Induced Huge Optical Activity in Nanoplatelet Superlattice.

Chiral superstructures with unique chiroptical properties that are not inherent in the individual units are essential in applications such as 3D displays, spintronic devices, biomedical sensors, and beyond. Generally, chiral superstructures are obtained by tedious procedures exploring various physical and chemical forces to break spatial symmetry during the self-assembly of discrete nanoparticles. In contrast, we herein present a simple and efficient approach to chiral superstructures by intercalating small chiral molecules into preformed achiral superstructures. As a model system, the chiral CdSe nanoplatelet (NPL) superlattice exhibits a giant and tunable optical activity with the highest g-factor reaching 3.09 × 10-2 to the excitonic transition of the NPL superlattice, nearly 2 orders of magnitude higher than that of the corresponding separated chiral NPLs. The theoretical analysis reveals that the chiral deformation in the NPL superlattice induced by the chiral perturbation of the small chiral molecules is critical to the observed huge optical activity. We anticipate that this research lays a foundation for understanding and applying chiral inorganic nanosystems.

True and False Chirality in Chiral Magnetic Nanoparticles.

Determining the true or false chirality of a system is essential for the design of advanced chiral materials and for improving their applications. Typically, a magnetic field would cause false optical activity in the chiral material system, thus confusing the true chirality's influence. Here, we provide a simple way to uncover the true and false chirality in chiral ferrimagnetic nanoparticles (FNPs) by using the gel as a rigid frame. The remnant local magnetic field of the FNP gel can be easily adjusted by an external magnetic field or by controlling the concentration of the FNPs. Moreover, the potential application of the FNP gel is detected by induced magnetic circularly polarized luminescence. This work provides deep insight into the true and false chirality in magnetic nanosystems and offers a strategy to construct new optic elements with an adjustable local magnetic field.

Prognostic factors of MINOCA and their possible mechanisms.

Objective: Despite not showing substantial stenosis of coronary arteries, Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) presents with myocardial ischemia injury, thus having a grave prognosis and a high risk of long-term complications. This necessitates increased clinical attention and exploration of its root causes to prevent a similar crisis. Methods: Research on MINOCA is limited, especially in terms of its clinical attributes, long-term outlook, risk stratification, and prognosis-linked cardiometabolic risk factors. This review aims to fill these gaps, providing an extensive overview of clinical trials and studies on MINOCA to separate the issue from the presence of non-obstructive coronary arteries in cardiac patients. Results: It has been found that MINOCA patients still face a high risk of long-term adverse events. Due to social and physiological factors, the hospital mortality rate is higher among women, and they are also more susceptible to MINOCA. Cardiac metabolic risk factors, including disorder of glucose and lipid metabolism, as well as changes in serum CysC levels, have significant impacts on the occurrence and prognosis of MINOCA. Conclusions: Further research is still needed to fully understand the complex biological mechanisms underlying the prognostic factors of MINOCA. A profound understanding of these factors could reveal potential targets for improving prognosis, thereby indicating new strategies for managing this cardiovascular condition.

Enantiomer-Dependent Supramolecular Immunosuppressive Modulation for Tissue Reconstruction.

Modulating the properties of biomaterials in terms of the host immune response is critical for tissue repair and regeneration. However, it is unclear how the preference for the cellular microenvironment manipulates the chiral immune responses under physiological or pathological conditions. Here, we reported that in vivo and in vitro oligopeptide immunosuppressive modulation was achieved by manipulation of macrophage polarization using chiral tetrapeptide (Ac-FFFK-OH, marked as FFFK) supramolecular polymers. The results suggested that chiral FFFK nanofibers can serve as a defense mechanism in the restoration of tissue homeostasis by upregulating macrophage M2 polarization via the Src-STAT6 axis. More importantly, transiently acting STAT6, insufficient to induce a sustained polarization program, then passes the baton to EGR2, thereby continuously maintaining the M2 polarization program. It is worth noting that the L-chirality exhibits a more potent effect in inducing macrophage M2 polarization than does the D-chirality, leading to enhanced tissue reconstruction. These findings elucidate the crucial molecular signals that mediate chirality-dependent supramolecular immunosuppression in damaged tissues while also providing an effective chiral supramolecular strategy for regulating macrophage M2 polarization and promoting tissue injury repair based on the self-assembling chiral peptide design.

Integrated BSA-seq and RNA-seq analysis to identify candidate genes associated with nitrogen utilization efficiency (NUtE) in rapeseed (Brassica napus L.).

Rapeseed (Brassica napus L.) is one of the important oil crops, with a high demand for nitrogen (N). It is essential to explore the potential of rapeseed to improve nitrogen utilization efficiency (NUtE). Rapeseed is an allotetraploid crop with a relatively large and complex genome, and there are few studies on the mapping of genes related to NUtE regulation. In this study, we used the combination of bulk segregant analysis sequencing (BSA-Seq) and RNA sequencing (RNA-Seq) to analyze the N-efficient genotype 'Zheyou 18' and N-inefficient genotype 'Sollux', to identify the genetic regulatory mechanisms. Several candidate genes were screened, such as the high-affinity nitrate transporter gene NRT2.1 (BnaC08g43370D) and the abscisic acid (ABA) signal transduction-related genes (BnaC02g14540D, BnaA03g20760D, and BnaA05g01330D). BnaA05g01330D was annotated as ABA-INDUCIBLE bHLH-TYPE TRANSCRIPTION FACTOR (AIB/bHLH17), which was highly expressed in the root. The results showed that the primary root length of the ataib mutant was significantly longer than that of the wild type under low N conditions. Overexpression of BnaA5.AIB could reduce the NUtE under low N levels in Arabidopsis (Arabidopsis thaliana). Candidate genes identified in this study may be involved in the regulation of NUtE in rapeseed, and new functions of AIB in orchestrating N uptake and utilization have been revealed. It is indicated that BnaA5.AIB may be the key factor that links ABA to N signaling and a negative regulator of NUtE. It will provide a theoretical basis and application prospect for resource conservation, environmental protection, and sustainable agricultural development.

Smart Enzyme-Like Polyphenol-Copper Spray for Enhanced Bacteria-Infected Diabetic Wound Healing.

Developing functional medical materials is urgent to treat diabetic wounds with a high risk of bacterial infections, high glucose levels and oxidative stress. Here, a smart copper-based nanocomposite acidic spray has been specifically designed to address this challenge. This copper-based nanocomposite is pH-responsive and has multienzyme-like properties. It enables the spray to effectively eliminate bacteria and alleviate tissue oxidative pressure, thereby accelerating the healing of infected diabetic wounds. The spray works by generating hydroxyl radicals through catalysing H2O2, which has a high sterilization efficiency of 97.1%. As alkaline micro-vessel leakage neutralizes the acidic spray, this copper-based nanocomposite modifies its enzyme-like activity to eliminate radicals. This reduces the level of reactive oxygen species in diabetic wounds by 45.3%, leading to a similar wound-healing effect between M1 diabetic mice and non-diabetic ones by day 8. This smart nanocomposite spray provides a responsive and regulated microenvironment for treating infected diabetic wounds. It also offers a convenient and novel approach to address the challenges associated with diabetic wound healing.

Down syndrome child with multiple heart diseases: A case report.

BACKGROUND: Down syndrome, also known as trisomy 21 syndrome, is commonly associated with congenital heart disease, and can often result in early formation of pulmonary hypertension. The development of pulmonary hypertension can result from factors such as intracardiac and macrovascular shunts, and upper airway obstruction or hypoplasia of lung tissue. Individuals with Down syndrome and congenital heart disease have a significantly lower average life expectancy, with surgical intervention being the most viable treatment option to improve longevity. CASE SUMMARY: We report the case of a 13-year-old boy with Down syndrome presenting with atrial septal defect and patent ductus arteriosus along with severe pulmonary hypertension. The electrocardiogram shows sinus rhythm and right ventricular hypertrophy. The echocardiogram shows an atrial septal defect with interrupted echo in the interatrial septum, measuring 0.813 cm in length. The patient was initially refused to be offered surgical treatment by many hospitals due to the high surgical risk and pulmonary artery resistance. After discussing the patient's diagnosis and treatment options, we ultimately recommended surgical treatment. However, the patient and their family declined this recommendation and chose to be discharged. During the follow-up period of 6 mo, there were no significant improvements or deteriorations in the patient's condition. CONCLUSION: In conclusion, this case highlights the challenges faced by individuals with Down syndrome and congenital heart disease complicated by severe pulmonary hypertension. Timely intervention and a multidisciplinary approach are crucial for improving prognosis and life expectancy. Further research is needed to enhance our understanding and develop effective interventions for this population.

LILRB2/PirB mediates macrophage recruitment in fibrogenesis of nonalcoholic steatohepatitis.

Inhibition of immunocyte infiltration and activation has been suggested to effectively ameliorate nonalcoholic steatohepatitis (NASH). Paired immunoglobulin-like receptor B (PirB) and its human ortholog receptor, leukocyte immunoglobulin-like receptor B (LILRB2), are immune-inhibitory receptors. However, their role in NASH pathogenesis is still unclear. Here, we demonstrate that PirB/LILRB2 regulates the migration of macrophages during NASH by binding with its ligand angiopoietin-like protein 8 (ANGPTL8). Hepatocyte-specific ANGPTL8 knockout reduces MDM infiltration and resolves lipid accumulation and fibrosis progression in the livers of NASH mice. In addition, PirB-/- bone marrow (BM) chimeras abrogate ANGPTL8-induced MDM migration to the liver. And yet, PirB ectodomain protein could ameliorate NASH by sequestering ANGPTL8. Furthermore, LILRB2-ANGPTL8 binding-promoted MDM migration and inflammatory activation are also observed in human peripheral blood monocytes. Taken together, our findings reveal the role of PirB/LILRB2 in NASH pathogenesis and identify PirB/LILRB2-ANGPTL8 signaling as a potential target for the management or treatment of NASH.

Efficacy and prognostic impact of Pericarpium Trichosanthis injection combined with nicorandil for intractable angina pectoris in elderly patients: A retrospective study.

BACKGROUND: Coronary artery disease (CAD) is a leading cause of global cardiovascular mortality. Refractory angina pectoris, a manifestation of CAD, requires effective drug treatments. Pericarpium Trichosanthis injection, a traditional Chinese medicine, improves cardiovascular symptoms, while nicorandil alleviates spasms and angina. Both have potential in treating CAD. AIM: To investigate the therapeutic effects of combining Pericarpium Trichosanthis injection and nicorandil in elderly patients suffering from refractory angina caused by coronary heart disease. METHODS: A retrospective analysis was conducted on the data of 130 patients diagnosed with refractory coronary heart disease. Based on the different treatment regimens administered during hospitalization, the patients were divided into a control group (58 cases) and a study group (72 cases). The control group received conventional treatment, which included aspirin, statins, and nitrate vasodilators. In addition to the conventional medication, the study group received a combination treatment of Pericarpium Trichosanthis injection and nicorandil. RESULTS: After treatment, the study group showed significantly higher left ventricular ejection fraction and cardiac output, and lower brain natriuretic peptide and C-reactive protein levels compared to the control group. The study group also exhibited improvements in angina, quality of life, exercise endurance, and lipid profiles. Multivariate logistic regression analysis revealed a relationship of lipid levels and heart function with the combined treatment. Some patients in the study group experienced headaches during treatment, but no significant adverse reactions were observed. Follow-up showed that the treatment was well-tolerated, with no drug-related adverse reactions detected. CONCLUSION: Combination of Pericarpium Trichosanthis injection and nicorandil is more effective than conventional treatment in improving symptoms and heart function in elderly patients with refractory angina pectoris.

Molecular Identification of the G-Protein Genes and Their Expression Profiles in Response to Nitrogen Deprivation in Brassica napus.

Heterotrimeric guanine nucleotide binding protein (G-protein) consisting of Gα, Gß, and Gγ subunits is one of the key signal transducers in plants. Recent studies indicated that G-protein has been proposed as an important mediator of nitrogen responses in rice, wheat, and Arabidopsis. However, little is known about these G-proteins in Brassica napus (B. napus), except for three identified G-proteins, BnGA1, BnGB1, and BnGG2. Therefore, the aim of the present study is to characterize the members of the G-protein gene family in allotetraploid B. napus and to analyze their expression profiles in response to nitrogen deprivation. In total, 21 G-protein family members were identified in B. napus, encoding two Gα, six Gß, and 13 Gγ. Sequence and phylogenetic analyses showed that although genome-wide triploid events increased the number of genes encoding Gα, Gß, and Gγ subunits, the gene structure and protein properties of the genes encoding each G-protein subunit were extremely conserved. Collinearity analysis showed that most G-protein genes in B. napus had syntenic relationships with G-protein members of Arabidopsis, Brassica rape (B. rapa), and Brassica oleracea (B. oleracea). Expression profile analysis indicated that Gα and C-type Gγ genes (except BnGG10 and BnGG12 were highly expressed in flower and ovule) were barely expressed in most organs, whereas most Gß and A-type Gγ genes tended to be highly expressed in most organs. G-protein genes also showed various expression patterns in response to nitrogen-deficient conditions. Under nitrogen deficiency, Gα and five C-type Gγ genes were upregulated initially in roots, while in leaves, Gα was downregulated initially and five C-type Gγ genes were highly expressed in different times. These results provide a complex genetic dissection of G-protein genes in B. napus, and insight into the biological functions of G-protein genes in response to nitrogen deficiency.

Corneal Endothelial Characteristics in Normal Chinese Han Children and Youngsters: A Study from the Specular Microscopy Descriptions.

Objective: To observe the morphological changes of corneal endothelial cells in healthy Chinese children and youngsters and analyze the sensitive and specificity of the endothelial assessments. Methods: 14,670 Chinese healthy volunteers enrolled were examined by specular microscopy, and the endothelial descriptive indexes: the central corneal thickness (CCT), endothelial cell density (ECD), coefficient of variation in average cell size (CV), the percentage of regular hexagonal cells (hexagonality, HEX), cell size of minimal cell (S min), cell size of maximal cell (S max), average cell size (S avg), and size of standard deviation of cell area (S sd) as well as sex and age were analyzed. Results: The average age of this study is 17.36 ± 7.58 (4-30) years. There is no sex predominance: 7,260 male (49.5%) and 7,410 female (50.5%). The mean CCT, ECD, CV, HEX, S min/max, S avg, and S sd are 529.94 ± 31.53 (437-644) µm, 3,051.28 ± 375.49 (2,031-4,074) cells/mm2, 28.34 ± 4.36 (18-40) %, 61.21 ± 10.29 (17-89) %, (147.79 ± 21.94 to 678.29 ± 120.96) µm2, 332.74 ± 44.62 µm2, and 95.02 ± 23.17 µm2, respectively. The CCTs keep consistency. The ECD decreased rate is 1.02%/year. The curve of ECD and hexagonality expresses the same linear tender. The CCT and endothelial evaluation indexes have no sex predominant (p > 0.05); the quantitative indicators: CCT, ECD, and HEX are significant negative associated with age (p = 0.001 or p < 0.001); the variability indexes: the CV, S min, S max, S avg, and S sd are positive correlation (p < 0.001). The coefficients of CCT, HE, and S min are -0.35, -0.59, and 1.17, respectively. Conclusions: The ECD decrease rate is 1.02%/year of the normal Chinese Han childhood to the earlier adulthood. The ages 4 to 12, 13 to 20, and 21 to 30 can be named as the childhood, puberty and adulthood from endothelial biologic identity. The HEX is the sensitivity marks for the polymorphisms while the S min is the specificity indicator CVs upon the Topcon Noncon Specular microscopy results.

A new strategy based on PCA for inter-batches quality consistency evaluation.

Due to cultivation position, climate, harvest times, storage conditions and processing method, the evaluation of intra- and inter- batches quality consistency of botanical drugs has always been a thorny problem since it concerns safety and efficacy. The combination of fingerprint based on instrumental analysis and chemometrics is a common evaluation method in recent years. The differences between groups can be judged intuitively and superficially through principal component analysis (PCA) multi-dimensional score plots, but there is a lack of scientific and quantitative index to quantify the differences between groups. How to quantify the difference between groups is basically a blank area of research. Based on traditional F-statistic, we proposed a new F*-statistic to quantify the difference between groups in PCA score plots from the perspective of statistics. As the results revealed, the calculated F*-statistic was 2.58, smaller than the critical value 3.17 (α = 0.05), which indicated that there was no significant difference between groups. Our study add another dimension for PCA application, which offers a new strategy to quantify differences between groups by a new perspective, namely, a combination of fingerprint, chemometrics and statistics to evaluate inter-batches quality consistency quantitatively and objectively. Therefore, this manuscript could provide new ideas and technical references for the quality consistency evaluation of natural drugs, thus better guarantee their clinical efficacy and safety, and better promote industrial development.

Mechanism of GLP-1 Receptor Agonists-Mediated Attenuation of Palmitic Acid-Induced Lipotoxicity in L6 Myoblasts.

Methods: Cells were divided into 5 groups-control, high-fat, 10 nmol/L LR + 0.6 mmol/L palmitic acid (PA) (10LR), 100 nmol/L LR + 0.6 mmol/L PA (100LR), and 1000 nmol/L LR + 0.6 mmol/L PA (1000LR). CCK-8 method to detect cell viability, GPO-PAP enzymatic method to detect intracellular triglyceride content, and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting methods to detect fatty acid translocase CD36 (FAT/CD36) and fatty acid binding protein 4 (FABP4) in L6 cells, glucose-regulated protein 78 (GRP78), glucose transporter 4 (GLUT4) expression at the mRNA and protein levels, respectively, were performed. Results: We found that after PA intervention for 24 h, the cell viability decreased significantly; the cell viability of the LR group was higher than that of the high-fat group (P < 0.01). After PA intervention, compared with those in the high-fat group, GRP-78, FAT/CD36, FABP4 mRNA ((4.36 ± 0.32 vs. 8.15 ± 0.35); (1.00 ± 0.04 vs. 2.46 ± 0.08); (2.88 ± 0.55 vs. 8.29 ± 0.52), P < 0.01) and protein ((3338.13 ± 333.15 vs. 4963.98 ± 277.29); (1978.85 ± 124.24 vs. 2676.07 ± 100.64); (3372.00 ± 219.84 vs. 6083.20 ± 284.70), both P < 0.01) expression decreased in the LR group. The expression levels of GLUT4 mRNA ((0.75 ± 0.04 vs. 0.34 ± 0.03), P < 0.01) and protein ((3443.71 ± 191.89 vs. 2137.79 ± 118.75), P < 0.01) increased. Conclusion: Therefore, we conclude that LR can reverse PA-induced cell inactivation and lipid deposition, which may be related to the change in GRP-78, FAT/CD36, FABP4, GLUT4, and other factors.

Role of the CTRP family in tumor development and progression.

C1q tumor necrosis factor-related proteins (CTRPs), which are members of the adipokine superfamily, have gained significant interest in the recent years. CTRPs are homologs of adiponectin with numerous functions and are closely associated with metabolic diseases, such as abnormal glucose and lipid metabolism and diabetes. Previous studies have demonstrated that CTRPs are highly involved in the regulation of numerous physiological and pathological processes, including glycolipid metabolism, protein kinase pathways, cell proliferation, cell apoptosis and inflammation. CTRPs also play important roles in the development and progression of numerous types of tumor, including liver, colon and lung cancers. This observation can be attributed to the fact that diabetes, obesity and insulin resistance are independent risk factors for tumorigenesis. Numerous CTRPs, including CTRP3, CTRP4, CTRP6 and CTRP8, have been reported to be associated with tumor progression by activating multiple signal pathways. CTRPs could therefore be considered as diagnostic markers and therapeutic targets in some cancers. However, the underlying mechanisms of CTRPs in tumorigenesis remain unknown. The present review aimed to determine the roles and underlying mechanisms of CTRPs in tumorigenesis, which may help the development of novel cancer treatments in the future.

Identification and Expression Analysis of SLAC/SLAH Gene Family in Brassica napus L.

Slow type anion channels (SLAC/SLAHs) play important roles during anion transport, growth and development, abiotic stress responses and hormone responses in plants. However, there is few report on SLAC/SLAHs in rapeseed (Brassica napus). Genome-wide identification and expression analysis of SLAC/SLAH gene family members were performed in B. napus. A total of 23 SLAC/SLAH genes were identified in B. napus. Based on the structural characteristics and phylogenetic analysis of these members, the SLAC/SLAHs could be classified into three main groups. Transcriptome data demonstrated that BnSLAH3 genes were detected in various tissues of the rapeseed and could be up-regulated by low nitrate treatment in roots. BnSLAC/SLAHs were exclusively localized on the plasma membrane in transient expression of tobacco leaves. These results will increase our understanding of the evolution and expression of the SLAC/SLAHs and provide evidence for further research of biological functions of candidates in B. napus.

Activation of hypoxia-inducible factor 1 (Hif-1) enhanced bactericidal effects of macrophages to Mycobacterium tuberculosis.

BACKGROUND: Tuberculosis is chronic infection caused by Mycobacterium tuberculosis (M.tb), which infects specifically macrophages. Hif-1, hypoxia-inducible factor-1, was reported to act as master regulator of killing functions in macrophages. AIM: To investigate whether Hif-1 activation would enhance bactericidal effect of macrophages and anti-tuberculosis effect of chemical reagent. METHODS: Hif-1 and LC3B were detected in tissues from pulmonary tuberculosis. U937, human monocytic leukemia cell line, was stimulated with PMA and differentiated into macrophages. Cells were pretreated with Hif-1 chemical inhibitor YC-1, stimulated with CoCl2 (Hif-1 activator), to detect LC3B with Western blot and confocal microscopy. Cells were infected with M. tb H37Rv strain, stimulated with CoCl2, following rifampine treatment. Expression of autophagy markers was detected using Western blot. IL-6 and TNF-α were detected in cell supernatant with ELISA. Acid-fast staining and CFU assay were performed to evaluate intracellular bacterial load. RESULTS AND CONCLUSIONS: Hif-1 and LC3B increased in tissues of pulmonary tuberculosis. Hif-1 activation enhanced autophagy in M. tb infected U937 cells and production of IL-6 and TNF-α. Data from acid-fast staining and CFU indicated that Hif-1 activation enhanced anti-tuberculosis effect of rifampine in macrophages. Conclusively, to activate Hif-1 would strengthen bactericidal effect of macrophages, to further enhance anti-tuberculosis effect of chemical reagent.

Analysis of Peripheral Blood IL-6 and Leukocyte Characteristics in 364 COVID-19 Patients of Wuhan.

SARS-CoV-2, the pathogen of COVID-19, is spreading around the world. Different individuals infected with COVID-19 have different manifestations. It is urgent to determine the risk factors of disease progress of COVID-19. 364 patients diagnosed with COVID-19, who were admitted to Wuhan Pulmonary Hospital from February 3, 2020 to March 16, 2020, were divided into mild, ordinary, severe, and critical groups, according to Chinese novel coronavirus pneumonia diagnosis and treatment plan. Peripheral blood IL-6 and leukocyte characteristics were analyzed, to evaluate the correlation with the severity of COVID-19. The levels of peripheral blood IL-6 were 2.35 ± 0.46 pg/ml (mild), 6.48 ± 1.13 pg/ml (ordinary), 20.30 ± 5.15 pg/ml (severe), and 123.48 ± 44.31 pg/ml (critical). The leukocytes were 5.70 ± 0.41×109/L (mild), 6.21 ± 0.14×109/L (ordinary), 6.37 ± 0.26×109/L (severe), and 10.03 ± 1.43×109/L (critical). The lymphocytes were 1.46 ± 0.19×109/L (mild), 1.89 ± 0.14×109/L (ordinary), 1.26 ± 0.07×109/L (severe), and 1.17 ± 0.23×109/L (critical). The neutrophils were 3.63 ± 0.36×109/L (mild), 3.78 ± 0.11×109/L (ordinary), 4.47 ± 0.25×109/L (severe), and 7.92 ± 1.19×109/L (critical). The monocytes were 0.42 ± 0.05×109/L (mild), 0.44 ± 0.01×109/L (ordinary), 0.46 ± 0.02×109/L (severe), and 0.78 ± 0.25×109/L (critical). Conclusively, increase of peripheral blood IL-6 and decrease of lymphocytes can be used as the indicators of severe COVID-19. The increase of neutrophils and monocytes was noticed in critical cases of COVID-19, suggesting that the increase of neutrophils and monocytes should be considered as risk factors of critical cases of COVID-19. Peripheral blood IL-6 and leukocyte characteristics were also analyzed in different age groups. The increase of serum IL-6, decrease of lymphocytes, and increase of neutrophils were noticed in patients over 60 years old.

Bnip3 interacts with vimentin, an intermediate filament protein, and regulates autophagy of hepatic stellate cells.

Bnip3, which is regulated by Hif-1 in cells under oxygen deprivation, is a death related protein associated with autophagy and apoptosis. Hif-1 was reported to regulate autophagy to activate hepatic stellate cells (HSCs), while the specific molecular mechanism is vague. The possible mechanism of Hif-1 regulating autophagy of HSCs via Bnip3 was explored in this study. Bnip3 was detected in fibrotic liver tissues from humans and mice. Hif-1 was inhibited by chemical inhibitor and Bnip3 was detected in activated HSCs. The co-localization of Bnip3 and LC3B was captured by confocal microscopy and autophagic flow was assessed in Bnip3 siRNA transfected cells. Bnip3 interacted proteins were screened with mass spectrometry. The interaction of Bnip3 and vimentin was detected with co-immunoprecipitation and confocal microscopy. The results showed that Bnip3 was increased in fibrotic liver tissues and activated HSCs. Hif-1 inhibition suppressed Bnip3 expression in activated HSCs. Bnip3 was partially co-localized with autophagosomes and Bnip3 inhibition suppessed autophagy in activated HSCs. Bnip3 interacted with vimentin and Bnip3 expression was inhibited as vimentin was inhibited in activated HSCs. Conclusively, this study indicated that Bnip3 promoted autophagy and activation of HSCs, via interacting with vimentin, an intermediate filament protein with highly abundant expression in HSCs.

Exosomes from activated hepatic stellate cells contain GLUT1 and PKM2: a role for exosomes in metabolic switch of liver nonparenchymal cells.

The mechanism of exosomes derived from activated hepatic stellate cells (HSCs) involved in liver fibrosis is poorly understood. We previously reported that hypoxia-inducible factor 1 (Hif-1) regulated HSC activation, and, therefore, we investigated in current work whether Hif-1 regulates exosome secretion and the metabolic switch of HSCs, thus affecting the metabolism of liver nonparenchymal cells. In this study, the characteristics of exosomes from HSCs were assessed via electron microscopy, Western blot analysis, and acetylcholinesterase activity. Confocal microscopy was used to measure the uptake of exosomes by quiescent HSCs, Kupffer cells (KCs), and liver sinusoidal endothelial cells (LSECs). Hif-1α was inhibited via 2-ME or specific small interfering RNAs to investigate its role in exosomes derived from HSCs. It was determined that glucose transporter 1 and pyruvate kinase M2 were increasingly expressed in fibrotic liver samples, cell lysates, and exosomes derived from activated HSCs. Exosomes released from HSCs were associated with activation and glucose uptake of HSCs. Delivery of exosomes from activated HSCs induced glycolysis of quiescent HSCs, KCs, and LSECs. Disruption of Hif-1 expression suppressed the glycolysis effect delivered by exosomes. Conclusively, our results demonstrated that exosomes secreted by activated HSCs affect the metabolic switch of liver nonparenchymal cells via delivery of glycolysis-related proteins. These findings represent a novel mechanism that contributes to liver fibrosis and has significant implications for new diagnosis and treatment of liver diseases.-Wan, L., Xia, T., Du, Y., Liu, J., Xie, Y., Zhang, Y., Guan, F., Wu, J., Wang, X., Shi, C. Exosomes from activated hepatic stellate cells contain GLUT1 and PKM2: a role for exosomes in metabolic switch of liver nonparenchymal cells.