Circ-phkb promotes cell apoptosis and inflammation in LPS-induced alveolar macrophages via the TLR4/MyD88/NF-kB/CCL2 axis.

BACKGROUND: Circular RNAs (CircRNAs) have been associated with acute lung injury (ALI), but their molecular mechanisms remain unclear. METHODS: This study developed a rat model of lipopolysaccharide (LPS)-induced ALI and evaluated the modeling effect by hematoxylin and eosin staining, Masson's trichrome staining, lung wet-to-dry weight ratio, terminal deoxynucleotidyl transferase UTP nick end labeling (TUNEL), and enzyme-linked immunosorbent assay (ELISA) detection of inflammatory factors (interleukin-1ß, tumor necrosis factor alpha, and interleukin-6). Using lung tissues from a rat model of LPS-induced ALI, we then conducted circRNA sequencing, mRNA sequencing, and bioinformatics analysis to obtain differential circRNA and mRNA expression profiles as well as potential ceRNA networks. Furthermore, we performed quantitative real-time polymerase chain reaction (qRT-PCR) assays to screen for circ-Phkb in ALI rat lung tissues, alveolar macrophages, and LPS-induced NR8383 cells. We conducted induction with or without LPS with circ-Phkb siRNA and overexpression lentivirus in NR8383. Cell Counting Kit-8, C5-Ethynyl-2'-deoxyuridine (Edu), TUNEL, and cytometry were used to identify proliferation and apoptosis, respectively. We detected inflammatory factors using ELISA. Finally, we used Western blot to detect the apoptosis-related proteins and TLR4/MyD88/NF-kB/CCL2 pathway activation. RESULTS: Our results revealed that both circRNA and mRNA profiles are different from those of the Sham group. We observed a significant circ-Phkb upregulation in NR8383 cells and LPS-exposed rats. Apoptosis and inflammation were greatly reduced when circ-Phkb expression was reduced in NR8383 cells, cell proliferation was increased, and circ-Phkb overexpression was decreased. CONCLUSIONS: In terms of mechanism, circ-Phkb suppression inhibits CCL2 expression via the TLR4/MyD88/NF-kB pathway in LPS-induced alveolar macrophages.

Machine learning-based identification of CYBB and FCAR as potential neutrophil extracellular trap-related treatment targets in sepsis.

Objective: Sepsis related injury has gradually become the main cause of death in non-cardiac patients in intensive care units, but the underlying pathological and physiological mechanisms remain unclear. The Third International Consensus Definitions for Sepsis and Septic Shock (SEPSIS-3) definition emphasized organ dysfunction caused by infection. Neutrophil extracellular traps (NETs) can cause inflammation and have key roles in sepsis organ failure; however, the role of NETs-related genes in sepsis is unknown. Here, we sought to identify key NETs-related genes associate with sepsis. Methods: Datasets GSE65682 and GSE145227, including data from 770 patients with sepsis and 54 healthy controls, were downloaded from the GEO database and split into training and validation sets. Differentially expressed genes (DEGs) were identified and weighted gene co-expression network analysis (WGCNA) performed. A machine learning approach was applied to identify key genes, which were used to construct functional networks. Key genes associated with diagnosis and survival of sepsis were screened out. Finally, mouse and human blood samples were collected for RT-qPCR verification and flow cytometry analysis. Multiple organs injury, apoptosis and NETs expression were measured to evaluated effects of sulforaphane (SFN). Results: Analysis of the obtained DEGs and WGCNA screened a total of 3396 genes in 3 modules, and intersection of the results of both analyses with 69 NETs-related genes, screened out seven genes (S100A12, SLC22A4, FCAR, CYBB, PADI4, DNASE1, MMP9) using machine learning algorithms. Of these, CYBB and FCAR were independent predictors of poor survival in patients with sepsis. Administration of SFN significantly alleviated murine lung NETs expression and injury, accompanied by whole blood CYBB mRNA level. Conclusion: CYBB and FCAR may be reliable biomarkers of survival in patients with sepsis, as well as potential targets for sepsis treatment. SFN significantly alleviated NETs-related organs injury, suggesting the therapeutic potential by targeting CYBB in the future.

The heterogeneity-diversity-system performance nexus.

Ever-growing human population and nutritional demands, supply chain disruptions, and advancing climate change have led to the realization that changes in diversity and system performance are intimately linked. Moreover, diversity and system performance depend on heterogeneity. Mitigating changes in system performance and promoting sustainable living conditions requires transformative decisions. Here, we introduce the heterogeneity-diversity-system performance (HDP) nexus as the conceptual basis upon which to formulate transformative decisions. We suggest that managing the heterogeneity of systems will best allow diversity to provide multiple benefits to people. Based on ecological theory, we pose that the HDP nexus is broadly applicable across systems, disciplines, and sectors, and should thus be considered in future decision making as a way to have a more sustainable global future.

Coupling coordination and spatio-temporal evolution of land-use benefits under the dual carbon goal: A case study in Anhui, China.

According to the dual carbon goal, urban development should adhere to the principle of low-carbon sustainable development in order to reach the "carbon peak" in 2030 and "carbon neutrality" in 2060. To achieve the dual carbon goal and sustainable land resource utilization, it is necessary to seek ways to improve land-use benefits and promote the coordinated development of economic, social, and ecological benefits. Therefore, the study analysed the coupling coordination and spatio-temporal evolution of land-use benefits in Anhui province, aiming to provide a reference for improving the level of regional land-use benefits. First, we developed a land-use benefit evaluation indicator system that took into account the dual carbon goal from three perspectives: economic benefits, social benefits, and ecological benefits or economic, social, and ecological benefits. Following that, we evaluated the spatial-temporal characteristics of land-use benefits using the coupling coordination model and coupling coordination gravity model. The results showed: (1) From the time scale, the comprehensive land-use benefits showed an increasing trend from 2011 to 2020, the coordination state changed from "moderately uncoordinated" to "on the verge of uncoordinated". (2) From the perspective of spatial differences, the coupling coordination level of land-use benefits in 16 prefecture-level cities increased year by year, but no prefecture-level cities reached the coordination stage. (3) As for the spatial linkage strength of coupling coordination of land-use benefits, 16 prefecture-level cities in 2011, 2015 and 2020 presented a similar spatial linkage pattern, and the coupling coordination of prefecture-level cities in southeast Anhui province was strongly influenced by regional factors.

The application of metagenomic next-generation sequencing in patients with infection or colonization caused by Lichtheimia species.

Background: Mucormycosis is considered the fourth most common invasive fungal disease after candidiasis, aspergillosis and cryptococcosis. Lichtheimia species accounted for 5%-29% of all mucormycosis. However, available data on species-specific analysis of Lichtheimia infections are limited. Methods: This study included nine patients hospitalized in five hospitals in two cities in south China with mucormycosis or colonization caused by Lichtheimia species, diagnosed mainly by metagenomic next-generation sequencing (mNGS). The corresponding medical records were reviewed, and the clinical data analyzed included demographic characteristics, site of infection, host factors and type of underlying disease, diagnosis, clinical course, management, and prognosis. Results: In this study, nine patients with Lichtheimia infections or colonization had a recent history of haematological malignancy (33.3%), solid organ transplants (33.3%), pulmonary disease (22.2%), and trauma (11.1%) and were categorized as 11.1% (one case) proven, 66.7% (six cases) probable mucormycosis and 22.2% (two cases) colonization. Pulmonary mucormycosis or colonization was the predominant presentation in 77.8% of cases and mucormycosis caused by Lichtheimia resulted in death in four out of seven patients (57.1%). Conclusion: These cases highlight the importance of early diagnosis and combined therapy for these sporadic yet life-threatening infections. Further studies on the diagnosis and control of Lichtheimia infection in China are required.

Mesenchymal stromal cells alleviate acute respiratory distress syndrome through the cholinergic anti-inflammatory pathway.

Mesenchymal stromal cells (MSCs) have been considered a promising alternative for treatment of acute respiratory distress syndrome (ARDS). However, there is significant heterogeneity in their therapeutic efficacy, largely owing to the incomplete understanding of the mechanisms underlying the therapeutic activities of MSCs. Here, we hypothesize that the cholinergic anti-inflammatory pathway (CAP), which is recognized as a neuroimmunological pathway, may be involved in the therapeutic mechanisms by which MSCs mitigate ARDS. Using lipopolysaccharide (LPS) and bacterial lung inflammation models, we found that inflammatory cell infiltration and Evans blue leakage were reduced and that the expression levels of choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) in lung tissue were significantly increased 6 hours after MSC infusion. When the vagus nerve was blocked or α7 nicotinic acetylcholine (ACh) receptor (α7nAChR)-knockout mice were used, the therapeutic effects of MSCs were significantly reduced, suggesting that the CAP may play an important role in the effects of MSCs in ARDS treatment. Our results further showed that MSC-derived prostaglandin E2 (PGE2) likely promoted ACh synthesis and release. Additionally, based on the efficacy of nAChR and α7nAChR agonists, we found that lobeline, the nicotinic cholinergic receptor excitation stimulant, may attenuate pulmonary inflammation and alleviate respiratory symptoms of ARDS patients in a clinical study (ChiCTR2100047403). In summary, we reveal a previously unrecognized MSC-mediated mechanism of CAP activation as the means by which MSCs alleviate ARDS-like syndrome, providing insight into the clinical translation of MSCs or CAP-related strategies for the treatment of patients with ARDS.

Donor with HLA-C2 is associated with acute rejection following liver transplantation in Southern Chinese.

Apart from presenting peptides to T cells, class I HLA molecules serve as ligands for killer cell immunoglobulin-like receptor (KIRs) and regulate the response of natural killer (NK) cells. The role played by HLA and KIR in the acute rejection (AR) following liver transplantation has been controversial. In this retrospective study, we assessed the influence of class I HLA alleles, HLA matching between donor-recipient pairs, recipient KIR and donor HLA ligands on AR following liver transplantation in southern Chinese. In total, 143 recipients and 78 donors obtained from a single transplant center were included in the study cohort. Thirty-three recipients with histologically confirmed AR were observed. We found that the incidence of AR did not correlate with donor or recipient class I HLA alleles and HLA matching. Neither recipient KIR gene nor the KIR genotype was associated with AR, moreover, high-resolution genotyping of 14 functional KIR genes of recipients showed that no KIR allele was independently associated with AR. However, the frequency of HLA-C2+ donor significantly increased in AR group compared with NAR group (52.9% vs. 24.6%, p = 0.03). In the presence of HLA-C2 by the donor allograft, AR was more frequently observed in recipients with normal expressed KIR2DS4 (43.8% vs. 15.0%, p = 0.03). Donor with HLA-C2 is therefore a major determinant of AR, which can confer risk effect in liver transplantation. Our findings can provide valuable clues for better understanding pathogenesis of AR and have important clinical implications in liver transplantation for Chinese.

Intrathecal Injection of Tigecycline and Polymyxin B in the Treatment of Extensively Drug-Resistant Intracranial Acinetobacter baumannii Infection: A Case Report and Review of the Literature.

Purpose: Intracranial infection after neurosurgery is one of the most serious complications, especially extensively drug-resistant (XDR) Acinetobacter baumannii (A. baumannii) seriously affects the prognosis of patients. At present, there is little experience in the treatment of this infection and limited effective treatment options, like tigecycline or polymyxin B. Therefore, this report aims to describe the efficacy of tigecycline combined with polymyxin B by intrathecal (ITH) injection in the treatment of XDR intracranial infection with A. baumannii. Methods: We report a case of intracranial infection with XDR A. baumannii after ventricular drainage, treated by daily ITH and intravenous (IV) tigecycline, combined with polymyxin B ITH route. Moreover, tigecycline and polymyxin B treatments for XDR intracranial infection with A. baumannii that were reported in the literature were also reviewed and summarized. Results: The white blood cells (WBCs) of the patient's cerebrospinal fluid dropped to normal, and the symptoms of intracranial infection disappeared. The patient finally obtained good clinical results and transferred to the local hospital. Conclusion: The polymyxin B ITH route is an ideal treatment strategy for XDR A. baumannii. The IV plus ITH tigecycline may be an effective treatment option. However, more researches should be conducted to confirm our observation.

Mg ion pre-intercalated MnO2 nanospheres as high-performance cathode materials for aqueous Zn-ion batteries.

Rechargeable Zn-MnO2 batteries with mild and nearly neutral aqueous electrolytes have shown great potential for large-scale energy storage because of their high safety, low cost, environmental friendliness and high energy density. However, MnO2 cathode materials usually have disadvantages such as low capacity and poor cycling stability, which limit the development of Zn-MnO2 batteries. In this study, mesoporous MnO2 nanospheres were prepared by in situ Mg ion pre-intercalation via a simple chemical method. The prepared MnO2 shows a high reversible capacity (247 mA h g-1 at 0.3 A g-1), excellent cycling stability (a capacity retention of 93% over 800 cycles at 0.8 A g-1) and good rate performance. The GITT, in situ EIS, ex situ XRD, ex situ XPS and ex situ SEM show that the zinc storage mechanism of MnO2 should be H+/Zn2+ co-intercalation/de-intercalation. This research could provide specific inspiration and promotion for the development and mechanism research of high-performance rechargeable Zn-MnO2 batteries.

Efficacy of comprehensive unit-based safety program to prevent ventilator associated-pneumonia for mechanically ventilated patients in China: A propensity-matched analysis.

Background: Ventilator-associated pneumonia (VAP) is the most common healthcare-associated infection (HAI) in patients with mechanical ventilation. VAP is largely preventable, and a comprehensive unit-based safety program (CUSP) has effectively reduced HAI. In this study, we aim to comprehensively investigate the effect of implementing the CUSP in patients requiring mechanical ventilation. Methods: In this uncontrolled before-and-after trial conducted in two intensive care unit (ICU) settings in China, patients requiring invasive mechanical ventilation were enrolled. Patients were divided into two groups based on the implementation of CUSP. The primary outcome was the incidence of VAP. The secondary outcomes were the time from intubation to VAP, days of antibiotic use for VAP treatments, rate of other infection, length of stay (LOS) in ICU, hospital LOS, and safety culture score. Joinpoint regression analysis was used to test the changes in trends of VAP rate for statistical significance. Propensity score matching (1:1 matching) was used to reduce the potential bias between CUSP and no CUSP groups. Univariate and multivariate logistic/linear regression analyses were performed to evaluate the association between the use of CUSP and clinical outcomes. This study was registered at the Chinese Clinical Trial Registry (chictr.org.cn), registration number: ChiCTR1900025391. Results: A total of 1,004 patients from the transplant ICU (TICU) and 1,001 patients from the surgical ICU (SICU) were enrolled in the study from January 2016 to March 2022. Before propensity score matching, the incidences of VAP decreased from 35.1/1,000 ventilator days in the no CUSP group to 12.3/1,000 ventilator days in the CUSP group in the TICU setting (adjusted odds ratio [OR], 0.30; 95% confidence interval [CI], 0.15-0.59). The results of the joinpoint regression analysis confirmed that the implementation of CUSP significantly decreased the incidences of VAP. After propensity score matching in TICU setting, the CUSP group reported a lower incidence of VAP (30.4 vs. 9.7‰, P = 0.003; adjusted OR = 0.26, 95% CI: 0.10-0.76), lower wound infection (3.4 vs. 0.9%, P = 0.048; adjusted OR = 0.73, 95% CI: 0.50-0.95), shorter ICU LOS [3.5(2.3-5.3) vs. 2.5(2.0-4.5) days; P = 0.003, adjusted estimate = -0.34, 95% CI: -0.92 to -0.14], and higher safety culture score (149.40 ± 11.74 vs. 153.37 ± 9.74; P = 0.002). Similar results were also observed in the SICU setting between the no CUSP and CUSP group. Conclusions: The implementation of CSUP for patients receiving mechanical ventilation could significantly reduce the incidences of VAP, and other infections, prolong the time until the VAP occurrence, reduces the days of antibiotic use for VAP, shorten the ICU and hospital LOS, and enhance the awareness of safety culture.

Key Factors for Binders to Enhance the Electrochemical Performance of Silicon Anodes through Molecular Design.

Silicon is considered the most promising candidate for anode material in lithium-ion batteries due to the high theoretical capacity. Unfortunately, the vast volume change and low electric conductivity have limited the application of silicon anodes. In the silicon anode system, the binders are essential for mechanical and conductive integrity. However, there are few reviews to comprehensively introduce binders from the perspective of factors affecting performance and modification methods, which are crucial to the development of binders. In this review, several key factors that have great impact on binders' performance are summarized, including molecular weight, interfacial bonding, and molecular structure. Moreover, some commonly used modification methods for binders are also provided to control these influencing factors and obtain the binders with better performance. Finally, to overcome the existing problems and challenges about binders, several possible development directions of binders are suggested.

Heat shock preconditioning mesenchymal stem cells attenuate acute lung injury via reducing NLRP3 inflammasome activation in macrophages.

OBJECTIVES: Acute lung injury (ALI) remains a common cause of morbidity and mortality worldwide, and to date, there is no effective treatment for ALI. Previous studies have revealed that topical administration of mesenchymal stem cells (MSCs) can attenuate the pathological changes in experimental acute lung injury. Heat shock (HS) pretreatment has been identified as a method to enhance the survival and function of cells. The present study aimed to assess whether HS-pretreated MSCs could enhance immunomodulation and recovery from ALI. MATERIALS AND METHODS: HS pretreatment was performed at 42 °C for 1 h, and changes in biological characteristics and secretion functions were detected. In an in vivo mouse model of ALI, we intranasally administered pretreated umbilical cord-derived MSCs (UC-MSCs), confirmed their therapeutic effects, and detected the phenotypes of the macrophages in bronchoalveolar lavage fluid (BALF). To elucidate the underlying mechanisms, we cocultured pretreated UC-MSCs with macrophages in vitro, and the expression levels of inflammasome-related proteins in the macrophages were assessed. RESULTS: The data showed that UC-MSCs did not exhibit significant changes in viability or biological characteristics after HS pretreatment. The administration of HS-pretreated UC-MSCs to the ALI model improved the pathological changes and lung damage-related indexes, reduced the proinflammatory cytokine levels, and modulated the M1/M2 macrophage balance. Mechanistically, both the in vivo and in vitro studies demonstrated that HS pretreatment enhanced the protein level of HSP70 in UC-MSCs, which negatively modulated NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in alveolar macrophages. These effects were partially reversed by knocking down HSP70 expression. CONCLUSION: HS pretreatment can enhance the beneficial effects of UC-MSCs in inhibiting NLRP3 inflammasome activation in macrophages during ALI. The mechanism may be related to the upregulated expression of HSP70.

Co9S8 nanoparticles-embedded porous carbon: A highly efficient sorbent for mercury capture from nonferrous smelting flue gas.

In this study, a novel Co9S8 nanoparticles-embedded porous carbon (Co9S8-PC) was designed as an effective reusable sorbent for Hg0 capture from smelting flue gas. Some flue gas components can create more active sites on Co9S8-PC for Hg0 adsorption, but compete with Hg0 for the same sulfur sites over nano Co1-xS/Co3S4 (CoS) and Co1-xS/Co3S4 embedded porous carbon (CoS-PC), which can be ascribed to the difference in crystal structure between Co9S8 and Co1-xS/Co3S4. Therefore, Co9S8-PC shows much better Hg0 capture ability than CoS and CoS-PC under smelting flue gas. O2, SO2 and HCl improve Hg0 adsorption on Co9S8-PC mainly through creating Co3+ site, but H2O has neglectable effect on Hg0 capture. Co9S8-PC shows a remarkably large Hg0 adsorption capacity of 43.18 mg/g, which is greatly higher than the representative metal sulfides for Hg0 removal from smelting flue gas. During Hg0 adsorption, Co3+ is the primary site to directly interact with Hg0, and the adsorbed mercury exists as HgS. Co9S8-PC exhibits an excellent recyclability for capturing Hg0, which is mainly assigned to the replenishment of consumed Co3+ site by O2, SO2 and HCl. Therefore, Co9S8 nanoparticles-embedded porous carbon is an efficient, sustainable and highly recyclable sorbent for Hg0 recovery from smelting flue gas.

A novel MSC-based immune induction strategy for ABO-incompatible liver transplantation: a phase I/II randomized, open-label, controlled trial.

BACKGROUND: ABO-incompatible liver transplantation (ABO-i LT) has become a rescue therapeutic option for patients with severe hepatic failure. Although the use of rituximab greatly reduces the morbidity of antibody-mediated rejection (AMR), severe adverse effects, such as infection and biliary complications, still seriously threaten the survival of transplant recipients. The aim of this study was to evaluate the safety and feasibility of using mesenchymal stem cells (MSCs) to replace rituximab in ABO-i LT. METHODS: Twenty-two patients with severe hepatic failure undergoing ABO-i LT were enrolled and randomly divided into two groups: the MSC group and the rituximab group. The safety of the application of MSCs and the incidence of allograft rejection, including antibody-mediated rejection (AMR) and acute cellular rejection (ACR), were evaluated in both groups at the 2-year follow-up period as primary endpoints. Recipients and graft survival and other postoperative complications were compared as secondary endpoints. RESULTS: No severe MSC-related adverse events were observed during the trial. MSC treatment yielded comparable, if not better, results than rituximab at decreasing the incidence of acute rejection (9.1% vs 27.3%). Inspiringly, compared to those in the rituximab group, the rates of biliary complications (0% vs 45.5%) and infection (9.1% vs 81.8%) were significantly decreased in the MSC group. In addition, there were no significant differences in 2-year graft and recipient survival between the two groups (81.8% vs 72.7%). CONCLUSIONS: Our data show that MSC transfusion is comparable to rituximab treatment for AMR prophylaxis following ABO-i LT. Additionally, the results indicate that MSCs are more beneficial to the prevention of infection and biliary complications and may be introduced as a novel immunosuppressive approach for ABO-i LT. TRIAL REGISTRATION: Trial registration: chictr.org.cn , ChiCTR2000037732. Registered 31 August 2020- Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=57074 .

Diagnosis and Management of Intraabdominal Infection: Guidelines by the Chinese Society of Surgical Infection and Intensive Care and the Chinese College of Gastrointestinal Fistula Surgeons.

The Chinese guidelines for IAI presented here were developed by a panel that included experts from the fields of surgery, critical care, microbiology, infection control, pharmacology, and evidence-based medicine. All questions were structured in population, intervention, comparison, and outcomes format, and evidence profiles were generated. Recommendations were generated following the principles of the Grading of Recommendations Assessment, Development, and Evaluation system or Best Practice Statement (BPS), when applicable. The final guidelines include 45 graded recommendations and 17 BPSs, including the classification of disease severity, diagnosis, source control, antimicrobial therapy, microbiologic evaluation, nutritional therapy, other supportive therapies, diagnosis and management of specific IAIs, and recognition and management of source control failure. Recommendations on fluid resuscitation and organ support therapy could not be formulated and thus were not included. Accordingly, additional high-quality clinical studies should be performed in the future to address the clinicians' concerns.

Correction: MicroRNA-377-3p released by mesenchymal stem cell exosomes ameliorates lipopolysaccharide-induced acute lung injury by targeting RPTOR to induce autophagy.

This work was supported by National 13th Five-Year Science and Technology Plan Major Projects of China (2017ZX10203205-006-001); National Key R&D Plan (2017YFA0104304); National Natural Science Foundation of China (81770648 81972286); Guangdong Natural Science Foundation (2015A030312013, 2018A0303130305); Science and Technology Program of Guangdong Province (2017B020209004, 20169013, 2017B030314027). This has now been corrected in both the PDF and HTML versions of the Article.

MicroRNA-377-3p released by mesenchymal stem cell exosomes ameliorates lipopolysaccharide-induced acute lung injury by targeting RPTOR to induce autophagy.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the severe lung damage and respiratory failure without effective therapy. However, there was a lack of understanding of the mechanism by which exosomes regulate autophagy during ALI/ARDS. Here, we found lipopolysaccharide (LPS) significantly increased inflammatory factors, administration of exosomes released by human umbilical cord mesenchymal stem cells (hucMSCs) successfully improved lung morphometry. Further studies showed that miR-377-3p in the exosomes played a pivotal role in regulating autophagy, leading to protect LPS induced ALI. Compared to exosomes released by human fetal lung fibroblast cells (HFL-1), hucMSCs-exosomes overexpressing miR-377-3p more effectively suppressed the bronchoalveolar lavage (BALF) and inflammatory factors and induced autophagy, causing recoveration of ALI. Administration of miR-377-3p expressing hucMSCs-exosomes or its target regulatory-associated protein of mTOR (RPTOR) knockdown significantly reduced ALI. In summary, miR-377-3p released by hucMSCs-exosomes ameliorated Lipopolysaccharide-induced acute lung injury by targeting RPTOR to induce autophagy in vivo and in vitro.