LncRNA495810 Promotes Proliferation and Migration of Hepatocellular Carcinoma Cells by Interacting with FABP5.

Hepatocellular carcinoma (HCC) is one of the malignant tumors with high morbidity and mortality. Long non-coding RNAs (lncRNAs) are frequently dysregulated in human cancers and play an important role in the initiation and progression of HCC. Here, we investigated the expression of a new reported lncRNA495810 in our previous study by analyzing the publicly available datasets and using RT-qPCR assay. The cell proliferation experiment, cell cycle and apoptosis assay, wound healing assay, cell migration assay were used to explore the biological function of lncRNA495810 in HCC. The western blot, RNA pull down and RNA immunoprecipitation (RIP) detection were used to investigate the potential molecular mechanisms of lncRNA495810. The results demonstrated that lncRNA495810 was significantly upregulated in hepatocellular carcinoma and associated with poor prognosis of hepatocellular carcinoma patients. Moreover, it proved that lncRNA495810 promotes the proliferation and metastasis of hepatoma cells by directly binding and upregulating the expression of fatty acid-binding protein 5. These results reveal the oncogenic roles of lncRNA495810 in HCC and provide a potential therapeutic target for HCC.

Repeated Transcranial Magnetic Stimulation Combined with Action Observation Training in Children with Spastic Cerebral Palsy.

This study presents the results of a randomized controlled trial utilizing a 2 x 2 factorial design, comparing the effects of repeated transcranial magnetic stimulation (rTMS) and action observation training (AOT) intervention methods on spasticity, balance function, and motor function in children with spastic cerebral palsy (SCP). The study aimed to investigate whether the combination of the two interventions produces greater improvement than either treatment alone or conventional treatment. Subject children in this study, in accordance with the random number table, were randomly divided into four groups: conventional group, rTMS group, AOT group, and combined intervention group. All the children in the four groups received conventional rehabilitation treatment, on the basis of which they were given different therapeutic programs of rehabilitation measures. The conventional group had no other treatment while the rTMS group received rTMS, the AOT group received AOT and the combined intervention group was given a combined intervention of rTMS and AOT. They were trained five days per week for 12 weeks. Changes in scores of spasticity, balance function, walking ability, and gross motor function were assessed at the onset of the training program and upon completion of 12 weeks of treatment. A total of 64 Children with SCP completed the study, and their results were analyzed. The total gross motor function efficiency of 87.50% in the experimental group was significantly higher than that of 25.00% in the conventional group, 62.50% in the rTMS group, and 68.75% in the AOT group. The preliminary results showed that combined intervention of rTMS and AOT could effectively improve the balance function and motor function of children, and the therapeutic effect of the combined intervention was better than that of conventional treatment, rTMS or AOT alone. Finally, clinical efficacy and optimal treatment parameters of the combined intervention were clarified to provide a clinical basis for therapists to conduct lower limb function rehabilitation for children with SCP.

Synergistic induction of mitotic pyroptosis and tumor remission by inhibiting proteasome and WEE family kinases.

Mitotic catastrophe (MC), which occurs under dysregulated mitosis, represents a fascinating tactic to specifically eradicate tumor cells. Whether pyroptosis can be a death form of MC remains unknown. Proteasome-mediated protein degradation is crucial for M-phase. Bortezomib (BTZ), which inhibits the 20S catalytic particle of proteasome, is approved to treat multiple myeloma and mantle cell lymphoma, but not solid tumors due to primary resistance. To date, whether and how proteasome inhibitor affected the fates of cells in M-phase remains unexplored. Here, we show that BTZ treatment, or silencing of PSMC5, a subunit of 19S regulatory particle of proteasome, causes G2- and M-phase arrest, multi-polar spindle formation, and consequent caspase-3/GSDME-mediated pyroptosis in M-phase (designated as mitotic pyroptosis). Further investigations reveal that inhibitor of WEE1/PKMYT1 (PD0166285), but not inhibitor of ATR, CHK1 or CHK2, abrogates the BTZ-induced G2-phase arrest, thus exacerbates the BTZ-induced mitotic arrest and pyroptosis. Combined BTZ and PD0166285 treatment (named BP-Combo) selectively kills various types of solid tumor cells, and significantly lessens the IC50 of both BTZ and PD0166285 compared to BTZ or PD0166285 monotreatment. Studies using various mouse models show that BP-Combo has much stronger inhibition on tumor growth and metastasis than BTZ or PD0166285 monotreatment, and no obvious toxicity is observed in BP-Combo-treated mice. These findings disclose the effect of proteasome inhibitors in inducing pyroptosis in M-phase, characterize pyroptosis as a new death form of mitotic catastrophe, and identify dual inhibition of proteasome and WEE family kinases as a promising anti-cancer strategy to selectively kill solid tumor cells.

Transcriptomic profiling and discovery of key transcription factors involved in adventitious roots formation from root cuttings of mulberry.

ARs plays a crucial role in plant morphogenesis and development. The limited and inefficient rooting of scions poses a significant challenge to the efficiency and quality of clonal propagation of forest trees in silvicultural practices. Building on previous research conducted by our team, we found that applying IBA at a concentration of 1000 mg/L significantly enhanced mulberry rooting. This study aims to uncover the molecular mechanisms underlying this effect by analyzing RNA sequencing data from mulberry phloem before and after treatment with IBA over time intervals of 10, 20, 30, and 40 days. We identified 5226 DEGs, which were then classified into GO terms and KEGG pathways, showing significant enrichment in hormone signaling processes. Using WGCNA, we identified eight co-expression modules, two of which were significantly correlated with the IBA treatment. Additionally, 18 transcription factors that potentially facilitate ARs formation in mulberry were identified, and an exploratory analysis on the cis-regulatory elements associated with these transcription factors was conducted. The findings of this study provide a comprehensive understanding of the mechanisms of ARs in mulberry and offer theoretical support for the discovery and utilization of exceptional genetic resources within the species.

Value of multiparametric magnetic resonance imaging in distinguishing sinonasal lymphoma from sinonasal carcinoma: a case control study.

BACKGROUND: The study aimed to evaluate the diagnostic efficacy of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) parameters in distinguishing sinonasal lymphoma from sinonasal carcinoma. METHODS: Forty-two participants with histologically confirmed sinonasal lymphomas and fifty-two cases of sinonasal carcinoma underwent imaging with a 3.0T MRI scanner. DCE-MRI and DWI were conducted, and various parameters including type of time-intensity curve(TIC), time to peak, peak enhancement, peak contrast enhancement, washout rate, apparent diffusion coefficient (ADC), and relative ADC were measured. Binary logistic regression and receiver operating characteristic (ROC) curve analysis were employed to assess the diagnostic capability of individual and combined indices for differentiating nasal sinus lymphoma from nasal sinus carcinoma. RESULTS: Sinonasal lymphoma predominantly exhibited type II TIC(n = 20), whereas sinonasal carcinoma predominantly exhibited type III TIC(n = 23). Significant differences were observed in all parameters except washout ratio (p < 0.05), and ADC value emerged as the most reliable diagnostic tool in single parameter. Combined DCE-MRI parameters demonstrated superior diagnostic efficacy compared to individual parameters, with the highest efficiency (area under curve = 0.945) achieved when combining all parameters of DCE-MRI and DWI. CONCLUSIONS: Multiparametric evaluation involving contrast-enhanced dynamic MRI and DWI holds considerable diagnostic value in distinguishing sinonasal lymphoma from sinonasal carcinoma.

Icariin Ameliorates D-galactose-induced Cell Injury in Neuron-like PC12 Cells by Inhibiting MPTP Opening.

OBJECTIVE: Icariin (ICA) has a good neuroprotective effect and can upregulate neuronal basal autophagy in naturally aging rats. Mitochondrial dysfunction is associated with brain aging-related neurodegenerative diseases. Abnormal opening of the mitochondrial permeability transition pore (mPTP) is a crucial factor in mitochondrial dysfunction and is associated with excessive autophagy. This study aimed to explore that ICA protects against neuronal injury by blocking the mPTP opening and down-regulating autophagy levels in a D-galactose (D-gal)-induced cell injury model. METHODS: A cell model of neuronal injury was established in rat pheochromocytoma cells (PC12 cells) treated with 200 mmol/L D-gal for 48 h. In this cell model, PC12 cells were pre-treated with different concentrations of ICA for 24 h. MTT was used to detect cell viability. Senescence associated ß-galactosidase (SA-ß-Gal) staining was used to observe cell senescence. Western blot analysis was performed to detect the expression levels of a senescence-related protein (p21), autophagy markers (LC3B, p62, Atg7, Atg5 and Beclin 1), mitochondrial fission and fusion-related proteins (Drp1, Mfn2 and Opa1), and mitophagy markers (Pink1 and Parkin). The changes of autophagic flow were detected by using mRFP-GFP-LC3 adenovirus. The intracellular ultrastructure was observed by transmission electron microscopy. Immunofluorescence was used to detect mPTP, mitochondrial membrane potential (MMP), mitochondrial reactive oxygen species (mtROS) and ROS levels. ROS and apoptosis levels were detected by flow cytometry. RESULTS: D-gal treatment significantly decreased the viability of PC12 cells, and markedly increased the SA-ß-Gal positive cells as compared to the control group. With the D-gal stimulation, the expression of p21 was significantly up-regulated. Furthermore, D-gal stimulation resulted in an elevated LC3B II/I ratio and decreased p62 expression. Meanwhile, autophagosomes and autolysosomes were significantly increased, indicating abnormal activation of autophagy levels. In addition, in this D-gal-induced model of cell injury, the mPTP was abnormally open, the ROS generation was continuously increased, the MMP was gradually decreased, and the apoptosis was increased. ICA effectively improved mitochondrial dysfunction to protect against D-gal-induced cell injury and apoptosis. It strongly inhibited excessive autophagy by blocking the opening of the mPTP. Cotreatment with ICA and an mPTP inhibitor (cyclosporin A) did not ameliorate mitochondrial dysfunction. However, the protective effects were attenuated by cotreatment with ICA and an mPTP activator (lonidamine). CONCLUSION: ICA inhibits the activation of excessive autophagy and thus improves mitochondrial dysfunction by blocking the mPTP opening.

The cumulative impact of temperature and nitrogen availability on the potential nitrogen fixation and extracellular polymeric substances secretion by Dolichospermum.

Nitrogen-fixing cyanobacteria not only cause severe blooms but also play an important role in the nitrogen input processes of lakes. The production of extracellular polymeric substances (EPS) and the ability to fix nitrogen from the atmosphere provide nitrogen-fixing cyanobacteria with a competitive advantage over other organisms. Temperature and nitrogen availability are key environmental factors in regulating the growth of cyanobacteria. In this study, Dolichospermum (formerly known as Anabaena) was cultivated at three different temperatures (10 °C, 20 °C, and 30 °C) to examine the impact of temperature and nitrogen availability on nitrogen fixation capacity and the release of EPS. Initially, confocal laser scanning microscopy (CLSM) and the quantification of heterocysts at different temperatures revealed that lower temperatures (10 °C) hindered the differentiation of heterocysts under nitrogen-deprived conditions. Additionally, while heterocysts inhibited the photosynthetic activity of Dolichospermum, the secretion of EPS was notably affected by nitrogen limitation, particularly at 30 °C. Finally, real-time quantitative polymerase chain reaction (qPCR) was used to measure the expression of nitrogen-utilizing genes (ntcA and nifH) and EPS synthesis-related genes (wzb and wzc). The results indicated that under nitrogen-deprived conditions, the expression of each gene was upregulated, and there was a significant correlation between the upregulation of nitrogen-utilizing and EPS synthesis genes (P < 0.05). Our findings suggested that Dolichospermum responded to temperature variation by affecting the formation of heterocysts, impacting its potential nitrogen fixation capacity. Furthermore, the quantity of EPS released was more influenced by nitrogen availability than temperature. This research enhances our comprehension of interconnections between nitrogen deprivation and EPS production under the different temperatures.

Effects of myo-inositol on regulating glucose and lipid metabolism and alternative splicing events coexpressed with lncRNAs in the liver tissues of diabetic mice.

Objective: Recent studies have shown that gene alternative splicing (AS) and long noncoding RNAs (lncRNAs) are involved in diabetes mellitus (DM) and its complications. Currently, myo-inositol (MI) is considered as effective for the treatment of insulin resistance and lipid metabolism disorders in diabetes patients. We hope to better explore the potential roles of gene AS and lncRNAs in liver glucose and lipid metabolism in diabetes, as well as the effects of myo-inositol treatment, through transcriptome analysis. Methods: This study analysed glucose and lipid metabolism-related biochemical indicators and liver HE staining in four groups of mice: the control group (Ctrl group), the diabetes group (DM group), the myo-inositol treatment group (MI group), and the metformin treatment group (Met group). The changes in relevant gene-regulated alternative splicing events (RASEs) and lncRNAs were analysed by RNA sequencing of liver tissue, and coexpression analysis and functional enrichment analysis were used to predict the possible lncRNAs and RASEs involved in liver glucose and lipid metabolism. Result: Metformin and myo-inositol alleviated insulin resistance, lipid metabolism disorders, and hepatic steatosis in diabetic mice. Transcriptome sequencing analysis revealed differential splicing events of genes related to lipid metabolism and differentially expressed lncRNAs (DElncRNAs). Six different lncRNAs and their potentially interacting splicing events were predicted. Conclusion: The present study revealed novel changes in RASEs and lncRNAs in the livers of diabetic mice following treatment with myo-inositol, which may shed light on the potential mechanisms by which myo-inositol delays and treats the progression of hepatic glucose and lipid metabolism in diabetes.

Icariin improves oxidative stress injury during ischemic stroke via inhibiting mPTP opening.

BACKGROUND: Ischemic stroke presents a significant threat to human health due to its high disability rate and mortality. Currently, the clinical treatment drug, rt-PA, has a narrow therapeutic window and carries a high risk of bleeding. There is an urgent need to find new effective therapeutic drugs for ischemic stroke. Icariin (ICA), a key ingredient in the traditional Chinese medicine Epimedium, undergoes metabolism in vivo to produce Icaritin (ICT). While ICA has been reported to inhibit neuronal apoptosis after cerebral ischemia-reperfusion (I/R), yet its underlying mechanism remains unclear. METHODS: PC-12 cells were treated with 200 µM H2O2 for 8 h to establish a vitro model of oxidative damage. After administration of ICT, cell viability was detected by Thiazolyl blue tetrazolium Bromide (MTT) assay, reactive oxygen species (ROS) and apoptosis level, mPTP status and mitochondrial membrane potential (MMP) were detected by flow cytometry and immunofluorescence. Apoptosis and mitochondrial permeability transition pore (mPTP) related proteins were assessed by Western blotting. Middle cerebral artery occlusion (MCAO) model was used to establish I/R injury in vivo. After the treatment of ICA, the neurological function was scored by ZeaLonga socres; the infarct volume was observed by 2,3,5-Triphenyltetrazolium chloride (TTC) staining; HE and Nissl staining were used to detect the pathological state of the ischemic cortex; the expression changes of mPTP and apoptosis related proteins were detected by Western blotting. RESULTS: In vitro: ICT effectively improved H2O2-induced oxidative injury through decreasing the ROS level, inhibiting mPTP opening and apoptosis. In addition, the protective effects of ICT were not enhanced when it was co-treated with mPTP inhibitor Cyclosporin A (CsA), but reversed when combined with mPTP activator Lonidamine (LND). In vivo: Rats after MCAO shown cortical infarct volume of 32-40%, severe neurological impairment, while mPTP opening and apoptosis were obviously increased. Those damage caused was improved by the administration of ICA and CsA. CONCLUSIONS: ICA improves cerebral ischemia-reperfusion injury by inhibiting mPTP opening, making it a potential candidate drug for the treatment of ischemic stroke.

Nature-Inspired Micro/Nano-Structured Antibacterial Surfaces.

The problem of bacterial resistance has become more and more common with improvements in health care. Worryingly, the misuse of antibiotics leads to an increase in bacterial multidrug resistance and the development of new antibiotics has virtually stalled. These challenges have prompted the need to combat bacterial infections with the use of radically different approaches. Taking lessons from the exciting properties of micro-/nano-natural-patterned surfaces, which can destroy cellular integrity, the construction of artificial surfaces to mimic natural functions provides new opportunities for the innovation and development of biomedicine. Due to the diversity of natural surfaces, functional surfaces inspired by natural surfaces have a wide range of applications in healthcare. Nature-inspired surface structures have emerged as an effective and durable strategy to prevent bacterial infection, opening a new way to alleviate the problem of bacterial drug resistance. The present situation of bactericidal and antifouling surfaces with natural and biomimetic micro-/nano-structures is briefly reviewed. In addition, these innovative nature-inspired methods are used to manufacture a variety of artificial surfaces to achieve extraordinary antibacterial properties. In particular, the physical antibacterial effect of nature-inspired surfaces and the functional mechanisms of chemical groups, small molecules, and ions are discussed, as well as the wide current and future applications of artificial biomimetic micro-/nano-surfaces. Current challenges and future development directions are also discussed at the end. In the future, controlling the use of micro-/nano-structures and their subsequent functions will lead to biomimetic surfaces offering great potential applications in biomedicine.

Toxin genotypes, antibiotic resistance and their correlations in Clostridioides difficile isolated from hospitals in Xi'an, China.

BACKGROUND: Clostridioides difficile is the main pathogen of antimicrobial-associated diarrhoea and health care facility-associated infectious diarrhoea. This study aimed to investigate the prevalence, toxin genotypes, and antibiotic resistance of C. difficile among hospitalized patients in Xi'an, China. RESULTS: We isolated and cultured 156 strains of C. difficile, representing 12.67% of the 1231 inpatient stool samples collected. Among the isolates, tcdA + B + strains were predominant, accounting for 78.2% (122/156), followed by 27 tcdA-B + strains (27/156, 17.3%) and 6 binary toxin gene-positive strains. The positive rates of three regulatory genes, tcdC, tcdR, and tcdE, were 89.1% (139/156), 96.8% (151/156), and 100%, respectively. All isolates were sensitive to metronidazole, and the resistance rates to clindamycin and cephalosporins were also high. Six strains were found to be resistant to vancomycin. CONCLUSION: Currently, the prevalence rate of C. difficile infection (CDI) in Xi'an is 12.67% (156/1231), with the major toxin genotype of the isolates being tcdA + tcdB + cdtA-/B-. Metronidazole and vancomycin were still effective drugs for the treatment of CDI, but we should pay attention to antibiotic management and epidemiological surveillance of CDI.

Safety, immunogenicity and protective effect of sequential vaccination with inactivated and recombinant protein COVID-19 vaccine in the elderly: a prospective longitudinal study.

The safety and efficacy of COVID-19 vaccines in the elderly, a high-risk group for severe COVID-19 infection, have not been fully understood. To clarify these issues, this prospective study followed up 157 elderly and 73 young participants for 16 months and compared the safety, immunogenicity, and efficacy of two doses of the inactivated vaccine BBIBP-CorV followed by a booster dose of the recombinant protein vaccine ZF2001. The results showed that this vaccination protocol was safe and tolerable in the elderly. After administering two doses of the BBIBP-CorV, the positivity rates and titers of neutralizing and anti-RBD antibodies in the elderly were significantly lower than those in the young individuals. After the ZF2001 booster dose, the antibody-positive rates in the elderly were comparable to those in the young; however, the antibody titers remained lower. Gender, age, and underlying diseases were independently associated with vaccine immunogenicity in elderly individuals. The pseudovirus neutralization assay showed that, compared with those after receiving two doses of BBIBP-CorV priming, some participants obtained immunological protection against BA.5 and BF.7 after receiving the ZF2001 booster. Breakthrough infection symptoms last longer in the infected elderly and pre-infection antibody titers were negatively associated with the severity of post-infection symptoms. The antibody levels in the elderly increased significantly after breakthrough infection but were still lower than those in the young. Our data suggest that multiple booster vaccinations at short intervals to maintain high antibody levels may be an effective strategy for protecting the elderly against COVID-19.

A Randomized Trial to Address Food Insecurity and Promote Smoking Cessation Among Low-Income Adults.

Many low-income adults who smoke also have unmet social needs, such as food insecurity, which can serve as a barrier to smoking cessation. We developed a novel intervention to jointly address smoking cessation and food insecurity and assessed its feasibility, acceptability, and preliminary outcomes. We enrolled participants who screened for food insecurity, reported smoking daily, and were ready to quit. All participants received 3 months of resources navigation from a community health worker through monthly telephone calls for referrals and check-ins for smoking cessation and food access resources. Participants randomized to the intervention group received an economic intervention equivalent to the cost of 1 week of groceries/month for 3 months. We randomized 55 participants who were smoking on average 13 cigarettes/day. The trial was feasible and acceptable based on 3-month retention rates (80%) and end-of-study qualitative feedback (91% would recommend the study to others). At 3 months, participants in the intervention versus control group reported a longer length of abstinence from smoking and had a higher proportion of serious quit attempts. Results from this pilot study suggest the importance of attending to social needs, particularly food insecurity, as a strategy to promote smoking cessation among low-income adults who smoke.

Input-to-state stability of stochastic nonlinear system with delayed impulses.

Stochastic input-to-state stability (SISS) of the stochastic nonlinear system has received extensive research. This paper aimed to investigate SISS of the stochastic nonlinear system with delayed impulses. First, when all subsystems were stable, using the average impulsive interval method and Lyapunov approach, some theoretical conditions ensuring SISS of the considered system were established. The SISS characteristic of the argumented system with both stable and unstable subsystems was also discussed, then the stochastic nonlinear system with multiple delayed impulse jumps was considered and SISS property was explored. Additionally, it should be noted that the Lyapunov rate coefficient considered in this paper is positively time-varying. Finally, several numerical examples confirmed validity of theoretical results.

How does exotic Spartina alterniflora affect the contribution of iron-bound organic carbon to soil organic carbon in salt marshes?

Iron-bound organic carbon (OC-FeR) is important for the stability of soil organic carbon (SOC) in salt marshes, and the Spartina alterniflora invasion reshaped local salt marshes and changed the SOC pool. To evaluate the effects of S. alterniflora invasion on the contribution of OC-FeR to SOC, we determined the OC-FeR content and soil characteristics in the 0-50 cm soil profile along the vegetation sequence, including mudflats (MF), S. alterniflora marshes established in 2003 (SA03) and 1989 (SA89), the ecotone of S. alterniflora and Phragmites australis (SE), S. salsa marsh (SS), and P. australis marsh (PA). The SOC content was 6.55-17.5 mg g-1 in the S. alterniflora marshes. Reactive iron oxides (Fed, Feo, Fep) accumulated significantly in the S. alterniflora and P. australis salt marshes. PA and S. alterniflora marshes had higher DOC contents of 0.28-0.77 mg g-1. The OC-FeR content in the 0-50 cm soil profile in these ecosystems ranged from 0.3 to 3.29 mg g-1, with a contribution to the SOC content (fOC-FeR) of approximately 11 %, which was highest in SA03 (16.3 % ~ 18.8 %), followed by SA89, SE, and PA. In addition, the molar ratios of OC-FeR to Fed were <1, indicating that the iron oxides were associated with SOC through sorption more than coprecipitation. According to the structural equation model, SOC, DOC and iron oxides were the direct driving factors of OC-FeR formation, while the vegetation zone indirectly functioned by regulating organic C inputs, iron oxide formation, and pH. This study suggested that S. alterniflora invasion promotes iron-bound organic carbon accumulation by increasing organic C inputs and regulating iron oxide formation in salt marshes, but such promotion will degenerate with development duration.

Role of low-density lipoprotein in mediating the effect of air pollution on coronary heart disease: a two-step multivariate Mendelian randomization study.

OBJECTIVE: Air pollution is affecting the health of millions of people all over the world. The causal correlations of PM2.5, PM10, and nitrogen dioxide (NOx), as the main fine particulate matter, and coronary heart disease (CHD) are yet to be explored. Low-density lipoprotein (LDL) has been a principal factor in the pathogenesis of CHD. It is an interesting issue to consider whether LDL mediates the effect of air pollutants in CHD pathogenesis. MATERIALS AND METHODS: A genome-wide association study (GWAS) on the European population, followed up from 2010 to 2018, involving over 400,000 participants, was based on a land-use regression model. The annual mean concentrations of major air pollutant particles, PM2.5 (n=423,796), PM10 (n=423,796), and NOx (n=456,380), were recorded. The large GWAS database of CHD covered over ten million SNPs with independent single nucleotide polymorphisms (SNPs). LDL database collected major biochemical blood parameters from over 400,000 patients (n=440,546). Taken together, we conducted independent two-sample Mendelian randomization (MR) analyses for the causality between air pollutants (PM2.5, PM10, and NOx) and CHD. Multivariate MR analysis was conducted using causal relationships to determine the direct effects of exposure on outcome. The fixed-effect inverse variance weighted (IVW2) method was mainly employed to assess this relationship, with a confidence interval of 95% for the odds ratio (OR). Also, MR-Egger, weighted median, maximum likelihood ratio method, and random-effects inverse variance-weighted (IVW1) method were adopted as supplementary methods. RESULTS: Two-sample MR results based on the IVW2 method suggested positive correlations between PM2.5 and CHD [OR 1.875 (1.279-2.748), p=0.001], PM10 and CHD [OR 2.586 (1.479-4.523), p=0.001], and NOx and CHD [OR 2.991 (2.021-4.427), p=4.37E-08]. The direct effect and mediating proportion were calculated using multivariable Mendelian randomization (MVMR). Lastly, the mediating proportions of LDL in the regulatory roles of PM2.5, PM10, and NOx in CHD were 2.82%, 4.73%, and 9.54%, respectively. CONCLUSIONS: PM2.5, PM10, and NOx share direct causal associations with CHD, and LDL performs a mediating role in this pathogenic process. Early prevention against air pollution (such as increasing green areas and reducing large-scale industrial dust emissions) and early lipid-lowering treatment can effectively prevent the occurrence of CHD.

Regulation of overexpression lncRNA ATP2B1-AS1 on lung adenocarcinoma progression.

BACKGROUND: LncRNA ATP2B1-AS1 (ATP2B1-AS1) is involved in the occurrence and development of various diseases, while the relationship between lung adenocarcinoma (LUAD) and ATP2B1-AS1 is unclear. This study was to investigate the expression of ATP2B1-AS1 in LUAD and its influence on survival and prognosis of patients. METHODS: LUAD tissue samples from patients participating in this study were collected, and the expression levels of ATP2B1-AS1 and miR-141-3p in LUAD sampleswere detected by real-time quantitative polymerase chain reaction (RT-qPCR). The effect of ATP2B1-AS1 on the growth of A549 cells was investigated through cell counting kit-8 (CCK-8) and transwell experiments. Besides, the prognostic value of ATP2B1-AS1 in LUAD was assessed via Kaplan-Meier curve and multivariate Cox regression. RESULTS: ATP2B1-AS1 was downregulated in LUAD tissues and cells, whereas miR-141-3p was upregulated. After pcDNA3.1-ATP2B1-AS1 was transfected into A549 cells, the proliferation ability of A549 cells was decreased, and the migration level and invasion of A549 cells were also inhibited. High expression of ATP2B1-AS1 sponge miR-141-3p exerted prognostic value. CONCLUSIONS: ATP2B1-AS1 sponge miR-141-3p alleviated the progression of LUAD, and ATP2B1-AS1 may be deemed as a prognostic marker for LUAD.

Longitudinal experience of food insecurity & cigarette use in the early COVID-19 Pandemic, United States.

Food insecurity is associated with cigarette smoking, yet little is known about how variability in the experience of food insecurity may relate to patterns of cigarette use. We sought to examine patterns of food insecurity and cigarette use during the COVID-19 pandemic (April 2020-March 2021). We analyzed longitudinal survey data from a nationally representative panel of adults in the United States (N = 7,880) from the Understanding Coronavirus in America Study. The primary independent variable was ten trajectories of food insecurity. Our dependent variable was past 7-day cigarette use (count of days used cigarettes). Poisson regression using generalized estimating equations was run controlling for key covariates. The prevalence of cigarette use on at least one day in the past week was lowest (17.5 %) for those who Remained Food Secure, and highest (57.9 %) among those who Became Fully Food Insecure, a group characterized by having high probability of becoming food insecure during the study period. Among those who reported at least one day of cigarette use in the past week, fewer than half (40.1 %) reported sustained use across all waves of the study. Those who Became Fully Food Insecure had an incidence rate ratio (IRR) of 1.73 (95 % CI: 1.18, 2.54) compared to those who Remained Food Secure with respect to number of smoking days. While different patterns of food insecurity are related to cigarette smoking at the population level, these results highlight that food insecurity, a key social need, may represent a novel strategy for informing reduction of tobacco use disparities.

Association of plasma homocysteine with peripheral arterial disease in the hypertensive adults: A cross-sectional study.

Increased plasma homocysteine (Hcy) has been identified as one of the important risk factors for cardiovascular disease. However, the association between plasma Hcy and peripheral artery disease (PAD) is still controversial. This study aimed to investigate the association between plasma Hcy and PAD and the potential modifier factors in Chinese hypertensive adults. A total of 25 300 hypertensive patients aged 18 years or older were included in the analysis in this cross-sectional study. The outcome was PAD, which defined as an ankle-brachial index ≤0.90 in either limb. Multiple logistic regression was used to analyze the relationship between plasma Hcy and PAD. The median plasma Hcy was 14.00 (interquartile range: 11.60-17.80) µmol/L. There was a significant positive association between plasma Hcy and PAD (per SD increment; OR: 1.13; 95% CI: 1.06-1.19). Patients in the upper plasma Hcy tertile (≥16.16 µmol/L) were associated with a 53% increased risk of PAD compared with patients in the lower tertile (<12.33 µmol/L) after adjustment for multiple potential confounders. Subgroup analyses showed the association between Hcy and PAD was robust among various strata. Among Chinese adults with hypertension, plasma Hcy is an independent risk factor for PAD. This finding may improve the risk stratification of PAD.

The role of type VI secretion system genes in antibiotic resistance and virulence in Acinetobacter baumannii clinical isolates.

Introduction: The type VI secretion system (T6SS) is a crucial virulence factor in the nosocomial pathogen Acinetobacter baumannii. However, its association with drug resistance is less well known. Notably, the roles that different T6SS components play in the process of antimicrobial resistance, as well as in virulence, have not been systematically revealed. Methods: The importance of three representative T6SS core genes involved in the drug resistance and virulence of A. baumannii, namely, tssB, tssD (hcp), and tssM was elucidated. Results: A higher ratio of the three core genes was detected in drug-resistant strains than in susceptible strains among our 114 A. baumannii clinical isolates. Upon deletion of tssB in AB795639, increased antimicrobial resistance to cefuroxime and ceftriaxone was observed, alongside reduced resistance to gentamicin. The ΔtssD mutant showed decreased resistance to ciprofloxacin, norfloxacin, ofloxacin, tetracycline, and doxycycline, but increased resistance to tobramycin and streptomycin. The tssM-lacking mutant showed an increased sensitivity to ofloxacin, polymyxin B, and furazolidone. In addition, a significant reduction in biofilm formation was observed only with the ΔtssM mutant. Moreover, the ΔtssM strain, followed by the ΔtssD mutant, showed decreased survival in human serum, with attenuated competition with Escherichia coli and impaired lethality in Galleria mellonella. Discussion: The above results suggest that T6SS plays an important role, participating in the antibiotic resistance of A. baumannii, especially in terms of intrinsic resistance. Meanwhile, tssM and tssD contribute to bacterial virulence to a greater degree, with tssM being associated with greater importance.