Protective role of TRPV2 in synaptic plasticity through the ERK1/2-CREB-BDNF pathway in chronic unpredictable mild stress rats.

PURPOSE: Chronic stress is a significant risk factor for mood disorders such as depression, where synaptic plasticity plays a central role in pathogenesis. Transient Receptor Potential Vanilloid Type-2 (TRPV2) Ion Channels are implicated in hypothalamic-pituitary-adrenal axis disorders. Previous proteomic analysis indicated a reduction in TRPV2 levels in the chronic unpredictable mild stress (CUMS) rat model, yet its role in synaptic plasticity during depression remains to be elucidated. This study aims to investigate TRPV2's role in depression and its underlying mechanisms. METHODS: In vivo and in vitro experiments were conducted using the TRPV2-specific agonist probenecid and ERK1/2 inhibitors SCH772984. In vivo, rats underwent six weeks of CUMS before probenecid administration. Depressive-like behaviors were assessed through behavioral tests. ELISA kits measured 5-HT, DA, NE levels in rat hippocampal tissues. Hippocampal morphology was examined via Nissl staining. In vitro, rat hippocampal neuron cell lines were treated with ERK1/2 inhibitors SCH772984 and probenecid. Western blot, immunofluorescence, immunohistochemical staining, and RT-qPCR assessed TRPV2 expression, neurogenesis-related proteins, synaptic markers, and ERK1/2-CREB-BDNF signaling proteins. RESULTS: Decreased hippocampal TRPV2 levels were observed in CUMS rats. Probenecid treatment mitigated depressive-like behavior and enhanced hippocampal 5-HT, NE, and DA levels in CUMS rats. TRPV2 activation countered CUMS-induced synaptic plasticity inhibition. Probenecid activated the ERK1/2-CREB-BDNF pathway, suggesting TRPV2's involvement in this pathway via ERK1/2. CONCLUSION: These findings indicate that TRPV2 activation offers protective effects against depressive-like behaviors and enhances hippocampal synaptic plasticity in CUMS rats via the ERK1/2-CREB-BDNF pathway. TRPV2 emerges as a potential therapeutic target for depression.

Organoboron flank-substituted donor-acceptor polymer anode with ultra-long cycling stability for lithium ion batteries.

The tunable structure and other properties of organic materials suggest that they can potentially solve the shortcomings of traditional anodes such as graphite. We successfully introduced an organoboron unit into the thiophene-based polymer PBT-2 to construct a donor-acceptor polymer anode. The charge delocalization and LUMO energy level resulting from the unique structure of this material enabled good redox activity and a very stable electrochemical performance in electrochemical tests, with a reversible capacity of 262 mA h g-1 at 0.5 A g-1 and >10 000 cycles at 1 A g-1 with a decay of 0.056‰ per cycle. Accordingly, targeted structural design to overcome the shortcomings of active units such as thiophene can effectively regulate their electrochemical performance, providing a solution for the development of high-performance anode materials for use in lithium ion batteries.

Modulating the Electrolyte Microenvironment in Electrical Double Layer for Boosting Electrocatalytic Nitrate Reduction to Ammonia.

Electrochemical nitrate reduction reaction (NO3RR) is a promising approach to achieve remediation of nitrate-polluted wastewater and sustainable production of ammonia. However, it is still restricted by the low activity, selectivity and Faraday efficiency for ammonia synthesis. Herein, we propose an effective strategy to modulate the electrolyte microenvironment in electrical double layer (EDL) by mediating alkali metal cations in the electrolyte to enhance the NO3RR performance. Taking bulk Cu as a model catalyst, the experimental study reveals that the NO3 --to-NH3 performance in different electrolytes follows the trend Li+

Dynamic Reconstructed RuO2 /NiFeOOH with Coherent Interface for Efficient Seawater Oxidation.

Developing efficient oxygen evolution reaction (OER) electrocatalysts for seawater electrolysis is still a big challenge. Herein, a facile one-pot approach is reported to synthesize RuO2 -incorporated NiFe-metal organic framework (RuO2 /NiFe-MOF) with unique nanobrick-nanosheet heterostructure as precatalyst. Driven by electric field, the RuO2 /NiFe-MOF dynamically reconstructs into RuO2 nanoparticles-anchored NiFe oxy/hydroxide nanosheets (RuO2 /NiFeOOH) with coherent interface, during which the dissolution and redeposition of RuO2 are witnessed. Owing to the synergistic interaction between RuO2 and NiFeOOH, the as-reconstructed RuO2 /NiFeOOH exhibits outstanding alkaline OER activity with an ultralow overpotential of 187.6 mV at 10 mA cm-2 and a small Tafel slope of 31.9 mV dec-1 and excellent durability at high current densities of 840 and 1040 mA cm-2 in 1 m potassium hydroxide (KOH). When evaluated for seawater oxidation, the RuO2 /NiFeOOH only needs a low overpotential of 326.2 mV to achieve 500 mA cm-2 and can continuously catalyze OER at 500 mA cm-2 for 100 h with negligible activity degradation. Density function theory calculations reveal that the presence of strong interaction and enhanced charge transfer along the coherent interface between RuO2 and NiFeOOH ensures improved OER activity and stability.

Interfacially Engineered Nanoporous Cu/MnOx Hybrids for Highly Efficient Electrochemical Ammonia Synthesis via Nitrate Reduction.

Electrochemical reduction of nitrate to ammonia (NH3 ) not only offers a promising strategy for green NH3 synthesis, but also addresses the environmental issues and balances the perturbed nitrogen cycle. However, current electrocatalytic nitrate reduction processes are still inefficient due to the lack of effective electrocatalysts. Here 3D nanoporous Cu/MnOx hybrids are reported as efficient and durable electrocatalysts for nitrate reduction reaction, achieving the NH3 yield rates of 5.53 and 29.3 mg h-1 mgcat. -1 with 98.2% and 86.2% Faradic efficiency in 0.1 m Na2 SO4 solution with 10 and 100 mm KNO3 , respectively, which are higher than those obtained for most of the reported catalysts under similar conditions. Both the experimental results and density functional theory calculations reveal that the interface effect between Cu/MnOx interface could reduce the free energy of rate determining step and suppress the hydrogen evolution reaction, leading to the enhanced catalytic activity and selectivity. This work provides an approach to design advanced materials for NH3 production via electrochemical nitrate reduction.

Blocking Two-Pore Domain Potassium Channel TREK-1 Inhibits the Activation of A1-Like Reactive Astrocyte Through the NF-κB Signaling Pathway in a Rat Model of Major Depressive Disorder.

Major depressive disorder (MDD) refers to a widespread psychiatric disorder. Astrocytes play a pivotal role in regulating inflammation which is a well-acknowledged key component in depression pathogenesis. However, the effects of the neuroinflammation-inducing A1-like astrocytes on MDD are still unknown. TWIK-related K+ channel 1 (TREK-1) has been demonstrated to regulate the action of antidepressants. Nevertheless, its mechanisms and effects on A1-like astrocyte stimulation in MDD are not clear. Therefore, we conducted in vivo and in vitro experiments using TREK-1 specific inhibitor spadin. In vivo, rats were subjected to a 6-week chronic unpredictable mild stress (CUMS) followed by spadin treatment. Behavioral tests were employed to surveil depressive-like behaviors. Hippocampal proteomic analysis was carried out with the purpose of identifying differentially expressed proteins after CUMS and spadin treatments. In vitro, astrocyte-conditioned medium and spadin were used to treat rat astrocyte cell line. The activated microglia, inflammatory factors, A1 astrocyte markers, and activated nuclear factor kappa B (NF-κB) pathway were later analyzed using immunofluorescence, western blot, and RT-qPCR. Our findings indicated that blockage of TREK-1 reduced CUMS-induced depressive-like behavior in rats, inhibited the microglial stimulation, reduced inflammatory factor levels, and suppressed the activation of A1-like reactive astrocytes in the hippocampus. We also verified that the suppression of A1-like astrocytes by spadin necessitated the NF-κB pathway. According to the findings, blocking TREK-1 inhibited the activation of A1-like reactive astrocytes via the NF-κB signaling pathway in MDD. Our study preliminarily identifies a novel antidepressant mechanism of TREK-1 action and provides a therapeutic path for MDD.

Comparison of three nutritional assessment methods associated with the prognostic impact of laryngeal cancer.

BACKGROUND: Several studies have found that the prognostic nutritional index (PNI), controlling nutritional status (CONUT), and Glasgow Prognostic Score (GPS) of patients with laryngeal cancer accurately predict their prognosis. However, there is no consensus regarding the best assessment tool. Therefore, this study aimed to confirm the predictive value of the three nutritional scoring systems for the prognosis of patients with laryngeal cancer. METHODS: This study analyzed a cohort of 427 patients with laryngeal cancer who visited our hospital. PNI, CONUT, and GPS were calculated, and the relationship between these indicators and prognosis was examined. RESULTS: The optimal cut-off levels for overall survival (OS) of laryngeal cancer patients determined by PNI, CONUT, and GPS were 45, 3, and 0, respectively. When patients were stratified based on these thresholds, OS and disease-free survival (DFS) were significantly decreased in the malnutrition group (all three, p < 0.05). The OS rates of patients with laryngeal cancer were significantly affected by the three scores according to multivariate analysis. CONCLUSIONS: The three scoring methods had a high predictive value for the prognosis of patients with laryngeal cancer, with GPS having the strongest correlation with the prognosis of laryngeal cancer patients.

Cyclodextrin-supported Co(OH)2 Clusters as Electrocatalysts for Efficient and Selective H2 O2 Synthesis.

Co-based material catalysts have shown attractive application prospects in the 2 e- oxygen reduction reaction (ORR). However, for the industrial synthesis of H2 O2 , there is still lack of Co-based catalysts with high production yield rate. Here, novel cyclodextrin-supported Co(OH)2 cluster catalysts were prepared via a mild and facile method. The catalyst exhibited remarkable H2 O2 selectivity (94.2 % ~ 98.2 %), good stability (99 % activity retention after 35 h), and ultra-high H2 O2 production yield rate (5.58 mol gcatalyst -1 h-1 in the H-type electrolytic cell), demonstrating its promising industrial application potential. Density functional theory (DFT) reveals that the cyclodextrin-mediated Co(OH)2 electronic structure optimizes the adsorption of OOH* intermediates and significantly enhances the activation energy barrier for dissociation, leading to the high reactivity and selectivity for the 2 e- ORR. This work offers a valuable and practical strategy to design Co-based electrocatalysts for H2 O2 production.

Baclofen attenuates cognitive deficits in post-cardiac arrest brain injury.

Between 30% and 50% of survivors of cardiac arrest (CA) suffer from cognitive deficits. However, no effective medical intervention is available to alleviate cognitive deficits. Baclofen is known to protect damaged neurons, but researchers have still not clearly whether baclofen alleviates CA-induced cognitive deficits. The present study aimed to investigate whether baclofen protects against post-CA cognitive deficits and to reveal the protective mechanism of baclofen. Rats underwent 10 min of asphyxia to establish CA models. Intriguingly, our results indicated that baclofen improved spatial memory 72 h after CA. Baclofen increased plasticity-related protein (PSD95, and GAP43) expression in the brain after CA. Baclofen reduced microglial number and the release of inflammatory factors (IL-1ß and IL-18). Furthermore, baclofen significantly reduced the expression of pyroptosis-related molecules after CA. Notably, activation of NLRP3 abolished the anti-pyroptosis effect of baclofen and reduced the expression of synaptic plasticity-related proteins after CA. Taken together, this study first shows that baclofen attenuates cognitive deficits induced by brain injury after CA. The mechanism is at least partially attributed to baclofen regulating pyroptosis by inhibition of NLRP3 activation.

Inequitable Distribution of FTP Marketing by Neighborhood Characteristics: Further Evidence for Targeted Marketing.

INTRODUCTION: Flavored tobacco products (FTPs) are disproportionately used among young people and racial/ethnic minority populations. However, few studies have examined the retail distribution of such product marketing beyond menthol cigarettes. This study created geographic-based predictions about marketing of FTPs (overall, cigarettes, cigars, e-cigarettes, and smokeless) in stores across Washington, DC neighborhoods. We examined neighborhood-level demographic correlates of the amount of FTP and non-FTP marketing. METHODS: We conducted photographic audits of interior and exterior tobacco marketing in 96 Washington, DC tobacco retailers visited by 149 young adult respondents between 2018-2019. We created a geographic predictive surface of overall and product-specific tobacco marketing and then estimated the average predicted amount of marketing at the census-tract level using zonal statistics. Using linear regression, we examined neighborhood demographic correlates (race/ethnicity, family poverty, and youth population under 18) of FTP and non-FTP marketing. RESULTS: The predicted amount of non-FTP ads/displays were evenly distributed with no neighborhood variability (Range 8.46-8.46). FTP marketing overall was geographically concentrated with greater range across neighborhoods (Range 6.27-16.77). Greater FTP marketing overall and flavored cigar marketing was available in neighborhoods with higher percentages of Black residents. Flavored cigar marketing was less available in neighborhoods with more Hispanic residents, but there was greater flavored smokeless tobacco marketing. Nonflavored marketing overall and by product did not vary across neighborhoods. CONCLUSIONS: This study provides evidence of disproportionate distribution of FTP marketing in Black neighborhoods, especially for flavored cigars, at the point-of-sale. Policies that restrict the sale of FTPs may enhance health equity. IMPLICATIONS: Tobacco marketing has frequently been shown to be more prevalent in neighborhoods with lower household income and more Black residents. Using geographic-based predictions, we find that greater flavored tobacco marketing in these neighborhoods, not decreased marketing for nonflavored tobacco, is driving this disparity. Targeting Black neighborhoods with increased marketing of flavored tobacco products, which has been found to be more appealing, easier to use, and harder to quit is a social justice issue.

Nanoporous Intermetallic Cu3 Sn/Cu Hybrid Electrodes as Efficient Electrocatalysts for Carbon Dioxide Reduction.

Designing highly selective and cost-effective electrocatalysts toward electrochemical carbon dioxide (CO2 ) reduction is crucial for desirable transformation of greenhouse gas into fuels or high-value chemical products. Here, the authors report intermetallic Cu3 Sn that is in situ formed and seamlessly integrated on self-supported bimodal nanoporous Cu skeleton (Cu3 Sn/Cu) via a spontaneous alloying of Sn and Cu as robust electrocatalyst for selective electroreduction of CO2 to CO. By virtue of Sn atoms strengthening CO adsorption on Cu atoms, the intermetallic Cu3 Sn has an intrinsic activity of ≈10.58 µA cm-2 , more than 80-fold higher than that of monometallic Cu. By virtue of hierarchical bicontinuous nanoporous Cu architecture facilitating electron transfer and CO2 and proton mass transport and offering high specific surface areas for full use of electroactive Cu3 Sn sites, the nanoporous Cu3 Sn/Cu hybrid electrodes produce CO at a low overpotential of 0.09 V, and exhibit high partial current density of ≈15 mA cm-2 geo at overpotential of 0.59 V, along with excellent stability and selectivity of 91.5% Faradaic efficiency. The outstanding electrochemical performance make them attractive alternatives to precious Au- and Ag-based electrocatalysts for building low-cost CO2 electrolyzers to selectively produce CO.

Intensive Longitudinal Study of the Relationship Between Cigalike E-cigarette Use and Cigarette Smoking Among Adult Cigarette Smokers Without Immediate Plans to Quit Smoking.

INTRODUCTION: This study examined the association between the introduction of an e-cigarette and subsequent change in cigarette smoking among smokers who were not immediately interested in quitting. AIMS AND METHODS: The Moment Study was a 21-day intensive longitudinal study with an online follow-up survey at 30 days. After observing baseline cigarette smoking for 1 week, participants received 10 cigalike e-cigarettes on study days 6 and 13. Participants reported cigarettes per day, e-cigarette puffs per day, and e-cigarette satisfaction using text-message-based surveys. RESULTS: The sample of 96 daily smokers was majority female (53.1%), African American (67.7%), and non-Hispanic (95.8%). When e-cigarettes were provided (day 6), average cigarettes per day dropped by 1.82 cigarettes (p < .0001). The within-person e-cigarette puff effect on daily cigarette smoking was significantly negative (ß = -0.023; p = .005); a participant who consumed 100 more e-cigarette puffs in a day than usual for that person was expected to smoke 2.3 fewer cigarettes that day, but this was only true for non-menthol smokers (p = .006). Smokers older than 45 and those who started smoking at a younger age rated e-cigarettes as less satisfying (ps < .05). Participants with greater than the median reported satisfaction were 6.5 times more likely to use an e-cigarette at follow-up. CONCLUSIONS: Giving e-cigarettes to smokers who did not intend to quit reduced their cigarette smoking on days when they used e-cigarette more frequently, but this relationship did not hold for menthol smokers. Satisfaction with e-cigarette use was predictive of continued use 30 days later. IMPLICATIONS: A greater amount of cigalike e-cigarette use resulted in less smoking among adult daily smokers without immediate plans to quit, but a lack of nicotine delivery and satisfaction for these devices may have limited their utility as a replacement for cigarette smoking, especially among menthol smokers. The global concept of "satisfaction" may be an important driver of e-cigarette use among adult smokers.

Smoking cessation among US adults: use of e-cigarettes, including JUUL, and NRT use.

BACKGROUND: Electronic cigarettes (e-cigarettes) are a common tobacco product in the US. Despite lacking Food and Drug Administration (FDA) approval for cessation, e-cigarettes, including JUUL, a popular device, have been viewed by some as a potential tool for tobacco users seeking to quit combustible tobacco use. It is unknown how current and former smokers report using these products for cigarette smoking cessation. METHODS: Online surveys were collected from a probability-based panel of US adults aged 18-64, with an oversample of past 12-month JUUL users (n=3415). Weighted past 12-month and past 30-day use of popular e-cigarette brands were measured. Former smokers with a quit attempt in the past 4 years and current smokers with a quit attempt in the past 12 months were asked about methods for smoking cessation, including e-cigarettes and nicotine replacement therapies (NRTs) use. RESULTS: Among former smokers (n=157), 21.2% used e-cigarettes and/or NRTs to help them quit. Specifically, 2.2% used JUUL only, compared with 10.3% who used NRTs only, and 6.9% used other e-cigarettes only to quit. Among current smokers with a quit attempt (n=308), 24.0% used any product (NRT or e-cigarettes) to quit, and only 1.1% used JUUL only. Current smokers reported relatively low use of NRTs only (10.1%), other e-cigarettes only (5.6%) and other e-cigarettes and NRTs (5.1%). CONCLUSIONS: Data suggest that few smokers in the US use e-cigarettes, and JUUL specifically, for cessation, and NRTs use is relatively low. All e-cigarettes should undergo FDA review to minimise recreational use and understand their cessation efficacy.

Boosting Production of HCOOH from CO2 Electroreduction via Bi/CeOx.

Formic acid (HCOOH) is one of the most promising chemical fuels that can be produced through CO2 electroreduction. However, most of the catalysts for CO2 electroreduction to HCOOH in aqueous solution often suffer from low current density and limited production rate. Herein, we provide a bismuth/cerium oxide (Bi/CeOx ) catalyst, which exhibits not only high current density (149 mA cm-2 ), but also unprecedented production rate (2600 µmol h-1 cm-2 ) with high Faradaic efficiency (FE, 92 %) for HCOOH generation in aqueous media. Furthermore, Bi/CeOx also shows favorable stability over 34 h. We hope this work could offer an attractive and promising strategy to develop efficient catalysts for CO2 electroreduction with superior activity and desirable stability.

Exposure to Multimedia Tobacco Marketing and Product Use Among Youth: A Longitudinal Analysis.

INTRODUCTION: Tobacco companies continue to reach youth through direct-to-consumer marketing, which has been associated with overall tobacco use. We examine how exposure to these marketing activities influences product-specific use behaviors. METHODS: We analyzed data from 10 081 youth (aged 12-18 years) who participated in Waves 1 and 2 (2013-2015) of the Population Assessment of Tobacco and Health (PATH) Study. Participants reported past 6-month tobacco coupon receipt and online tobacco marketing engagement, and susceptibility to ever and current use of cigarette, e-cigarettes, cigars, smokeless tobacco, and hookah. Weighted multivariable logistic regression examined Wave 1 predictors of coupon receipt at Wave 2, and associations between coupon receipt, online engagement, and past 30-day use of different tobacco products. RESULTS: Youth received tobacco coupons at one (9.7%) or both waves (1.2%) and 11.1% engaged with online tobacco marketing. Coupon receipt and online marketing engagement at Wave 1 predicted Wave 2 coupon receipt among susceptible-never, ever-but-not-current, and current tobacco users (p < .05). Coupon receipt and online engagement at Wave 1 was positively associated with past 30-day use of cigarettes, e-cigarettes, cigars, smokeless tobacco, and hookah at Wave 2 (p < .05). The relationships were stronger for those who received coupons at both waves or engaged with more sources of online marketing. CONCLUSIONS: Tobacco direct-to-consumer marketing is reaching youth. Repeated exposure to these marketing activities within and across media is associated with use of different tobacco products. New policies and strong enforcement of existing regulations prohibiting these illegal marketing tactics are critical to protect youth from future tobacco use. IMPLICATIONS: Tobacco companies utilize coupons and online engagement activities to increase brand awareness, knowledge, and sales of their products. These kinds of marketing activities can be influential among youth at a time when they may develop tobacco use behaviors. Our findings suggest that tobacco companies may be targeting at-risk youth through cross-media marketing activities. The findings also indicate that exposure to these marketing activities predicts subsequent use of different tobacco products, with suggestive dose-response relationships. Increased regulations are needed to protect youth from these marketing activities.

Flavour types used by youth and adult tobacco users in wave 2 of the Population Assessment of Tobacco and Health (PATH) Study 2014-2015.

BACKGROUND: Most youth and young adult (YA) tobacco users use flavoured products; however, little is known about specific flavours used. METHODS: We report flavour types among US tobacco users from the Population Assessment of Tobacco and Health Study, wave 2, 2014-2015. At wave 2, we examined (1) flavour use and type at past 30-day use; (2) new flavoured tobacco product use and type; (3) product-specific flavour patterns across youth (ages 12-17) (n=920), YA (18-24) (n=3726) and adult (25+) (n=10 346) past 30-day and new tobacco users and (4) concordance between self-coded and expert-coded brand flavour type among all adults (18+). RESULTS: Prevalence of flavoured tobacco product use was highest among youth, followed by YA and adult 25+ any tobacco users. Within each age group, flavoured use was greatest among hookah, e-cigarette and snus users. Overall, menthol/mint, fruit and candy/sweet were the most prevalent flavour types at first and past 30-day use across age groups. For past 30-day use, all flavour types except menthol/mint exhibited an inverse age gradient, with more prevalent use among youth and YAs, followed by adults 25+. Prevalence of menthol/mint use was high (over 50% youth, YAs; 76% adults 25+) and exhibited a positive age gradient overall, though the reverse for cigarettes. Brand-categorised and self-reported flavour use measures among adults 18+ were moderately to substantially concordant across most products. CONCLUSIONS: Common flavours like menthol/mint, fruit and candy/sweet enhance appeal to young tobacco users. Information on flavour types used by product and age can inform tobacco flavour regulations to addess flavour appeal especially among youth.

Characteristics and Reach Equity of Policies Restricting Flavored Tobacco Product Sales in the United States.

In 2009, flavored cigarettes (except menthol) were banned in the United States, but other flavored tobacco products (FTPs) were allowed. Women, populations of color, youth, sexual minority, and low-socioeconomic status populations disproportionately use FTPs. Localities have passed sales restrictions on FTPs that may reduce disparities if vulnerable populations are reached. This study assessed the extent to which FTP restrictions reached these subgroups ("reach equity"). We identified 189 U.S. jurisdictions with FTP policies as of December 31, 2018. We linked jurisdictions with demographics of race/ethnicity, gender, age, partnered same-sex households and household poverty, and stratified by policy strength. We calculated Reach Ratios (ReRas) to assess reach equity among subgroups covered by FTP policies relative to their U.S. population representation. Flavor policies covered 6.3% of the U.S. population (20 million individuals) across seven states; 0.9% were covered by strong policies (12.7% of policies). ReRas indicated favorable reach equity to young adults, women, Hispanics, African Americans, Asians, partnered same-sex households, and those living below poverty. Youth, American Indians/Alaska Natives (AIAN) and Native Hawaiians/Pacific Islanders (NHPI) were underrepresented. Strong policies had favorable reach equity to young adults, those living below poverty, Asians, NHPIs, individuals of 2+ races, and partnered same-sex households, but unfavorable reach equity to women, youth, Hispanic, AIAN, and African American populations. U.S. flavor policies have greater reach to many, but not all, subgroups at risk of FTP use. Increased enactment of strong policies to populations not covered by flavor policies is warranted to ensure at-risk subgroups sufficiently benefit.

Retracted: MicroRNA-34a inhibit hepatocellular carcinoma progression by repressing hexokinase-1.

Hepatocellular carcinoma (HCC) is known as a frequent type of primary cancer in the liver, and it is the third-most common cause of cancer-related death all over the world. However, the molecular mechanism in the progression of HCC is still unclear. The current study was designed to investigate the expression and function of microRNA-34a (miR-34a) in HCC. In HCC tissues and cells, the expression levels of miR-34a were analyzed by quantitative real-time polymerase chain reaction. The association between the level of miR-34a and hexokinase (HK)-1 was also investigated via luciferase reporter assay. Cell viability and proliferation were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry. To assess whether miR-34a can limit tumor growth in vivo, animal models and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were used for examining the role of miR-34a on the development of HCC and cell apoptosis. The expression level of miR-34a was reduced in HCC samples and cells. The expression of miR-34a was associated with the viability and proliferation capacity of HCC cells, and miR-34a could inhibit HCC cells proliferation by inhibiting HK1. In the mouse model of HCC, volumes and weight of the tumors were significantly decreased by transfection with miR-34a mimic compared with the control group. Furthermore, miR-34a mimics could induce apoptosis in a greater proportion of cells compared with the control group. Taken together, the data may provide some novel insights into the molecular mechanism of miR-34a and HK1 in the progression of HCC. Thus, miR-34a/HK1 axis might be a novel promising therapeutic target for treating HCC.

Longitudinal Response to Restrictions on Menthol Cigarettes Among Young Adult US Menthol Smokers, 2011-2016.

Objectives. To examine responses to hypothetical restrictions on menthol cigarettes among young adult menthol smokers in the United States.Methods. We surveyed Truth Initiative Young Adult Cohort respondents 18 to 34 years of age every 6 months from December 2011 through October 2016. Menthol cigarette smokers (n = 806, n = 1963 observations) indicated their response if menthol cigarettes were unavailable. Weighted analyses accounting for repeated measures were used to estimate the prevalence and correlates of responses and trends over time.Results. Overall, 23.5% of young adult menthol smokers said they would quit if menthol cigarettes were unavailable, with this response largely unchanged between 2011 and 2016. There was a significant increase in the switch to another tobacco product response (from 7.4% to 13.2%; P = .01) associated with current noncigarette use. In adjusted analyses, African Americans, women, those with less than a high school education, and those with any quit intention were more likely to say they would quit smoking.Conclusions. Increased intentions to switch products suggest the acceptability and availability of alternatives to menthol cigarette smokers. Menthol cigarette restrictions benefit vulnerable groups and those interested in quitting, but the availability of menthol in noncigarette products could limit benefits.

JUUL use and reasons for initiation among adult tobacco users.

BACKGROUND: The electronic nicotine delivery system (ENDS) JUUL has quickly captured the ENDS market, representing 74.6% of the total dollar share for this category as of November 2018. Although JUUL is marketed as an alternative to cigarettes intended for current adult smokers, evidence suggests that a majority of ENDS users are concurrently current cigarette smokers. Little is known about the dual use of JUUL and cigarettes, as well as the reasons for trying JUUL among adult tobacco users. METHODS: A survey fielded via web and phone of 1332 current cigarette, cigar, little cigar or cigarillo (CLCC), and ENDS users aged 18-54 years was conducted from March to May 2018. Weighted descriptive and bivariate analyses examined JUUL use and reasons for trying JUUL by demographics, combustible tobacco use, ENDS use and intention to quit. RESULTS: Approximately 81% of our sample reported current use of two or more tobacco products, including cigarettes, CLCCs or ENDS. Among current tobacco users, 15% ever used JUUL and 12% used JUUL in the past 30 days. Most individuals (74%) reporting ever JUUL use indicated using it for 5 days or fewer in the past 30 days. The most common reason for trying JUUL was trying to quit smoking cigarettes (37%), followed by family, friends or colleagues using the product (32%). CONCLUSION: Although some tobacco users may be initiating JUUL to decrease combustible use, most were using the product infrequently and concurrently with other products. Findings have significant implications for cessation intervention efforts and policy development to help smokers quit.