Metabolomic insights into pulmonary fibrosis: a mendelian randomization study.

BACKGROUND: This study leverages a two-sample Mendelian Randomization (MR) approach to explore the causal relationships between 1,400 metabolites and pulmonary fibrosis, using genetic variation as instrumental variables. By adhering to stringent criteria for instrumental variable selection, the research aims to uncover metabolic pathways that may influence the risk and progression of pulmonary fibrosis, providing insights into potential therapeutic targets. METHODS: Utilizing data from the OpenGWAS project, which includes a significant European cohort, and metabolite GWAS data from the Canadian Longitudinal Aging Study (CLSA), the study employs advanced statistical methods. These include inverse variance weighting (IVW), weighted median estimations, and comprehensive sensitivity analyses conducted using the R software environment to ensure the robustness of the causal inferences. RESULTS: The study identified 62 metabolites with significant causal relationships with pulmonary fibrosis, highlighting both risk-enhancing and protective metabolic factors. This extensive list of metabolites presents a broad spectrum of potential therapeutic targets and biomarkers for early detection, underscoring the metabolic complexity underlying pulmonary fibrosis. CONCLUSIONS: The findings from this MR study significantly advance our understanding of the metabolic underpinnings of pulmonary fibrosis, suggesting that alterations in specific metabolites could influence the risk and progression of the disease. These insights pave the way for the development of novel diagnostic and therapeutic strategies, emphasizing the potential of metabolic modulation in managing pulmonary fibrosis.

Inhibition of OGG1 ameliorates pulmonary fibrosis via preventing M2 macrophage polarization and activating PINK1-mediated mitophagy.

BACKGROUND: 8-Oxoguanine DNA glycosylase (OGG1), a well-known DNA repair enzyme, has been demonstrated to promote lung fibrosis, while the specific regulatory mechanism of OGG1 during pulmonary fibrosis remains unclarified. METHODS: A bleomycin (BLM)-induced mouse pulmonary fibrosis model was established, and TH5487 (the small molecule OGG1 inhibitor) and Mitochondrial division inhibitor 1 (Mdivi-1) were used for administration. Histopathological injury of the lung tissues was assessed. The profibrotic factors and oxidative stress-related factors were examined using the commercial kits. Western blot was used to examine protein expression and immunofluorescence analysis was conducted to assess macrophages polarization and autophagy. The conditional medium from M2 macrophages was harvested and added to HFL-1 cells for culture to simulate the immune microenvironment around fibroblasts during pulmonary fibrosis. Subsequently, the loss- and gain-of function experiments were conducted to further confirm the molecular mechanism of OGG1/PINK1. RESULTS: In BLM-induced pulmonary fibrosis, OGG1 was upregulated while PINK1/Parkin was downregulated. Macrophages were activated and polarized to M2 phenotype. TH5487 administration effectively mitigated pulmonary fibrosis, M2 macrophage polarization, oxidative stress and mitochondrial dysfunction while promoted PINK1/Parkin-mediated mitophagy in lung tissues of BLM-induced mice, which was partly hindered by Mdivi-1. PINK1 overexpression restricted M2 macrophages-induced oxidative stress, mitochondrial dysfunction and mitophagy inactivation in lung fibroblast cells, and OGG1 knockdown could promote PINK1/Parkin expression and alleviate M2 macrophages-induced mitochondrial dysfunction in HFL-1 cells. CONCLUSION: OGG1 inhibition protects against pulmonary fibrosis, which is partly via activating PINK1/Parkin-mediated mitophagy and retarding M2 macrophage polarization, providing a therapeutic target for pulmonary fibrosis.

Research progress of protein complex systems and their application in food: A review.

Among the common natural biomolecules, the excellent properties of proteins have attracted extensive attention from researchers for functional applications, however, in native form proteins have many limitations in the performance of their functional attribute. However, with the deepening of research, it has been found that the combination of natural active substances such as polyphenols, polysaccharides, etc. with protein molecules will make the composite system have stronger functional properties, while the utilization of pH-driven method, ultrasonic treatment, heat treatment, etc. not only provides a guarantee for the overall protein-based composite system, but also gives more possibilities to the protein-composite system. Protein composite systems are emerging in the fields of novel active packaging, functional factor delivery systems and gel systems with high medical value. The products of these protein composite systems usually have high functional properties, mainly due to the interaction of the remaining natural active substances with protein molecules, which can be broadly categorized into covalent interactions and non-covalent interactions, and which, despite the differences in these interactions, together constitute the cornerstone for the stability of protein composite systems and for in-depth research.

Distinct latitudinal patterns and drivers of topsoil nitrogen and phosphorus across urban forests in eastern China.

Nitrogen (N) and phosphorus (P) are the two most important macronutrients supporting forest growth. Unprecedented urbanization has created growing areas of urban forests that provide key ecosystem services for city dwellers. However, the large-scale patterns of soil N and P content remain poorly understood in urban forests. Based on a systematic soil survey in urban forests from nine large cities across eastern China, we examined the spatial patterns and key drivers of topsoil (0-20 cm) total N content, total P content, and N:P ratio. Topsoil total N content was found to change significantly with latitude in the form of an inverted parabolic curve, while total P content showed an opposite latitudinal pattern. Variance partition analysis indicated that regional-scale patterns of topsoil total N and P contents were dominated by climatic drivers and partially regulated by time and pedogenic drivers. Conditional regression analyses showed a significant increase in topsoil total N content with lower mean annual temperature (MAT) and higher mean annual precipitation (MAP), while topsoil total P content decreased significantly with higher MAP. Topsoil total N content also increased significantly with the age of urban park and varied with pre-urban soil type, while no such effects were found for topsoil total P content. Moreover, topsoil N:P ratio showed a latitudinal pattern similar to that of topsoil total N content and also increased significantly with lower MAT and higher MAP. Our findings demonstrate distinct latitudinal trends of topsoil N and P contents and highlight a dominant role of climatic drivers in shaping the large-scale patterns of topsoil nutrients in urban forests.

Inhalable Textile Microplastic Fibers Impair Airway Epithelial Differentiation.

Rationale: Microplastics are a pressing global concern, and inhalation of microplastic fibers has been associated with interstitial and bronchial inflammation in flock workers. However, how microplastic fibers affect the lungs is unknown. Objectives: Our aim was to assess the effects of 12 × 31 µm nylon 6,6 (nylon) and 15 × 52 µm polyethylene terephthalate (polyester) textile microplastic fibers on lung epithelial growth and differentiation. Methods: We used human and murine alveolar and airway-type organoids as well as air-liquid interface cultures derived from primary lung epithelial progenitor cells and incubated these with either nylon or polyester fibers or nylon leachate. In addition, mice received one dose of nylon fibers or nylon leachate, and, 7 days later, organoid-forming capacity of isolated epithelial cells was investigated. Measurements and Main Results: We observed that nylon microfibers, more than polyester, inhibited developing airway organoids and not established ones. This effect was mediated by components leaching from nylon. Epithelial cells isolated from mice exposed to nylon fibers or leachate also formed fewer airway organoids, suggesting long-lasting effects of nylon components on epithelial cells. Part of these effects was recapitulated in human air-liquid interface cultures. Transcriptomic analysis revealed upregulation of Hoxa5 after exposure to nylon fibers. Inhibiting Hoxa5 during nylon exposure restored airway organoid formation, confirming Hoxa5's pivotal role in the effects of nylon. Conclusions: These results suggest that components leaching from nylon 6,6 may especially harm developing airways and/or airways undergoing repair, and we strongly encourage characterization in more detail of both the hazard of and the exposure to microplastic fibers.

Quercetin influences intestinal dysbacteriosis and delays alveolar epithelial cell senescence by regulating PTEN/PI3K/AKT signaling in pulmonary fibrosis.

Pulmonary fibrosis is a chronic and progressive lung disease with high mortality. This study aims to explore the protective mechanism of quercetin against pulmonary fibrosis regarding cell senescence and gut microbiota. Rats were intratracheally injected with bleomycin (BLM) to establish a pulmonary fibrosis rat model. RLE-6TN cells were stimulated with BLM to build the model of alveolar epithelial cell senescence, and RLE-6TN-derived conditional medium (CM) was harvested to further culture fibroblasts. Histopathological changes were assessed by H&E and Masson staining. α-SMA expression was assessed by immunofluorescence assay. Senescence-associated ß-galactosidase (SA-ß-gal) staining and senescence-associated secretory phenotype (SASP) cytokine assay were conducted to assess cellular senescence. Gut microbiota was analyzed by 16S rRNA gene sequencing. The fibrosis-, senescence-, and PTEN/PI3K/AKT signaling-related proteins were examined by western blot. In BLM-induced pulmonary fibrosis rats, quercetin exerted its protective effects by reducing histological injury and collagen deposition, lessening cellular senescence, and regulating gut microbiota. In BLM-induced alveolar epithelial cell senescence, quercetin inhibited senescence, lessened SASP cytokine secretion of alveolar epithelial cells, and further ameliorated collagen deposition in fibroblasts. In addition, quercetin might exert its functional effects by regulating the PTEN/PI3K/AKT signaling pathway. Moreover, quercetin regulated intestinal dysbacteriosis in BLM-induced pulmonary fibrosis rats, especially boosting the abundance of Akkermansia. To conclude, our findings provide an in-depth understanding of the potential mechanism behind the protective role of quercetin against pulmonary fibrosis.

Buyang Huanwu decoction ameliorates bleomycin-induced pulmonary fibrosis in rats by attenuating the apoptosis of alveolar type II epithelial cells mediated by endoplasmic reticulum stress.

ETHNOPHARMACOLOGICAL RELEVANCE: According to the theory of traditional Chinese medicine, the pathogenesis of idiopathic pulmonary fibrosis (IPF) can be attributed to qi deficiency and blood stasis. Buyang Huanwu decoction (BHD), a representative Chinese herbal prescription for qi deficiency and blood stasis syndrome, is widely used to treat IPF in clinical practice. However, its potential mechanisms against IPF remain unclear. AIMS OF THE STUDY: This study was carried out to explore the therapeutic effects and underlying mechanisms of BHD on bleomycin (BLM)-induced pulmonary fibrosis in rats. MATERIALS AND METHODS: UPLC-MS/MS method was performed to identify the quality of BHD used in this study. Concurrently, a IPF rat model was established by single intratracheal injection of BLM. Pulmonary function test, H&E staining, Masson staining, hydroxyproline assay were conducted to evaluate the therapeutic effects of BHD on BLM-induced pulmonary fibrosis in rats, and the regulatory effect of BHD on endoplasmic reticulum stress (ERS)-mediated alveolar type II epithelial cells (AEC2s) apoptosis in rats was further investigated by TUNEL staining, Western blot, real-time fluorescence quantitative PCR and immunofluorescence co-staining to reveal the potential mechanisms of BHD against IPF. RESULTS: The UPLC-MS/MS analysis showed that the BHD we used complied with the relevant quality control standards. The data from animal experiments confirmed that BHD administration ameliorated BLM-induced pulmonary function decline, lung fibrotic pathological changes and collagen deposition in rats. Further mechanism study revealed that BHD increased the Bcl-2 protein expression, decreased the Bax protein expression and inhibited the cleavage of CASP3 via suppressing the activation of PERK-ATF4-CHOP pathway under continuous ERS, thereby alleviating BLM-induced AEC2s apoptosis of rats. CONCLUSION: This study demonstrated that BHD ameliorated BLM-induced pulmonary fibrosis in rats by suppressing ERS-mediated AEC2s apoptosis. Our findings can provide some fundamental research basis for the clinical application of BHD in the treatment of IPF.

Iodine-Doped 3D Print Ti Alloy for Antibacterial Therapy on Orthopedic Implants.

This study presents a novel approach to mitigating bacterial infections and antibiotic resistance in medical implants through the integration of iodine-doping and 3D printing techniques. Iodine, with its potent antibacterial properties, and titanium alloy (Ti), a popular metal for implants due to its mechanical and biological properties, were combined via electrodeposition on 3D-printed titanium alloy (3D-Ti) implants. Scanning electron microscopy, energy dispersive spectroscopy, and X-ray photoelectron spectroscopy confirmed the successful creation of iodine-doped titanium implants with improved iodine content due to the rough surface of the 3D-printed material. In vitro studies revealed that these implants significantly inhibited bacterial adhesion and biofilm formation and showed favorable release kinetics for iodine ions. Biocompatibility tests demonstrated no cytotoxic effects and good hemocompatibility. The implants demonstrated enhanced antimicrobial efficacy against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria strains. The findings imply that the integration of iodine-doping and 3D printing technologies is a promising strategy for treating postoperative infections associated with medical implants, consequently bettering the prognosis for patients. Future investigations are encouraged to delve into the long-standing impacts and prospective clinical utility of this groundbreaking methodology.

Associations between eating speed and food temperature and type 2 diabetes mellitus: a cross-sectional study.

Objective: This study aimed to evaluate the relationship between eating speed and food temperature and type 2 diabetes mellitus (T2DM) in the Chinese population. Methods: A cross-sectional survey was conducted between December 2020 to March 2022 from the department of Endocrinology at the Shandong Provincial Hospital. All recruited participants were asked to complete structured questionnaires on their eating behaviors at the time of recruitment. Clinical demographic data such as gender, age, height, weight, familial history of T2DM, prevalence of T2DM and various eating behaviors were collected. Univariate and multivariate logistic regression analyses were used to analyze the associations between eating behaviors and T2DM. Results: A total of 1,040 Chinese adults were included in the study, including 344 people with T2DM and 696 people without T2DM. Multivariate logistic regression analysis of the general population showed that gender (OR = 2.255, 95% CI: 1.559-3.260, p < 0.001), age (OR = 1.091, 95% CI: 1.075-1.107, p < 0.001), BMI (OR = 1.238, 95% CI: 1.034-1.483, p = 0.020), familial history of T2DM (OR = 5.709, 95% CI: 3.963-8.224, p < 0.001), consumption of hot food (OR = 4.132, 95% CI: 2.899-5.888, p < 0.001), consumption of snacks (OR = 1.745, 95% CI: 1.222-2.492, p = 0.002), and eating speed (OR = 1.292, 95% CI:1.048-1.591, p = 0.016) were risk factors for T2DM. Conclusion: In addition to traditional risk factors such as gender, age, BMI, familial history of T2DM, eating behaviors associated with Chinese culture, including consumption of hot food, consumption of snacks, and fast eating have shown to be probable risk factors for T2DM.

EGFL6 promotes bone metastasis of lung adenocarcinoma by increasing cancer cell malignancy and bone resorption.

Lung adenocarcinoma is the most common and aggressive type of lung cancer with the highest incidence of bone metastasis. Epidermal growth factor-like domain multiple 6 (EGFL6) is an exocrine protein, and the expression of EGFL6 is correlated with survival of patient with lung adenocarcinoma. However, the association between EGFL6 expression in lung adenocarcinoma and bone metastasis has not been investigated. In this study, we found that EGFL6 levels in lung adenocarcinoma tissues correlate with bone metastasis and TNM stages in surgical patients. In vitro, overexpression of EGFL6 in lung adenocarcinoma cells promoted their proliferation, migration, and invasion ability compared with control by enhancing EMT process and activating Wnt/ß-catenin and PI3K/AKT/mTOR pathways. In the nude mouse model, overexpression of EGFL6 enhanced tumor growth and caused greater bone destruction. Moreover, the exocrine EGFL6 of human lung adenocarcinoma cells increased osteoclast differentiation of bone marrow mononuclear macrophages (BMMs) of mice via the NF-κB and c-Fos/NFATc1 signaling pathways. However, exocrine EGFL6 had no effect on osteoblast differentiation of bone marrow mesenchymal stem cells (BMSCs). In conclusion, high expression of EGFL6 in lung adenocarcinomas is associated with bone metastasis in surgical patients. The underlying mechanism may be the increased metastatic properties of lung adenocarcinoma cells with high EGFL6 level and the enhanced osteoclast differentiation and bone resorption by exocrine EGFL6 from tumors. Therefore, EGFL6 is a potential therapeutic target to reduce the ability of lung adenocarcinomas to grow and metastasize and to preserve bone mass in patients with bone metastases from lung adenocarcinomas.

Genetic association of telomere length, obesity and tobacoo smoking with idiopathic pulmonary fibrosis risk.

BACKGROUND: Due to the inadequacy of published evidence, association of telomere length (TL), obesity and tobacco smoking with idiopathic pulmonary fibrosis (IPF) remains unclear. The aim of the study was to explore whether these exposures genetically affected the risk of the disease. METHODS: Genetic variants from genome-wide association studies for TL, body mass index (BMI), body fat percentage (BFP) and tobacco smoking (including maternal smoking) were used as instrumental variables. Inverse-variance weighted were mainly adopted to determine the genetic association of these exposures with IPF. All analyses were conducted by R-software (version 3.6.1). RESULTS: Firstly, longer TL was associated with the decreased risk of IPF (OR = 0.475 per SD increase in TL, 95%CI = 0.336 ~ 0.670, P<0.001). Secondly, higher levels of BMI and BFP were related to the increased risk of the disease (OR = 1.425 per SD increase in BMI level, 95%CI = 1.114 ~ 1.823, P = 0.005; OR = 1.702 per SD increase in BFP level, 95%CI = 1.202 ~ 2.409, P = 0.003). Thirdly, maternal smoking was implicated in the increased risk of the disease (OR = 13.183 per SD increase in the prevalence of maternal smoking, 95%CI = 1.820 ~ 95.484, P = 0.011). CONCLUSION: TL should be a genetic risk factor for IPF. Obesity and exposure to tobacco smoking as a fetus might also contribute to the development of this fibrotic diseases. These findings should be verified by future studies.

The m6A-regulation and single cell effect pattern in sunitinib resistance on clear cell renal cell carcinoma: Identification and validation of targets.

Background: Sunitinib is the main target drug for clear cell renal cell carcinoma. However, the effect of sunitinib is often limited by acquired drug resistance. Methods: The open-accessed data used in this study were obtained from different online public databases, which were analyzed using the R software. The RNA level of specific genes was detected using quantitative Real-Time PCR. Sunitinib-resistant cell lines were constructed based on protocol get from the previous study. Colony formation and Cell Counting Kit-8 assays were applied to detect cell proliferation ability. Results: In this study, through publicly available data and high-quality analysis, we deeply explored the potential biological mechanisms that affect the resistance of sunitinib. Detailed, data from GSE64052, GSE76068 and The Cancer Genome Atlas were extracted. We identified the IFITM1, IL6, MX2, PCOLCE2, RSAD2 and SLC2A3 were associated with sunitinib resistance. Single-cell analysis, prognosis analysis and m6A regulatory network were conducted to investigate their role. Moreover, the MX2 was selected for further analysis, including its biological role and effect on the ccRCC microenvironment. Interestingly, we noticed that MX2 might be an immune-related gene that could affect the response rate of immunotherapy. Then, in vitro experiments validated the overexpression of MX2 in sunitinib-resistance cells. Colony formation assay indicated that the knockdown of MX2 could remarkably inhibit the proliferation ability of 786-O-Res and Caki-1-Res when exposed to sunitinib. Conclusion: In summary, through publicly available data and high-quality analysis, we deeply explored the potential biological mechanisms that affect the resistance of sunitinib. MX2 was selected for further analysis, including its biological role and effect on the ccRCC microenvironment. Finally, in vitro experiments were used to validate its role in ccRCC.

Pericytes: The lung-forgotten cell type.

Pericytes are a heterogeneous population of mesenchymal cells located on the abluminal surface of microvessels, where they provide structural and biochemical support. Pericytes have been implicated in numerous lung diseases including pulmonary arterial hypertension (PAH) and allergic asthma due to their ability to differentiate into scar-forming myofibroblasts, leading to collagen deposition and matrix remodelling and thus driving tissue fibrosis. Pericyte-extracellular matrix interactions as well as other biochemical cues play crucial roles in these processes. In this review, we give an overview of lung pericytes, the key pro-fibrotic mediators they interact with, and detail recent advances in preclinical studies on how pericytes are disrupted and contribute to lung diseases including PAH, allergic asthma, and chronic obstructive pulmonary disease (COPD). Several recent studies using mouse models of PAH have demonstrated that pericytes contribute to these pathological events; efforts are currently underway to mitigate pericyte dysfunction in PAH by targeting the TGF-ß, CXCR7, and CXCR4 signalling pathways. In allergic asthma, the dissociation of pericytes from the endothelium of blood vessels and their migration towards inflamed areas of the airway contribute to the characteristic airway remodelling observed in allergic asthma. Although several factors have been suggested to influence this migration such as TGF-ß, IL-4, IL-13, and periostin, recent evidence points to the CXCL12/CXCR4 pathway as a potential therapeutic target. Pericytes might also play an essential role in lung dysfunction in response to ageing, as they are responsive to environmental risk factors such as cigarette smoke and air pollutants, which are the main drivers of COPD. However, there is currently no direct evidence delineating the contribution of pericytes to COPD pathology. Although there is a lack of human clinical data, the recent available evidence derived from in vitro and animal-based models shows that pericytes play important roles in the initiation and maintenance of chronic lung diseases and are amenable to pharmacological interventions. Therefore, further studies in this field are required to elucidate if targeting pericytes can treat lung diseases.

Does the Digital Economy Promote the Reduction of Urban Carbon Emission Intensity?

The impact of the digital economy is increasing, and its environmental effect has attracted more and more attention. The digital economy promotes the improvement of production efficiency and the government's environmental governance capacity, and contributes to the reduction of urban carbon emission intensity. In order to study the impact of digital economy development on urban carbon emission intensity, this paper analyzes the theoretical basis of the digital economy on the reduction of carbon emission intensity, and then, based on the panel data of cities from 2011 to 2019, uses the two-way fixed effect model for empirical testing. The regression results show that the development of the digital economy has promoted the reduction of carbon emission intensity of cities, promoted the green transformation and upgrading of cities, and lays a foundation for China to achieve carbon peaking and carbon neutralization through the improvement of human capital investment and green innovation level. The basic conclusion is robust by changing core explanatory variables, changing samples, replacing regression methods, and shrinking and truncating tests. The impact of the digital economy on urban carbon emission intensity varies with the location, grade and size of the city. Specifically, the development of the digital economy in cities in the eastern and central regions, cities at or above the sub provincial level, large cities and non-resource-based cities has promoted the reduction of urban carbon emission intensity. In terms of resource-based cities, the development of the digital economy in renewable resource-based cities and resource-based cities dominated by iron ore and oil mining has promoted the decline in urban carbon emission reduction intensity.

Review on the Diverse Biological Effects of Glabridin.

Glabridin is a prenylated isoflavan from the roots of Glycyrrhiza glabra Linne and has posed great impact on the areas of drug development and medicine, due to various biological properties such as anti-inflammation, anti-oxidation, anti-tumor, anti-microorganism, bone protection, cardiovascular protection, neuroprotection, hepatoprotection, anti-obesity, and anti-diabetes. Many signaling pathways, including NF-κB, MAPK, Wnt/ß-catenin, ERα/SRC-1, PI3K/AKT, and AMPK, have been implicated in the regulatory activities of glabridin. Interestingly, glabridin has been considered as an inhibitor of tyrosinase, P-glycoprotein (P-gp), and CYP2E1 and an activator of peroxisome proliferator-activated receptor γ (PPARγ), although their molecular regulating mechanisms still need further investigation. However, poor water solubility and low bioavailability have greatly limited the clinical applications of glabridin. Hopefully, several effective strategies, such as nanoemulsions, microneedles, and smartPearls formulation, have been developed for improvement.

Machine learning identifies characteristics molecules of cancer associated fibroblasts significantly correlated with the prognosis, immunotherapy response and immune microenvironment in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is a highly lethal disease with a dramatic pro-fibrocytic response. Cancer-associated fibroblasts (CAFs) have been reported to play a key role in lung adenocarcinoma. Methods: Marker genes of CAFs were obtained from the Cell Marker website. Single sample gene set enrichment analysis (ssGSEA) was used for CAFs quantification. R and GraphPad Prism software were utilized for all analysis. Quantitative real-time PCR (qRT-PCR) was utilized to detect the RNA level of specific molecules. Results: Based on the ssGSEA algorithm and obtained CAFs markers, the LUAD patients with low- and high-CAFs infiltration were successfully identified, which had different response patterns to immunotherapy. Through the machine learning algorithm - LASSO logistic regression, we identified 44 characteristic molecules of CAFs. Furthermore, a prognosis signature consisting of seven characteristic genes was established, which showed great prognosis prediction ability. Additionally, we found that patients in the low-risk group might have better outcomes when receiving immunotherapy of PD-1, but not CTLA4. Also, the biological enrichment analysis revealed that immune response-related pathways were significantly associated with CAFs infiltration. Meanwhile, we investigated the underlying biological and microenvironment difference in patients with high- and low-risk groups. Finally, we identified that AMPD1 might be a novel target for LUAD immunotherapy. Patients with a high level of AMPD1 were correlated with worse responses to immunotherapy. Moreover, immunohistochemistry showed that the protein level of AMPD1 was higher in lung cancer. Results of qRT-PCR demonstrated that AMPD1 was upregulated in A549 cells compared with BEAS-2B. Meanwhile, we found that the knockdown of AMPD4 can significantly reduce the expression of CTLA4 and PDCD1, but not CD274 and PDCD1LG2. Conclusion: We comprehensively explored the role of CAFs and its characteristics molecules in LUAD immunotherapy and developed an effective signature to indicate patients prognosis and immunotherapy response. Moreover, AMPD1 was identified as a novel target for lung cancer immunotherapy.

Rotator cuff repair with biodegradable high-purity magnesium suture anchor in sheep model.

Background: Rotator cuff tear has become one of the diseases affecting people's living quality. Conventional anchor materials such as titanium alloy and poly-lactic acid can lead to postoperative complications like bone defects and aseptic inflammation. Magnesium (Mg)-based implants are biodegradable and biocompatible, with strong potential to be applied in orthopaedics. Methods: In this study, we developed a high-purity (HP) Mg suture anchor and studied its mechanical properties and degradation behavior in vitro. Furthermore, we described the use of high-purity Mg to prepare suture anchor for the rotator cuff repair in sheep. Results: The in vitro tests showed that HP Mg suture anchor possess proper degradation behavior and appropriate mechanical property. Animal experiment indicated that HP Mg suture anchor provided reliable anchoring function in 12 weeks and showed no toxic effect on animal organs. Conclusion: In summary, the HP Mg anchor presented in this study had favorable mechanical property and biosecurity.The translational potential of this article: The translational potential of this article is to use high-purity Mg to develop a degradable suture anchor and verify the feasibility of the application in animal model. This study provides a basis for further research on the clinical application of biodegradable high-purity Mg suture anchor.