High-sensitivity fiber optic graphene resonant accelerometer.

This study proposes a high-sensitivity resonant graphene accelerometer based on a pressure-induced sensing mechanism. The accelerometer design encompasses an optical fiber and a vacuum-sealed graphene resonator affixed to a silicon sensitive film, incorporating a proof mass. This indirect sensing mechanism effectively mitigates the vibration mode aliasing of graphene and the proof mass while ensuring a minimal energy loss in the operating resonator. The mechanical vibration of graphene is excited and detected through an all-fiber optical system. Notably, the proposed sensor demonstrates a sensitivity of 34.3 kHz/g within the range of 0-3.5 g, which is eight times higher than comparable accelerometers utilizing a proof mass on a graphene membrane. This work exhibits a novel, to the best of our knowledge, approach to an acceleration measurement using 2D resonators, exhibiting distinct advantages in terms of compact size and heightened sensitivity.

Highly Luminescent Chiral Double π-Helical Nanoribbons.

Unveiling the mechanism behind chirality propagation and dissymmetry amplification at the molecular level is of significance for the development of chiral systems with comprehensively outstanding chiroptical performances. Herein, we have presented a straightforward Cu-mediated Ullmann homocoupling approach to synthesize perylene diimide-entwined double π-helical nanoribbons encompassing dimer, trimer, and tetramer while producing homochiral or heterochiral linking of chiral centers. A significant dissymmetry amplification was achieved, with absorption dissymmetry factors (|gabs|) increasing from 0.009 to 0.017 and further to 0.019, and luminescence dissymmetry factors (|glum|) rising from 0.007 to 0.013 and eventually to 0.015 for homochiral double π-helical oligomers. The disparity of magnetic transition dipole moment (m) densities in homochiral and heterochiral tetramers by time-dependent density functional theory calculations confirmed that homochiral oligomerization can maximize the total m, which is favorable for achieving ever-increasing g factors. Notably, these double π-helices exhibited exceptional photoluminescence quantum yields (ΦPL) ranging from 83 to 95%. The circularly polarized luminescence brightness (BCPL) eventually reached a remarkable 575 M-1 cm-1 for the homochiral tetramer, which is among the highest values reported for chiral small molecules. This kind of linearly extended double π-helices offers a platform for a comprehensive understanding of the mechanism behind chirality propagation and dissymmetry amplification.

Hydrogen sulfide inhibits alveolar type II cell senescence and limits pulmonary fibrosis via promoting MDM2-mediated p53 degradation.

AIM: Senescence of alveolar type II (AT2) cells is an important driver of pulmonary fibrosis. This study aimed to investigate whether and how dysregulation of hydrogen sulfide (H2 S) production affected AT2 cell senescence, and then explored the effect of H2 S on the communication between AT2 and fibroblasts. METHODS: ICR mice were intratracheally administered with bleomycin (3 mg/kg). Sodium hydrosulfide (NaHS, 28 µmol/kg/d) was intraperitoneally injected for 2 weeks. The H2 S-generating enzyme cystathionine-ß-synthase (CBS) knockout heterozygous (CBS+/- ) mice were used as a low H2 S production model. RESULTS: Analysis of microarray datasets revealed downregulation of H2 S-generating enzymes in lung tissues of patients with pulmonary fibrosis. Decreased H2 S production was correlated with higher levels of cell senescence markers p53 and p21 in bleomycin-induced lung fibrosis. CBS+/- mice exhibited increased levels of p53 and p21. The numbers of AT2 cells positive for p53 and p21 were increased in CBS+/- mice as compared to control mice. H2 S donor NaHS attenuated bleomycin-induced AT2 cell senescence both in vivo and in vitro. H2 S donor suppressed bleomycin-induced senescence-associated secretory phenotype (SASP) of AT2 cells via inhibiting p53/p21 pathway, consequently suppressing proliferation and myofibroblast transdifferentiation of fibroblasts. Mechanically, H2 S suppressed p53 expression by enhancing the mouse double-minute 2 homologue (MDM2)-mediated ubiquitination and degradation of p53. CONCLUSION: H2 S inactivated p53-p21 pathway, consequently suppressing AT2 cell senescence as well as cell communication between senescent AT2 cells and fibroblasts. Aberrant H2 S synthesis may contribute to the development of pulmonary fibrosis through promoting the activation loop involving senescent AT2 cells and activated fibroblasts.

Investigation of a UPR-Related Gene Signature Identifies the Pro-Fibrotic Effects of Thrombospondin-1 by Activating CD47/ROS/Endoplasmic Reticulum Stress Pathway in Lung Fibroblasts.

Unfolded protein response (UPR) signaling and endoplasmic reticulum (ER) stress have been linked to pulmonary fibrosis. However, the relationship between UPR status and pulmonary function and prognosis in idiopathic pulmonary fibrosis (IPF) patients remains largely unknown. Through a series of bioinformatics analyses, we established a correlation between UPR status and pulmonary function in IPF patients. Furthermore, thrombospondin-1 (TSP-1) was identified as a potential biomarker for prognostic evaluation in IPF patients. By utilizing both bulk RNA profiling and single-cell RNA sequencing data, we demonstrated the upregulation of TSP-1 in lung fibroblasts during pulmonary fibrosis. Gene set enrichment analysis (GSEA) results indicated a positive association between TSP-1 expression and gene sets related to the reactive oxygen species (ROS) pathway in lung fibroblasts. TSP-1 overexpression alone induced mild ER stress and pulmonary fibrosis, and it even exacerbated bleomycin-induced ER stress and pulmonary fibrosis. Mechanistically, TSP-1 promoted ER stress and fibroblast activation through CD47-dependent ROS production. Treatment with either TSP-1 inhibitor or CD47 inhibitor significantly attenuated BLM-induced ER stress and pulmonary fibrosis. Collectively, these findings suggest that the elevation of TSP-1 during pulmonary fibrosis is not merely a biomarker but likely plays a pathogenic role in the fibrotic changes in the lung.

A nomogram for predicting echocardiogram prescription in outpatients: an analysis of the NAMCS database.

Background and objective: Cardiovascular disease is the leading cause of morbidity and mortality globally. Echocardiography is a commonly used method for assessing the condition of patients with cardiovascular disease. However, little is known about the population characteristics of patients who are recommended for echocardiographic examinations. Methods: The National Ambulatory Medical Care Survey was a cross-sectional survey previously undertaken in the USA. In this study, publicly accessible data from the National Ambulatory Medical Care Survey database (for 2007-2016 and 2018-2019; data for 2017 was not published) were utilized to create a nomogram based on significant risk predictors. The study was performed in accordance with the relevant guidelines and regulations stipulated in the National Ambulatory Medical Care Survey database. Patients were randomly assigned to one of two groups: training cohort or validation cohort. The latter was used to assess the reliability of the prediction nomogram. Decision curve analysis was performed to evaluate the net benefit. Propensity score matching analysis was used to evaluate the relevance of echocardiography to clinical decision-making. Results: A total of 217,178 outpatients were enrolled. Multivariable logistic regression analysis demonstrated that hypertension, hyperlipidemia, coronary artery disease/ischemic heart disease/history of myocardial infarction, congestive heart failure, major reason for visit, metropolitan statistical area, cerebrovascular disease/history of stroke or transient ischemic attack, previously assessed, insurance, referred, diagnosis, and reason for visit were all predictors of echocardiogram prescription in outpatients. The reliability of the predictive nomogram was confirmed in the validation cohort. After propensity score matching, there was a significant difference in new cardiovascular agent prescriptions between the echocardiogram and no echocardiogram groups (P < 0.01). Conclusion: In this cohort study, a nomogram based on the characteristics of outpatients was developed to predict the possibility of prescribing echocardiography. The echocardiogram group was more likely to be prescribed new cardiovascular agents. These findings may contribute to providing information about the gap between actual utilizations and guidelines and the actual outpatient practice, as well as meeting the needs of outpatients.

Molecular Carbons: How Far Can We Go?

The creation and development of carbon nanomaterials promoted material science significantly. Bottom-up synthesis has emerged as an efficient strategy to synthesize atomically precise carbon nanomaterials, namely, molecular carbons, with various sizes and topologies. Different from the properties of the feasibly obtained mixture of carbon nanomaterials, numerous properties of single-component molecular carbons have been discovered owing to their well-defined structures as well as potential applications in various fields. This Perspective introduces recent advances in molecular carbons derived from fullerene, graphene, carbon nanotube, carbyne, graphyne, and Schwarzite carbon acquired with different synthesis strategies. By selecting a variety of representative examples, we elaborate on the relationship between molecular carbons and carbon nanomaterials. We hope these multiple points of view presented may facilitate further advancement in this field.

Fibroblast Upregulation of Vitamin D Receptor Represents a Self-Protective Response to Limit Fibroblast Proliferation and Activation during Pulmonary Fibrosis.

Dysregulation of vitamin D receptor (VDR) is implicated in chronic obstructive pulmonary disease. However, whether VDR dysregulation contributes to the development of pulmonary fibrosis remains largely unknown. Analysis of bulk and single-cell RNA profiling datasets revealed VDR upregulation in lung fibroblasts from patients with pulmonary fibrosis or fibrotic mice, which was validated in lung fibroblasts from bleomycin-exposed mice and bleomycin-treated fibroblasts. Stable VDR knockdown promoted, whereas the VDR agonist paricalcitol suppressed lung fibroblast proliferation and activation. Gene set enrichment analysis (GSEA) showed that the JAK/STAT pathway and unfolded protein response (UPR), a process related to endoplasmic reticulum (ER) stress, were enriched in lung fibroblasts of fibrotic lungs. Stable VDR knockdown stimulated, but paricalcitol suppressed ER stress and JAK1/STAT3 activation in lung fibroblasts. The STAT3 inhibitor blocked bleomycin- or stable VDR knockdown-induced ER stress. Paricalcitol inhibited the bleomycin-induced enrichment of STAT3 to the ATF6 promoter, thereby suppressing ATF6 expression in fibroblasts. Paricalcitol or intrapulmonary VDR overexpression inactivated JAK1/STAT3 and suppressed ER stress in bleomycin-treated mice, thus resulting in the inhibition of fibroblast proliferation and activation. Collectively, this study suggests that fibroblast VDR upregulation may be a self-protective response to limit fibroblast proliferation and activation during pulmonary fibrosis by suppressing the JAK1/STAT3/ER stress pathway.

Increased R-spondin 3 contributes to aerobic exercise-induced protection against renal vascular endothelial hyperpermeability and acute kidney injury.

AIM: Exercise training exerts protective effects against sepsis-associated multiple organ dysfunction. This study aimed to investigate whether aerobic exercise protected against sepsis-associated acute kidney injury (AKI) via modulating R-spondin 3 (RSPO3) expression. METHODS: To investigate the effects of aerobic exercise on lipopolysaccharide (LPS)-induced AKI, LPS (20 mg/kg) was intraperitoneally injected after six weeks of treadmill training. To investigate the role of RSPO3 in LPS-induced AKI, wild-type (WT) or inducible endothelial cell-specific RSPO3 knockout (RSPO3EC-/- ) mice were intraperitoneally injected with 12 mg/kg LPS. RSPO3 was intraperitoneally injected 30 min before LPS treatment. RESULTS: Aerobic exercise-trained mice were more resistant to LPS-induced body weight loss and hypothermia and had a significant higher survival rate than sedentary mice exposed to LPS. Exercise training restored the LPS-induced decreases in serum and renal RSPO3 levels. Exercise or RSPO3 attenuated, whereas inducible endothelial cell-specific RSPO3 knockout exacerbated LPS-induced renal glycocalyx loss, endothelial hyperpermeability, inflammation, and AKI. Bioinformatics analysis results revealed significant increases in the expression of matrix metalloproteinases (MMPs) in kidney tissues of mice exposed to sepsis or endotoxaemia, which was validated in renal tissue from LPS-exposed mice and LPS-treated human microvascular endothelial cells (HMVECs). Both RSPO3 and MMPs inhibitor restored LPS-induced downregulation of tight junction protein, adherens junction protein, and glycocalyx components, thus ameliorating LPS-induced endothelial leakage. Exercise or RSPO3 reversed LPS-induced upregulation of MMPs in renal tissues. CONCLUSION: Increased renal expression of RSPO3 contributes to aerobic exercise-induced protection against LPS-induced renal endothelial hyperpermeability and AKI by suppressing MMPs-mediated disruption of glycocalyx and tight and adherens junctions.

ONX0914 inhibition of immunoproteasome subunit LMP7 ameliorates diabetic cardiomyopathy via restraining endothelial-mesenchymal transition.

Diabetic cardiomyopathy (DCM) is a chronic metabolic disease with few effective therapeutic options. Immunoproteasome is an inducible proteasome that plays an important role in the regulation of many cardiovascular diseases, while its role in DCM remains under discussion. The present study aims to demonstrate whether inhibiting immunoproteasome subunit low molecular weight polypeptide 7 (LMP7) could alleviate DCM. Here, we established a type I diabetes mellitus mouse model by streptozotocin (STZ) in 8-week-old male wild-type C57BL/6J mice. We found that immunoproteasome subunit LMP7 was overexpressed in the heart of diabetic mice, while inhibiting LMP7 with pharmacological inhibitor ONX0914 significantly alleviated myocardial fibrosis and improved cardiac function. Besides, compared with diabetic mice, ONX0914 treatment reduced protein levels of mesenchymal markers (Vimentin, α-smooth muscle actin, and SM22α) and increased endothelial markers (VE-cadherin and CD31). In TGFß1 stimulated HUVECs, we also observed that ONX0914 could inhibit endothelial-mesenchymal transition (EndMT). Mechanistically, we prove that ONX0914 could regulate autophagy activity both in vivo and vitro. Meanwhile, the protective effect of ONX0914 on TGFß1 stimulated HUVECs could be abolished by 3-methyladenine (3MA) or hydroxychloroquine (CQ). All in all, our data highlight that inhibition of LMP7 with ONX0914 could ameliorate EndMT in diabetic mouse hearts at least in part via autophagy activation. Thus, LMP7 may be a potential therapeutic target for the DCM.

The pattern of late gadolinium enhancement by cardiac MRI in fulminant myocarditis and its prognostic implication: a two-year follow-up study.

Background: Myocardial fibrosis, as quantified by late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR), provides valuable prognostic information for patients with myocarditis. However, due to the low incidence rate of fulminant myocarditis (FM) and accordingly small sample size, the knowledge about the role of LGE to patients with FM is limited. Methods and results: A total of 44 adults with viral-FM receiving the Chinese treating regimen were included in this retrospective study. They were divided into the low LGE group and the high LGE group according to the ratio of LGE to left ventricular mass (LGE mass%). CMR exams and LGE were performed after hemodynamic assistance at discharge in all patients with FM. Routine echocardiography parameters and global longitudinal strain (GLS) at discharge and at 2-year follow-up were obtained and then compared. Both left ventricular ejection fraction (LVEF) and GLS showed no significant difference in both groups at discharge, whereas significant differences were observed at 2-year follow-up between two groups. Moreover, there were significant improvements of LVEF and GLS in the low LGE group, but not in the high LGE group during the 2-year period. Furthermore, LGE mass% was negatively correlated with GLS and LVEF. Conclusions: There were two distinct forms of LGE presentation in patients with FM. Moreover, the cardiac function of patients with low LGE was significantly better than those with high LGE at 2-year follow-up. LGE mass% at discharge provided significant prognosis information about cardiac function of patients with FM.

Protocol for siRNA-mediated TET1 knockdown during differentiation of human embryonic stem cells into definitive endoderm cells.

TET1-mediated active DNA demethylation is required for endogenous retrovirus (ERV) enhancer activation during human ES differentiation into definitive endoderm (DE) cells. Here we present a protocol for siRNA-mediated TET1 knockdown during this process to decipher TET1's role in ERV activation and DE differentiation. We describe steps for inducing ES into DE cells. We then detail steps for knocking down TET1 during differentiation and for examining the effects of TET1 knockdown on LTR6B methylation, cell morphology, and gene expression. For complete details on the use and execution of this protocol, please refer to Wu et al. (2022).1.

High-Sensitivity Graphene MOEMS Resonant Pressure Sensor.

Nanomechanical resonators made from suspended graphene exhibit high sensitivity toward pressure variations. Nevertheless, these devices exhibit significant energy loss in nonvacuum environments due to air damping, as well as inevitably weak gas leakage within the reference cavity because of the slight permeation of graphene. We present a new type of graphene resonant pressure sensor utilizing micro-opto-electro-mechanical systems technology, which features a multilayer graphene membrane that is sealed in vacuum and adhered to pressure-sensitive silicon film with grooves. This approach innovatively employs an indirectly sensitive method, exhibiting 60 times smaller energy loss in atmosphere, and solving the long-standing issue of gas permeation between the substrate and graphene. Notably, the proposed sensor exhibits a high pressure sensitivity of 1.7 Hz/Pa, which is 5 times higher than the sensitivity of the silicon counterparts. Also, the all-optical encapsulating cavity structure contributes a high signal-to-noise ratio of 6.9 × 10-5 Pa-1 and a low temperature drift (0.014%/◦C). The proposed method offers a promising solution for long-term stability and energy loss suppression of pressure sensors using two-dimensional materials as the sensitive membrane.

A cell-free tissue-engineered tracheal substitute with sequential cytokine release maintained airway opening in a rabbit tracheal full circumferential defect model.

In this study, a cell-free tissue-engineered tracheal substitute was developed, which is based on a 3D-printed polycaprolactone scaffold coated with a gelatin-methacryloyl (GelMA) hydrogel, with transforming growth factor-ß1 (TGF-ß) and stromal cell-derived factor-1α (SDF-1) sequentially embedded, to facilitate cell recruitment and differentiation toward chondrocyte-phenotype. TGF-ß was loaded onto polydopamine particles, and then encapsulated into the GelMA together with SDF-1, and called G/S/P@T, which was used to coat 3D-printed PCL scaffold to form the tracheal substitute. A rapid release of SDF-1 was observed during the first week, followed by a slow and sustained release of TGF-ß for approximately four weeks. The tracheal substitute significantly promoted the recruitment of mesenchymal stromal cells (MSCs) or human bronchial epithelial cells in vitro, and enhanced the ability of MSCs to differentiate towards chondrocyte phenotype. Implantation of the tissue-engineered tracheal substitute with a rabbit tracheal anterior defect model improved regeneration of airway epithelium, recruitment of endogenous MSCs and expression of markers of chondrocytes at the tracheal defect site. Moreover, the tracheal substitute maintained airway opening for 4 weeks in a tracheal full circumferential defect model with airway epithelium coverage at the defect sites without granulation tissue accumulation in the tracheal lumen or underneath. The promising results suggest that this simple, cell-free tissue-engineered tracheal substitute can be used directly after tracheal defect removal and should be further developed towards clinical application.

Upregulation of KLK8 contributes to CUMS-induced hippocampal neuronal apoptosis by cleaving NCAM1.

Neuronal apoptosis has been well-recognized as a critical mediator in the pathogenesis of depressive disorders. Tissue kallikrein-related peptidase 8 (KLK8), a trypsin-like serine protease, has been implicated in the pathogenesis of several psychiatric disorders. The present study aimed to explore the potential function of KLK8 in hippocampal neuronal cell apoptosis associated with depressive disorders in rodent models of chronic unpredictable mild stress (CUMS)-induced depression. It was found that depression-like behavior in CUMS-induced mice was associated with hippocampal KLK8 upregulation. Transgenic overexpression of KLK8 exacerbated, whereas KLK8 deficiency attenuated CUMS-induced depression-like behaviors and hippocampal neuronal apoptosis. In HT22 murine hippocampal neuronal cells and primary hippocampal neurons, adenovirus-mediated overexpression of KLK8 (Ad-KLK8) was sufficient to induce neuron apoptosis. Mechanistically, it was identified that the neural cell adhesion molecule 1 (NCAM1) may associate with KLK8 in hippocampal neurons as KLK8 proteolytically cleaved the NCAM1 extracellular domain. Immunofluorescent staining exhibited decreased NCAM1 in hippocampal sections obtained from mice or rats exposed to CUMS. Transgenic overexpression of KLK8 exacerbated, whereas KLK8 deficiency largely prevented CUMS-induced loss of NCAM1 in the hippocampus. Both adenovirus-mediated overexpression of NCAM1 and NCAM1 mimetic peptide rescued KLK8-overexpressed neuron cells from apoptosis. Collectively, this study identified a new pro-apoptotic mechanism in the hippocampus during the pathogenesis of CUMS-induced depression via the upregulation of KLK8, and raised the possibility of KLK8 as a potential therapeutic target for depression.

Left ventricular function changes and echocardiographic predictors in adult survivors of fulminant myocarditis treated with the Chinese protocol.

Disagreement exists regarding the long-term prognosis and recovery of left ventricular (LV) function in patients with fulminant myocarditis (FM). This study reported the outcome and LV ejection fraction (EF) changes in FM treated with Chinese protocol, and assessed whether global longitudinal strain (GLS) by two-dimensional speckle tracking echocardiography (2-D STE) could provide additional information. This retrospective study included 46 FM adult patients who applied timely circulatory support and immunomodulatory therapy with adequate doses of both glucocorticoids and immunoglobulins as core approaches and survived after acute phase. They all presented with acute onset of cardiac symptoms < 2 weeks. LV end-diastolic dimensions, LVEF and GLS at discharge and 2-year were obtained and compared. We then performed linear regression and ROC analysis to determine independent factors to predict normalization of GLS at 2-year. At 2 years, the survival was 100% in our cohort. And the GLS improved modestly (15.40 ± 3.89% vs 17.24 ± 2.89%, P = 0.002). At two years, a proportion of patients whose LV function remained abnormal, being 22% evaluated by EF (< 55%) and higher to 37% by GLS (< 17%). Moreover, GLS at discharge but not at presentation correlated with GLS at 2-year (r = 0.402, P = 0.007). The FM adult treated with Chinese protocol have good survival and modest improvement of LV function during 2-year.

Echocardiographic phenotype for refined risk stratification and treatment selection in light chain amyloidosis with heart failure.

AIMS: Light chain amyloidosis (AL) patients with heart failure (HF) are usually with revised Mayo (rMayo) stage III/IV disease and have a poor prognosis. We sought to investigate whether and what echocardiographic phenotype provides value for further risk stratification and guiding optimal risk-adapted treatment in this subgroup of AL patients. METHODS AND RESULTS: 95 AL patients who presented with HF and were on rMayo stage III/IV were retrospectively included. Of them, 51 patients (53.7%) were with stage III, 44 (46.3%) were with stage IV, and 44 (46.3%) underwent chemotherapy. Laboratory and echocardiographic measurements were acquired before the initiation of chemotherapy. The relevance of different variables with survival was assessed in the entire cohort, chemotherapy, and non-chemotherapy group. By Multivariate Cox regression analysis, right ventricular wall thickness (RVT) [HR 1.145, 95% confidence interval (CI) 1.026-1.279, P = 0.016], relative wall thickness (RWT) (HR 6.709, 95% CI 1.101-40.877, P = 0.039), and left ventricular ejection fraction (LVEF) < 50% (HR 1.939, 95% CI 1.048-3.590, P = 0.035) were found to be independently associated with survival in the entire cohort, RWT (HR 15.488, 95% CI 2.045-117.292, P = 0.008) in the non-chemotherapy group, and RVT (HR 1.331, 95% CI 1.054-1.681, P = 0.016) in the chemotherapy group, respectively. Kaplan-Meier survival analysis revealed that survival was significantly reduced in the presence of RVT ≥ 6.5 mm or LVEF < 50% in the entire cohort, and the significance of RVT ≥ 6.5 mm was irrespective of rMayo stages. In the chemotherapy group, survival was decreased if RVT ≥ 6.5 mm alone or together with RWT ≥ 0.67 were present, particularly in patients on rMayo stage IV. CONCLUSIONS: Echocardiographic phenotype provides incremental value beyond rMayo staging for predicting survival and could further guide treatment in advanced AL with HF. Those with high-risk echocardiographic phenotypes as higher RVT and RWT and lower LVEF had a worse prognosis.

Stereoselective Chiral Molecular Carbon Imides Featuring 12-Fold [5]helicenes Around Four Cores.

Despite the great progress in research on molecular carbons containing multiple helicenes around one core, realizing the stereoselectivity of carbons containing multiple helicenes around more cores is still a great challenge. Herein, molecular carbon C204 featuring 12-fold [5]helicenes around four cores was successfully constructed by using nine perylene diimide (PDI) units, and exhibits good solubility and stability. Despite 256 possible stereoisomers caused by the 12-fold [5]helicenes, we only obtained one pair of enantiomers with D3 symmetry. There are four possible pairs of enantiomers with D3 symmetry, namely 7A, 7B, 7C and 7D. Theoretical and experimental results verify that the obtained structure belongs to 7C, which has the lowest energy. The enantiomers can also be separated by chiral HPLC. These results suggest that choosing PDIs as building blocks can not only improve the solubility and stability but also realize the stereoselectivity and chirality of molecular carbons.

Matrine Attenuates Lung Injury by Modulating Macrophage Polarization and Suppressing Apoptosis.

INTRODUCTION: Persistent lung inflammation is a characteristic of sepsis-induced lung injury. Matrine, the active ingredient from Sophora flavescens, has exhibited anti-inflammatory activities. This study investigated the effects of prophylactic administration of matrine on macrophage polarization, apoptosis, and tissue injury in a cecal ligation and puncture (CLP)-induced murine lung injury model. METHODS: Mice were randomly allocated into four groups: Sham, CLP, Sham + Matrine, and CLP + Matrine. Lung tissues were collected at 24 h post-CLP. Histopathology and immunofluorescence analysis were performed to evaluate lung injury and macrophage infiltration in the lung, respectively. Caspase-3 activities, TUNEL staining, and anti-apoptotic proteins were examined to assess apoptosis. To determine the mechanism of action of matrine, protein levels of Sirtuin 1 (SIRT1), nuclear factor κB (NF-κB), p53 and the messenger RNA levels of p53-mediated proapoptotic genes were examined to elucidate the associated signaling pathways. RESULTS: Histopathological evaluation showed that matrine prophylaxis attenuated sepsis-induced lung injury. Matrine prophylaxis attenuated sepsis-induced infiltration of the total population of macrophages in the lung. Matrine inhibited M1 macrophage infiltration, but increased M2 macrophage infiltration, thus resulting in a decrease in the proportion of M1 to M2 macrophages in septic lung. Sepsis-induced lung injury was associated with apoptotic cell death as evidenced by increases in caspase-3 activity, TUNEL-positive cells, and decreases in antiapoptotic proteins, all of which were reversed by matrine prophylaxis. Matrine restored sepsis-induced downregulation of SIRT1 and deacetylation of NF-κB p65 subunit and p53, thus inactivating NF-κB pathway and suppressing p53-induced proapoptotic pathway in septic lung. CONCLUSIONS: In summary, this study demonstrated that matrine exhibited pro-M2 macrophage polarization and antiapoptotic effects in sepsis-induced lung injury, which might be, at least partly, due to the modulation of SIRT1/NF-κB and SIRT1/p53 pathways.