Characteristics of dissolved organic matter during the cyanobacterial degradation in Chaohu Lake, China.

The actual DOM in Chaohu Lake was used to feed cyanobacterial to explore the changes of microbial communities, fluorescence spectral characteristics and molecular composition of DOM during the degradation of cyanobacteria. It is found that cyanobacterial grow periodically depending on the concentration of nutrients with the decreasing concentration of nutrient salts. Both Bacteroidetes and Actinobacteria have strong correlation with algae growth. Bacteroidetes has a positive correlation with algae growth, relationship on the contrary, Actinobacteria has a negative relationship. The humus-like components in the four groups are similar, but the protein-like component (C3) shows periodic changes with the life process of cyanobacteria. The average molecular weight of each sample detected by Orbitrap high-resolution mass spectrometer increases slightly and the DOM increase aromaticity in the end. In this study, the molecule of Carboxyl-Rich Alicyclic Molecules (CRAM) is difficult to be done by photodegradation and biodegradation in the early periods, but some molecules of CRAM are selectively degraded by microorganisms in the final period. The growth of cyanobacterial lead to increasing the concentration of protein-like and carbohydrate-like molecule of DOM in the water. In the final stage, the molecule group of CHO disappear significantly and the molecule group of heteroatomic group increase.

Purification of dredged water by magnetic coagulation: Response surface optimization and dissolved organic matter removal characteristics.

In the present study, magnetic coagulation was used to treat dredged water and the response surface method was used to optimize process parameters. The dissolved organic matter (DOM) removal characteristics were characterized by three-dimensional fluorescence spectrometry and ultra-high resolution mass spectrometry. During the magnetic coagulation process, the suspended solids (SS) removal rate increased initially and then decreased under conditions of increasing magnetic powder dosage and stirring rate. After magnetic coagulation and precipitation for 20 min, the contents of SS, ammonia nitrogen, chemical oxygen demand, and total phosphorus in the treated dredged water met the requirements of the discharge standard (GB8978-1996, China). Three-dimensional fluorescence results showed that magnetic coagulation selectively removed fulvic acids and humic acid substances. After magnetic coagulation with precipitation for 10 min and 20 min, the total relative content of lignins, tannins, proteins, lipids, aminosugars, unsaturated hydrocarbons, condensed aromatic structures, and carbohydrates decreased by 26.3% and 39.4%, respectively. After magnetic coagulation, the distribution range of small molecule DOM shifted to the low H/C and high O/C regions. This study provides a novel perspective for studies on the removal of DOM in dredged water by magnetic coagulation. PRACTITIONER POINTS: SS and DOM removal were significantly enhanced by the use of magnetic coagulation. SS removal efficiency was affected by stirring rate and magnetic powder dosage. Magnetic coagulation selectively removed fulvic acids and humic acid substances. DOM molecule shifted to low H/C and high O/C regions after magnetic coagulation.

Adipose Component Transplantation: An Advanced Fat-Grafting Strategy for Facial Rejuvenation.

BACKGROUND: Autologous fat grafting is frequently used for volume augmentation and tissue regeneration. The uniform physical and biological characteristics of fat grafts, however, limit their optimal effects in various situations. Subjecting fat tissue to different mechanical processes results in adipose-derived products with distinct biological components and physical features. The present study describes a novel facial fat-grafting strategy, adipose component transplantation (ACT), that yields different adipose products that can be applied to specific injection sites. METHODS: All patients who underwent ACT were evaluated retrospectively. Fat tissue samples were fractionated into high-density fat, adipose matrix complex, stromal vascular fraction gel, and adipose collagen fragment, as described. Each of these fractions was processed and injected into indicated recipient sites. Additional SVF gel was cryopreserved and, if necessary, injected during the following 3 months. Patients were followed up after 1, 2, 3, and 6 months, and annually thereafter. RESULTS: From March of 2020 to September of 2021, 78 patients underwent whole face fat grafting using the ACT strategy. All operations and secondary injections of cryopreserved SVF gel were uneventful. There were no major complications, and final aesthetic results were satisfactory in 91% of patients. CONCLUSIONS: The ACT strategy allows specific adipose products to be applied to specific injection sites, as warranted. Adipose matrix complex is indicated for sufficient rigid support, high-density fat when large volumes are required, SVF gel for precise injection and cryopreservation, and ACF as mesotherapy for skin rejuvenation. The ACT strategy optimizes the biological functions and physical features of different adipose-derived products. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Adipokines-enriched adipose extract restores skin barrier and ameliorates inflammatory dysregulation in an atopic dermatitis mouse model.

BACKGROUND: Atopic dermatitis (AD) is a chronic dermatosis with high incidence worldwide characterized by skin barrier abnormalities and immune dysregulation. Conventional therapies are usually limited by side effects and high cost. Given the anti-inflammatory and repairing properties, adipokines are increasingly considered as promising therapeutic agents for dermatoses. Adipose collagen fragments (ACF), a novel adipokine-enriched product, may alleviate AD through modulating immune microenvironment and restoring skin barrier. METHODS: ACF was extracted from adipose tissue via high-speed homogenization (10000 rpm/min, 1min) and centrifugation (3000 g, 3min). Ovalbumin-induced AD female BALB/c mice (6-week-old) were intradermally injected with 0.2ml of ACF or PBS (negative control), with normal mice being set as normal control (n=6). Dermatitis severity, inflammatory metrics (epidermal thickness, infiltrated mast cells, Th-type cytokines expression), and skin barrier-related metrics (transepidermal water loss [TEWL], skin barrier-related proteins expression) were evaluated after the AD induction period (day 50). ACF-derived bioactive components were also evaluated using proteomic analysis. RESULTS: ACF-derived adipokines contained anti-inflammatory, skin barrier- and lipid biosynthesis-related components. ACF treatment decreased dermatitis severity (6.2±1.8, p<0.0001), epidermal thickness (25.7±12.8 µm, p=0.0045), infiltrated mast cells (31.3±12.4 cells/field, p=0.0475), and Th-type cytokines expression (INF-γ, TNF-α, IL-4, IL-4R, IL-13, and IL-17A; p<0.05) in AD skins. TEWL (29.8±13.8 g/m 2.h, p=0.0306) and skin barrier-related proteins expression (filaggrin: 14258±4375, p=0.0162; loricrin: 6037±1728, p=0.0010; claudin-1: 20043±6406, p=0.0420; ZO-1: 4494±1114, p=0.0134) were also improved. CONCLUSIONS: ACF improved AD in murine model by ameliorating inflammatory dysregulation and skin barrier defects (Graphical abstract, Supplementary Digital Content 1). Further validation is needed in more advanced animal models.

Therapeutic potential of adipose tissue derivatives in skin photoaging.

Photoaging, the primary cause of exogenous skin aging and predominantly caused by ultraviolet radiation, is an essential type of skin aging characterized by chronic skin inflammation. Recent studies have shown that oxidative stress, inflammation, skin barrier homeostasis, collagen denaturation and pigmentation are the main contributors to it. As a composite tissue rich in matrix and vascular components, adipose tissue derivatives have been recently gaining attention as potential therapeutic agents for various human diseases with fat-processing technology upgrades. This review analyzes both 'minimally treated' and 'nonminimally treated' fat derivatives to give an overview of the preclinical and clinical relevance of adipose tissue derivatives for antiphotoaging application, highlighting their good clinical prospects as well as discussing their safety and potential risks.

Giant coronary aneurysm of Behcet's disease with sudden syncope: a case report.

Behcet's disease(BD) is a chronic inflammatory vasculitis that rarely affects the arteries, making myocardial infarction unlikely. We report a 28-year-old patient who was admitted to our hospital with multiple sudden syncope. Cardiovascular risk factors such as hypertension (HT), diabetes and obesity were not found in her. Preoperatively, imaging examinations suggested thrombosis of the inferior and superior vena cava and right heart combined with coronary artery aneurysm. The patient was finally diagnosed with a huge coronary artery aneurysm proximal to the left anterior descending artery. Syncope is considered to be caused right ventricular outflow tract obstruction. The patient received a successful aneurysm resection and had an uneventful postoperative recovery.

Association between adiposity and facial aging: results from a Mendelian randomization study.

BACKGROUND: Skin, as a sociologically meaningful interface, has psychological implications different from other organs, particularly in the context of the global population aging. Growing evidence suggests that facial aging is associated with an increased risk of adiposity. Existing research, however, were observational, and while they may find some correlations, it is difficult to simply disentangle non-causal or reverse-causal links because these associations may be confounded or fail to accurately reflect true causative linkages. OBJECTIVES: We conducted a 2-sample Mendelian randomization (MR) study to examine the potential effect of facial aging on the risk of broad obesity and its three major adiposity indicators, including body mass index (BMI), body fat percentage (BF%) and waist circumference (WC). METHODS: Genetic instruments from IEU OpenGWAS project, one of the largest available genome-wide association studies (GWAS) for facial aging (423,999 samples) were used to investigate the relation to broad obesity (32,858 cases, 65,839 controls). Using the inverse-variance weighted (IVW) technique, single nucleotide polymorphisms (SNPs) associated with adiposity indicators (BMI (461,460 samples), BF% (454,633 samples), and WC (462,166 samples)) were investigated in relationship to facial aging. Further sensitivity analyses were performed, including Mendelian randomization-Egger (MR-Egger), weighted median estimates, and leave-one-out analysis, to evaluate the consistency of the results and related potential issues in MR studies. RESULTS: We identified strong and significant correlations between adiposity and facial aging in the 17 broad obesity-associated SNPs (IVW estimate of odds ratio OR = 1.020, 95% CI 1.010-1.029, P = 7.303e - 05), 458 BMI-associated SNPs (IVW estimate of odds ratio OR = 1.047, 95% CI 1.0357-1.058, P = 1.154e - 16),for the 395 BF%-associated SNPs (OR = 1.056, 95%CI 1.040-1.072,P = 7.617e - 12), or for the 374 WC-associated SNPs (OR = 1.072, 95% CI 1057-1.087,P = 1.229e - 23). A range of complementary methodologies have been employed to evaluate horizontal pleiotropy and related potential caveats occurring in MR research. CONCLUSIONS: Using Mendelian randomization as an alternative approach to investigate causality, we found a causal relationship between adiposity and facial aging, which was statistically strong and significant.

A Novel Cell Volume Sensor for Real-Time Analysis of Ca2+-Activated K+ Channel.

Potassium channels play a vital role in cell volume regulation. A cell volume sensor was constructed by integrating regulatory volume decrease (RVD) with quartz-crystal microbalance (QCM) for studying potassium channels and their expression. The sensor successfully monitored the K+ channel's activities during RVD by sensitive and noninvasive means. It showed that Ca2+ activated the K+ channel (KCa) and enhanced the RVD level. The inhibition of blockers on K+ channels exhibited an obvious difference in RVD level between normal and cancerous nasopharyngeal cells, suggesting that the KCa channel contributes a dominant role to the RVD function and provides an approach to identify the activation of various K+ channels.

Long-term follow-up and exploration of the mechanism of stromal vascular fraction gel in chronic wounds.

BACKGROUND: Chronic refractory wounds easily relapse and seriously affect the patients' quality of life. Previous studies have shown that stromal vascular fraction gel (SVF-gel) significantly promotes the early healing of chronic wounds; however, the mechanisms of SVF-gel function per se remain unclear, and a long-term follow-up is lacking. This study aims to explore the mechanisms of SVF-gel promoting the healing of chronic wounds and follow up the long-term efficacy of SVF-gel. METHODS: Autologous SVF-gel transplantation was performed in 20 patients with chronic wounds (from March 2016 to September 2019), and the size of the wound before and after SVF-gel transplantation was observed. The conditioned medium (CM) was harvested from SVF-gel under serum-free, serum-deprivation and 10% fetal bovine serum (FBS) microenvironment in vitro, respectively. The concentration of the growth factors in the two kinds of gel-CM was tested, and their effects on the proliferation and migration of human dermal fibroblasts (HDFs) were detected. RESULTS: All patients had 100% wound closure eventually, and the average time to complete closure was 28.3 ± 9.7 days. The time of follow-up ranged from 2 to 6 years, and there was no wound recurrence. Interestingly, the concentrations of epidermal growth factor and transforming growth factor ß1 of the CM were higher in serum-free and serum-deprivation condition than in 10% FBS microenvironment (p < 0.05). Correspondingly, the proliferation and migration ability of HDFs treated with gel-CM from serum-free condition were stronger than those treated with gel-CM from serum-deprivation (2% FBS) or 10% FBS microenvironment (p < 0.05). CONCLUSION: These results indicate that it is safe, effective, and lasting in effect to treat chronic wounds with SVF-gel and mechanisms of action that include secreting various cytokines and promoting cell proliferation and migration ability. TRIAL REGISTRATION: Chinese Clinical Trail Registry, ChiCTR2000034624. Registered 12 July 2020-Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=56058.

QCM sensor provides insight into the role of pivotal ions in cellular regulatory volume decrease.

All vertebrate cells generally self-regulate for sustaining homeostasis and cell functions. As a major regulatory mechanism, regulatory volume decrease (RVD) occurs in hypotonicity-induced cell swelling, and then shrinking by the efflux of intracellular osmolytes and water, in which the ions K+, Cl-, and Ca2+ play a key role in the RVD process. We observed that these pivotal ions could result in novel RVD behaviors under repeatedly hypotonic stimulation. However, there is a lack of valid means for assessing the effect of pivotal ions on RVD. In this work, we proposed an effective measurement process based on a quartz crystal microbalance (QCM) combined with cell function of RVD for revealing acute variations in cell volume regulation induced by the pivotal ions. A QCM sensor was implemented by adhering MCF-7 cells to a poly-l-lysine-modified gold chip and cyclic stimulation with hypotonic NaCl medium, in which a frequency shift (Δf) showed the superior feasibility of the technique in exhibiting RVD behaviors. With the increase in the number of cycles, the RVD values decreased progressively under three stimulation cycles with hypotonic NaCl alone. Compared with the first cycle, the RVD level in the second and third cycles declined by 60.7±1.7% and 82.1±1.6% (n=3), respectively; conversely, it recovered in NaCl-KCl solution, but was significantly enhanced by 52.2±0.8% in NaCl-CaCl2 solution. Moreover, the inhibition of chloride channels to block Cl- efflux also decreased the RVD level by 56.2±3.0%. The results indicate that these ions (K+, Cl-, Ca2+) are all able to affect the function of RVD, among which intracellular Cl- depletion reduced RVD during measurement, but which recovered with K+ supplement, and Ca2+ enhanced RVD due to activation of ion channels. Therefore, this work provides a comprehensive assessment of cellular behavior and offers an innovative method for gaining insight into cellular functions and mechanisms. A novel strategy was conducted by integrating a quartz crystal microbalance (QCM) with the function of cell volume regulation for analyzing the role of the pivotal ions ( K+, Cl-, Ca2+) in NaCl media on the behaviors of regulatory cell volume decrease (RVD).

CD16+ fibroblasts foster a trastuzumab-refractory microenvironment that is reversed by VAV2 inhibition.

The leukocyte Fcγ receptor (FcγR)-mediated response is important for the efficacy of therapeutic antibodies; however, little is known about the role of FcγRs in other cell types. Here we identify a subset of fibroblasts in human breast cancer that express CD16 (FcγRIII). An abundance of these cells in HER2+ breast cancer patients is associated with poor prognosis and response to trastuzumab. Functionally, upon trastuzumab stimulation, CD16+ fibroblasts reduce drug delivery by enhancing extracellular matrix stiffness. Interaction between trastuzumab and CD16 activates the intracellular SYK-VAV2-RhoA-ROCK-MLC2-MRTF-A pathway, leading to elevated contractile force and matrix production. Targeting of a Rho family guanine nucleotide exchange factor, VAV2, which is indispensable for the function of CD16 in fibroblasts rather than leukocytes, reverses desmoplasia provoked by CD16+ fibroblasts. Collectively, our study reveals a role for the fibroblast FcγR in drug resistance, and suggests that VAV2 is an attractive target to augment the effects of antibody treatments.

Case report: Congenital mitral and tricuspid valve insufficiency in a patient with Axenfeld-Rieger syndrome.

Axenfeld-Rieger syndrome (ARS) is an autosomal dominant disorder that is primarily due to disruption of the development of neural crest cells. The onset of associated symptoms in both eyes accompanied by extraocular developmental defects is referred to as ARS. Cardiac defects associated with ARS have been reported, but the extent of the cardiac defects has yet to be defined. We report a case of a 17-year-old girl with ARS with typical facial malformations and severe mitral and tricuspid valve insufficiency. The patient was diagnosed with secondary glaucoma detected on ophthalmologic examination. Echocardiography showed severe mitral and tricuspid valve insufficiency. This case provides further evidence of the association of ARS with cardiac malformations and extends the reported range of cardiac malformations in patients with ARS.

Macrophage mitochondrial fission improves cancer cell phagocytosis induced by therapeutic antibodies and is impaired by glutamine competition.

Phagocytosis is required for the optimal efficacy of many approved and promising therapeutic antibodies for various malignancies. However, the factors that determine the response to therapies that rely on phagocytosis remain largely elusive. Here, we demonstrate that mitochondrial fission in macrophages induced by multiple antibodies is essential for phagocytosis of live tumor cells. Tumor cells resistant to phagocytosis inhibit mitochondrial fission of macrophages by overexpressing glutamine-fructose-6-phosphate transaminase 2 (GFPT2), which can be targeted to improve antibody efficacy. Mechanistically, increased cytosolic calcium by mitochondrial fission abrogates the phase transition of the Wiskott-Aldrich syndrome protein (WASP)-Wiskott-Aldrich syndrome interacting protein (WIP) complex and enables protein kinase C-θ (PKC-θ) to phosphorylate WIP during phagocytosis. GFPT2-mediated excessive use of glutamine by tumor cells impairs mitochondrial fission and prevents access of PKC-θ to compartmentalized WIP in macrophages. Our data suggest that mitochondrial dynamics dictate the phase transition of the phagocytic machinery and identify GFPT2 as a potential target to improve antibody therapy.

[Molecular Signatures of Dissolved Organic Matter in the Paihe River and Its Tributaries].

Dissolved organic matter (DOM) is an abundant and critical component of aquatic ecosystems, participating in many physicochemical and biogeochemical processes. The Paihe River is the only inflow river in the Jianghuai section of "Yangtze-Huaihe water diversion" clear water gallery project; however, its DOM molecular composition information and characteristics are still unclear. In this study, the molecular characterization of DOM in the Paihe River and Guangming Dayan River was determined using Orbitrap mass spectrometry. The Pearson's correlation and principal component analysis (PCA) were used to study the relationship between molecular composition information, characteristics, and sources of DOM in two rivers. The results showed that the molecular weight and oxygen content of DOM molecules in the Paihe River were relatively low; the molecular weight, aromaticity, and unsaturation of DOM molecules in the Guangming Dayan River were relatively high. From the element composition and compound composition of the two rivers' DOM, both rivers were mainly composed of CHO-compounds, lignin, and tannins derived from land plants, which indicates that both rivers were severely affected by terrestrial input. There were high percentages of CHOS, protein, and lipid compounds of DOM in the Paihe River. According to the results of the Pearson's correlation and PCA analyses, the DOM molecules of the Paihe River were also influenced by wastewater from sewage treatment plants, urbanization processes, and microbial activity. Molecular composition information and characteristics of DOM can provide a detailed reference to improve the theoretical support for the Paihe River clear water gallery project.

Adipose-derived stem cells ameliorate atopic dermatitis by suppressing the IL-17 expression of Th17 cells in an ovalbumin-induced mouse model.

BACKGROUND: Mesenchymal stem cells (MSCs) have therapeutic potential for atopic dermatitis (AD) owing to their immunoregulatory effects. However, the underlying mechanisms associated with the therapeutic efficacy of MSCs on AD are diverse and related to both cell type and delivery method. OBJECTIVES: This study investigated the therapeutic effect and mechanisms of adipose-derived stem cells (ADSCs) on AD using an ovalbumin (OVA)-induced AD mouse model. METHODS: AD mice were subcutaneously injected with mouse ADSCs, cortisone, or PBS, and the therapeutic effects were determined by gross and histological examinations and serum IgE levels. Additionally, qPCR, RNA-sequencing analyses of skin samples and co-culture of ADSCs and Th17 cells were conducted to explore the underlying therapeutic mechanisms. RESULTS: ADSCs treatment attenuated the AD pathology, decreased the serum IgE levels, and decreased mast cells infiltration in the skin of the model mice. Moreover, tissue levels of IL-4R and Th17-relevant products (IL-17A, CCL20, and MMP12) were suppressed in the ADSC- and cortisone-treated groups. Genomics and bioinformatics analyses demonstrated significant enrichment of inflammation-related pathways in the downregulated genes of the ADSC- and cortisone-treated groups, specifically the IL-17 signaling pathway. Co-culture experiments revealed that ADSCs significantly suppressed the proliferation of Th17 cells and the expression of proinflammatory cytokines (IL-17A and RORγT). Furthermore, expression levels of PD-L1, TGF-ß, and PGE2 were significantly upregulated in co-cultured ADSCs relative to those in monocultured ADSCs. CONCLUSION: ADSCs ameliorate OVA-induced AD in mice mainly by downregulating IL-17 secretion of Th17 cells.

Stimulation of Hyphal Ramification and Sporulation in Funneliformis mosseae by Root Extracts Is Host Phosphorous Status-Dependent.

A simulation of the environment inhabited by arbuscular mycorrhizal (AM) fungi could provide clues as to how to cultivate these obligate biotrophs axenically. Host intraradical and rhizospheric environments, root extracts and exudates in particular, would be crucial for AM fungi to complete their life cycles. In this study, we analyzed and compared the effects of root exudates (RE) and root extracts (RET) of white clover (Trifolium repens) on the asymbiotic growth of the AM fungus Funneliformis mosseae in vitro, and furtherly analyzed the chemical components of different RET with the LC-MS/MS technique in order to establish an asymbiotic cultivation system for this important and hardly domesticated AM fungus. RET is superior to RE in stimulating spore germination, hyphal elongation and branching, and secondary spore formation (p < 0.05). RET-induced effects were dependent on phosphate supplement levels, and the RET obtained following the treatment with low levels of phosphorus significantly promoted hyphal growth and sporulation (p < 0.05). A few newly formed secondary spores showed limited colonization of white clover roots. The low phosphorus-induced effects could be ascribed to the metabolic adjustment (mainly lipids and organic acids) of white clover roots under low phosphate conditions. Our findings demonstrate that the low phosphate-induced RET boosts the asymbiotic growth of AM fungus, and thus offers an alternative way to fulfill the life cycle of AM fungi asymbiotically.

Superior degradation of phenolic contaminants in different water matrices via non-radical Fenton-like mechanism mediated by surface-disordered WO3.

Heterogeneous Fenton-like catalysis mediated by solid catalyst is a promising oxidation technology for water purification. The redox reactivity, cost-effectiveness, and environmental compatibility of solid catalyst play governing roles in oxidant activation, radical generation, and pollutant degradation. Herein, the surface-disordered WO3 (D-WO3) functionally engineered by the unique crystalline-amorphous core-shell structure is proven to be a superior solid catalyst of heterogeneous Fenton-like catalysis for peroxymonosulfate (PMS) activation and pollutant degradation in various water matrices. Six typical phenolic and dye pollutants are effectively and selectively degraded in the D-WO3/PMS system with much reduced matrix effects. Both radical identifying and scavenging tests elucidate the important role of non-radical 1O2 and mediated electron transfer during PMS activation on the D-WO3 surface. The superior Fenton-like activity of D-WO3 can be mainly attributed to the surface and sub-surface distorted lattice sites with finely tailored atomic and electronic structures and surface chemistry. These distorted lattice sites can thermodynamically serve as the key reactive centers of dissociative adsorption and catalytic activation for both PMS and pollutant, with high adsorption energy, strong structural activation, and smooth electron transfer. Our findings provide a new chance for heterogeneous Fenton-like catalysis mediated by transition metal oxides with high capacity, low cost, and no toxicity for promising water purification.

Cancer metabolism and tumor microenvironment: fostering each other?

The changes associated with malignancy are not only in cancer cells but also in environment in which cancer cells live. Metabolic reprogramming supports tumor cell high demand of biogenesis for their rapid proliferation, and helps tumor cell to survive under certain genetic or environmental stresses. Emerging evidence suggests that metabolic alteration is ultimately and tightly associated with genetic changes, in particular the dysregulation of key oncogenic and tumor suppressive signaling pathways. Cancer cells activate HIF signaling even in the presence of oxygen and in the absence of growth factor stimulation. This cancer metabolic phenotype, described firstly by German physiologist Otto Warburg, insures enhanced glycolytic metabolism for the biosynthesis of macromolecules. The conception of metabolite signaling, i.e., metabolites are regulators of cell signaling, provides novel insights into how reactive oxygen species (ROS) and other metabolites deregulation may regulate redox homeostasis, epigenetics, and proliferation of cancer cells. Moreover, the unveiling of noncanonical functions of metabolic enzymes, such as the moonlighting functions of phosphoglycerate kinase 1 (PGK1), reassures the importance of metabolism in cancer development. The metabolic, microRNAs, and ncRNAs alterations in cancer cells can be sorted and delivered either to intercellular matrix or to cancer adjacent cells to shape cancer microenvironment via media such as exosome. Among them, cancer microenvironmental cells are immune cells which exert profound effects on cancer cells. Understanding of all these processes is a prerequisite for the development of a more effective strategy to contain cancers.

Eosinophil extracellular traps drive asthma progression through neuro-immune signals.

Eosinophilic inflammation is a feature of allergic asthma. Despite mounting evidence showing that chromatin filaments released from neutrophils mediate various diseases, the understanding of extracellular DNA from eosinophils is limited. Here we show that eosinophil extracellular traps (EETs) in bronchoalveolar lavage fluid are associated with the severity of asthma in patients. Functionally, we find that EETs augment goblet-cell hyperplasia, mucus production, infiltration of inflammatory cells and expressions of type 2 cytokines in experimental non-infection-related asthma using both pharmaceutical and genetic approaches. Multiple clinically relevant allergens trigger EET formation at least partially via thymic stromal lymphopoietin in vivo. Mechanically, EETs activate pulmonary neuroendocrine cells via the CCDC25-ILK-PKCα-CRTC1 pathway, which is potentiated by eosinophil peroxidase. Subsequently, the pulmonary neuroendocrine cells amplify allergic immune responses via neuropeptides and neurotransmitters. Therapeutically, inhibition of CCDC25 alleviates allergic inflammation. Together, our findings demonstrate a previously unknown role of EETs in integrating immunological and neurological cues to drive asthma progression.