Ficolin-A induces macrophage polarization to a novel pro-inflammatory phenotype distinct from classical M1.

BACKGROUND: Macrophages are key inflammatory immune cells that orchestrate the initiation and progression of autoimmune diseases. The characters of macrophage in diseases are determined by its phenotype in response to the local microenvironment. Ficolins have been confirmed as crucial contributors to autoimmune diseases, with Ficolin-2 being particularly elevated in patients with autoimmune diseases. However, whether Ficolin-A stimulates macrophage polarization is still poorly understood. METHODS: We investigated the transcriptomic expression profile of murine bone marrow-derived macrophages (BMDMs) stimulated with Ficolin-A using RNA-sequencing. To further confirm a distinct phenotype activated by Ficolin-A, quantitative RT-PCR and Luminex assay were performed in this study. Additionally, we assessed the activation of underlying cell signaling pathways triggered by Ficolin-A. Finally, the impact of Ficolin-A on macrophages were investigated in vivo through building Collagen-induced arthritis (CIA) and Dextran Sulfate Sodium Salt (DSS)-induced colitis mouse models with Fcna-/- mice. RESULTS: Ficolin-A activated macrophages into a pro-inflammatory phenotype distinct to LPS-, IFN-γ- and IFN-γ + LPS-induced phenotypes. The transcriptomic profile induced by Ficolin-A was primarily characterized by upregulation of interleukins, chemokines, iNOS, and Arginase 1, along with downregulation of CD86 and CD206, setting it apart from the M1 and M2 phenotypes. The activation effect of Ficolin-A on macrophages deteriorated the symptoms of CIA and DSS mouse models, and the deletion of Fcna significantly alleviated the severity of diseases in mice. CONCLUSION: Our work used transcriptomic analysis by RNA-Seq to investigate the impact of Ficolin-A on macrophage polarization. Our findings demonstrate that Ficolin-A induces a novel pro-inflammatory phenotype distinct to the phenotypes activated by LPS, IFN-γ and IFN-γ + LPS on macrophages.

The Intersection of cerebral cholesterol metabolism and Alzheimer's disease: Mechanisms and therapeutic prospects.

Alzheimer's disease (AD) is a common neurodegenerative disease in the elderly, the exact pathogenesis of which remains incompletely understood, and effective preventive and therapeutic drugs are currently lacking. Cholesterol plays a vital role in cell membrane formation and neurotransmitter synthesis, and its abnormal metabolism is associated with the onset of AD. With the continuous advancement of imaging techniques and molecular biology methods, researchers can more accurately explore the relationship between cholesterol metabolism and AD. Elevated cholesterol levels may lead to vascular dysfunction, thereby affecting neuronal function. Additionally, abnormal cholesterol metabolism may affect the metabolism of ß-amyloid protein, thereby promoting the onset of AD. Brain cholesterol levels are regulated by multiple factors. This review aims to deepen the understanding of the subtle relationship between cholesterol homeostasis and AD, and to introduce the latest advances in cholesterol-regulating AD treatment strategies, thereby inspiring readers to contemplate deeply on this complex relationship. Although there are still many unresolved important issues regarding the risk of brain cholesterol and AD, and some studies may have opposite conclusions, further research is needed to enrich our understanding. However, these findings are expected to deepen our understanding of the pathogenesis of AD and provide important insights for the future development of AD treatment strategies targeting brain cholesterol homeostasis.

Serum levels of IL-9 and IL-11 serve as predictors for the occurrence of early neurologic deterioration in patients with cerebral infarction.

BACKGROUND AND AIM: Early neurological deterioration (END) is a common complication of cerebral infarction and a significant contributor to poor prognosis. Our study aimed to investigate the predictive value of interleukin-9 (IL-9) and interleukin-11 (IL-11) in relation to the occurrence of END in patients with cerebral infarction. MATERIALS AND METHODS: 102 patients with cerebral infarction and 64 healthy controls were collected. Patients were categorized into two groups based on the development of END following admission: the END group (n = 44) and the non-END group (n = 58). Enzyme-linked immunosorbent assay was used to determine the serum levels of IL-9, IL-11, and BDNF. RESULTS: Serum IL-9 was higher and IL-11 lower in the END group than those in the non-END group (P < 0.01). IL-9 correlated positively with NIHSS score (r = 0.627) and infarction volume (r = 0.686), while IL-11 correlated negatively (r = -0.613, -0.679, respectively). Logistic regression identified age, NIHSS score, and IL-9 as risk factors (P < 0.01), and IL-11 as protective (P < 0.01). Combined IL-9 and IL-11 had an ROC curve area of 0.849. BDNF correlated negatively with IL-9 (r = -0.703) and positively with IL-11 (r = 0.711). CONCLUSION: Serum IL-9 and IL-11 levels can predict the occurrence of END in patient with cerebral infarction and are correlated with serum BDNF levels.

Deciphering the intricate linkage between the gut microbiota and Alzheimer's disease: Elucidating mechanistic pathways promising therapeutic strategies.

BACKGROUND: The gut microbiome is composed of various microorganisms such as bacteria, fungi, and protozoa, and constitutes an important part of the human gut. Its composition is closely related to human health and disease. Alzheimer's disease (AD) is a neurodegenerative disease whose underlying mechanism has not been fully elucidated. Recent research has shown that there are significant differences in the gut microbiota between AD patients and healthy individuals. Changes in the composition of gut microbiota may lead to the development of harmful factors associated with AD. In addition, the gut microbiota may play a role in the development and progression of AD through the gut-brain axis. However, the exact nature of this relationship has not been fully understood. AIMS: This review will elucidate the types and functions of gut microbiota and their relationship with AD and explore in depth the potential mechanisms of gut microbiota in the occurrence of AD and the prospects for treatment strategies. METHODS: Reviewed literature from PubMed and Web of Science using key terminologies related to AD and the gut microbiome. RESULTS: Research indicates that the gut microbiota can directly or indirectly influence the occurrence and progression of AD through metabolites, endotoxins, and the vagus nerve. DISCUSSION: This review discusses the future challenges and research directions regarding the gut microbiota in AD. CONCLUSION: While many unresolved issues remain regarding the gut microbiota and AD, the feasibility and immense potential of treating AD by modulating the gut microbiota are evident.

A Wind Bell Inspired Triboelectric Nanogenerator for Extremely Low­Speed and Omnidirectional Wind Energy Harvesting.

As one of the most promising renewable energies, wind energy is abundant in the natural environment. However, it is still challenging to effectively collect wind energy because of its variable wind speed and unpredictable direction. Here, a triboelectric nanogenerator, which is inspired by ancient Chinese wind bells, has been developed to collect energy from variable-speed and multi-directional wind. The wind-bell-inspired triboelectric nanogenerator (W-TENG) has the capability to generate electricity even at a very low wind speed of 0.5 m s-1. Furthermore, it is able to harvest wind energy effectively from all directions (0-360 degrees). The parameter-optimized W-TENG achieves a maximum output voltage of 9.3 V and a maximum current of 0.63 µA. Electronic devices including a digital watch and 40 light-emitting diodes (LEDs) are successfully powered by the designed W-TENG, demonstrating its applicability. In this study, it is believed that a novel and effective strategy is provided to harvest energy from variable-speed and multi-directional wind.

LLDT-8 ameliorates experimental autoimmune encephalomyelitis by mediating macrophage functions in the priming stage.

Multiple sclerosis (MS) is an inflammatory demyelinating disease in the central nervous system caused by T cell activation mediated by peripheral macrophages, resulting in severe neurological deficits and disability. Due to the currently limited and expensive treatments for MS, we here introduce an economic Chinese medicine extract, (5R)-5-Hydroxytriptolide (LLDT-8), which shows low toxicity and high immunosuppressive activity. We used the widely accepted mouse model of MS, experimental autoimmune encephalomyelitis (EAE), to examine the immunosuppressive effect of LLDT-8 in vivo. Through the RNA-sequence analysis of peripheral macrophages in EAE mice, we discovered that LLDT-8 alleviates the symptoms of EAE by inhibiting the proinflammatory effect of macrophages, thereby blocking the activation and proliferation of T cells. In all, we found that LLDT-8 could be a potential treatment for MS.

MFG-E8 Alleviates Cognitive Impairments Induced by Chronic Cerebral Hypoperfusion by Phagocytosing Myelin Debris and Promoting Remyelination.

Chronic cerebral hypoperfusion is one of the pathophysiological mechanisms contributing to cognitive decline by causing white matter injury. Microglia phagocytosing myelin debris in a timely manner can promote remyelination and contribute to the repair of white matter. However, milk fat globule-epidermal growth factor-factor 8 (MFG-E8), a microglial phagocytosis-related protein, has not been well studied in hypoperfusion-related cognitive dysfunction. We found that the expression of MFG-E8 was significantly decreased in the brain of mice after bilateral carotid artery stenosis (BCAS). MFG-E8 knockout mice demonstrated more severe BCAS-induced cognitive impairments in the behavioral tests. In addition, we discovered that the deletion of MFG-E8 aggravated white matter damage and the destruction of myelin microstructure through fluorescent staining and electron microscopy. Meanwhile, MFG-E8 overexpression by AAV improved white matter injury and increased the number of mature oligodendrocytes after BCAS. Moreover, in vitro and in vivo experiments showed that MFG-E8 could enhance the phagocytic function of microglia via the αVß3/αVß5/Rac1 pathway and IGF-1 production to promote the differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes. Interestingly, we found that MFG-E8 was mainly derived from astrocytes, not microglia. Our findings suggest that MFG-E8 is a potential therapeutic target for cognitive impairments following cerebral hypoperfusion.

Decoding the role of gut microbiota in Alzheimer's pathogenesis and envisioning future therapeutic avenues.

Alzheimer's disease (AD) emerges as a perturbing neurodegenerative malady, with a profound comprehension of its underlying pathogenic mechanisms continuing to evade our intellectual grasp. Within the intricate tapestry of human health and affliction, the enteric microbial consortium, ensconced within the milieu of the human gastrointestinal tract, assumes a role of cardinal significance. Recent epochs have borne witness to investigations that posit marked divergences in the composition of the gut microbiota between individuals grappling with AD and those favored by robust health. The composite vicissitudes in the configuration of the enteric microbial assembly are posited to choreograph a participatory role in the inception and progression of AD, facilitated by the intricate conduit acknowledged as the gut-brain axis. Notwithstanding, the precise nature of this interlaced relationship remains enshrouded within the recesses of obscurity, poised for an exhaustive revelation. This review embarks upon the endeavor to focalize meticulously upon the mechanistic sway exerted by the enteric microbiota upon AD, plunging profoundly into the execution of interventions that govern the milieu of enteric microorganisms. In doing so, it bestows relevance upon the therapeutic stratagems that form the bedrock of AD's management, all whilst casting a prospective gaze into the horizon of medical advancements.

MiR-431 attenuates synaptic plasticity and memory deficits in APPswe/PS1dE9 mice.

Synaptic plasticity impairment plays a critical role in the pathogenesis of Alzheimer's disease (AD), and emerging evidence has shown that microRNAs (miRs) are alternative biomarkers and therapeutic targets for synaptic dysfunctions in AD. In this study, we found that the level of miR-431 was downregulated in the plasma of patients with amnestic mild cognitive impairment and AD. In addition, it was decreased in the hippocampus and plasma of APPswe/PS1dE9 (APP/PS1) mice. Lentivirus-mediated miR-431 overexpression in the hippocampus CA1 ameliorated synaptic plasticity and memory deficits of APP/PS1 mice, while it did not affect amyloid-ß levels. Smad4 was identified as a target of miR-431, and Smad4 knockdown modulated the expression of synaptic proteins, including SAP102, and protected against synaptic plasticity and memory dysfunctions in APP/PS1 mice. Furthermore, Smad4 overexpression reversed the protective effects of miR-431, indicating that miR-431 attenuated synaptic impairment at least partially by Smad4 inhibition. Thus, these results indicated that miR-431/Smad4 might be a potential therapeutic target for AD treatment.

Controlling strong-field fragments of HD+ with a synthesized two-color laser pulse.

The possibility of controlling fragment branching in the dissociation and ionization channels of HD+ is theoretically explored by synthesized intense fields using 790 nm and 395 nm pulses. In the control scheme, the branching ratios of the fragments to different channels (H + D+, D + H+ and H+ + D+) are manipulated by regulating the relative phase and intensity between the 790 nm and 395 nm pulses. Altering the relative phase can induce constructive or destructive interference between the net two photon process and the direct one photon process, and the highest modulation reaches 80% between the two dissociation fragments (H + D+ and D + H+). The high selectivity of the ionization fragment (H+ + D+) is achieved by tuning the relative intensity, since the ionization rate is not only related to the internuclear distance, but also to the instantaneous intensity of field strength. The results demonstrate that the synthesized ω-2ω laser pulse can provide an efficient control over the strong-field fragments of HD+.

Effects and safety of Ginkgo biloba on blood metabolism in type 2 diabetes mellitus: a systematic review and meta-analysis.

Background: There has existed controversy regarding the use of Ginkgo biloba (GKB) for blood metabolism among type 2 diabetes mellitus(T2DM) patients, and we tried to analyze the effects and safety of GKB on T2DM patients. Methods: We conducted a literature search between January 2003 and December 2022 of seven online databases (PubMed, Scopus, Embase, Google Scholar, Web of Sciences, Cochrane Library, and China National Knowledge Infrastructure). A systematic literature review and meta-analysis were performed to compare the effects and safety of GKB among T2DM patients. Four groups of parameters were extracted and analyzed: hemorheology parameters, lipid profile, glycemic control markers, and adverse events. Results: In the end, 13 eligible articles with 11 indicators among 1573 patients were included. In the hemorheology parameters section, GKB showed significantly lower plasma viscosity (PV) (SMD=-0.91, 95%CI [-1.45, -0.36], P<0.01) and hematocrit (Hct) (SMD=-0.60, 95%CI [-0.97, -0.24], P<0.01) than the control group. GKB shoed higher velocity of the dorsalis pedis artery (VDPA) (SMD=0.51, 95%CI [0.26, 0.76], P<0.01) and ankle brachial index (ABI) (SMD=0.71, 95%CI [0.32, 1.10], P<0.01) than the control. In both the lipid profile and glycemic control markers sections, we did not find any difference between GKB and control groups, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), hemoglobin A1c (HbA1c), and fasting serum glucose (FSG). In addition, we saw no difference in adverse events (AE). The sensitivity analysis and funnel plot showed that the results in this research were robust and had no publication bias. Conclusion: In conclusion, GKB might safely reduce the risk of peripheral arterial or even systemic cardiovascular disease. However, GKB did not directly improve lipid and blood glucose levels in T2DM patients. Systematic review registration: https://inplasy.com/, identifier INPLASY202350096.

Identification of a Small Molecule with Strong Anti-Inflammatory Activity in Experimental Autoimmune Encephalomyelitis and Sepsis through Blocking Gasdermin D Activation.

Pyroptosis is a key inflammatory form of cell death participating in the progression of many inflammatory diseases, such as experimental autoimmune encephalomyelitis (EAE) and sepsis. Identification of small molecules to inhibit pyroptosis is emerging as an attractive strategy. In this study, we performed a screening based on in silico docking of compounds on the reported Gasdermin D (GSDMD) three-dimensional structure and found C202-2729 demonstrated strong anti-inflammatory effects in both endotoxin shock and EAE mouse models. Oral administration of C202-2729 was capable of attenuating EAE disease severity significantly and has the comparable effects to teriflunomide, the first-line clinical drug of multiple sclerosis. We found C202-2729 remarkably suppressed macrophage and T cell-associated immune inflammation. Mechanistically, C202-2729 neither impact GSDMD cleavage nor the upstream inflammasome activation in mouse immortalized bone marrow-derived macrophages. However, C202-2729 exposure significantly repressed the IL-1ß secretion and cell pyroptosis. We found C202-2729 directly bonds to the N terminus of GSDMD and blocks the migration of the N-terminal GSDMD fragment to cell membrane, restraining the pore-forming and mature IL-1ß release. Collectively, our findings provide a new molecule with the potential for translational application in GSDMD-associated inflammatory diseases.

γδ T cells aggravate blood-brain-barrier injury via IL-17A in experimental ischemic stroke.

BACKGROUND: γδ T cells were reported to play a key role in ischemic stroke. The integrity of the blood-brain barrier (BBB) directly affects the prognosis of ischemic stroke. This study aimed to determine whether γδ T cells aggravate BBB injury and determine the outcome of ischemic stroke. METHODS: Oxygen-glucosedeprivation (OGD) and middle cerebral artery occlusion (MCAO) were used as ischemic stroke models in vitro and in vivo. Flow cytometry was used to evaluate the intracranial infiltration of γδ T cells. RT-qPCR was used to evaluatethe mRNA levels of cytokines and γδ T cell markers. ELISA was used to test the levels of cytokines. Immunofluorescence, TEER and western blotting were used to measure BBB injury. RESULTS: In this study, we found that a large number of γδ T cells infiltrated the ischemic penumbra 24 h after MCAO. Knockout of γδ T cells improved the motor function injury induced by MCAO and significantly reduced the volume of cerebral infarction and blood-brain barrier injury. IL-17A neutralization could rescue the BBB injury induced by γδ T cells both in vitro and in vivo. CONCLUSIONS: Peripheral γδ T cells immediately infiltrated into the lesion site after ischemic stroke and aggravated BBB injury by releasing IL-17A, which might be a potential therapeutic target for ischemic stroke.

VEGF mitigates bisphosphonate-induced apoptosis and differentiation inhibition of MC3T3-E1 cells.

The present study aimed to investigate whether VEGF was involved in bisphosphonate (BP)-induced apoptosis and differentiation of osteoblasts. Murine MC3T3-E1 osteoblasts were stimulated with zoledronic acid (ZA) for 7 days. VEGF mRNA and protein expression levels were determined via reverse transcription-quantitative PCR and western blot analysis, respectively. Cell viability was evaluated using Cell Counting Kit-8 assay. In addition, the cell apoptotic rate and the expression levels of apoptosis-related proteins were measured using a TUNEL staining kit and western blot analysis, respectively. To evaluate mineralization, cells were stained with alizarin red, while the secretion levels of alkaline phosphatase (ALP) were measured using the corresponding assay kit. Finally, the expression levels of differentiation-related proteins and proteins of the Nod-like receptor family pyrin domain-containing 3 (NLRP3)/caspase 1/gasdermin D (GSDMD) pyroptosis pathway were measured by western blot analysis. VEGF expression level was notably decreased in ZA-stimulated MC3T3-E1 cells. However, the viability of these cells was enhanced following VEGF addition. Furthermore, VEGF attenuated apoptosis, promoted mineralization and increased ALP activity in ZA-stimulated MC3T3-E1 cells. The ZA-mediated decrease in the protein expression of the osteogenic genes osteopontin, osteocalcin and runt-related transcription factor 2 was restored after MC3T3-E1 cell treatment with 10 ng/ml VEGF. The present study demonstrated that VEGF could attenuate BP-induced apoptosis and differentiation of MC3T3 cells by regulating the NLRP3/caspase 1/GSDMD pathway.

High cortisol and the risk of Alzheimer disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Morning cortisol levels have been reported to be elevated among patients with Alzheimer disease (AD). We perform a protocol for systematic review and meta-analysis to assess morning central or peripheral cortisol levels in AD patients as compared with cognitively normal individuals. METHODS: Studies were identified through systematic searches in August 2021 with no restrictions on date and time, language, and publication status using the following bibliographic databases: Embase, Medline, PubMed, Web of Science, Science Direct, and the Cochrane Library. Studies were identified using search terms related to cortisol, Alzheimer disease, and cognitive impairment. The study quality of included papers was evaluated using the "National Institutes of Health (NIH) quality assessment tool for observational cohort and cross-sectional studies." Statistical analyses were performed using Stata (version 14, StataCorp, College Station, TX). RESULTS: The findings of this study will be submitted to peer-reviewed journals for publication. CONCLUSION: Morning cortisol was elevated in AD patients and may have diagnostic and prognostic values for AD.

Reversing Antibiotic Resistance Caused by Mobile Resistance Genes of High Fitness Cost.

The reversibility of antibiotic resistance is theoretically attractive due to the prospect of restoring the clinical potency of antibiotics. It is important to find out the factors that affect the reversibility of antibiotic resistance. Here, an mcr-1-positive multidrug-resistant (MDR) environmental Escherichia coli isolate was successively passaged under four antibiotic-free culture conditions. The relative abundances of multiple antibiotic resistance genes (ARGs) kept decreasing during the successive passages. The linear correlations between abundances of ARGs on the same MDR plasmid reflected that the decay of antibiotic resistance during the passage was mainly due to the elimination of the MDR plasmid (pMCR_W5-6). Colistin-susceptible strains were isolated at the end of the passage. The whole-genome sequencing of two susceptible isolates detected the elimination of the MDR plasmid and deletion of the mcr-1 gene. Deletions of DNA fragments from chromosome and plasmid were closely related to a variety of insertion sequences (ISs). The results of coculture of resistant and susceptible strains at different antibiotic concentrations indicated that the high fitness cost led to the poor stability of mobile ARGs. Strict control of the use of antibiotics can at least reverse the severe antibiotic resistance caused by mobile ARGs of high fitness cost. IMPORTANCE The dissemination of bacterial antibiotic resistance is a serious threat to human health. The development of new antibiotics faces both economic and technological challenges. The reversibility of antibiotic resistance has become an important issue causing wide concern due to the prospect of restoring the clinical potency of antibiotics. Our study suggests that the high mobility of ARGs of high fitness cost may just reflect their poor stability. Therefore, strict control of the use of antibiotics can at least reverse the severe antibiotic resistance caused by mobile ARGs of high fitness cost. This study brings hope for the possibility of curbing the dissemination of antibiotic resistance.

The role of lncRNAs in ischemic stroke.

Ischemic stroke is a leading cause of disability and mortality worldwide due to the narrow therapeutic time window of the only two approved therapies, intravenous thrombolysis and thrombectomy. The pathophysiological processes of ischemic stroke are driven by multiple complex molecular and cellular interactions that ultimately induce brain damage and neurobehavioral impairment. Long non-coding RNAs (LncRNAs) are significantly altered in the blood and brains of ischemic stroke patients and play a critical role in the pathogenesis of stroke, which serve as potential targets for stroke interventions. In this review, we provide an overview of the roles of lncRNAs in the pathophysiology of ischemic stroke and discuss the opportunities and challenges for the clinical application of lncRNAs in the diagnosis and treatment of ischemic stroke.

Microglial lnc-U90926 facilitates neutrophil infiltration in ischemic stroke via MDH2/CXCL2 axis.

Dysregulated long non-coding RNAs (lncRNAs) have been shown to contribute to the pathogenesis of ischemic stroke. However, the potential role of lncRNAs in post-stroke microglial activation remains largely unknown. Here, we uncovered that lncRNA-U90926 was significantly increased in microglia exposed to ischemia/reperfusion both in vivo and in vitro. In addition, adenovirus-associated virus (AAV)-mediated microglial U90926 silencing alleviated neurological deficits and reduced infarct volume in experimental stroke mice. Microglial U90926 knockdown could reduce the infiltration of neutrophils into ischemic lesion site, which might be attributed to the downregulation of C-X-C motif ligand 2 (CXCL2). Mechanistically, U90926 directly bound to malate dehydrogenase 2 (MDH2) and competitively inhibited the binding of MDH2 to the CXCL2 3' untranslated region (UTR), thus protecting against MDH2-mediated decay of CXCL2 mRNA. Taken together, our study demonstrated that microglial U90926 aggravated ischemic brain injury via facilitating neutrophil infiltration, suggesting that U90926 might be a potential biomarker and therapeutic target for ischemic stroke.

Galectin-1 Inhibited LPS-Induced Autophagy and Apoptosis of Human Periodontal Ligament Stem Cells.

Periodontitis is a widespread human chronic inflammatory disease of the tooth-surrounding tissues, which induces the destruction of periodontium and pathologic loss of teeth among adults. It has been reported that interleukin (IL)-17 was significantly increased in periodontitis patients compared to controls, while galectin-1 (Gal-1) was lower. Interestingly, it is found that Gal-1 treatment reduced systemic IL-17 levels. Hence, the aim of the present study was to explore the effect of Gal-1 on periodontitis development and investigate its underlying mechanism. In this study, Gal-1 was poorly expressed in lipopolysaccharide (LPS)-induced human periodontal ligament stem cells (hPDLSCs), and Gal-1 overexpression attenuated the production of inflammatory cytokines induced by LPS. Moreover, Gal-1 overexpression alleviated LPS-induced cell autophagy and apoptosis and reduced the expressions of IL-17A and IL-17R. Interestingly, IL-17A reversed the effect of Gal-1 on cell autophagy, inflammation, and cell apoptosis induced by the LPS challenge. In conclusion, Gal-1 inhibited LPS-induced autophagy and apoptosis of hPDLSC via regulation of IL-17A expression. Therefore, Gal-1 may have promising potential in regenerating periodontium.

Migratory birds-one major source of environmental antibiotic resistance around Qinghai Lake, China.

Migratory birds are potential transmitters of bacterial antibiotic resistance. However, their role in the environmental dissemination of bacterial antibiotic resistance and the extent of their impact on the environment are not yet clear. Qinghai Lake is one of the most important breeding and stopover ground for the migratory birds along the Central Asian Flyway. Here, we investigated the bacterial antibiotic resistance in the environment and among the migratory birds around the lake. The results of culture-based analysis of bacterial antibiotic resistance, quantitative PCR and metagenomic sequencing indicate that migratory birds are one major source of bacterial antibiotic resistance in the environment around Qinghai Lake. Network analysis reveals the co-occurrence patterns of antibiotic resistance genes (ARGs) and bacterial genera. Genetic co-localization analysis suggests high co-selection potential (with incidence of 35.8%) among different ARGs, but limited linkage (with incidence of only 3.7%) between ARGs and biocide/metal resistance genes (BMRGs). The high genetic linkage between ARGs and mobile genetic elements (MGEs) is still largely confined to the bacterial community in migratory birds (accounting for 96.0% of sequencing reads of MGE-linked ARGs), which indicates limited horizontal transfer of ARGs to the environment. Nevertheless, the antibiotic resistance determinants carried by migratory birds and their specific genetic properties (high co-selection and mobility potential of the ARGs) remind us that the role of migratory birds in the environmental dissemination of bacterial antibiotic resistance deserves more attention.