Sulfasalazine ameliorates lipopolysaccharide-induced acute lung injury by inhibiting oxidative stress and nuclear factor-kappaB pathways.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) has a high mortality rate and incidence of complications. The pathophysiology of ALI/ARDS is still not fully understood. The lipopolysaccharide (LPS)-induced mouse model of ALI has been widely used to study human ALI/ARDS. Sulfasalazine (SASP) has antibacterial and anti-inflammatory effects and is used for treating inflammatory bowel and rheumatic diseases. However, the effect of SASP on LPS-induced ALI in mice has not yet been reported. Therefore, we aimed to investigate the effect of SASP on LPS-induced ALI in mice. Mice were intraperitoneally injected with SASP 2 h before or 4 h after LPS modeling. Pulmonary pathological damage was measured based on inflammatory factor expression (malondialdehyde and superoxide dismutase levels) in the lung tissue homogenate and alveolar lavage fluid. The production of inflammatory cytokines and occurrence of oxidative stress in the lungs induced by LPS were significantly mitigated after the prophylactic and long-term therapeutic administration of SASP, which ameliorated ALI caused by LPS. SASP reduced both the production of inflammatory cytokines and occurrence of oxidative stress in RAW264.7 cells, which respond to LPS. Moreover, its mechanism contributed to the suppression of NF-κB and nuclear translocation. In summary, SASP treatment ameliorates LPS-induced ALI by mediating anti-inflammatory and antioxidant effects, which may be attributed to the inhibition of NF-κB activation and promotion of antioxidant defenses. Thus, SASP may be a promising pharmacologic agent for ALI therapy.

NMDAR activation attenuates the protective effect of BM-MSCs on bleomycin-induced ALI via the COX-2/PGE2 pathway.

N-methyl-d-aspartate (NMDA) receptor (NMDAR) activation mediates glutamate (Glu) toxicity and involves bleomycin (BLM)-induced acute lung injury (ALI). We have reported that bone marrow-derived mesenchymal stem cells (BM-MSCs) are NMDAR-regulated target cells, and NMDAR activation inhibits the protective effect of BM-MSCs on BLM-induced pulmonary fibrosis, but its effect on ALI remains unknown. Here, we found that Glu release was significantly elevated in plasma of mice at d 7 after intratracheally injected with BLM. BM-MSCs were pretreated with NMDA (the selective agonist of NMDAR) and transplanted into the recipient mice after the BLM challenge. BM-MSCs administration significantly alleviated the pathological changes, inflammatory response, myeloperoxidase activity, and malondialdehyde content in the damaged lungs, but NMDA-pretreated BM-MSCs did not ameliorate BLM-induced lung injury in vivo. Moreover, NMDA down-regulated prostaglandin E2 (PGE2) secretion and cyclooxygenase (COX)-2 expression instead of COX-1 expression in BM-MSCs in vitro. We also found that NMDAR1 expression was increased and COX-2 expression was decreased, but COX-1 expression was not changed in primary BM-MSCs of BLM-induced ALI mice. Further, the cultured supernatants of lipopolysaccharide (LPS)-pretreated RAW264.7 macrophages were collected to detect inflammatory factors after co-culture with NMDA-pretreated BM-MSCs. The co-culture experiments showed that NMDA precondition inhibited the anti-inflammatory effect of BM-MSCs on LPS-induced macrophage inflammation, and PGE2 could partially alleviate this inhibition. Our findings suggest that NMDAR activation attenuated the protective effect of BM-MSCs on BLM-induced ALI in vivo. NMDAR activation inhibited COX-2 expression and PGE2 secretion in BM-MSCs and weakened the anti-inflammatory effect of BM-MSCs on LPS-induced macrophage inflammation in vitro. In conclusion, NMDAR activation attenuates the protective effect of BM-MSCs on BLM-induced ALI via the COX-2/PGE2 pathway. Keywords: Acute Lung Injury, BM-MSCs, NMDA receptor, COX-1/2, PGE2.

Down-regulation of the Smad signaling by circZBTB46 via the Smad2-PDLIM5 axis to inhibit type I collagen expression.

BACKGROUND: Abnormal type I collagen (COL1) expression is associated with the development of many cardiovascular diseases. The TGF-beta/Smad signaling pathway and circRNAs have been shown to regulate COL1 gene expression, but the underlying molecular mechanisms are still not fully understood. METHODS: Gain- and loss-of-function experiments were prformed to study the effect of circZBTB46 on the expression of alpha 2 chain of type I collagen (COL1A2). Co-immunoprecipitation assay was performed to observe the interaction between two proteins. RNA immunoprecipitation assay and biotin pull-down assay were performed to observe the interaction of circZBTB46 with PDLIM5. RESULTS: In this study, we investigated the role of circZBTB46 in regulating COL1A2 expression in human vascular smooth muscle cells (VSMCs). We found that circZBTB46 is expressed in VSMCs and that TGF-beta inhibits circZBTB46 formation by downregulating KLF4 expression through activation of the Smad signaling pathway. CircZBTB46 inhibits the expression of COL1A2 induced by TGF-beta. Mechanistically, circZBTB46 mediates the interaction between Smad2 and PDLIM5, resulting in the inhibition of Smad signaling and the subsequent downregulation of COL1A2 expression. Furthermore, we found that the expression of TGF-beta and COL1A2 is decreased, while circZBTB46 expression is increased in human abdominal aortic aneurysm tissues, indicating that circZBTB46-mediated regulation of TGF-beta/Smad signaling and COL1A2 synthesis in VSMCs plays a crucial role in vascular homeostasis and aneurysm development. CONCLUSIONS: CircZBTB46 was identified as a novel inhibitor of COL1 synthesis in VSMCs, highlighting the importance of circZBTB46 and PDLIM5 in regulating TGF-beta/Smad signaling and COL1A2 expression.

NMDA receptor activation induces damage of alveolar type II cells and lung fibrogenesis through ferroptosis.

Ferroptosis, a newly discovered type of regulated cell death, has been implicated in numerous human diseases. Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal interstitial lung disease with poor prognosis and limited treatment options. Emerging evidence has linked ferroptosis and glutamate-determined cell fate which is considered a new light on the etiology of pulmonary fibrosis. Here, we observed that N-methyl d-aspartate receptor (NMDAR) activation promoted cell damage and iron deposition in MLE-12 cells in a dose-, time-, and receptor-dependent manner. This mediated substantial Ca2+ influx, upregulated the expression levels of nNOS and IRP1, and affected intracellular iron homeostasis by regulating the expression of iron transport-related proteins (i.e., TFR1, DMT1, and FPN). Excessive iron load promoted the continuous accumulation of total intracellular and mitochondrial reactive oxygen species, which ultimately led to ferroptosis. NMDAR inhibition reduced lung injury and pulmonary fibrosis in bleomycin-induced mice. Bleomycin stimulation upregulated the expression of NMDAR1, nNOS, and IRP1 in mouse lung tissues, which ultimately led to iron deposition via regulation of the expression of various iron metabolism-related genes. NMDAR activation initiated the pulmonary fibrosis process by inducing iron deposition in lung tissues and ferroptosis of alveolar type II cells. Our data suggest that NMDAR activation regulates the expression of iron metabolism-related genes by promoting calcium influx, increasing nNOS and IRP1 expression, and increasing iron deposition by affecting cellular iron homeostasis, ultimately leading to mitochondrial damage, mitochondrial dysfunction, and ferroptosis. NMDAR activation-induced ferroptosis of alveolar type II cells might be a key event to the initiation of pulmonary fibrosis.

MALAT1 binds to miR-188-3p to regulate ALOX5 activity in the lung inflammatory response of neonatal bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) causes high morbidity and mortality in infants, but no effective preventive or therapeutic agents have been developed to combat BPD. In this study, we assessed the expression of MALAT1 and ALOX5 in peripheral blood mononuclear cells from BPD neonates, hyperoxia-induced rat models and lung epithelial cell lines. Interestingly, we found upregulated expression of MALAT1 and ALOX5 in the experimental groups, along with upregulated expression of proinflammatory cytokines. According to bioinformatics prediction, MALAT1 and ALOX5 simultaneously bind to miR-188-3p, which was downregulated in the experimental groups above. Silencing MALAT1 or ALOX5 and overexpressing miR-188-3p inhibited apoptosis and promoted the proliferation of hyperoxia-treated A549 cells. Suppressing MALAT1 or overexpressing miR-188-3p increased the expression levels of miR-188-3p but decreased the expression levels of ALOX5. Moreover, RNA immunoprecipitation (RIP) and luciferase assays showed that MALAT1 directly targeted miR-188-3p to regulate ALOX5 expression in BPD neonates. Collectively, our study demonstrates that MALAT1 regulates ALOX5 expression by binding to miR-188-3p, providing novel insights into potential therapeutics for BPD treatment.

Heme oxygenase­1 inhibits renal tubular epithelial cell pyroptosis by regulating mitochondrial function through PINK1.

Endotoxin-induced acute kidney injury (AKI) is commonly observed in clinical practice. Renal tubular epithelial cell (RTEC) pyroptosis is one of the main factors leading to the development of endotoxin-induced AKI. Mitochondrial dysfunction can lead to pyroptosis. However, the biological pathways involved in the potential lipopolysaccharide (LPS)-induced pyroptosis of RTECs, notably those associated with mitochondrial dysfunction, are poorly understood. Previous studies have demonstrated that heme oxygenase (HO)-1 confers cell protection via the induction of PTEN-induced putative kinase 1 (PINK1) expression through PTEN to regulate mitochondrial fusion/fission during endotoxin-induced AKI in vivo. Therefore, the present study investigated the role of HO-1/PINK1 in maintaining mitochondrial function and inhibiting the pyroptosis of RTECs exposed to LPS. Primary cultures of RTECs were obtained from wild-type (WT) and PINK1-knockout (PINK1KO) rats. An in vitro model of endotoxin-associated RTEC injury was established following treatment of the cells with LPS. The WT RTECs were divided into the control, LPS, Znpp + LPS and Hemin + LPS groups, and the PINK1KO RTECs were divided into the control, LPS and Hemin + LPS groups. RTECs were exposed to LPS for 6 h to assess cell viability, inflammation, pyroptosis and mitochondrial function. In the LPS-treated RTECs, the mRNA and protein expression levels of HO-1 and PINK1 were upregulated. Cell viability, adenosine triphosphate (ATP) levels and the mitochondrial oxygen consumption rate were decreased, whereas the inflammatory response, pyroptosis and mitochondrial reactive oxygen species (ROS) levels were increased. The cell inflammatory response and the induction of pyroptosis were inhibited, whereas the levels of mitochondrial ROS were decreased. In addition, the cell viability and ATP levels were increased in the WT RTECs following the upregulation of HO-1 expression. These effects were reversed by the downregulation of HO-1 expression. However, no statistically significant differences were noted between the LPS and the Hemin + LPS groups in the PINK1KO RTECs. Collectively, the findings of the present study indicate that HO-1 inhibits inflammation and regulates mitochondrial function by inhibiting the pyroptosis of LPS-exposed RTECs via PINK1.

Consumption of Saturated Fatty Acids-Rich Lard Benefits Recovery of Experimental Arthritis by Activating PPAR-γ.

SCOPE: This study investigates the impacts of lard and related fatty acids intake on rheumatoid arthritis (RA) animal models. METHOD AND RESULTS: Collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) are induced in SD rats and C57 BL/6 mice respectively, which are fed by lard-rich diet (LRD) for 42 days with intake restriction or not. AIA SD rats are treated by representative fatty acids for 30 days. Body weight, arthritis score, and metabolic profile are periodically recorded. Monocyte distribution, cytokine/metabolites levels, gene expression, and tissue damages are investigated by flow cytometry, ELISA, colorimetry, PCR, and histological methods. After being treated by fatty acids in vitro, THP-1 monocytes and the corresponding medium are collected for ELISA, PCR, immunoblotting, and reporter gene assays. Irrespective of intake amounts, LRD decreases inflammatory cytokines and inhibits glycolysis in all rheumatic rodents. Furthermore, it alters monocyte distribution and promotes PPAR-γ expression in AIA mice. Overall evidences show that both saturated (SF) and unsaturated fatty acids (USF) from lard can attenuate inflammation by activating PPAR-γ. Silencing PPAR-γ abrogates their anti-inflammatory effects in vitro. Besides, SF can stimulate TLR4/NF-κB pathway. CONCLUSION: Lard consumption is beneficial for active inflammatory arthritis recovery. Even SF can activate PPAR-γ and consequently attenuate inflammation.

Multidentate Molecule Anchoring Halide Perovskite Surface and Regulating Crystallization Kinetics toward Efficient Light-Emitting Diodes.

Functional passivators are conventionally utilized in modifying the crystallization properties of perovskites to minimize the non-radiative recombination losses in perovskite light-emitting diodes (PeLEDs). However, the weak anchor ability of some commonly adopted molecules has limited passivation ability to perovskites and even may desorb from the passivated defects in a short period of time, which bring about plenty of challenges for further development of high-performance PeLEDs. Here, a multidentate molecule, formamidine sulfinic acid (FSA), is introduced as a novel passivator to perovskites. FSA has multifunctional groups (S≐O, C≐N and NH2 ) where the S≐O and C≐N groups enable coordination with the lead ions and the NH2 interacts with the bromide ions, thus providing the most effective chemical passivation for defects and in turn the formation of highly stable perovskite emitters. Moreover, the interaction between the FSA and octahedral [PbBr6 ]4- can inhibit the formation of unfavorable low-n domains to further minimize the inefficient energy transfer inside the perovskite emitters. Therefore, the FSA passivated green-emitting PeLED exhibits a high external quantum efficiency (EQE) of 26.5% with fourfold enhancement in operating lifetime as compared to the control device, consolidating that the multidentate molecule is a promising strategy to effectively and sustainably passivate the perovskites.

Side-Group Effect on the Slow Relaxations of {Dy2} Single-Molecule Magnets with Confined N2O6 Donors.

Deep insights into and substantial enhancement of the effective anisotropy energy barrier for magnetization reversal (Ueff) are vitally important for the technological applications of dysprosium(III)-based single-molecule magnets (Dy-SMMs). To fully refine the ligand-field effect on spin relaxation, four centrosymmetric {Dy2} entities with formula [Dy2(CH3OH)2L2(RCOO)2] (H2L = 2-hydroxy-N'-((pyridin-2-yl)methylene)benzohydrazide) have been solvothermally prepared by varying the side groups of carboxylate coligands (RCOO-, R = CF3 for 1, H for 2, CH3 for 3, and Cp2Fe for 4). Structural analyses reveal that all of the DyIII carriers in 1-4 have the same N2O6 donor environments, and the non-coordinative R groups attached to the equatorial carboxylate bridges have not substantially changed the binding ability of the shortest Dy-Ophenolate bonds located at the axial position of the ligand field. Interestingly, the side groups have monotonically decreased the zero-field Ueff barriers of these weak antiferromagnetically coupled {Dy2} analogues from 721 K down to 379 K. Further electronic structure calculations demonstrate that the main magnetic axes of 1-4 are highly dominated by these comparable Dy-Ophenolate short bonds, and the g tensors have produced gradually increased transverse components responsible significantly for the decreased Ueff barriers. Additionally, thermally assisted relaxations occur preferably through the second (for 1) and the first (for 2-4) Kramer doublets. These interesting findings afford a new side-group effect to comprehensively understand the magnetostructural relationships and advance the rational design of high-performance Dy-SMMs.

Systematic analysis of tRNA-derived small RNAs reveals therapeutic targets of Xuefu Zhuyu decoction in the cortexes of experimental traumatic brain injury.

BACKGROUND: Xuefu Zhuyu Decoction (XFZYD), a well-known traditional Chinese medicine prescription, has been widely used to treat traumatic brain injury (TBI). However, the underlying mechanisms involved in XFZYD therapy remain unclear. AIM OF THE STUDY: We explored new therapeutic targets of XFZYD in TBI by the tsRNA-sequencing (tsRNA-seq) method. MATERIAL AND METHODS: High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to assess the quality of XFZYD. Male Sprague-Dawley rats were randomly categorized into three groups: sham, TBI, and XFZYD. The protective effects of XFZYD were investigated in vivo by using the Morris water maze (MWM), modified neurological severity score (mNSS) tests, hematoxylin-eosin (H&E) staining, and Nissl staining. tsRNA-seq was applied to analyze the expression of tsRNAs in the rat cortex. Four tsRNAs were validated by qRT-PCR. The biological function of putative tsRNAs was investigated using bioinformatics techniques. The functions of tsRNAs targeting mRNAs were verified in vitro. RESULTS: The mNSS and MWM indicated that XFZYD notably improved neurological deficits and cognitive function after TBI (p < 0.05). H&E staining and Nissl staining demonstrated that XFZYD suppressed damage and neuronal loss in the TBI rat cortex. We evaluated the dysregulated expression of 732 tsRNAs (128 tsRNAs were significantly altered in the TBI/sham group (fold change > 2 and p < 0.05), and 97 tsRNAs were dysregulated in the XFZYD/TBI group (fold change > 2 and p < 0.05)) in the TBI rat cortex. Interestingly, 41 tsRNAs were distinctly regulated by XFZYD. The qRT-PCR results of the four randomly chosen tsRNAs (tRF-54-75-Glu-TTC-2, tRF-55-75-Gln-CTG-2-M2, tRF-55-76-Val-TAC-1, tRF-64-85-Leu-AAG-1-M4) exhibited trends similar to those of the tsRNA-seq data. We certified the possible targets of tsRNAs and suggested the crosscurrent in the expression trend of the target genes. Bioinformatics analysis showed that XFZYD-related tsRNAs could contribute to regulating insulin resistance, the calcium signaling pathway, autophagy, and axon guidance. CONCLUSIONS: The current research implies that tsRNAs are putative therapeutic targets of XFYZD for TBI treatment. This research provides new insight into the therapeutic targets of XFZYD in treating TBI.

Hybrid Passivated Red Organic LEDs with Prolonged Operation and Storage Lifetime.

In addition to mobile and TV displays, there is a trend of organic LEDs being applied in niche markets, such as microdisplays, automobile taillights, and photobiomodulation therapy. These applications mostly do not require to be flexible in form but need to have long operation lifetimes and storage lifespans. Using traditional glass encapsulation may not be able to fulfill the rigorous product specification, and a hybrid encapsulation method by combining glass and thin-film encapsulation will be the solution. Conventional thin-film encapsulation technology generally involves organic and inorganic multilayer films that are thick and have considerable stress. As a result, when subjected to extreme heat and stress, the film easily peels off. Herein, the water vapor transmission rate (WVTR) of a 2 µm silicon nitride film prepared at 85 °C is less than 5 × 10-5 g/m2/day and its stress is optimized to be 23 MPa. Red organic LEDs are passivated with the hybrid encapsulation, and the T95 lifetime reaches nearly 10 years if the LED is continuously driven at an initial luminance of 1000 cd/m2. In addition, a storage lifespan of over 17 years is achieved.

17ß-Estradiol Inhibits Proliferation and Oxidative Stress in Vascular Smooth Muscle Cells by Upregulating BHLHE40 Expression.

Background: Intimal hyperplasia is a major complication of restenosis after angioplasty. The abnormal proliferation and oxidative stress of vascular smooth muscle cells (VSMCs) are the basic pathological feature of neointimal hyperplasia. 17ß-Estradiol can inhibit VSMCs proliferation and inflammation. However, it is still unclear whether and how 17ß-Estradiol affects intimal hyperplasia. Methods: The neointima hyperplasia was observed by hematoxylin/eosin staining. The expression of PCNA, cyclin D1, NOX1, NOX4 and p47phox in neointima hyperplasia tissues and VSMCs was determined by qRT-PCR and Western blotting. MTS assay, cell counting and EdU staining were performed to detect cells proliferation. The oxidative stress was assessed by ROS staining. Results: 17ß-Estradiol suppressed carotid artery ligation-induced intimal hyperplasia, which is accompanied by an increase of BHLHE40 level. Furthermore, loss- and gain-of-function experiments revealed that BHLHE40 knockdown promotes, whereas BHLHE40 overexpression inhibits TNF-α-induced VSMC proliferation and oxidative stress. 17ß-Estradiol inhibited TNF-α-induced VSMC proliferation and oxidative stress by promoting BHLHE40 expression, thereby suppressing MAPK signaling pathways. In addition, enforcing the expression of BHLHE40 leads to amelioration of intimal hyperplasia. Conclusions: Our study demonstrates that 17ß-Estradiol inhibits proliferation and oxidative stress in vivo and in vitro by promotion of BHLHE40 expression.

Complete genome sequence of Shewanella marisflavi ECSMB14101, a red pigment synthesizing bacterium isolated from the East China Sea.

Bacteria of the genus Shewanella have been studied for their versatile electron-accepting abilities, particularly for extracellular electron transfer via minerals. Shewanella marisflavi ECSMB14101 was isolated from naturally formed biofilms in the East China Sea. The genome of S. marisflavi ECSMB14101 encodes 3891 genes with a total size of 4,343,492 bp in one chromosome. Its GC content is 49.89%. S. marisflavi ECSMB14101 is able to synthesize a red pigment, which may be achieved through Cytochrome c3 and electron transfer to reduce Fe(III) oxide. The genomic data presented here could provide fundamental insights to better understand the physiological characteristics of S. marisflavi, the ecological significance of red pigment synthesis, and its inductive effects on the settlement of marine invertebrate larvae.

Chromosome-level genome assembly of the hard-shelled mussel Mytilus coruscus, a widely distributed species from the temperate areas of East Asia.

BACKGROUND: The hard-shelled mussel (Mytilus coruscus) is widely distributed in the temperate seas of East Asia and is an important commercial bivalve in China. Chromosome-level genome information of this species will contribute not only to the development of hard-shelled mussel genetic breeding but also to studies on larval ecology, climate change biology, marine biology, aquaculture, biofouling, and antifouling. FINDINGS: We applied a combination of Illumina sequencing, Oxford Nanopore Technologies sequencing, and high-throughput chromosome conformation capture technologies to construct a chromosome-level genome of the hard-shelled mussel, with a total length of 1.57 Gb and a median contig length of 1.49 Mb. Approximately 90.9% of the assemblies were anchored to 14 linkage groups. We assayed the genome completeness using BUSCO. In the metazoan dataset, the present assemblies have 89.4% complete, 1.9% incomplete, and 8.7% missing BUSCOs. Gene modeling enabled the annotation of 37,478 protein-coding genes and 26,917 non-coding RNA loci. Phylogenetic analysis showed that M. coruscus is the sister taxon to the clade including Modiolus philippinarum and Bathymodiolus platifrons. Conserved chromosome synteny was observed between hard-shelled mussel and king scallop, suggesting that this is shared ancestrally. Transcriptomic profiling indicated that the pathways of catecholamine biosynthesis and adrenergic signaling in cardiomyocytes might be involved in metamorphosis. CONCLUSIONS: The chromosome-level assembly of the hard-shelled mussel genome will provide novel insights into mussel genome evolution and serve as a fundamental platform for studies regarding the planktonic-sessile transition, genetic diversity, and genomic breeding of this bivalve.

Magnolol protects against acute gastrointestinal injury in sepsis by down-regulating regulated on activation, normal T-cell expressed and secreted.

BACKGROUND: Sepsis is a major medical challenge. Magnolol is an active constituent of Houpu that improves tissue function and exerts strong anti-endotoxin and anti-inflammatory effects, but the mechanism by which it reduces intestinal inflammation in sepsis is yet unclear. AIM: To assess the protective effect of magnolol on intestinal mucosal epithelial cells in sepsis and elucidate the underlying mechanisms. METHODS: Enzyme-linked immunosorbent assay was used to measure tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, and regulated on activation, normal T-cell expressed and secreted (RANTES) levels in serum and ileal tissue in animal studies. The histopathological changes of the ileal mucosa in different groups were observed under a microscope. Cell Counting Kit-8 and cell permeability assays were used to determine the concentration of drug-containing serum that did not affect the activity of Caco2 cells but inhibited lipopolysaccharide (LPS)-induced decrease in permeability. Immunofluorescence and Western blot assays were used to detect the levels of RANTES, inhibitor of nuclear factor kappa-B kinase ß (IKKß), phosphorylated IKKß (p-IKKß), inhibitor of nuclear factor kappa-B kinase α (IκBα), p65, and p-p65 proteins in different groups in vitro. RESULTS: In rats treated with LPS by intravenous tail injection in the presence or absence of magnolol, magnolol inhibited the expression of proinflammatory cytokines, IL-1ß, IL-6, and TNF-α in a dose-dependent manner. In addition, magnolol suppressed the production of RANTES in LPS-stimulated sepsis rats. Moreover, in vitro studies suggested that magnolol inhibited the increase of p65 nucleation, thereby markedly downregulating the production of the phosphorylated form of IKKß in LPS-treated Caco2 cells. Specifically, magnolol inhibited the translocation of the transcription factor nuclear factor-kappa B (NF-κB) from the cytosol into the nucleus and down-regulated the expression level of the chemokine RANTES in LPS-stimulated Caco2 cells. CONCLUSION: Magnolol down-regulates RANTES levels by inhibiting the LPS/NF-κB signaling pathways, thereby suppressing IL-1ß, IL-6, and TNF-α expression to alleviate the mucosal barrier dysfunction in sepsis.

Optimized self-immolative near-infrared probe based on hemicyanine for highly specific monitoring thiophenols in living systems.

In this paper, utilizing the same recognition group dinitrophenyl and hydroxyl functional NIR fluorophore hemicyanine, directly-linked probe CyNO2 and self-immolative probe CyBNO2 were developed for evaluation of sensing PhSH. Though CyNO2 was easily synthesized and sensitive to mercapto, the probe CyBNO2 showed higher selectivity, broader linear range from 1.0 × 10-7 to 7.0 × 10-6 M with lower detection limit of 22 nM for PhSH. Moreover, CyBNO2 was successfully applied for monitoring PhSH in living cells and in vivo, indicating the great potential of self-immolative probes.

[The construction and application of online open courses in Chinese colleges and universities--Taking the physiology course at Central South University of China as an example].

Massive open online course (MOOC) is a new learning model, which integrates the progress of novel educational concepts and the breakthrough of information technology. MOOC uses new web-based tools and online-environments to deliver knowledge education and lecture classes in a new paradigm. In this paper, we firstly reviewed the achievements through four stages of the construction and development of online courses of physiology in China in the past 20 years. Then, taking the physiology MOOC at Central South University of China as an example, we introduced the specific practices and experiences to construct the online physiological open course, including the online open course-based offline and online flipped classroom teaching practice. Finally, we discussed several important issues during the construction and application of online open courses, aiming to provide practical information for other universities.

Promotion of Bronchopulmonary Dysplasia Progression Using Circular RNA circabcc4 via Facilitating PLA2G6 Expression by Sequestering miR-663a.

Circular RNA (circRNA) has been increasingly proven as a new type of promising therapeutic RNA molecule in a variety of human diseases. However, the role of circRNA in bronchopulmonary dysplasia (BPD) has not yet been elucidated. Here, a new circRNA circABCC4 was identified from the Agilent circRNA chip as a differentially expressed circRNA in BPD. The relationship between circABCC4 level and BPD clinicopathological characteristics was analyzed. The function of circABCC4 was evaluated by performing CCK-8 and apoptosis analysis in vitro and BPD model analysis in vivo. RNA immunoprecipitation (RIP), luciferase reporter and rescue experiments were used to elucidate the interaction between circABCC4 and miR-663a. Luciferase reporter assay and rescue experiments were used to elucidate the interaction between PLA2G6 and miR-663a. CircABCC4 and PLA2G6 levels were increased, while miR-663a levels were decreased in the BPD group, compared to the control group. MiR-663a inhibited apoptosis by repressing PLA2G6 expression, while circABCC4 enhanced the apoptosis and inhibited the proliferation of A549 cells by sponging miR-663a and increasing PLA2G6 expression. In conclusion, circABCC4 promotes the evolving of BPD by spongening miR-663a and up-regulating PLA2G6 expression, which makes circABCC4 an ideal molecular target for early diagnosis and intervention of BPD.

[The metabolic networks of ferroptosis and links to lung diseases].

Ferroptosis is a newly discovered non-apoptotic form of regulated cell death driven by iron-dependent lipid peroxidation. The present studies have shown that many metabolic processes and homeostasis are affected by ferroptosis. It is related to many lung diseases, including acute lung injury, chronic obstructive pulmonary disease and pulmonary fibrosis, etc. Currently, the research on ferroptosis is still in its infancy. Previous studies have confirmed that ferroptosis is regulated by a variety of genes, and the mechanism is complex, mainly involving iron homeostasis and lipid peroxidation metabolism. This review summarizes some regulation networks of metabolic processes associated with ferroptosis and discusses the roles of ferroptosis in the pathophysiological progression of many lung diseases. We expected to provide new ideas and references for the treatment of these diseases.

Porphyromonas gingivalis promotes progression of esophageal squamous cell cancer via TGFß-dependent Smad/YAP/TAZ signaling.

Microbial dysbiosis in the upper digestive tract is linked to an increased risk of esophageal squamous cell carcinoma (ESCC). Overabundance of Porphyromonas gingivalis is associated with shorter survival of ESCC patients. We investigated the molecular mechanisms driving aggressive progression of ESCC by P. gingivalis. Intracellular invasion of P. gingivalis potentiated proliferation, migration, invasion, and metastasis abilities of ESCC cells via transforming growth factor-ß (TGFß)-dependent Drosophila mothers against decapentaplegic homologs (Smads)/Yes-associated protein (YAP)/Transcriptional coactivator with PDZ-binding motif (TAZ) activation. Smads/YAP/TAZ/TEA domain transcription factor1 (TEAD1) complex formation was essential to initiate downstream target gene expression, inducing an epithelial-mesenchymal transition (EMT) and stemness features. Furthermore, P. gingivalis augmented secretion and bioactivity of TGFß through glycoprotein A repetitions predominant (GARP) up-regulation. Accordingly, disruption of either the GARP/TGFß axis or its activated Smads/YAP/TAZ complex abrogated the tumor-promoting role of P. gingivalis. P. gingivalis signature genes based on its activated effector molecules can efficiently distinguish ESCC patients into low- and high-risk groups. Targeting P. gingivalis or its activated effectors may provide novel insights into clinical management of ESCC.