOLECULAR SCIENCE were the periodicals with most publications. Keyword co-occurrence analysis identified three clusters, including gut microbiota, inflammation, and IBD. Combined with the visualized analysis of documents and keyword co-occurrence as well as literature reading, we recognized three key topics of gut microbiota: cancer and therapy; immunity, inflammation and IBD; acute injuries and metabolic diseases. This article revealed researches on gut microbiota and immune microenvironment were growing. More attention should be given to the latest hotspots like gut microbiota, inflammation, IBD, cancer and immunotherapy, acute traumas, and metabolic diseases.IMPORTANCEGut microbiota can regulate many physiological processes within gastrointestinal tract and other distal sites. Dysbiosis may not only influence chronic diseases like inflammatory bowel disease (IBD), metabolic disease, tumor and its therapeutic efficacy, but also deteriorate acute injuries. While the application of bibliometrics in the field of gut microbiota and immune microenvironment still remains blank, which focused more on the regulation of the gut microbiota on the immune microenvironment of different kinds of diseases. Here, we intended to review and summarize the presented documents in gut microbiota and immune microenvironment field by bibliometrics. And we revealed researches on gut microbiota and immune microenvironment were growing. More attention should be given to the latest hotspots like gut microbiota, inflammation, IBD, cancer and immunotherapy, acute traumas, and metabolic diseases.

Homozygous variants in CDC23 cause female infertility characterized by oocyte maturation defects.

Oocyte maturation defects are major phenotypes resulting in female infertility. Although many genetic factors have been found to be responsible for these phenotypes, the underlying pathogenic genes and variants remain to be identified. The anaphase promoting complex or cyclosome (APC/C) is known to be essential in the metaphase-to-anaphase transition. In this study, we identified two homozygous missense variants (c.986A > G, p.Y329C and c.988C > T, p.R330C) in CDC23 that are responsible for female infertility characterized by oocyte maturation defects in three infertile individuals. CDC23 (cell division cycle 23) is one of the core subunits of the APC/C. In vitro experiments showed that the variant c.986A > G (p.Y329C) led to a decrease in CDC23 protein level and the variant c.988C > T (p.R330C) changed the localization of CDC23 in HeLa cells and mouse oocytes. In vivo studies showed that Cdc23Y329C/Y329C mice successfully mimicked the patients' phenotype by causing low expression of CDC23 and APC4 and the accumulation of securin and cyclin B1 in oocytes. AZ3146 treatment was able to rescue the phenotype. Taken together, our findings reveal the important roles of CDC23 in human oocyte maturation and provide a new genetic marker for female infertility.

Conformational Switch of the 250s Loop Enables the Efficient Transglycosylation in GH Family 77.

Amylomaltases (AMs) play important roles in glycogen and maltose metabolism. However, the molecular mechanism is elusive. Here, we investigated the conformational dynamics of the 250s loop and catalytic mechanism of Thermus aquaticus TaAM using path-metadynamics and QM/MM MD simulations. The results demonstrate that the transition of the 250s loop from an open to closed conformation promotes polysaccharide sliding, leading to the ideal positioning of the acid/base. Furthermore, the conformational dynamics can also modulate the selectivity of hydrolysis and transglycosylation. The closed conformation of the 250s loop enables the tight packing of the active site for transglycosylation, reducing the energy penalty and efficiently preventing the penetration of water into the active site. Conversely, the partially closed conformation for hydrolysis results in a loosely packed active site, destabilizing the transition state. These computational findings guide mutation experiments and enable the identification of mutants with an improved disproportionation/hydrolysis ratio. The present mechanism is in line with experimental data, highlighting the critical role of conformational dynamics in regulating the catalytic reactivity of GHs.

An adhesive peptide specifically induces microtubule condensation.

Cell function-associated biomolecular condensation has great potential in modulation of molecular activities. We develop a microtubule-trapping peptide that first self-assembles into nanoparticles and then in situ transforms into nanofibers via ligand-receptor interactions when targeted to tubulin. The nanofibers support the increased exposed targets for further adhering to microtubules and induce the self-assembly of microtubules into networks due to multivalent effects. Microtubule condensation with prolonged retention in cells for up to 24 h, which is 6 times longer than that of the non-transformable nanoparticle group, efficiently induces in vitro cell apoptosis and inhibits in vivo tumour growth. These smart transformable peptide materials for targeted protein condensation have the potential for improving retention and inducing cell apoptosis in tumour therapy.

MiR-590-3p promotes the phenotypic switching of vascular smooth muscle cells by targeting LOX.

ABSTRACT: We investigated the clinical characteristics of patients with acute aortic dissection (AAD) and miR-590-3p levels in serum, tissue, and vascular smooth muscle cells (VSMCs). The effect of miR-590-3p on the VSMC phenotype was assessed, and the regulation of lysyl oxidase (LOX) by miR-590-3p was determined. C57BL/6 mice were used to investigate the incidence of AAD and effects of miR-590-3p on AAD. MiR-590-3p levels were measured in the aortae of mice, and hematoxylin and eosin (H&E) staining and Masson staining were performed to identify the morphological features of the aorta. Comparative analysis revealed significant differences in clinical characteristics between AAD patients and healthy controls, with most patients with AAD exhibiting concomitant hypertension and nearly 50% having atherosclerosis. LOX was a direct target of miR-590-3p. LOX overexpression inhibited switching of the VSMC phenotype from contractile to synthetic, but miR-590-3p overexpression significantly reversed this change. In the mouse model, miR-590-3p upregulation increased the incidence of AAD to 93.3%, and its incidence decreased to 13.3% following miR-590-3p inhibition. H&E and Masson staining revealed that the miR-590-3p agomiR group had a greater loss of the contractile phenotype in the dissected aortic wall and an increased number of muscle fibers in the aortic wall, which contributed to thickening of the aortic wall and the formation of a false lumen in AD. miR-590-3p might be pivotal in the pathogenesis of AAD. Thus, targeting miR-590-3p or its downstream pathways could represent a therapeutic approach for AAD.

Optically pumped Milliwatt Whispering-Gallery microcavity laser.

Whispering-gallery-mode microcavity lasers possess remarkable characteristics such as high Q factors and compact geometries, making them an essential element in the evolution of microlasers. However, solid-state whispering-gallery-mode lasers have previously suffered from low output power and limited optical conversion efficiency, hindering their applications. Here, we present the achievement of milliwatt laser emissions at a wavelength of 1.06 µm from a solid-state whispering-gallery-mode laser. To accomplish this, we construct a whispering-gallery-mode microcavity (with a diameter of 30 µm) using a crystalline Nd: YAG thin film obtained through carbon-implantation enhanced etching of a Nd: YAG crystal. This microcavity laser demonstrates a maximum output power of 1.12 mW and an optical conversion efficiency of 12.4%. Moreover, our unique eccentric microcavity design enables efficient coupling of free-space pump light, facilitating integration with a waveguide. This integration allowed for single-wavelength laser emission from the waveguide, achieving an output power of 0.5 mW and an optical conversion efficiency of 6.18%. Our work opens up new possibilities for advancing solid-state whispering-gallery-mode lasers, providing a viable option for compact photonic sources.

Anatomic versus non-anatomic resection for early-stage intrahepatic cholangiocarcinoma: a propensity score matching and stabilized inverse probability of treatment weighting analysis.

BACKGROUND: Radical resection is still the most cost-effectiveness curative strategy for intrahepatic cholangiocarcinoma (ICC), but it remains controversial on the survival benefit of anatomic resection (AR). In this study, we sought to compare the oncologic outcomes between AR versus non-AR (NAR) as the primary treatment for early-stage ICC patients. METHODS: Data of ICC patients who underwent hepatectomy and staged at AJCC I were retrospectively collected from 12 hepatobiliary centers in China between Dec 2012 and Dec 2015. Propensity score matching (PSM) and stabilized inverse probability of treatment weighting (IPTW) analysis were performed to minimize the effect of potential confounders, and the perioperative and long-term outcomes between AR and NAR groups were compared. RESULTS: Two hundred seventy-eight ICC patients staged at AJCC I were eligible for this study, including 126 patients receiving AR and 152 patients receiving NAR. Compared to the NAR group, the AR group experienced more intraoperative blood loss before and after PSM or stabilized IPTW (all P > 0.05); AR group also experienced more intraoperative transfusion after stabilized IPTW (P > 0.05). In terms of disease-free survival (DFS) and overall survival (OS), no significant differences were observed between the two groups before and after PSM or stabilized IPTW (all P > 0.05). Multivariable Cox regression analyses found that AR was not an independent prognostic factor for either DFS or OS (all P > 0.05). Further analysis also showed that the survival benefit of AR was not found in any subgroup stratified by Child-Pugh grade (A or B), cirrhosis (presence or absence), tumor diameter (≤ 5 cm or > 5 cm) and pathological type (mass-forming or non-mass-forming) with all P > 0.05. CONCLUSION: Surgical approach does not influence the prognosis of patients with stage I primary ICC, and NAR might be acceptable and oncological safety.

Interpretable machine-learning model for real-time, clustered risk factor analysis of sepsis and septic death in critical care.

BACKGROUND AND OBJECTIVE: Interpretable and real-time prediction of sepsis and risk factor analysis could enable timely treatment by clinicians and improve patient outcomes. To develop an interpretable machine-learning model for the prediction and risk factor analysis of sepsis and septic death. METHODS: This is a retrospective observational cohort study based on the Medical Information Mart for Intensive Care (MIMIC-IV) dataset; 69,619 patients from the database were screened. The two outcomes include patients diagnosed with sepsis and the death of septic patients. Clinical variables from ICU admission to outcomes were analyzed: demographic data, vital signs, Glasgow Coma Scale scores, laboratory test results, and results for arterial blood gasses (ABGs). Model performance was compared using the area under the receiver operating characteristic curve (AUROC). Model interpretations were based on the Shapley additive explanations (SHAP), and the clustered analysis was based on the combination of K-means and dimensionality reduction algorithms of t-SNE and PCA. RESULTS: For the analysis of sepsis and septic death, 47,185 and 2480 patients were enrolled, respectively. The XGBoost model achieved a predictive value of area under the curve (AUC): 0.745 [0.731-0.759] for sepsis prediction and 0.8 [0.77, 0.828] for septic death prediction. The real-time prediction model was trained to predict by day and visualize the individual or combined risk factor effects on the outcomes based on SHAP values. Clustered analysis separated the two phenotypes with distinct risk factors among patients with septic death. CONCLUSION: The proposed real-time, clustered prediction model for sepsis and septic death exhibited superior performance in predicting the outcomes and visualizing the risk factors in a real-time and interpretable manner to distinguish and mitigate patient risks, thus promising immense potential in effective clinical decision making and comprehensive understanding of complex diseases such as sepsis.

Different Dissolution Molecular Pathways of Azilsartan Crystals with Different Forms Revealed by In Situ Atomic Force Microscopy.

Here, using in situ atomic force microscopy (AFM), the dissolution behaviors and dissolution molecular pathways of two azilsartan crystals, the isopropanol solvate (AZ-IPA), and form I (AZ-I), in pure water and 6-30% poly(ethylene glycol) (PEG) aqueous solutions are revealed. The dissolution behaviors of step retreat and etch pit formation are observed on the (100) faces of the two crystals, with a single step corresponding to one molecular monolayer in crystal structures. Etching rates of pits increase with PEG concentration. Furthermore, our results show that AZ-IPA dissolves by the direct detachment of molecules from the step front to solution. Such a mechanism remains even when the PEG concentration changes. However, AZ-I dissolves primarily by the surface diffusion mechanism involving molecular detachment from the step front at first and then diffusion over the terraces before desorption into solution. PEG promotes the dissolution of AZ-I crystals by favoring the molecular detachment from the step front.

Perilipin1 deficiency prompts lipolysis in lipid droplets and aggravates the pathogenesis of persistent immune activation in Drosophila.

Lipid droplets (LDs) are highly dynamic intracellular organelles, which are involved in lots of biological processes. However, the dynamic morphogenesis and functions of intracellular LDs during persistent innate immune responses remain obscure. In this study, we induce long-term systemic immune activation in Drosophila through genetic manipulation. Then, the dynamic pattern of LDs is traced in the Drosophila fat body. We find that deficiency of Plin1, a key regulator of LDs' reconfiguration, blocks LDs minimization at the initial stage of immune hyperactivation but enhances LDs breakdown at the later stage of sustained immune activation via recruiting the lipase Brummer (Bmm, homologous to human ATGL). The high wasting in LDs shortens the lifespan of flies with high-energy-cost immune hyperactivation. Therefore, these results suggest a critical function of LDs during long-term immune activation and provide a potential treatment for the resolution of persistent inflammation.