Neuropilin-1 mediates lung tissue-specific control of ILC2 function in type 2 immunity.

Group 2 innate lymphoid cells (ILC2s) are highly heterogeneous tissue-resident lymphocytes that regulate inflammation and tissue homeostasis in health and disease. However, how these cells integrate into the tissue microenvironment to perform tissue-specific functions is unclear. Here, we show neuropilin-1 (Nrp1), which is induced postnatally and sustained by lung-derived transforming growth factor beta-1 (TGFß1), is a tissue-specific marker of lung ILC2s. Genetic ablation or pharmacological inhibition of Nrp1 suppresses IL-5 and IL-13 production by ILC2s and protects mice from the development of pulmonary fibrosis. Mechanistically, TGFß1-Nrp1 signaling enhances ILC2 function and type 2 immunity by upregulating IL-33 receptor ST2 expression. These findings identify Nrp1 as a tissue-specific regulator of lung-resident ILC2s and highlight Nrp1 as a potential therapeutic target for pulmonary fibrosis.

Real-time, random-access organ screening for carbapenem-resistant organisms (CRO) reduces CRO-associated, donor-derived infection mortality in lung transplant recipients.

PURPOSE: Donor-derived infection (DDI) has become an important factor affecting the prognosis of lung transplantation patients. The risks versus benefits of using donor organs infected with multidrug-resistant organisms (MDRO), especially carbapenem-resistant organisms (CRO), are frequently debated. Traditional microbial culture and antimicrobial susceptibility testing at present fail to meet the needs of quick CRO determination for donor lungs before acquisition. In this study, we explored a novel screening method by using Xpert® Carba-R assay for CRO in donor lungs in a real-time manner to reduce CRO-associated DDI mortality. METHODS: This study was registered on chictr.org.cn (ChiCTR2100053687) on November 2021. In the Xpert Carba-R screening group, donor lungs were screened for CRO infection by the Xpert Carba-R test on bronchoalveolar fluid (BALF) before acquisition. If the result was negative, donor lung acquisition and subsequent lung transplantation were performed. In the thirty-five potential donors, nine (25.71%) with positive Xpert Carba-R results in BALF were declined for lung transplantation. Twenty-six recipients and the matching CRO-negative donor lungs (74.29%) were included in the Xpert Carba-R screening group. In the control group, nineteen recipients underwent lung transplants without Xpert Carba-R screening. The incidence and mortality of CRO-associated DDI were collected and contrasted between the two groups. RESULTS: Multivariate analysis showed that CRO-related death due to DDI within 60 days was significantly lower in the Xpert Carba-R screening group than that in the control group (OR = 0.05, 95% CI 0.003-0.74, p = 0.03). CONCLUSION: Real-time CRO screening of donor lungs before transplantation at the point of care by the Xpert Carba-R helps clinicians formulate lung transplantation strategies quickly and reduces the risk of subsequent CRO infection improving the prognosis of lung transplantation.

Sparse group selection and analysis of function-related residue for protein-state recognition.

Machine learning methods have helped to advance wide range of scientific and technological field in recent years, including computational chemistry. As the chemical systems could become complex with high dimension, feature selection could be critical but challenging to develop reliable machine learning based prediction models, especially for proteins as bio-macromolecules. In this study, we applied sparse group lasso (SGL) method as a general feature selection method to develop classification model for an allosteric protein in different functional states. This results into a much improved model with comparable accuracy (Acc) and only 28 selected features comparing to 289 selected features from a previous study. The Acc achieves 91.50% with 1936 selected feature, which is far higher than that of baseline methods. In addition, grouping protein amino acids into secondary structures provides additional interpretability of the selected features. The selected features are verified as associated with key allosteric residues through comparison with both experimental and computational works about the model protein, and demonstrate the effectiveness and necessity of applying rigorous feature selection and evaluation methods on complex chemical systems.

Glucagon-like peptide-1 receptor mediates the beneficial effect of liraglutide in an acute lung injury mouse model involving the thioredoxin-interacting protein.

Repurposing clinically used drugs is among the important strategies in drug discovery. Glucagon-like peptide-1 (GLP-1) and its diabetes-based drugs, such as liraglutide, possess a spectrum of extra-pancreatic functions, while GLP-1 receptor (GLP-1R) is most abundantly expressed in the lung. Recent studies have suggested that GLP-1-based drugs exert beneficial effects in chronic, as well as acute, lung injury rodent models. Here, we show that liraglutide pretreatment reduced LPS induced acute lung injury in mice. It significantly reduced lung injury score, wet/dry lung weight ratio, bronchoalveolar lavage fluid immune cell count and protein concentration, and cell apoptosis in the lung, and it was associated with reduced lung inflammatory cytokine and chemokine gene expression. Importantly, these effects were virtually absent in GLP-1R-/- mice. A well-known function of GLP-1 and GLP-based drugs in pancreatic ß-cells is the attenuation of high-glucose stimulated expression of thioredoxin-interacting protein (TxNIP), a key component of inflammasome. LPS-challenged lungs showed elevated TxNIP mRNA and protein expression, which was attenuated by liraglutide treatment in a GLP-1R-dependent manner. Hence, our observations suggest that GLP-1R is essential in mediating beneficial effects of liraglutide in acute lung injury, with the inflammasome component TxNIP as a potential target.

Analysis of predictive factors for postoperative survival for non small cell lung carcinoma patients with unexpected mediastinal lymph nodes metastasis.

OBJECTIVES: To discuss the predictive factors of postoperative survival for non small cell lung carcinoma (NSCLC) patients with clinical N0 stage but postoperative pathological N2 stage (cN0-pN2). METHODS: From January 1, 2005, to December 31, 2009, the clinical data of NSCLC patients with cN0-pN2 after radical surgery were retrospectively collected, and their survival information was collected through follow-up. The expiration date for follow-up was December 31, 2011. The predictive factors of postoperative survival for NSCLC patients with unexpected mediastinal lymph node metastasis were analyzed using Cox proportional hazards regression. RESULTS: A total of 263 patients were enrolled. The follow-up rate was 91.63%. The overall 1-, 3-, and 5-year survival rates were 94.6, 55.2, and 26.3%, respectively. Video-assisted thoracotomy surgery (VATS; odds ratio [OR] 0.659; 95% confidence interval [CI] 0.469 to 0.927; p = 0.017), multiple stations of metastatic mediastinal lymph nodes (OR 1.605; 95% CI 1.180 to 2.183; p = 0.003), and no adjuvant chemotherapy (OR 1.576; 95% CI 1.105 to 2.246; p = 0.012) were independent predictive factors for unexpected N2 patients. The median survival after VATS was superior to that after thoracotomy for patients with a single station of metastatic mediastinal lymph node (48.45 m vs 37.34 m, p = 0.018). The median survival without any adjuvant chemotherapy was inferior to that after adjuvant chemotherapy for patients with multiple stations of metastatic mediastinal lymph nodes (20.32 m vs 31.55 m, p = 0.001). CONCLUSION: The postoperative survival for NSCLC patients with cN0-pN2 was related to operational method, adjuvant chemotherapy, and the number of metastatic mediastinal lymph node stations. Patients with a single station of metastatic mediastinal lymph node are likely to benefit from VATS, whereas patients with multiple stations of metastatic mediastinal lymph nodes are likely to benefit from adjuvant chemotherapy.

Effect of Th17 and Treg axis disorder on outcomes of pulmonary arterial hypertension in connective tissue diseases.

This prospective cohort study is to verify the hypothesis that the balance of Th17 and Treg cells frequencies in the peripheral circulation is disturbed in patients with varying degrees of connective tissue diseases-associated pulmonary arterial hypertension (CTD-aPAH) and to prove the influence of Th17/Treg imbalance on prognosis. We detected the frequencies and absolute counts of Th17 and Treg cells and related serum cytokines secretion and expressions of key transcription factors in 117 patients with connective tissue diseases (CTD), 53 patients with CTD-aPAH, and 48 healthy volunteers. Moreover, the median value according to levels of Th17/Treg ratios in patients with CTD-aPAH was chosen as basis of group division for survival analysis. CTD-aPAH patients revealed significant increase in peripheral Th17 cells, Th17-related cytokines, and ROR γt mRNA levels. They also presented a significant decrease in Treg cells, Treg-related cytokines, and Foxp3 mRNA levels as compared with CTD patients and healthy controls. More importantly, the Th17/Treg ratio was significantly related to the severity and prognosis of CTD-aPAH. This study indicated that the Th17/Treg axis disorder plays a critical role in CTD-aPAH. Furthermore, the dynamic balance between Th17 and Treg cells was likely to influence prognosis of patients with CTD-aPAH.

LKB1 prevents ILC2 exhaustion to enhance antitumor immunity.

Group 2 innate lymphoid cells (ILC2s) play crucial roles in mediating allergic inflammation. Recent studies also indicate their involvement in regulating tumor immunity. The tumor suppressor liver kinase B1 (LKB1) inactivating mutations are associated with a variety of human cancers; however, the role of LKB1 in ILC2 function and ILC2-mediated tumor immunity remains unknown. Here, we show that ablation of LKB1 in ILC2s results in an exhausted-like phenotype, which promotes the development of lung melanoma metastasis. Mechanistically, LKB1 deficiency leads to a marked increase in the expression of programmed cell death protein-1 (PD-1) in ILC2s through the activation of the nuclear factor of activated T cell pathway. Blockade of PD-1 can restore the effector functions of LKB1-deficient ILC2s, leading to enhanced antitumor immune responses in vivo. Together, our results reveal that LKB1 acts to restrain the exhausted state of ILC2 to maintain immune homeostasis and antitumor immunity.

MiR-138 inhibits tumor growth through repression of EZH2 in non-small cell lung cancer.

BACKGROUND/AIMS: MicroRNAs (miRNAs) play important roles in tumorigenesis. We investigated the roles and mechanisms of miR-138 in human non-small cell lung cancer (NSCLC). METHODS: The expression of miR-138 was first examined in NSCLC cell lines and tumour tissues by real-time PCR The in vitro and in vivo functional effect of miR-138 was examined further. A luciferase reporter assay was conducted to confirm target association between miR-138 and the enhancer of zeste homolog 2 (EZH2). RESULTS: miR-138 was frequently downregulated in NSCLC cells and tissues. Overexpression of miR-138 inhibited proliferation of NSCLC cells in vitro and tumor growth in vivo. The EZH2 oncogene, which is often overexpressed in various human cancers and acts as an important regulator of cell growth and tumor invasion, was identified as a novel target of miR-138. miR-138 can bind to the 3' untranslated region (3' UTR) of EZH2 and suppress the expression of EZH2 at both mRNA and protein levels. Furthermore, knockdown of EZH2 phenocopied the tumor suppressive effects of miR-138 in cell models, whereas ectopic expression of EZH2 rescued the suppressive effects of miR-138. CONCLUSION: These findings define a tumor suppressor function for miR-138 in NSCLC and further suggest that miR-138 may represent a potential therapeutic target for NSCLC patients.

Transforming growth factor-ß1 induces epithelial-to-mesenchymal transition in human lung cancer cells via PI3K/Akt and MEK/Erk1/2 signaling pathways.

Metastasis of tumor cells is associated with epithelial-to-mesenchymal transition (EMT), which is a process whereby epithelial cells lose their polarity and acquire new features of mesenchyme. EMT has been reported to be induced by transforming growth factor-ß1 (TGF-ß1), but its mechanism remains elusive. In this study, we performed a study to investigate whether PI3K/Akt and MAPK/Erk1/2 signaling pathways involved in EMT in the human lung cancer A549 cells. The results showed that after treated with TGF-ß1 for 48 h, A549 cells displayed more fibroblast-like shape, lost epithelial marker E-cadherin and increased mesenchymal markers Vimentin and Fibronectin. Moreover, TGF-ß1-induced EMT after 48 h was accompanied by increased of cell migration and change of Akt and Erk1/2 phosphorylation. In addition, EMT was reversed by PI3K inhibitor LY294002 and MEK1/2 inhibitor U0126, which suggested that A549 cells under stimulation of TGF-ß1 undergo a switch into mesenchymal cells and PI3K/Akt and MAPK/Erk1/2 signaling pathways serve to regulate TGF-ß1-induced EMT of A549 cells.

Identification of Sports Athletes' High-Strength Sports Injuries Based on NMR.

In order to study the high-strength sports injury in sports, this paper proposes a method based on NMR to identify the high-strength sports injury of sports athletes. This method carries out a questionnaire survey and research on the athletes who are excellent in sports dance major from 2019 to 2021 in the Institute of Physical Education. The athletes' age range is 18-25 years, and the training period of sports dance is 3-5 years. The results show that compared with other recognition methods, the recognition method based on NMR has higher accuracy and efficiency. The method of this study is helpful to improve the recognition efficiency and accuracy. Athletes are very easy to get injured during sports. In order to reduce the degree of injury of athletes, we should strictly follow the action standards in the training process to avoid serious injury.

Circular RNA circRNA-0039459 promotes the migration, invasion, and proliferation of liver cancer cells through the adsorption of miR-432.

This study aimed to investigate the molecular mechanism of circular RNA circ-0039459 and its effects on the apoptosis, proliferation, invasion, and migration of hepatocellular carcinoma cells. The expression of circ-0039459, miR-432, and synoviolin 1 (SYVN1) mRNA was determined using real-time quantitative reverse transcription PCR. Cell proliferation was detected by cell counting kit-8 assay, and the apoptosis rate was detected using flow cytometry. Cell migration and invasion were detected using Transwell assay. The expression of E-cadherin, N-cadherin, and vimentin was detected using western blot. The targeting relationship between circ-0039459 and miR-432 as well as that between miR-432 and SYVN1 were detected using the dual-luciferase reporter and RNA pull-down assays. We found that circ-0039459 and SYVN1 mRNA were highly expressed, whereas miR-432 was lowly expressed in hepatocellular carcinoma cells and tissues. After treatment with ribonuclease R or actinomycin D, the expression of linear RNA was reduced, whereas that of circular RNA was not significantly changed. circ-0039459 knockdown or miR-432 overexpression can inhibit cell proliferation, invasion, and migration and the expression of N-cadherin and vimentin proteins in carcinoma cells as well as promote apoptosis and increase the E-cadherin level. circ-0039459 targeted and regulated miR-432, which targeted and regulated SYVN1. The decreased miR-432 expression reversed the effects of circ-0039459 knockout in cancer cells. Furthermore, SYVN1 overexpression reversed the effect of miR-432 overexpression in hepatoma cells. Hence, circ-0039459 can affect the proliferation, apoptosis, migration, and invasion of hepatocellular carcinoma cells through the adsorption of miR-432, thereby regulating the expression of SYVN1.

The correlation between lncRNA NEAT1 and serum hepcidin in the peripheral blood of non-alcoholic fatty liver disease patients.

OBJECTIVES: To explore and analyze the correlation between lncRNA NEAT1 and serum hepcidin (HEPC) in the peripheral blood of non-alcoholic fatty liver disease patients. METHODS: 119 patients, confirmed to have non-alcoholic fatty liver disease (NAFLD) and admitted to our hospital from January 2017 to June 2019, were enrolled in the NAFLD group, and 100 healthy subjects during the same period were enrolled in the control group. We recorded the two groups' general information and routine laboratory examination results and performed correlation analyses on the lncRNA NEAT1 expressions in their peripheral blood mononuclear cells (PBMCs) and HEPC. RESULTS: The BMI, the waist circumferences, and the ALT, GGT, TC, and TG levels in the NAFLD group were critically higher than they were in the control group (P<0.05). The relative expressions of lncRNA NEAT1 in the PBMCs of the NAFLD group were remarkably higher than they were in the control group (P<0.05). The HEPC levels in the NAFLD group were significantly higher than they were in the control group (P<0.05). The lncRNA NEAT1 expressions in the NAFLD patients presented a remarkable positive correlation with the ALT, GGT, TC, and TG levels (P<0.05). The HEPC levels were positively correlated with the ALT, GGT, TC, and TG levels in the NAFLD patients (P<0.05), and the lncRNA NEAT1 expressions in the peripheral blood had a positive correlation with HEPC (P<0.05). We used ROC curves to analyze the diagnostic value of lncRNA NEAT1 in the peripheral blood to NAFLD, and the area under the curve was 0.822 (95% confidence interval of overall probability: 0.612~0.921). The sensitivity was 86.47%, and the specificity was 82.03%. CONCLUSION: lncRNA NEAT1 is abnormally overexpressed in the PBMCs of patients with NAFLD. The regulatory effect of lncRNA NEAT1 on NAFLD may be related to the mechanism of HEPC, which is expected to be a potential biological indicator for the prevention and treatment of NAFLD.

Case report: Complete resection of invasive thymoma invading the superior vena cava and right atrium under cardiopulmonary bypass support.

Here we describe an uncommon case of a 48-year-old male patient with an invasive thymoma invading the superior vena cava, bilateral innominate veins, right internal jugular vein, right subclavian vein, right atrium, azygos vein, and part of the lung tissues. The tumor was resected entirely under cardiopulmonary bypass support, and the venous bypass using a vascular graft was successfully established between the left innominate vein and the right atrium. The postoperative course was uneventful, and the patient was discharged 15 days after surgery without complications.

Transforming growth factor-ß1 promotes lung adenocarcinoma invasion and metastasis by epithelial-to-mesenchymal transition.

Lung cancer is a highly malignant carcinoma, and most deaths of lung cancer are caused by metastasis. The alterations associated with epithelial-to-mesenchymal transition (EMT) may be related to the cancer cell metastasis. Nevertheless, the mechanism of lung cancer metastasis remains unclear. We conducted a study in vitro to investigate whether transforming growth factor-ß1 (TGF-ß1) could induce changes of, such as cell morphology, expression of relative protein markers, and cellular motile and invasive activities. In this research, the changes of cell morphology were first investigated under a phase contrast microscope, then western blotting was employed to detect the expression of E-cadherin, vimentin, and fibronectin, and finally cell motility and invasion were evaluated by cell wound-healing as well as invasion assays. The data indicated that human lung adenocarcinoma cell lines, A-549 and PC-9 cells of epithelial cell characteristics, were induced to undergo EMT by TGF-ß1. Following TGF-ß1 treatment, cells showed dramatic morphological changes assessed by phase contrast microscopy, accompanied by decreased epithelial marker E-cadherin and increased mesenchymal markers vimentin and fibronectin. More importantly, cell motility and invasion were also enhanced in the EMT process. These results indicated that TGF-ß1 may promote lung adenocarcinoma invasion and metastasis via the mechanism of EMT.

[Epithelial-mesenchymal transition (EMT) and its effect on microRNA expression in lung cancer].

OBJECTIVE: To investigate the effect of epithelial-mesenchymal transition (EMT) on the expression of microRNAs (miRNAs) in lung cancer A549 cells. METHODS: Transforming growth factor beta-1 (TGF-beta 1) in different concentrations was used to induce EMT in lung cancer A549 cells. The morphological changes were observed under phase-contrast microscope. The changes of EMT-related proteins were analyzed by Western blot. The changes of miRNAs expression after EMT were detected by microRNA (miRNA) array. Real time quantitative RT-PCR was applied to verify the reliability of miRNA array results. RESULTS: The lung cancer A549 cells became elongated and the cell-cell junction became loose after EMT. The epithelial protein marker E-cadherin was down-regulated and the mesenchymal protein markers vimentin and fibronectin up-regulated. There were 51 miRNAs showing statistically significant changes of expression more than double (P<0.05) after EMT. Among them 18 were up-regulated and 33 down-regulated. Of them, mir-33a was down-regulated by 92.8% and mir-193a-3p by 86.5%. Real time quantitative RT-PCR showed that mir-33a was down-regulated by 73.1% and mir-193a-3p by 56.6%. CONCLUSION: Epithelial-mesenchymal transition has effects on the expression of miRNAs, and miRNAs may regulate the invasion and metastasis of lung cancer cells via EMT.

[Video-assisted thoracic surgery lobectomy versus open lobectomy for mini pathologic N2 non-small cell lung cancer].

OBJECTIVE: To assess early and late outcomes of patients with minimal mediastinal lymph nodes metastasis N2 non-small cell lung cancer disease unexpectedly detected during the operation, who underwent video-assisted thoracic surgery lobectomy for clinical stage I. METHODS: This study retrospectively reviewed and analyzed the medical records of 263 patients underwent surgery between January 2004 and December 2007, who were diagnosed as having early-stage non-small cell lung cancer (clinical stage was cT1-2N0M0, stage I) before the surgery, but were found to have mini mediastinal lymph nodes metastasis disease (clinical stage was pT1-2N2M0, stage IIIa) unexpectedly detected during the operation and after the operation. All patients underwent lobectomy and systematic lymph nodes dissection as radical treatments. Among them, 63 patients underwent video-assisted thoracic surgery (VATS) lobectomy, including 37 male patients (58.7%) with a mean age of (58 ± 11) years old. Two hundred patients underwent open thoracotomy lobectomy, including 132 male patients (66%) with a mean age of (59 ± 11) years old. To compare and analyze clinical features, early and late outcomes of patients in these two groups. RESULTS: A total of 263 patients with an average survival time (34.9 ± 1.2) months (median 31 months), 63 cases in VATS lobectomy group with an average survival time (40.3 ± 2.2) months (median 37 months), 200 cases in open pulmonary lobectomy group with an average survival time (33.1 ± 1.3) months (median 29 months). The 1-, 2-, 3-year over survival rate of all the patients was 92.0%, 57.4%, 29.3%. The 1-, 2-, 3-year survival rate of patients in VATS lobectomy group was 92.1%, 82.5%, 41.3%. The 1, 2, 3 year survival rate of patients in thoracotomy lobectomy group was 92.0%, 49.5%, 25.5%. There was significant difference between the two groups in this factor (χ(2) = 5.58, P = 0.018). CONCLUSIONS: VATS lobectomy is feasibility and safety for unexpected mini N2 disease. Even if lymph node metastasis is unexpectedly detected during video-assisted thoracic surgery lobectomy for clinical stage I disease after rigorous evaluation of preoperative, it is no need to convert to conventional thoracotomy.

A Novel Circular RNA circCSPP1 Promotes Liver Cancer Progression by Sponging miR-1182.

INTRODUCTION: Aberrant circular RNA (circRNA) expression has been extensively discovered for its involvement in both the initiation and progression of various cancers. Through screening circRNA profile, we identified a novel circRNA has_circ_0001806, which is termed as circCSPP1 in liver cancer. In the present study, we aim to investigate the role of circCSPP1 in the progression of liver cancer. METHODS: Fluorescence in situ hybridization (FISH) was used to detect the location of circCSPP1. Function studies including MTT, colony formation assay, transwell assay and flow cytometry were carried out to detect the malignant behaviour of circCSPP1 on liver cancer cells. Luciferase assay and RNA pull down were used to detect the interaction between miR-1182 and circCSPP1 as well as RAB15. Quantitative realtime (qPCR) and Western blot were performed to evaluate the RNA and protein expression, respectively. RESULTS: CircCSPP1 knockdown inhibited the proliferation, migration and invasion while promoted apoptosis of liver cancer cells. Mechanically, we predicted and verified the target miR of circCSPP1 which is miR-1182. miR-1182 was capable of reversing the effect of circCSPP1 on liver cancer cells. Moreover, miR-1182 was found to also target RAB15 to participate in the regulation of cell phenotype. DISCUSSION: Taken together, circCSPP1 promoted progression of liver cancer cells via sponging miR-1182 which may serve as a novel prognostic and therapeutic target for liver cancer.

Ischemia-Reperfusion Injury in a Simulated Lung Transplant Setting Differentially Regulates Transcriptomic Profiles between Human Lung Endothelial and Epithelial Cells.

Current understanding of mechanisms of ischemia-reperfusion-induced lung injury during lung preservation and transplantation is mainly based on clinical observations and animal studies. Herein, we used cell and systems biology approaches to explore these mechanisms at transcriptomics levels, especially by focusing on the differences between human lung endothelial and epithelial cells, which are crucial for maintaining essential lung structure and function. Human pulmonary microvascular endothelial cells and human lung epithelial cells were cultured to confluent, subjected to different cold ischemic times (CIT) to mimic static cold storage with preservation solution, and then subjected to warm reperfusion with a serum containing culture medium to simulate lung transplantation. Cell morphology, viability, and transcriptomic profiles were studied. Ischemia-reperfusion injury induced a CIT time-dependent cell death, which was associated with dramatic changes in gene expression. Under normal control conditions, endothelial cells showed gene clusters enriched in the vascular process and inflammation, while epithelial cells showed gene clusters enriched in protein biosynthesis and metabolism. CIT 6 h alone or after reperfusion had little effect on these phenotypic characteristics. After CIT 18 h, protein-biosynthesis-related gene clusters disappeared in epithelial cells; after reperfusion, metabolism-related gene clusters in epithelial cells and multiple gene clusters in the endothelial cells also disappeared. Human pulmonary endothelial and epithelial cells have distinct phenotypic transcriptomic signatures. Severe cellular injury reduces these gene expression signatures in a cell-type-dependent manner. Therapeutics that preserve these transcriptomic signatures may represent new treatment to prevent acute lung injury during lung transplantation.

[Forensic medicine identification of manual strangulation: an analysis of 21 cases].

OBJECTIVE: To analyze and summarize the rule of manual strangulation, as well as to look for the key points of injury identification, in order to provide information for formulating and revising the identification regulations. METHODS: Twenty-one cases of manual strangulation from 1963 to 2004 in Xiangfan were reviewed and analyzed according to the characters, symptoms and appraisements. RESULTS: The majority of assaulters in manual strangulation was young adult male and often could find the counteracted wounds on them. The throttling mark reaction usually could be found in victims and the cardinal symptoms were contusion in throat and asphyxiation in ocular region. CONCLUSION: The degree of injuries is mainly moderate and slight. There is some inadaptability in the current regulations.

HDAC6-specific inhibitor suppresses Th17 cell function via the HIF-1α pathway in acute lung allograft rejection in mice.

Background: Previous animal experiments and clinical studies indicated the critical role of Th17 cells in lung transplant rejection. Therefore, the downregulation of Th17 cell function in lung transplant recipients is of great interest. Methods: We established an orthotopic mouse lung transplantation model to investigate the role of histone deacetylase 6-specific inhibitor (HDAC6i), Tubastatin A, in the suppression of Th17 cells and attenuation of pathologic lesions in lung allografts. Moreover, mechanism studies were conducted in vitro. Results: Tubastatin A downregulated Th17 cell function in acute lung allograft rejection, prolonged the survival of lung allografts, and attenuated acute rejection by suppressing Th17 cell accumulation. Consistently, exogenous IL-17A supplementation eliminated the protective effect of Tubastatin A. Also, hypoxia-inducible factor-1α (HIF-1α) was overexpressed in a lung transplantation mouse model. HIF-1α deficiency suppressed Th17 cell function and attenuated lung allograft rejection by downregulating retinoic acid-related orphan receptor γt (ROR γt) expression. We showed that HDAC6i downregulated HIF-1α transcriptional activity under Th17-skewing conditions in vitro and promoted HIF-1α protein degradation in lung allografts. HDAC6i did not affect the suppression of HIF-1α-/- naïve CD4+ T cell differentiation into Th17 cell and attenuation of acute lung allograft rejection in HIF-1α-deficient recipient mice. Conclusion: These findings suggest that Tubastatin A downregulates Th17 cell function and suppresses acute lung allograft rejection, at least partially, via the HIF-1α/ RORγt pathway.