LncRNA Gm15834 Aggravates Cardiac Hypertrophy by Interacting with Sam68 and Activating NF-κB Mediated Inflammation.

BACKGROUND: Cardiac hypertrophy is the common pathological process of multiple cardiovascular diseases. However, the molecular mechanisms of cardiac hypertrophy are unclear. Long non-coding RNA (lncRNA), a newly discovered type of transcript that has been demonstrated to function as crucial regulators in the development of cardiovascular diseases. This study revealed a novel regulatory pathway of lncRNA in cardiac hypertrophy. METHODS: The cardiac hypertrophy models were established by transverse aortic constriction (TAC) in mice and angiotensin II (Ang II) in HL-1 cardiomyocytes. Adeno-associated virus 9 (AAV9) in vivo and lncRNA Gm15834 and shRNA plasmids in vitro were used to overexpress and knock down lncRNA Gm15834. The myocardial tissue structure, cardiomyocyte area, cardiac function, protein expressions, and binding of lncRNA Gm15834 and Src-associated substrate during mitosis of 68 KDa (Sam68) were detected by hematoxylin and eosin (HE) staining, immunofluorescence staining, echocardiography, western blot and RNA immunoprecipitation (RIP), respectively. RESULTS: In cardiac hypertrophy models, inhibiting lncRNA Gm15834 could decrease Sam68 expression and nuclear factor kappa-B (NF-κB) mediated inflammatory activities in vivo and in vitro, but overexpressing lncRNA Gm15834 showed the opposite results. RIP experiments validated the binding activities between lncRNA Gm15834 and Sam68. Overexpression of Sam68 could counteract the anti-hypertrophy effects of lncRNA Gm15834 knockdown. Meanwhile, in vivo inhibition of lncRNA Gm15834 could inhibit Sam68 expression, reduce NF-κB mediated inflammatory activity and attenuate cardiac hypertrophy. CONCLUSION: Our study revealed a novel regulatory axis of cardiac hypertrophy, which comprised lncRNA Gm15834/Sam68/NF-κB/inflammation, shedding a new light for identifying therapy target of cardiac hypertrophy in clinic.

CPD-002, a novel VEGFR2 inhibitor, relieves rheumatoid arthritis by reducing angiogenesis through the suppression of the VEGFR2/PI3K/AKT signaling pathway.

Synovial angiogenesis is a key player in the development of rheumatoid arthritis (RA), and anti-angiogenic therapy is considered a promising approach for treating RA. CPD-002 has demonstrated efficacy in suppressing tumor angiogenesis as a VEGFR2 inhibitor, but its specific impacts on RA synovial angiogenesis and possible anti-RA effects need further study. We examined the influences of CPD-002 on the migration and invasion of human umbilical vein endothelial cells (HUVECs) and its impacts on HUVECs' tube formation and vessel sprouting ex vivo. The therapeutic potential of CPD-002 in adjuvant-induced arthritis (AIA) rats and its suppression of synovial angiogenesis were examined. The involvement of the VEGFR2/PI3K/AKT pathway was assessed both in HUVECs and AIA rat synovium. Here, CPD-002 inhibited the migration and invasion of VEGF-stimulated HUVECs, decreased their chemotactic response to RA fibroblast-like synoviocyte-released chemoattractants, and exhibited anti-angiogenic effects in vitro and ex vivo. CPD-002's targeting of VEGFR2 was confirmed with molecular docking and cellular thermal shift assays, supported by the abolishment of CPD-002's effects upon using VEGFR2 siRNA. CPD-002 relieved paw swelling, arthritis index, joint damage, and synovial angiogenesis, indicating its anti-arthritic and anti-angiogenic effects in AIA rats. Moreover, the anti-inflammatory effects in vivo and in vitro of CPD-002 contributed to its anti-angiogenic effects. Mechanistically, CPD-002 hindered the activation of VEGFR2/PI3K/AKT pathway in VEGF-induced HUVECs and AIA rat synovium, as evidenced by reduced p-VEGFR2, p-PI3K, and p-AKT protein levels alongside elevated PTEN protein levels. Totally, CPD-002 showed anti-rheumatoid effects via attenuating angiogenesis through the inhibition of the VEGFR2/PI3K/AKT pathway.

Rapid start-up of an innovative pilot-scale staged PN/A continuous process for enhanced nitrogen removal from mature landfill leachate via robust NOB elimination and efficient biomass retention.

The start-up and stable operation of partial nitritation-anammox (PN/A) treatment of mature landfill leachate (MLL) still face challenges. This study developed an innovative staged pilot-scale PN/A system to enhance nitrogen removal from MLL. The staged process included a PN unit, an anammox upflow enhanced internal circulation biofilm (UEICB) reactor, and a post-biofilm unit. Rapid start-up of the continuous flow PN process (full-concentration MLL) was achieved within 35 days by controlling dissolved oxygen and leveraging free ammonia and free nitrous acid to selectively suppress nitrite-oxidizing bacteria (NOB). The UEICB was equipped with an annular flow agitator combined with the enhanced internal circulation device of the guide tube, which achieved an efficient enrichment of Candidatus Kuenenia in the biofilm (relative abundance of 33.4 %). The nitrogen removal alliance formed by the salt-tolerant anammox bacterium (Candidatus Kuenenia) and denitrifying bacteria (unclassified SBR1031 and Denitratisoma) achieved efficient nitrogen removal of UEICB (total nitrogen removal percentage: 90.8 %) and at the same time effective treatment of the refractory organic matter (ROM). The dual membrane process of UEICB fixed biofilm combined with post-biofilm is effective in sludge retention, and can stably control the effluent suspended solids (SS) at a level of less than 5 mg/L. The post-biofilm unit ensured that effluent total nitrogen (TN) remained below the 40 mg/L discharge standard (98.5 % removal efficiency). Compared with conventional nitrification-denitrification systems, the staged PN/A process substantially reduced oxygen consumption, sludge production, CO2 emissions and carbon consumption by 22.8 %, 67.1 %, 87.1 % and 87.1 %, respectively. The 195-day stable operation marks the effective implementation of the innovative pilot-scale PN/A process in treating actual MLL. This study provides insights into strategies for rapid start-up, robust NOB suppression, and anammox biomass retention to advance the application of PN/A in high-ammonia low-carbon wastewater.

Sulfide:quinone oxidoreductase alleviates ferroptosis in acute kidney injury via ameliorating mitochondrial dysfunction of renal tubular epithelial cells.

Ferroptosis is iron-dependent and regulates necrosis caused by lipid peroxidation and mitochondrial damage. Recent evidence has revealed an emerging role for ferroptosis in the pathophysiology of acute kidney injury (AKI). Sulfide:quinone oxidoreductase (SQOR) is a mitochondrial inner membrane protein highly expressed in the renal cortex. However, the effects of SQOR on ferroptosis and AKI have not been elucidated. In this study, we evaluated the effects of SQOR in several AKI models. We observed a rapid decrease in SQOR expression after cisplatin stimulation in both in vivo and in vitro models. SQOR-deletion mice exhibit exacerbated kidney impairment and ferroptosis in renal tubular epithelial cells following cisplatin injury. Additionally, our results showed that the overexpression of SQOR or ADT-OH (the slow-releasing H2S donor) preserved renal function in the three AKI mouse models. These effects were evidenced by lower levels of serum creatinine (SCr), blood urea nitrogen (BUN), renal neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule 1 (KIM-1). Importantly, SQOR knockout significantly aggravates cisplatin-induced ferroptosis by promoting mitochondrial dysfunction in renal tubular epithelial cells (RTECs). Moreover, online database analysis combined with our study revealed that SYVN1, an upregulated E3 ubiquitin ligase, may mediate the ubiquitin-mediated degradation of SQOR in AKI. Consequently, our results suggest that SYVN1-mediated ubiquitination degradation of SQOR may induce mitochondrial dysfunction in RTECs, exacerbating ferroptosis and thereby promoting the occurrence and development of AKI. Hence, targeting the SYVN1-SQOR axis could be a potential therapeutic strategy for AKI treatment.

N2O emission reduction in the biological nitrogen removal process for wastewater with low C/N ratios: mechanisms and strategies.

Urban wastewater, as the main influent type of Waste Water Treatment Plants (WWTPs), has the characteristic of low carbon to nitrogen ratio (C/N). In the biological nitrogen removal (BNR) process, insufficient carbon source often affects the nitrogen removal efficiency and leads to more N2O emissions. We review recent researches on N2O emissions in the BNR process of wastewater with low C/N. The availability of carbon sources affects heterotrophic denitrification (HD) and autotrophic nitrification/denitrification processes, which are the main reasons for N2O emissions in BNR. For the sustainable development of BNR in WWTPs, we introduce strategies suitable for reducing N2O emissions in the BNR process of low C/N wastewater from two aspects: traditional process innovation and new process development. These strategies mainly include carbon source addition, adjustment of aeration strategy, optimization of oxidation ditch and biofilm facilities, and application of Anammox related processes. In the future, it is still necessary to further deepen this research direction through the normalization of N2O emission quantification standards, exploration of N2O metabolism mechanisms, assessment of environmental effects of emission reduction strategies, and practical application of new processes.

Strategies for Optimizing the Zn Anode/Electrolyte Interfaces Toward Stable Zn-Based Batteries.

Aqueous rechargeable Zn-ion batteries (ARZIBs) have attracted extensive attention because of the advantages of high energy density, high safety, and low cost. However, the commercialization of ARZIBs is still challenging, mainly because of the low efficiency of Zn anodes. Several undesirable reactions (e.g., Zn dendrite and byproduct formation) always occur at the Zn anode/electrolyte interfaces, resulting in low Coulombic efficiency and rapid decay of ARZIBs. Motivated by the great interest in addressing these issues, various optimization strategies and related mechanisms have been proposed to stabilize the Zn anode-electrolyte interfaces and enlengthen the cycling lifespan of ARZIBs. Therefore, considering the rapid development of this field, updating the optimization strategies in a timely manner and understanding their protection mechanisms are highly necessary. This review provides a brief overview of the Zn anode/electrolyte interfaces from the fundamentals and challenges of Zn anode chemistry to related optimization strategies and perspectives. Specifically, these strategies are systematically summarized and classified, while several representative works are presented to illustrate the effect and corresponding mechanism in detail. Finally, future challenges and research directions for the Zn anode/electrolyte interfaces are comprehensively clarified, providing guidelines for accurate evaluation of the interfaces and further fostering the development of ARZIBs.

Super-enhancer-driven lncRNA Snhg7 aggravates cardiac hypertrophy via Tbx5/GLS2/ferroptosis axis.

Long non-coding RNAs (lncRNAs) are expressed aberrantly in cardiac disease, but their roles in cardiac hypertrophy are still unknown. Here we sought to identify a specific lncRNA and explore the mechanisms underlying lncRNA functions. Our results revealed that lncRNA Snhg7 was a super-enhancer-driven gene in cardiac hypertrophy by using chromatin immunoprecipitation sequencing (ChIP-seq). We next found that lncRNA Snhg7 induced ferroptosis by interacting with T-box transcription factor 5 (Tbx5), a cardiac transcription factor. Moreover, Tbx5 bound to the promoter of glutaminase 2 (GLS2) and regulated cardiomyocyte ferroptosis activity in cardiac hypertrophy. Importantly, extra-terminal domain inhibitor JQ1 could suppress super-enhancers in cardiac hypertrophy. Inhibition of lncRNA Snhg7 could block the expressions of Tbx5, GLS2 and levels of ferroptosis in cardiomyocytes. Furthermore, we verified that Nkx2-5 as a core transcription factor, directly bound the super-enhancer of itself and lncRNA Snhg7, increasing both of their activation. Collectively, we are the first to identify lncRNA Snhg7 as a novel functional lncRNA in cardiac hypertrophy, might regulate cardiac hypertrophy via ferroptosis. Mechanistically, lncRNA Snhg7 could transcriptionally regulate Tbx5/GLS2/ferroptosis in cardiomyocytes.

mTOR in programmed cell death and its therapeutic implications.

Mechanistic target of rapamycin (mTOR), a highly conserved serine/threonine kinase, is involved in cellular metabolism, protein synthesis, and cell death. Programmed cell death (PCD) assists in eliminating aging, damaged, or neoplastic cells, and is indispensable for sustaining normal growth, fighting pathogenic microorganisms, and maintaining body homeostasis. mTOR has crucial functions in the intricate signaling pathway network of multiple forms of PCD. mTOR can inhibit autophagy, which is part of PCD regulation. Cell survival is affected by mTOR through autophagy to control reactive oxygen species production and the degradation of pertinent proteins. Additionally, mTOR can regulate PCD in an autophagy-independent manner by affecting the expression levels of related genes and phosphorylating proteins. Therefore, mTOR acts through both autophagy-dependent and -independent pathways to regulate PCD. It is conceivable that mTOR exerts bidirectional regulation of PCD, such as ferroptosis, according to the complexity of signaling pathway networks, but the underlying mechanisms have not been fully explained. This review summarizes the recent advances in understanding mTOR-mediated regulatory mechanisms in PCD. Rigorous investigations into PCD-related signaling pathways have provided prospective therapeutic targets that may be clinically beneficial for treating various diseases.

Comprehensive bioinformatics analysis and molecular validation of lncRNAs-mediated ceRNAs network in schizophrenia.

AIMS: The present study aimed to investigate how Schizophrenia (SCZ)-specific long non-coding RNAs (lncRNAs) served as competing endogenous RNAs (ceRNAs) to modulate the biological functions and pathways involved in the pathogenesis of SCZ. MAIN METHODS: Microarray dataset (GSE54913) was obtained from Gene Expression Omnibus (GEO) database. Differently expressed (DE) lncRNAs and mRNAs were identified by "limma" package. The binding miRNAs of lncRNAs and target mRNAs of shared miRNAs were predicted by miRcode, miRDB, miRTarbase and targetscan databases. Following the ceRNAs theory, interaction network was established and visualized with the cytoscape. Functional enrichment analysis uncovered the concentrated functions and signaling pathways that may be associated with SCZ progression. Protein-protein interaction (PPI) analysis was utilized to determine hub genes. Quantitative real-time PCR (qRT-PCR) and receiver operating characteristic curve (ROC) were performed to evaluate the expression and diagnostic value of ceRNAs members, respectively. KEY FINDINGS: DElncRNAs and DEmRNAs were initially screened from GSE54913 to construct the SCZ-related ceRNAs network with 42 nodes and 53 edges. Functional enrichment analysis revealed that ceRNAs members appeared to be highly correlated with transcription factor activation, cell replication and tumor-related pathways. Once validated, a significant ceRNAs subnetwork was proposed as being implicated in the pathogenesis of SCZ. ROC analysis indicated that SCZ-related ceRNAs members may be sensitive diagnostic biomarkers for SCZ. SIGNIFICANCE: The significant SCZ-related ceRNAs subnetworks (lncRNA-C2orf48A/hsa-miR-20b-5p,-17-5p/KIF23, FOXJ2) may represent promising predictive and diagnostic biomarkers and provide novel insights into the mechanism by which lncRNAs act as microRNA sponges and contribute to the pathogenesis of SCZ.

Advances in the regulatory mechanisms of mTOR in necroptosis.

The mammalian target of rapamycin (mTOR), an evolutionarily highly conserved serine/threonine protein kinase, plays a prominent role in controlling gene expression, metabolism, and cell death. Programmed cell death (PCD) is indispensable for maintaining homeostasis by removing senescent, defective, or malignant cells. Necroptosis, a type of PCD, relies on the interplay between receptor-interacting serine-threonine kinases (RIPKs) and the membrane perforation by mixed lineage kinase domain-like protein (MLKL), which is distinguished from apoptosis. With the development of necroptosis-regulating mechanisms, the importance of mTOR in the complex network of intersecting signaling pathways that govern the process has become more evident. mTOR is directly responsible for the regulation of RIPKs. Autophagy is an indirect mechanism by which mTOR regulates the removal and interaction of RIPKs. Another necroptosis trigger is reactive oxygen species (ROS) produced by oxidative stress; mTOR regulates necroptosis by exploiting ROS. Considering the intricacy of the signal network, it is reasonable to assume that mTOR exerts a bifacial effect on necroptosis. However, additional research is necessary to elucidate the underlying mechanisms. In this review, we summarized the mechanisms underlying mTOR activation and necroptosis and highlighted the signaling pathway through which mTOR regulates necroptosis. The development of therapeutic targets for various diseases has been greatly advanced by the expanding knowledge of how mTOR regulates necroptosis.

Grisel's syndrome associated with mumps: A case report.

Grisel's syndrome (GS) is defined as atlantoaxial rotatory subluxation/fixation not associated with trauma or bone disease, usually following head and neck infection/inflammation or ear, nose, and throat (ENT) surgery. Many conditions could lead to Grisel's syndrome, of which mumps is rarely to be seen. This report discusses a case of GS in children with Type I atlantoaxial joint subluxation and previously diagnosed mumps. A 6-year-old boy who had cervical pain and torticollis for 2 weeks was admitted to our hospital. There was no trauma and he had not had ENT surgery but was diagnosed with mumps 2 weeks previously due to swelling of the left cheek and cervical lymph node. Physical examination and computed tomography confirmed a diagnosis of Grisel's syndrome with an ADI (atlanto-dens interval) of 1.6 mm. The patient then received occipito-mandibular traction for 6 days and recovered. No recurrence was observed at 1 year follow-up. Physicians should raise awareness of this rare complication of mumps to avoid life-threatening neurological impairments owing to Grisel's syndrome.

A new unmanned aerial vehicle intrusion detection method based on belief rule base with evidential reasoning.

With the growing security demands in the public, civil and military fields, unmanned aerial vehicle (UAV) intrusion detection has attracted increasing attention. In view of the shortcomings of the current UAV intrusion detection model using Wi-Fi data traffic in terms of detection accuracy, sample size reduction, and model interpretability, this paper proposes a new detection algorithm for UAV intrusion. This paper presents an interpretable intrusion detection model for UAVs based on the belief rule base (BRB). BRB can effectively use various types of information to establish any nonlinear relationship between the model input and output. It can model and simulate any nonlinear model and optimize the model parameters. However, the rule combination explosion problem is encountered in BRB if there are too many attributes. Therefore, an evidential reasoning (ER) algorithm is proposed for solving this problem. By combining the capabilities of the ER and the BRB methodologies, a new evaluation model, named the EBRB-based model, is proposed here for predicting UAV intrusion detection, even in the case of a massive number of attributes. The global optimization of the model is ensured. A new interpretable and globally optimized UAV intrusion detection model is proposed, which is the main contribution of this paper. An experimental case is used to demonstrate the implementation and application of the proposed UAV intrusion detection method.

[Analysis and Treatment Experience of 25 Cases of Primary Gastric Lymphoma with Acute Upper Gastrointestinal Bleeding as the Primary Manifestation].

Objective: To summarize the clinical characteristics and treatment experience of gastric primary lymphoma with acute upper gastrointestinal bleeding as the primary manifestation, and to provide support for clinical treatment. Methods: Information on gastric primary lymphoma patients admitted to the Department of Gastroenterology, West China Hospital of Sichuan University between January 2010 and March 2021 for acute upper gastrointestinal bleeding was retrospectively collected. Data on endoscopic morphology, tumor staging, pathology typing, severity of bleeding, risks of rebleeding, treatment and inhospital prognosis were documented and analyzed. Results: A total of 25 patients with a mean age of 57.2 years were included in the study, all of whom presented clinically with melena (100%), 9 (36%) had hematemesis, and 6 (24%) was accompanied with abdominal pain. Twenty, or 80%, of the gastric lymphoma patients with bleeding as the primary manifestation showed endoscopically a tumor-forming phenotype (Yao Classification), mostly involving the middle and lower parts of the gastric body (44% and 32%, respectively). After conservative treatment with medication, rebleeding occurred in 4 patients during hospitalization. One of them required endoscopic hemostasis, two required surgical resection to stop the bleeding, and one decided not to undergo any further treatment. Only one patient died from infection and no death resulted directly from severe bleeding. Conclusion: Gastric primary lymphoma presenting acute upper gastrointestinal bleeding as the sole clinical manifestation rarely occurs, but when the condition does occur, it shows a wide range of endoscopic involvement. It has a higher risk of rebleeding, and endoscopic or surgical treatment may be attempted when conservative medication treatment for acute upper gastrointestinal bleeding fails.

Characterization and Validation of ceRNA-Mediated Pathway-Pathway Crosstalk Networks Across Eight Major Cardiovascular Diseases.

Pathway analysis is considered as an important strategy to reveal the underlying mechanisms of diseases. Pathways that are involved in crosstalk can regulate each other and co-regulate downstream biological processes. Furthermore, some genes in the pathways can function with other genes via the relationship of the competing endogenous RNA (ceRNA) mechanism, which has also been demonstrated to play key roles in cellular biology. However, the comprehensive analysis of ceRNA-mediated pathway crosstalk is lacking. Here, we constructed the landscape of the ceRNA-mediated pathway-pathway crosstalk of eight major cardiovascular diseases (CVDs) based on sequencing data from ∼2,800 samples. Some common features shared by numerous CVDs were uncovered. A fraction of the pathway-pathway crosstalk was conserved in multiple CVDs and a core pathway-pathway crosstalk network was identified, suggesting the similarity of pathway-pathway crosstalk among CVDs. Experimental evidence also demonstrated that the pathway crosstalk was functioned in CVDs. We split all hub pathways of each pathway-pathway crosstalk network into three categories, namely, common hubs, differential hubs, and specific hubs, which could highlight the common or specific biological mechanisms. Importantly, after a comparison analysis of the hub pathways of networks, ∼480 hub pathway-induced common modules were identified to exert functions in CVDs broadly. Moreover, we performed a random walk algorithm on the hub pathway-induced sub-network and identified 23 potentially novel CVD-related pathways. In summary, our study revealed the potential molecular regulatory mechanisms of ceRNA crosstalk in pathway-pathway crosstalk levels and provided a novel routine to investigate the pathway-pathway crosstalk in cardiology. All CVD pathway-pathway crosstalks are provided in http://www.licpathway.net/cepathway/index.html.

Up-regulation of IRF3 is required for docosahexaenoic acid suppressing ferroptosis of cardiac microvascular endothelial cells in cardiac hypertrophy rat.

The molecular characteristics of ferroptosis in cardiac hypertrophy have been rarely studied. Especially, there have been no studies to investigate the regulatory mechanisms of docosahexaenoic acid (DHA) on ferroptosis in cardiac hypertrophy. This study was designed to determine the role of ferroptosis in microvascular injury, and investigate the contribution of DHA in suppressing ferroptosis and preventing pressure overload-mediated endothelial damage. Our results indicated that the expression of interferon regulating factor 3 (IRF3) was primarily inhibited by pressure overload and consequently caused endothelial ferroptosis. Nevertheless, administration of DHA increased IRF3 expression and provided a pro-survival advantage for the endothelial system in the context of pressure overload. Experimental studies clearly showed that inhibition of IRF3 down-regulated SLC7A11 expression, and the latter leaded to the increase in the activities of arachidonate 12-lipoxygenase, which obligated cardiac microvascular endothelial cells to undergo ferroptosis via augmenting lipid peroxides. Interestingly, DHA supplementation suppressed endothelial ferroptosis via up-regulation of IRF3. Taken together, our studies identified the IRF3-SLC7A11-arachidonate 12-lipoxygenase axis as a new pathway responsible for pressure overload-mediated microvascular damage via initiating endothelial ferroptosis. In contrast, DHA treatment up-regulated the expression of IRF3 and thus reduced cellular ferroptosis, conferring a protective advantage to the endothelial system in pressure overload. These findings revealed that targeting IRF3 might be a useful therapeutic strategy for cardioprotection in cardiac hypertrophy and heart failure.

Neutrophil-like cell membrane-coated siRNA of lncRNA AABR07017145.1 therapy for cardiac hypertrophy via inhibiting ferroptosis of CMECs.

Cardiac microvascular dysfunction is associated with cardiac hypertrophy and can eventually lead to heart failure. Dysregulation of long non-coding RNAs (lncRNAs) has recently been recognized as one of the key mechanisms involved in cardiac hypertrophy. However, the potential roles and underlying mechanisms of lncRNAs in cardiac microvascular dysfunction have not been explicitly delineated. Our results confirmed that cardiac microvascular dysfunction was related to cardiac hypertrophy and ferroptosis of cardiac microvascular endothelial cells (CMECs) occurred during cardiac hypertrophy. Using a combination of in vivo and in vitro studies, we identified a lncRNA AABR07017145.1, named as lncRNA AAB for short, and revealed that lncRNA AAB was upregulated in the hearts of cardiac hypertrophy rats as well as in the Ang II-induced CMECs. Importantly, we found that lncRNA AAB sponged and sequestered miR-30b-5p to induce the imbalance of MMP9/TIMP1, which enhanced the activation of transferrin receptor 1 (TFR-1) and then eventually led to the ferroptosis of CMECs. Moreover, we have developed a delivery system based on neutrophil membrane (NM)-camouflaged mesoporous silica nanocomplex (MSN) for inhibition of cardiac hypertrophy, indicating the potential role of silenced lncRNA AAB (si-AAB) and overexpressed miR-30b-5p as the novel therapy for cardiac hypertrophy.

LncRNA4930473A02Rik promotes cardiac hypertrophy by regulating TCF7 via sponging miR-135a in mice.

Cardiac hypertrophy is a common pathological change accompanied by various cardiovascular diseases; however, its underlying mechanisms remain elusive. Mounting evidence indicates that long non-coding RNAs (lncRNAs) are novel transcripts involved in regulating multiple biological processes. However, little is known about their role in regulating cardiac hypertrophy. This study revealed a novel lncRNA4930473A02Rik (abbreviated as lncRNAA02Rik), which showed considerably increased expression in hypertrophic mouse hearts in vivo and angiotensin-II (Ang-II)-induced hypertrophic cardiomyocytes in vitro. Notably, lncRNAA02Rik knockdown partly ameliorated Ang-II induced hypertrophic cardiomyocytes in vitro and hypertrophic mouse heart function in vivo, whereas lncRNAA02Rik overexpression promoted cardiac hypertrophy in vitro. Furthermore, lncRNAA02Rik acted as a competing endogenous RNA by sponging miR-135a, while forced expression of lncRNAA02Rik could repress its activity and expression. Furthermore, forcing miR-135a overexpression exerted a significant protective effect against cardiac hypertrophy by inhibiting the activity of its downstream target TCF7, a critical member of Wnt signaling, and the protective effect could be reversed by AMO-135a. Luciferase assay showed direct interactions among lncRNAA02Rik, miR-135a, and TCF7. Altogether, our study demonstrated that lncRNAA02Rik upregulation could promote cardiac hypertrophy development via modulating miR-135a expression levels and TCF7 activity. Therefore, lncRNAA02Rik inhibition might be considered as a novel potential therapeutic strategy for cardiac hypertrophy.

Effect of 405-nm light-emitting diode on environmental tolerance of Cronobacter sakazakii in powdered infant formula.

Cronobacter sakazakii is an opportunistic pathogen that can survive extreme desiccation, heat, acid, and osmotic stress. This can increase the risk of infection, resulting in severe diseases, mainly in neonates. The inactivation effect of 405 ± 5-nm light-emitting diode (LED) illumination on C. sakazakii with different initial concentrations and C. sakazakii strains isolated from powdered infant formula (PIF) and baby rice cereal (BRC) were firstly evaluated. Then, the effect of 405 ± 5-nm LED on the tolerance of diverse environmental conditions of C. sakazakii in PIF was investigated. Conditions involving desiccation [PIF, Water activity (aw): 0.2-0.5], heat (45, 50, and 55 °C), acid (simulated gastric fluid: SGF, pH 4.75 ± 0.25), and bile salt (0.2%, bile salt solution) were used to study the effects of 405-nm LED on C. sakazakii resistance. The transcription levels of ten tolerance-associated genes and changes in bacterial cell membrane were examined to understand the response of C. sakazakii to LED illumination. The results showed that 405-nm LED effectively inactivated C. sakazakii ATCC 29544 with initial concentration from 8 to 1 log CFU/g in PIF and strains isolated from PIF and BRC. Moreover, 405-nm LED could decrease the tolerance of C. sakazakii in PIF to desiccation, heat treatment at 50 and 55 °C, SGF, and bile salt to different degrees, but the resistance to the heat treatment at 45 °C was not influenced by LED illumination. In addition, the transcription levels of the ten tolerance-associated genes measured in the LED-illuminated C. sakazakii cells were significantly downregulated compared with those in unilluminated controls. The damage on cell membrane was confirmed for LED-treated cells by LIVE/DEAD® assay. These results indicate that 405-nm LED illumination may be effective at reducing the environmental resistance of C. sakazakii in PIF. Furthermore, this study suggests the potential for applying 405-nm LED technology in the prevention and control of pathogens in food processing, production, and storage environments.

The impact of albumin infusion on the risk of rebleeding and in-hospital mortality in cirrhotic patients admitted for acute gastrointestinal bleeding: a retrospective study of a single institute.

BACKGROUND: To investigate the effect of albumin infusion on cirrhotic patients admitted for acute gastrointestinal bleeding. METHODS: Medical records of cirrhotic patients who admitted due to acute gastrointestinal bleeding through January 2009 to December 2018 were reviewed. Clinical data and the total amount of albumin and red blood cell used during hospitalization were recorded. For patients with rebleeding, the amount of albumin and red blood cell used before rebleeding was also documented. The primary outcome was the occurrence of rebleeding, and the second outcome was in-hospital mortality. Univariate and multivariate logistic analysis was performed to identify risk factors associated with rebleeding and in-hospital mortality. RESULTS: A total of 1503 cirrhotic patients were included in the analysis. There were 146 episodes of in-patient rebleeding occurred, while 81 patients died. Overall, more red blood cells and albumin were prescribed to patients who suffered rebleeding. In terms of the amount before rebleeding, the red blood cell was higher in patients with rebleeding, but the albumin infusion was similar. In the multivariate model, the albumin infusion before rebleeding was an independent risk factor associated with rebleeding (adjusted OR for ≤40 g vs 0 g, 0.469 [0.269-0.793], p = 0.006; adjusted OR for > 40 g vs 0 g, 0.272 [0.115-0.576], p = 0.001). In Child-Pugh C class patients, the use of albumin more than 40 g during hospitalization associated with a lower risk of in-patient mortality (adjusted OR for > 40 g vs 0 g, 0.136 [0.019-0.741], p = 0.031). CONCLUSIONS: Albumin infusion was associated with a lower risk of rebleeding and in-hospital deaths in cirrhosis admitted for acute gastrointestinal bleeding.

Inactivation of Pseudomonas aeruginosa Biofilms by 405-Nanometer-Light-Emitting Diode Illumination.

Biofilm formation by Pseudomonas aeruginosa contributes to its survival on surfaces and represents a major clinical threat because of the increased tolerance of biofilms to disinfecting agents. This study aimed to investigate the efficacy of 405-nm light-emitting diode (LED) illumination in eliminating P. aeruginosa biofilms formed on stainless steel coupons under different temperatures. Time-dependent killing assays using planktonic and biofilm cells were used to determine the antimicrobial and antibiofilm activities of LED illumination. We also evaluated the effects of LED illumination on the disinfectant susceptibility, biofilm structure, extracellular polymeric substance (EPS) structure and composition, and biofilm-related gene expression of P. aeruginosa biofilm cells. Results showed that the abundance of planktonic P. aeruginosa cells was reduced by 0.88, 0.53, and 0.85 log CFU/ml following LED treatment for 2 h compared with untreated controls at 4, 10, and 25°C, respectively. For cells in biofilms, significant reductions (1.73, 1.59, and 1.68 log CFU/cm2) were observed following LED illumination for 2 h at 4, 10, and 25°C, respectively. Moreover, illuminated P. aeruginosa biofilm cells were more sensitive to benzalkonium chloride or chlorhexidine than untreated cells. Scanning electron microscopy and confocal laser scanning microscopic observation indicated that both the biofilm structure and EPS structure were disrupted by LED illumination. Further, reverse transcription-quantitative PCR revealed that LED illumination downregulated the transcription of several genes associated with biofilm formation. These findings suggest that LED illumination has the potential to be developed as an alternative method for prevention and control of P. aeruginosa biofilm contamination.IMPORTANCEPseudomonas aeruginosa can form biofilms on medical implants, industrial equipment, and domestic surfaces, contributing to high morbidity and mortality rates. This study examined the antibiofilm activity of 405-nm light-emitting diode (LED) illumination against mature biofilms formed on stainless steel coupons. We found that the disinfectant susceptibility, biofilm structure, and extracellular polymeric substance structure and composition were disrupted by LED illumination. We then investigated the transcription of several critical P. aeruginosa biofilm-related genes and analyzed the effect of illumination temperature on the above characteristics. Our results confirmed that LED illumination could be developed into an effective and safe method to counter P. aeruginosa biofilm contamination. Further research will be focused on the efficacy and application of LED illumination for elimination of complicated biofilms in the environment.