A novel MCGDM technique based on correlation coefficients under probabilistic hesitant fuzzy environment and its application in clinical comprehensive evaluation of orphan drugs.

Probabilistic hesitant fuzzy sets (PHFSs) are superior to hesitant fuzzy sets (HFSs) in avoiding the problem of preference information loss among decision makers (DMs). Owing to this benefit, PHFSs have been extensively investigated. In probabilistic hesitant fuzzy environments, the correlation coefficients have become a focal point of research. As research progresses, we discovered that there are still a few unresolved issues concerning the correlation coefficients of PHFSs. To overcome the limitations of existing correlation coefficients for PHFSs, we propose new correlation coefficients in this study. In addition, we present a multi-criteria group decision-making (MCGDM) method under unknown weights based on the newly proposed correlation coefficients. In addition, considering the limitations of DMs' propensity to use language variables for expression in the evaluation process, we propose a method for transforming the evaluation information of the DMs' linguistic variables into probabilistic hesitant fuzzy information in the newly proposed MCGDM method. To demonstrate the applicability of the proposed correlation coefficients and MCGDM method, we applied them to a comprehensive clinical evaluation of orphan drugs. Finally, the reliability, feasibility and efficacy of the newly proposed correlation coefficients and MCGDM method were validated.

Distinct roles of excitatory and inhibitory neurons in the medial prefrontal cortex in the expression and reconsolidation of methamphetamine-associated memory in male mice.

Methamphetamine, a commonly abused drug, is known for its high relapse rate. The persistence of addictive memories associated with methamphetamine poses a significant challenge in preventing relapse. Memory retrieval and subsequent reconsolidation provide an opportunity to disrupt addictive memories. However, the key node in the brain network involved in methamphetamine-associated memory retrieval has not been clearly defined. In this study, using the conditioned place preference in male mice, whole brain c-FOS mapping and functional connectivity analysis, together with chemogenetic manipulations of neural circuits, we identified the medial prefrontal cortex (mPFC) as a critical hub that integrates inputs from the retrosplenial cortex and the ventral tegmental area to support both the expression and reconsolidation of methamphetamine-associated memory during its retrieval. Surprisingly, with further cell-type specific analysis and manipulation, we also observed that methamphetamine-associated memory retrieval activated inhibitory neurons in the mPFC to facilitate memory reconsolidation, while suppressing excitatory neurons to aid memory expression. These findings provide novel insights into the neural circuits and cellular mechanisms involved in the retrieval process of addictive memories. They suggest that targeting the balance between excitation and inhibition in the mPFC during memory retrieval could be a promising treatment strategy to prevent relapse in methamphetamine addiction.

Hyperactive lateral habenula mediates the comorbidity between rheumatoid arthritis and depression-like behaviors.

Rheumatoid arthritis (RA) patients have a high prevalence for depression. On the other hand, comorbid with depression is associated with worse prognosis for RA. However, little is known about the underlying mechanisms for the comorbidity between RA and depression. It remains to be elucidated which brain region is critically involved in the development of depression in RA, and whether alterations in the brain may affect pathological development of RA symptoms. Here, by combining clinical and animal model studies, we show that in RA patients, the level of depression is significantly correlated with the severity of RA disease activity and affects patients' quality of life. The collagen antibody-induced arthritis (CAIA) mouse model of RA also develops depression-like behaviors, accompanied by hyperactivity and alterations in gene expression reflecting cerebrovascular disruption in the lateral habenula (LHb), a brain region critical for processing negative valence. Importantly, inhibition of the LHb not only alleviates depression-like behaviors, but also results in rapid remission of RA symptoms and amelioration of RA-related pathological changes. Together, our study highlights a critical but previously overlooked contribution of hyperactive LHb to the comorbidity between RA and depression, suggesting that targeting LHb in conjunction with RA treatments may be a promising strategy for RA patients comorbid with depression.

Multilayer network-based channel selection for motor imagery brain-computer interface.

Objective. The number of electrode channels in a motor imagery-based brain-computer interface (MI-BCI) system influences not only its decoding performance, but also its convenience for use in applications. Although many channel selection methods have been proposed in the literature, they are usually based on the univariate features of a single channel. This leads to a loss of the interaction between channels and the exchange of information between networks operating at different frequency bands.Approach. We integrate brain networks containing four frequency bands into a multilayer network framework and propose a multilayer network-based channel selection (MNCS) method for MI-BCI systems. A graph learning-based method is used to estimate the multilayer network from electroencephalogram (EEG) data that are filtered by multiple frequency bands. The multilayer participation coefficient of the multilayer network is then computed to select EEG channels that do not contain redundant information. Furthermore, the common spatial pattern (CSP) method is used to extract effective features. Finally, a support vector machine classifier with a linear kernel is trained to accurately identify MI tasks.Main results. We used three publicly available datasets from the BCI Competition containing data on 12 healthy subjects and one dataset containing data on 15 stroke patients to validate the effectiveness of our proposed method. The results showed that the proposed MNCS method outperforms all channels (85.8% vs. 93.1%, 84.4% vs. 89.0%, 71.7% vs. 79.4%, and 72.7% vs. 84.0%). Moreover, it achieved significantly higher decoding accuracies on MI-BCI systems than state-of-the-art methods (pairedt-tests,p< 0.05).Significance. The experimental results showed that the proposed MNCS method can select appropriate channels to improve the decoding performance as well as the convenience of the application of MI-BCI systems.

Psychological distress and aggression among adolescents with internet gaming disorder symptoms.

The present study aimed to investigate the current situation of internet gaming disorder (IGD) in Chinese adolescents and explore the impact of IGD-related factors on adolescent aggression. We hypothesized that IGD symptoms in adolescents would be associated with aggressive behavior and that risk factors for IGD symptoms could increase the aggressive tendencies of adolescents. To verify the above hypothesis, a cross-sectional survey of junior and senior high school students from southern, southwestern, central, and eastern China was conducted. A total of 9306 valid questionnaires were collected. The results showed that the prevalence of IGD symptoms was 1.78 % among Chinese adolescents. The adolescents in the disordered gamer group had the most severe IGD symptoms, with the highest levels of psychological distress and aggression. Interestingly, adolescents in the casual gamer group had the lowest psychological distress and aggression scores. Linear regression analysis further showed that higher levels of aggression were significantly associated with male sex, younger age, more severe psychological distress and IGD symptoms, and more violent game exposure. Our results suggested that excessive online gaming not only contributes to psychological distress in adolescents but also increases their levels of aggressive behavior. Apart from male sex and younger age, severe IGD symptoms and psychological distress are the most important predictors of the development of aggressive behavior.

ZEA mediates autophagy through the ROS-AMPK-m-TOR pathway to enhance the susceptibility of mastitis induced by Staphylococcus aureus in mice.

Mastitis is an inflammatory response of the mammary tissue caused by pathogenic bacterial infections, especially Staphylococcus aureus (S. aureus). Zearalenone (ZEA) is one of the common mycotoxins in moldy feed, which usually affects the cow's resistance to pathogenic microorganisms. However, it is not well understood whether ZEA affects the development of mastitis. Therefore, this study aimed to investigate the role of ZEA in the development of S. aureus-induced mastitis in mice. The results showed that administered daily by gavage for one week of ZEA (40 mg/kg) aggravated the severity of mastitis induced by S. aureus. Furthermore, we found that ZEA promotes the adhesion and invasion of S. aureus into mouse mammary epithelial cells (MMEC) by activating autophagy, and the activation of autophagy mediated by ROS-AMPK-m-TOR pathway. Taken together, the results showed that ZEA enhances S. aureus-induced mastitis susceptibility through activating autophagy mediated by ROS-AMPK-mTOR signaling pathway.

Assessing stroke rehabilitation degree based on quantitative EEG index and nonlinear parameters.

The assessment of motor function is critical to the rehabilitation of stroke patients. However, commonly used evaluation methods are based on behavior scoring, which lacks neurological indicators that directly reflect the motor function of the brain. The objective of this study was to investigate whether resting-state EEG indicators could improve stroke rehabilitation evaluation. We recruited 68 participants and recorded their resting-state EEG data. According to Brunnstrom stage, the participants were divided into three groups: severe, moderate, and mild. Ten quantitative electroencephalographic (QEEG) and five non-linear parameters of resting-state EEG were calculated for further analysis. Statistical tests were performed, and the genetic algorithm-support vector machine was used to select the best feature combination for classification. We found the QEEG parameters show significant differences in Delta, Alpha1, Alpha2, DAR, and DTABR (P < 0.05) among the three groups. Regarding nonlinear parameters, ApEn, SampEn, Lz, and C0 showed significant differences (P < 0.05). The optimal feature classification combination accuracy rate reached 85.3%. Our research shows that resting-state EEG indicators could be used for stroke rehabilitation evaluation.

Prevalence and risk factors of post-traumatic stress disorder symptoms among Chinese health care workers following the COVID-19 pandemic.

In December 2019, coronavirus disease 2019 (COVID-19) appeared in Wuhan (Hubei, China) and subsequently swept the globe. In addition to the risk of infection, there is a strong possibility that post-traumatic stress disorder (PTSD) may be a secondary effect of the pandemic. Health care workers (HCWs) participating in the pandemic are highly exposed to and may bear the brunt out of stressful or traumatic events. In this cross-sectional study, we assessed the morbidity and risk factors of PTSD symptoms among Chinese HCWs. A total of 457 HCWs were recruited from March 15, 2020, to Mach 22, 2020, including HCWs in Wuhan and Hubei Province (excluding Wuhan), the areas first and most seriously impacted by COVID-19. The morbidity of PTSD symptoms was assessed by the Event Scale-Revised (IES-R). The risk factors for PTSD symptoms were explored by means of logistic regression analysis. Over 40% of the respondents experienced PTSD symptoms more than one month after the COVID-19 outbreak, and this proportion increased to 57.7% in Wuhan HCWs, especially females and HCWs on the frontline. Thus, rapid mental health assessment and effective psychological interventions need to be developed for frontline HCWs to prevent long-term PTSD-related disabilities. Moreover, Negative coping style and neuroticism personality may be regarded as high risk factors for PTSD symptoms. Improving individual coping strategies to enhance resilience should be the focus of further preventive intervention strategies.

Cysteine conjugate beta-lyase 2 (CCBL2) expression as a prognostic marker of survival in breast cancer patients.

OBJECTIVE: Cysteine conjugate beta-lyase 2 (CCBL2), also known as kynurenine aminotransferase 3 (KAT3) or glutamine transaminase L (GTL), plays an essential role in transamination and cytochrome P450. Its correlation with some other cancers has been explored, but breast cancer (BC) not yet. METHODS: The mRNA and protein expression of CCBL2 in BC cell lines and patient samples were detected by RT-qPCR and immunohistochemistry (IHC). BC patients' clinical information and RNA-Seq expression were acquired via The Cancer Genome Atlas (TCGA) database. Patients were categorized into high/low CCBL2 expression groups based on the optimal cutoff value (8.973) determined by receiver operating characteristic (ROC) curve. We investigated CCBL2 and clinicopathological characteristics' relationship using Chi-square tests, estimated diagnostic capacity using ROC curves and drew survival curves using Kaplan-Meier estimate. We compared survival differences using Cox regression and externally validated using Gene Expression Omnibus (GEO) database. We evaluated enriched signaling pathways using gene set enrichment analysis (GSEA), explored CCBL2 and relevant genes' relationship using tumor immunoassay resource (TIMER) databases and used the human protein atlas (HPA) for pan-cancer analysis and IHC. RESULTS: CCBL2 was overexpressed in normal human cell lines and tissues. CCBL2 expression was lower in BC tissues (n = 1104) than in normal tissues (n = 114), validated by GEO database. Several clinicopathologic features were related to CCBL2, especially estrogen receptor (ER), progesterone receptor (PR) and clinical stages. The low expression group exhibited poor survival. CCBL2's area under curve (AUC) analysis showed finite diagnostic capacity. Multivariate cox-regression analysis indicated CCBL2 independently predicted BC survival. GSEA showed enriched pathways: early estrogen response, MYC and so on. CCBL2 positively correlated with estrogen, progesterone and androgen receptors. CCBL2 was downregulated in most cancers and was associated with their survival, including renal and ovarian cancers. CONCLUSIONS: Low CCBL2 expression is a promising poor BC survival independent prognostic marker.

Insight in degradation of tetracycline in mariculture wastewater by ultraviolet/persulfate advanced oxidation process.

The direct discharge of trace amounts of antibiotics in mariculture wastewater results in adverse effect on the ecological environment of receiving waters. Hence, the degradation of tetracycline (TC) in mariculture wastewater by the ultraviolet/peroxydisulfate (UV/PS) process was investigated in this study. The results revealed that 95.73% removal of TC with 5 mg/L dosage was achieved after 30 min UV/PS treatment. Chloride ion (Cl-) in mariculture wastewater slightly inhibited TC degradation by scavenging free radicals. Comparably, bromine ion (Br-) significantly enhanced the removal of TC and even doubled the degradation rate. Reactive bromine species (RBS) made a major contribution to the TC removal, followed by free chlorine and other reactive chlorine species (RCS). The TC degradation pathway revealed that functional group shedding and ring-opening reactions occurred successively. In addition, TC mineralization rate was low within 30 min, causing the inefficient reduction of acute toxicity of TC and its intermediates, which could be improved by optimizing the process parameters. These results indicated that UV/PS is a new alternative process for the harmless treatment of mariculture wastewater containing the antibiotics.

Effect of sulfamethoxazole on nitrate removal by simultaneous heterotrophic aerobic denitrification.

The increase in mariculture activities worldwide has not only led to a rise of nitrogen compounds in the ecosystem but has also intensified the accumulation of antibiotics in both terrestrial and marine environments. This study focused on the effect of typical antibiotics, specifically sulfamethoxazole (SMX) on nitrate removal from mariculture wastewater by aerobic denitrification process; an aerobic denitrification system feeding with 148.2 mg/L COD, 8.59 mg/L nitrate, 0.72 mg/L nitrite, and 4.75 mg/L ammonium was set up. The hydraulic retention time (HRT) was 8 h. As the aerobic bioreactor started up successfully without SMX dosage, an excellent removal of ammonium, nitrite, and nitrate was achieved at 91.35%, 93.33%, and 88.51%, respectively; the corresponding effluent concentrations were 0.41 mg/L, 0.048 mg/L, and 0.96 mg/L. At the influent SMX doses of 0, 1, 5, and 10 mg/L, the COD removal reached 96.91%, 96.27%, 88.69%, and 85.89%, resulting in effluent concentrations of 4.53, 5.45, 17.38, and 20.6 mg/L, respectively. Nitrification was not inhibited by SMX dosage. However, aerobic denitrification was inhibited by 10 mg/L SMX. Proteobacteria was the most abundant phylum, and surprisingly its abundance increased with the increase in SMX concentration. An excellent SMX degradation was noted at initial SMX dosages of 1, 5, and 10 mg/L; the removal rate was 100%,100%, and 99.8%, respectively. The SMX degrading genera Comamonas sp., Acinetobacter sp., and Thauera sp. are of great validity to wastewater engineers because they have demonstrated efficiency in simultaneous heterotrophic aerobic denitrification and antibiotic degradation as well as COD removal. PRACTITIONER POINTS: Nitrification was not inhibited by increase in SMX dosage. An increase in SMX dosage inhibited aerobic denitrification. COD removal was not affected by increased SMX dosage. Comamonas, Acinetobacter, and Thauera had high efficiency in COD removal and SMX degradation.

Sleep Deprivation Impairs Learning-Induced Increase in Hippocampal Sharp Wave Ripples and Associated Spike Dynamics during Recovery Sleep.

Sleep deprivation (SD) causes deficits in off-line memory consolidation, but the underlying network oscillation mechanisms remain unclear. Hippocampal sharp wave ripple (SWR) oscillations play a critical role in off-line memory consolidation. Therefore, we trained mice to learn a hippocampus-dependent trace eyeblink conditioning (tEBC) task and explored the influence of 1.5-h postlearning SD on hippocampal SWRs and related spike dynamics during recovery sleep. We found an increase in hippocampal SWRs during postlearning sleep, which predicted the consolidation of tEBC in conditioned mice. In contrast, sleep-deprived mice showed a loss of tEBC learning-induced increase in hippocampal SWRs during recovery sleep. Moreover, the sleep-deprived mice exhibited weaker reactivation of tEBC learning-associated pyramidal cells in hippocampal SWRs during recovery sleep. In line with these findings, tEBC consolidation was impaired in sleep-deprived mice. Furthermore, sleep-deprived mice showed augmented fast excitation from pyramidal cells to interneurons and enhanced participation of interneurons in hippocampal SWRs during recovery sleep. Among various interneurons, parvalbumin-expressing interneurons specifically exhibited overexcitation during hippocampal SWRs. Our findings suggest that altered hippocampal SWRs and associated spike dynamics during recovery sleep may be candidate network oscillation mechanisms underlying SD-induced memory deficits.

"Four-in-One" Nanozyme and Natural Enzyme Symbiotic System of Cu2-x Se-GOx for Cervical Cancer Therapy.

Cervical cancer, as a common malignant tumor of the reproductive system, seriously threatens women's life and health, and is difficult to be cured by traditional treatments, such as surgery, chemotherapy and radiotherapy. Fortunately, tumor microenvironment (TME)-activated catalytic therapy with high efficiency and reduced off-target toxicity has emerged as a novel treatment model. Herein, we designed a "four-in-one" nanozyme and natural enzyme symbiotic system of Cu2-x Se-GOx for TME-triggered cascaded catalytic enhanced cancer treatment. In response to unique TME, Cu2-x Se with catalase activity could effectively catalyze over-expressed H2 O2 in cancer cells into O2 . Subsequently, the glucose oxidase (GOx) could deplete intracellular glucose with the assistance of O2 ; this not only achieves starvation therapy, but also regenerates H2 O2 to boost the generation of highly cytotoxic . OH due to the peroxidase activity of Cu2-x Se. Moreover, although the free-radical scavenger glutathione (GSH) is overexpressed in tumor cells, Cu2-x Se with glutathione oxidase activity could effectively consume GSH for enhanced ROS production. Thus, the "four-in-one" nanozyme@natural enzyme symbiotic system of Cu2-x Se-GOx could induce significant ROS accumulation at the tumor regions, thus providing a potential approach for the treatment of cervical cancer.

A Case Study on a Soluble Dibenzothiophene-S,S-dioxide-Based Conjugated Polyelectrolyte for Photocatalytic Hydrogen Production: The Film versus the Bulk Material.

Most of the traditional polymeric photocatalysts are generally insoluble in organic solvents, which might exclude their compatibility with large-area processing technology. Herein, we have synthesized a novel quaternized ammonium conjugated polyelectrolyte (PSO-FNBr) that can be processed to prepare an active film by a drop-casting method. PSO-FNBr shows a remarkably enhanced hydrogen evolution rate (HER) of 20.5 mmol h-1 g-1 in the thin film form in comparison to that of the powder form. Furthermore, we prepared a new type of thin film-based photocatalytic device, which provided a rare example of a "three-in-one" (rapid sampling + easy-to-use + cost-effective) photocatalytic system. The PSO-FNBr thin film over the Pt substrate can maintain a competitive HER, even though the Pt substrate was recycled and reused 50 times. Considering the features of impressive activity and low cost, we believe that PSO-FNBr will be a promising material for potential application in photocatalysis.

Propofol Downregulates lncRNA MALAT1 to Alleviate Cerebral Ischemia-Reperfusion Injury.

Propofol (PPF) is reported to play a protective role in ischemia/reperfusion (I/R) injury, including cerebral ischemia-reperfusion injury (CIRI). This study aims to investigate the mechanism by which PPF ameliorates CIRI. Kunming mice were used to establish the middle cerebral artery occlusion (MCAO)/reperfusion mouse model in vivo. PPF pre-treatment was performed before CIRI. Lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) levels were detected to evaluate the tissue injury. PC12 cells were exposed to hypoxia/reoxygenation (H/R) to construct the in vitro CIRI model, and PC12 cells were pre-treated with PPF before H/R. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect the expression of lncRNA MALAT1 and miR-182-5p. Flow cytometry was used to detect the apoptosis of PC12 cells. Bioinformatics analysis, qRT-PCR, dual-luciferase reporter gene experiments, and RNA immunoprecipitation (RIP) experiments were performed to predict and validate the targeting relationship between MALAT1 and miR-182-5p. Western blot was used to detect Toll-like receptor 4 (TLR4) expression at protein level. PPF pre-treatment remarkably inhibited LDH and CPK levels in the serum of the mice with CIRI, and reduced the apoptosis of PC12 cells exposed to H/R. Besides, PPF pre-treatment markedly suppressed MALAT1 expression in both in vivo and in vitro models and upregulated miR-182-5p expression. MiR-182-5p was validated to be a downstream target gene of MALAT1, and MALAT1 could increase the expression of TLR4 by suppressing miR-182-5p. The effects of PPF on the injury of the mice brain and PC12 cells were partly counteracted by the restoration of MALAT1. PPF protects the brain against I/R-induced injury by regulating MALAT1/miR-182-5p/TLR4 axis.

[Enrichment of Antibiotic Resistant Bacteria and Antibiotic Resistance Genes by Sulfamethoxazole in the Biological Treatment System of Mariculture Wastewater].

Although antibiotics are heavily used in mariculture, only a small portion of the added antibiotics is absorbed. Little is known about the response process of antibiotics, antibiotic resistant bacteria, and antibiotic resistance genes to antibiotic-containing wastewater entering a wastewater treatment system. In this study, an anoxic/aerobic moving bed biofilm reactor (A/O-MBBR) was used to treat marine aquaculture wastewater containing sulfamethoxazole (SMX). The antibiotics and resistance genes in the reactor were then evaluated under selective SMX pressure, and the changing abundance patterns and the response of microbial communities and cultivable resistant bacterial populations were further explored. The results show that with an influent SMX concentration of 500 µg ·L-1 and a hydraulic retention time of 8 h, SMX had a slight effect on the removal rate of NH4+-N and NO2--N, following which the performance gradually recovered. During this stage, SMX removal reached approximately 32%, with more than 78% of SMX removed from the hypoxic zone. The resistance gene was more significantly enriched in the hypoxic zone than in the aerobic zone. In the hypoxic zone, the absolute abundance of gene sul1 increased by 2.43 log, whereas that of gene sul2 increased by 1.71 log. In the region, the absolute abundance of sul1 increased by 1.17 log, whereas that of sul2 increased by 0.91 log. Resistant plate culture and high-throughput sequencing showed that the genus Pseudoalteromonas was the most dominant culturable resistant bacteria in the reactor. The genus Pseudomonas predominated in the uncultured resistant bacteria in the reactor. This study showed that marine aquaculture wastewater containing SMX promotes the enrichment of resistance genes, causing the abundance of some resistant bacteria to increase significantly.

Propofol attenuates renal ischemia/reperfusion injury by regulating the MALAT1/miR-126-5p axis.

BACKGROUND: Propofol (PPF) plays a protective role in ischemia-reperfusion (I/R) in multiple organs, including renal ischemia-reperfusion injury (RIRI). The present study aimed to investigate the underlying mechanisms by which PPF exerts its protective functions in RIRI. METHODS: BALB/c mice were employed for the construction of RIRI animal model. PPF pre-treatment was carried out before I/R. An in vitro I/R model was established with HK-2 cells after hypoxia/reoxygenation (H/R) culture, and PPF was utilized to treat the cells before H/R. A quantitative-polymerase chain reaction (qPCR) was conducted to detect long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and miR-126-5p expression levels. Flow cytometry was adopted to detect the apoptosis of HK-2 cells. Bioinformatics analysis, qPCR, a luciferase reporter gene experiment and a RNA immunoprecipitation experiment were used to determine the regulatory relationship between MALAT1 and miR-126-5p. The expression level of vascular endothelial growth factor A (VEGFA) was examined by western blotting. RESULTS: MALAT1 expression was augmented and miR-126-5p was decreased in RIRI models. PPF pre-treatment remarkably reduced creatinine and urea nitrogen levels in the serum of BALB/c mice with RIRI, and diminished the apoptosis of HK-2 cells treated with H/R. In addition, PPF pre-treatment markedly restrained the expression of MALAT1 in both in vivo and in vitro models and up-regulated miR-126-5p expression. MALAT1 could adsorb miR-126-5p to repress it and up-regulate VEGFA. MALAT1 overexpression reversed the protective effects of PPF on RIRI. CONCLUSIONS: PPF protects the kidney against RIRI by inhibiting MALAT1 and up-regulating miR-126-5p expression, as well as indirectly inhibiting the expression of VEGFA.

HOTAIR/miR-17-5p Axis is Involved in the Propofol-Mediated Cardioprotection Against Ischemia/Reperfusion Injury.

BACKGROUND: Propofol (PPF) ameliorates ischemia/reperfusion (I/R) injury in multiple organs by reducing apoptosis and release of pro-inflammatory cytokines. This study aims to explore the mechanism of PPF in attenuating myocardial ischemia-reperfusion injury (MIRI). MATERIALS AND METHODS: Rat MIRI model was established, and PPF pre-treatment was performed 10 min before I/R. H9c2 cardiomyocytes treated with hypoxia/reoxygenation (H/R) were used to establish an in vitro model. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to evaluate HOTAIR and miR-17-5p expression levels. Flow cytometry was employed to detect the apoptosis of H9c2 cells. The interaction between HOTAIR and miR-17-5p was determined by bioinformatics analysis, luciferase reporter gene analysis, and RNA immunoprecipitation experiments. STAT3 and p-STAT3 expressions were detected by Western blot. RESULTS: PPF pre-treatment significantly reduced creatine kinase isoenzyme (CK-MB) and serum lactate dehydrogenase (LDH) levels in the serum of the rats with MIRI. PPF pre-treatment remarkably up-regulated HOTAIR expression and down-regulated miR-17-5p expression in both in vivo and in vitro models. HOTAIR adsorbed miR-17-5p to repress the expression of miR-17-5p. PPF pre-treatment markedly inhibited cardiomyocyte apoptosis induced by I/R or H/R. HOTAIR knockdown could partially reverse the protective effects of PPF on MIRI. HOTAIR could activate STAT3 signaling via repressing miR-17-5p expression. CONCLUSION: PPF protects the MIRI by modulating the HOTAIR/miR-17-5p/STAT3 axis.

Long non­coding RNA ASAP1­IT1 suppresses ovarian cancer progression by regulating Hippo/YAP signaling.

Long non­coding RNAs (lncRNAs) are a class of non­protein coding transcripts that are involved in the regulation of gene expression in mammalian cells. Transcriptional co­activator Yes associated protein 1 (YAP1) plays a key role in the progression of ovarian cancer. However, the regulation of Hippo/YAP signaling in ovarian cancer remains elusive. In the present study, the expression levels of lncRNA ASAP1­IT1 were investigated. The analysis indicated that lncRNA ASAP1­IT1 expression was downregulated in ovarian tumor samples and ovarian cancer cells. The overexpression of ASAP1­IT1 inhibited ovarian cancer cell proliferation and induced cell apoptosis. Bioinformatics analysis predicted that miR­2278, a previously reported upregulated miRNA in ovarian tumors, may bind to ASAP1­IT1. Dual luciferase assay confirmed the direct regulatory association between ASAP1­IT1 and miR­2278. In addition, the data demonstrated that large tumor suppressor 2 (LATS2) was a target gene of miR­2278, whose expression was upregulated by ASAP1­IT1 in ovarian cancer cells. By regulating the expression of LATS2, ASAP1­IT1 induced the downregulation of YAP1 expression in ovarian cancer cells. Moreover, the silencing of LATS2 attenuated the inhibition of cell proliferation and the apoptosis induced by ASAP1­IT1 overexpression in ovarian cancer cells. The association among the expression levels of ASAP1­IT1, miR­2278 and LATS2 was observed in specimens obtained from patients with ovarian cancer. Taken together, the data presented herein demonstrate that ASAP1­IT1 functions as a potential tumor suppressor lncRNA by upregulating LATS2 expression in ovarian cancer.

LncRNA ANRIL Regulates Ovarian Cancer Progression and Tumor Stem Cell-Like Characteristics via miR-324-5p/Ran Axis.

OBJECTIVE: Long non-coding RNA (lncRNA) ANRIL is emerging as a crucial role in ovarian cancer progression and prognosis. However, the precise molecular mechanism of ANRIL on ovarian cancer is not known. Thus, we aim to study the underlying mechanism of ANRIL on the action. METHODS: The MTT assay assessed cell viability. Cell migration and invasion were determined using the wound healing assay, Transwell migration, and invasion assay. The relationships of ANRIL, miR-324-5p, and RAN were evaluated using luciferase activity assay and RNA pull-down assay. Cancer stem cell was identified by flow cytometry. Sphere formation assay was conducted to determine the stem-like properties. Xenograft tumor was established to assess tumor growth in vivo. qRT-PCR and Western blot were used to detect gene expression. RESULTS: ANRIL was elevated while miR-324-5p was decreased in ovarian cancer tissues and cells. Besides, downregulated ANRIL enhanced miR-324-5p expression, and the luciferase reporting experiment and RNA pull-down assay showed the binding interaction between ANRIL and miR-324-5p. miR-324-5p directly targeted Ran and negatively modulated the expression of Ran. Besides, Ran was promoted by overexpressed ANRIL, which was reversed by overexpression of miR-324-5p. Furthermore, decreased ANRIL and increased miR-324-5p suppressed tumor growth, migration capacity, drug resistance, and alleviated stem-like characteristics in vitro and in vivo. Ran mediated the regulation of ANRIL on cell viability, stem-like properties, and drug resistance of ovarian cancer cells. CONCLUSION: The ANRIL/miR-324-5p/Ran axis regulated ovarian cancer development, making the axis meaningful targets for ovarian cancer therapy.