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Yu-Sen Feng,1,&ast; Zheng-Yun Sun,2,&ast; Fei Jiang,3 Peng-Cheng Ma,1 Xing-Rui Liu,1 Yuan-Yuan Meng,2 Cheng-De Liao,1 Gui-Fang Sun1 1Department of Radiology, Kunming Yan’an Hospital, Kunming, 650051, People’s Republic of China; 2Department of Radiology, Lincang First People’s Hospital, Lincang, 677000, People’s Republic of China; 3Department of Radiology, Wenshan First People’s Hospital, Wenshan, 663599, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gui-Fang Sun, Department of Radiology, Kunming Yan’an Hospital, No. 245 Renmin East Road, Panlong District, Kunming, Yunnan, 650051, People’s Republic of China, Tel +86 13759518529, Email guifang_sun07@126.comObjective: This study aims to evaluate the relationship between the pericoronary fat attenuation index (FAI), derived from coronary artery computed tomography angiography, and post-lipid management levels of low-density lipoprotein cholesterol in patients with coronary artery disease (CAD). Additionally, the study investigates coronary inflammation across different lipid management strategies.Methods: We selected a cohort comprising 521 CAD patients who met the inclusion criteria. Patients were categorized into well-managed (LDL-C< 2.6 mmol/L) and poorly managed (LDL-C≥ 2.6 mmol/L) groups based on lipid management efficacy. We collected anthropometric measures (height, weight, body mass index, and body surface area) and clinical indicators, including Gensini score, and FAI-related parameters for coronary atherosclerotic lesions. We analyzed the interrelations along these parameters and lipid management using statistical methods and assessed diagnostic value via receiver operating characteristic (ROC) curve analysis of these parameters was assessed through.Results: The poorly managed group exhibited significantly higher levels of total cholesterol, triglycerides, and lower levels of high-density lipoprotein compared to the well-managed group (P < 0.05). Significant differences were observed between the groups in terms of lesion length in the proximal segment of the left anterior descending artery, FAI value in the proximal segment of lesions in the right coronary artery (RCA), volume thickness in the middle segment of RCA lesions, and lesion length in the distal segment of RCA (P < 0.05). ROC curve analysis revealed areas under the curve ranging from 0.484 to 0.660 for the parameters, indicating limited diagnostic efficacy.Conclusion: The FAI in the RCA varies with lipid management strategies, suggesting it as a valuable metric for monitoring both perivascular inflammation and lipid status in CAD patients. However, its current diagnostic efficacy is limited, indicating the need for further research to improve its clinical utility.Keywords: coronary artery CT angiography, coronary atherosclerotic heart disease, coronary inflammation, lipids, low-density lipoprotein cholesterol, pericoronary fat attenuation index

Wen-Chao Liu, Liang Wen, Hao Wang, Jiang-Biao Gong, Tian-Xiang Zhan, Yuan-Yuan Meng, Xiao-Feng Yang Department of Neurosurgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China Abstract: In the present study, we evaluated the changes in autophagy after hyperbaric oxygen (HBO) treatment for traumatic brain injury (TBI) and investigated whether autophagy takes part in the neuroprotection after HBO treatment. Male Sprague Dawley rats were assigned to four groups randomly: sham injury, sham injury and HBO, TBI, and TBI and HBO. The HBO rats received HBO treatment for 100 min immediately after injury. Rats were sacrificed at 24 h after the brain injury and the levels of cleaved caspase-3 and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells in the injured cortex were measured to determine cell death. The expression levels of autophagy-associated proteins were measured by immunohistochemistry and Western blotting to assess changes in autophagy. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cell density and cleaved caspase-3 expression were increased 24 h after TBI. These increases were suppressed by post-TBI HBO treatment. Immunohistochemistry and Western blotting of autophagy-associated proteins showed that TBI can induce autophagy and that HBO treatment can further upregulate the expression of autophagy makers, as shown by an increase in LC3, ATG-5, and Beclin-1 expression and reduction in P62 expression. In conclusion, HBO treatment can reduce apoptosis and further upregulate autophagy in the injured cortex after brain injury, and the autophagy pathway may take part in the neuroprotection provided by HBO treatment for TBI. Keywords: autophagy, hyperbaric oxygen treatment, traumatic brain injury, apoptosis, neuroprotective effect

Background: 5-hydroxymethylcytosine (5hmC) as an epigenetic modification can regulate gene expression, and its abnormal level is related with various tumor invasiveness and poor prognosis. Nevertheless, the current methods for 5hmC assay usually involve expensive instruments/antibodies, radioactive risk, high background, laborious bisulfite treatment procedures, and non-specific/long amplification time., Results: We develop a glycosylation-mediated fluorescent biosensor based on helicase-dependent amplification (HDA) for label-free detection of site-specific 5hmC in cancer cells with zero background signal. The glycosylated 5hmC-DNA (5ghmC) catalyzed by β-glucosyltransferase (β-GT) can be cleaved by AbaSI restriction endonuclease to generate two dsDNA fragments with sticky ends. The resultant dsDNA fragments are complementary to the biotinylated probes and ligated by DNA ligases, followed by being captured by magnetic beads. After magnetic separation, the eluted ligation products act as the templates to initiate HDA reaction, generating abundant double-stranded DNA (dsDNA) products within 20 min. The dsDNA products are measured in a label-free manner with SYBR Green I as an indicator. This biosensor can measure 5hmC with a detection limit of 2.75 fM and a wide linear range from 1 × 10 -14 to 1 × 10 -8  M, and it can discriminate as low as 0.001% 5hmC level in complex mixture. Moreover, this biosensor can measure site-specific 5hmC in cancer cells, and distinguish tumor cells from normal cells., Significance: This biosensor can achieve a zero-background signal without the need of either 5hmC specific antibody or bisulfite treatment, and it holds potential applications in biological research and disease diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Histidine triad nucleotide-binding protein 2 (HINT2) is an enzyme found in mitochondria that functions as a nucleotide hydrolase and transferase. Prior studies have demonstrated that HINT2 plays a crucial role in ischemic heart disease, but its importance in cardiac remodelling remains unknown. Therefore, the current study intends to determine the role of HINT2 in cardiac remodelling. HINT2 expression levels were found to be lower in failing hearts and hypertrophy cardiomyocytes. The mice that overexpressed HINT2 exhibited reduced myocyte hypertrophy and cardiac dysfunction in response to stress. In contrast, the deficiency of HINT2 in the heart of mice resulted in a worsening hypertrophic phenotype. Further analysis indicated that upregulated genes were predominantly associated with the oxidative phosphorylation and mitochondrial complex I pathways in HINT2-overexpressed mice after aortic banding (AB) treatment. This suggests that HINT2 increases the expression of NADH dehydrogenase (ubiquinone) flavoprotein (NDUF) genes. In cellular studies, rotenone was used to disrupt mitochondrial complex I, and the protective effect of HINT2 overexpression was nullified. Lastly, we predicted that thyroid hormone receptor beta might regulate HINT2 transcriptional activity. To conclusion, the current study showcased that HINT2 alleviates pressure overload-induced cardiac remodelling by influencing the activity and assembly of mitochondrial complex I. Thus, targeting HINT2 could be a novel therapeutic strategy for reducing cardiac remodelling., (© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Instruction: To help determine the health protectiveness of government regulations and policies for air pollutant control for Americans, our study aimed to investigate the health and economic impacts of work loss due to sickness associated with daily all-source and wildfire-specific PM 2.5 (particulate matter with an aerodynamic diameter smaller than 2.5 μm) exposures in California., Methods: We linked the 2015-2018 California Health Interview Survey respondents' geocoded home addresses to daily PM 2.5 estimated by satellites and atmospheric modelling simulations and wildfire-related PM 2.5 from Community Multiscale Air Quality models. We calculated and applied the coefficient for the association between daily PM 2.5 exposure and work loss from regression analyses to the Environmental Benefits Mapping and Analysis Program-Community Edition (BenMAP-CE) platform to assess the health and economic impacts of PM 2.5 exposure on work loss due to sickness., Results: We observed that each 1 µg/m 3 increase in daily total PM 2.5 exposure will lead to about 1 million days of work loss per year ranging from 1.1 to 1.6 million person-days, and the related economic loss was $310-390 million. Wildfire smoke alone could contribute to 0.7-2.6 million work-loss days with a related economic loss of $129-521 million per year in 2015-2018. Using the function coefficient in the current BenMAP, the excess work-loss days due to sickness was about 250 000 days and the estimated economic loss was about $45-50 million for each 1 µg/m 3 increase in daily total PM 2.5 exposure, and wildfire smoke alone would lead to 0.17-0.67 million work-loss days with related economic loss of $31-128 million per year during the same period., Conclusions: Both conventional and wildfire-specific sources of PM 2.5 produced substantial work loss and cost in California. Updating the current BenMAP-CE calculations for work-loss days will be essential in quantifying the current health impacts of PM 2.5 to help inform the policies and regulations to protect public health., Competing Interests: None declared., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. Published by BMJ.)

This study aims to decipher the mechanism of Buzhong Yiqi Decoction(BZYQD) in the treatment of spleen deficiency syndrome via gut microbiota. The mouse models of spleen deficiency syndrome were established by fecal microbiota transplantation(FMT, from patients with spleen deficiency syndrome) and administration of Sennae Folium(SF, 10 g·kg~(-1)), respectively, and treated with BZYQD for 5 d. The pseudosterile mice(administrated with large doses of antibiotics) and the mice transplanted with fecal bacteria from healthy human were taken as the controls. The levels of IgA, interleukin(IL)-2, IL-1β, interferon(IFN)-γ, tumor necrosis factor-alpha(TNF-α), and 5-hydroxytryptamine(5-HT) in the intestinal tissue of two models were measured by enzyme-linked immunosorbent assay, and the CD8~+/CD3~+ ratio was determined by flow cytometry. The composition and changes of the gut microbiota were determined by 16S rRNA high-throughput sequencing and qPCR. Furthermore, the correlation analysis was performed to study the mediating role of gut microbiota in the treatment. The results showed that BZYQD elevated the IgA level, lowered the IL-1β, TNF-α, and 5-HT levels, and decreased the CD8~+/CD3~+ ratio in the intestinal tissue of the two models. Moreover, BZYQD had two-way regulatory effects on the levels of IL-2 and IFN-γ. BZYQD inhibited the overgrowth and reduced the richness of gut microbiota in the SF model, and improved the gut microbiota structure in the two models. Algoriphagus, Mycobacterium, and CL500＿29＿marine＿group were the common differential genera in the two models compared with the control. Acinetobacter, Parabacteroides, and Ruminococcus were the differential genera unique to the FMT model, and Sphingorhabdus, Lactobacillus, and Anaeroplasma were the unique differential genera in the SF model. BZYQD was capable of regulating all these genera. The qPCR results showed that BZYQD increased the relative abundance of Akkermansia muciniphila and decreased that of Bacteroides uniformis in the two models. The correlation analysis revealed that the levels of above intestinal cytokines were significantly correlated with characteristic gut microorganisms in different mo-dels. The IL-1β level had a significantly positive correlation with Acinetobacter and CL500＿29＿marine＿group in the two models, while the different levels of IL-2 and IFN-γ in the two models may be related to its different gut microbiota structures. In conclusion, BZYQD could regulate the disordered gut microbiota structure in different animal models of spleen deficiency syndrome to improve the intestinal immune status, which might be one of the mechanisms of BZYQD in treating spleen deficiency syndrome.

Ammonium, as a major inorganic source of nitrogen (N) for sweet potato N utilization and growth, is specifically transported by ammonium transporters ( AMTs ). However, the activities of AMT family members in sweet potatoes have not been analyzed. In the present study, the sweet potato cultivar 'Pushu 32', which is planted in a large area in China, was used in field experiments at the Agricultural Base of Hainan University (20°06' N, 110°33' E) in 2021, and Sanya Nanfan Research Institute of Hainan University (18°30' N, 109°60' E) in 2022. Four N levels were tested: 0, 60, 120, and 180 kg ha -1 . The results are as follows. Twelve IbAMT genes were identified in the sweet potato genome, which were classified into three distinct subgroups based on phylogeny; the same subgroup genes had similar properties and structures. IbAMT1.3 and IbAMT1.5 were mostly expressed in the storage roots under N deficiency. Compared with the NN and HN groups, IbAMT1.3 and IbAMT1.5 expressions, N content in storage roots, N uptake efficiency at the canopy closure, N fertilization contribution rates, number of storage roots per plant, storage root weight, and yield were all increased in the MN group. Furthermore, there was a significant positive correlation between the expressions of IbAMT1.3 and IbAMT1.5 with N content in the storage roots of sweet potato. In a word, IbAMT1.3 and IbAMT1.5 may regulate N utilization, affect the development of the storage root. and determine the yield of sweet potato. The results provide valuable insights into the AMT gene family's role in the use of N and effects on storage root development and yield in sweet potatoes.

Enzymes are closely associated with the onset and progression of numerous diseases, making enzymes a primary target in innovative drug development. However, the challenge remains in identifying compounds that exhibit potent inhibitory effects on the target enzymes. With the continuous expansion of the total number of natural products and increasing difficulty in isolating and enriching new compounds, traditional high-throughput screening methods are finding it increasingly challenging to meet the demands of new drug development. Virtual screening, characterized by its high efficiency and low cost, has gradually become an indispensable technology in drug development. It represents a prominent example of the integration of artificial intelligence with biopharmaceuticals and is an inevitable trend in the rapid development of innovative drug screening in the future. Therefore, this article primarily focused on systematically reviewing the recent applications of virtual screening technology in the development of enzyme inhibitors and explored the prospects and advantages of using this technology in developing new drugs, aiming to provide essential theoretical insights and references for the application of related technologies in the field of new drug development.

Fish skeletal muscle is composed of two anatomically and functionally different fiber layers, white or fast and red or slow muscles. Myosin, the major structural protein of fish skeletal muscle, contains multiple myosin heavy chain (MYH) isoforms involved in the high plasticity of muscle in response to varying functional demands and/or environmental changes. In this study, we comparatively assayed the cellular and ultrastructural feature of white and red skeletal muscles. Then, a total of 28 class II myosin heavy chain genes were identified in by searching the Chinese perch genome database. Among them, 14 genes code for the fast-muscle-type myosin heavy chain, and 7 genes code for the slow-muscle-type myosin heavy chain. Further, the different isoform gene structures, function domains, phylogenetic relations, and muscle-fiber type-specific expression were characterized. This is the first systematic work on the molecular characterization of class II myosin heavy chain isoforms and the differential analysis of their expression in red and white muscle tissues in Chinese perch Siniperca chuatsi. Our work provided valuable information for a better understanding of myh genes and their molecular characteristics, and the correlations of multiple myosin isoforms with potential functions in response to varying functional demands and/or environmental changes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Vibrio parahaemolyticus must endure various challenging circumstances while being swallowed by phagocytes of the innate immune system. Moreover, bacteria should recognize and react to environmental signals quickly in host cells. Two-component system (TCS) is an important way for bacteria to perceive external environmental signals and transmit them to the interior to trigger the associated regulatory mechanism. However, the regulatory function of V. parahaemolyticus TCS in innate immune cells is unclear. Here, the expression patterns of TCS in V. parahaemolyticus -infected THP-1 cell-derived macrophages at the early stage were studied for the first time. Based on protein-protein interaction network analysis, we mined and analyzed seven critical TCS genes with excellent research value in the V. parahaemolyticus regulating macrophages, as shown below. VP1503, VP1502, VPA0021, and VPA0182 could regulate the ATP-binding-cassette (ABC) transport system. VP1735, uvrY, and peuR might interact with thermostable hemolysin proteins, DNA cleavage-related proteins, and TonB-dependent siderophore enterobactin receptor, respectively, which may assist V. parahaemolyticus in infected macrophages. Subsequently, the potential immune escape pathways of V. parahaemolyticus regulating macrophages were explored by RNA-seq. The results showed that V. parahaemolyticus might infect macrophages by controlling apoptosis, actin cytoskeleton, and cytokines. In addition, we found that the TCS (peuS/R) could enhance the toxicity of V. parahaemolyticus to macrophages and might contribute to the activation of macrophage apoptosis. IMPORTANCE This study could offer crucial new insights into the pathogenicity of V. parahaemolyticus without tdh and trh genes. In addition, we also provided a novel direction of inquiry into the pathogenic mechanism of V. parahaemolyticus and suggested several TCS key genes that may assist V. parahaemolyticus in innate immune regulation and interaction., Competing Interests: The authors declare no conflict of interest.

Background: Few studies investigated the impact of particulate matter (PM 2.5 ) on some symptom exacerbations that are not perceived as severe enough to search for medical assistance. We aimed to study the association of short-term daily total PM 2.5 exposure with work loss due to sickness among adults living in California., Methods: We included 44,544 adult respondents in the workforce from 2015 to 2018 California Health Interview Survey data. Daily total PM 2.5 concentrations were linked to respondents' home addresses from continuous spatial surfaces of PM 2.5 generated by a geostatistical surfacing algorithm. We estimated the effect of a 2-week average of daily total PM 2.5 exposure on work loss using logistic regression models., Results: About 1.69% (weighted percentage) of adult respondents reported work loss in the week before the survey interview. The odds ratio of work loss was 1.45 (odds ratio [OR] = 1.45, 95% confidence interval [CI]: 1.03, 2.03) when a 2-week average of daily total PM 2.5 exposure was higher than 12 µg/m 3 . The OR for work loss was 1.05 (95% CI: 0.98, 1.13) for each 2.56ug/m 3 increase in the 2-week average of daily total PM 2.5 exposure, and became stronger among those who were highly exposed to wildfire smoke (OR = 1.06, 95% CI: 1.00, 1.13), compared to those with lower wildfire smoke exposure (OR = 1.04, 95% CI: 0.79, 1.39)., Conclusions: Our findings suggest that short-term ambient PM 2.5 exposure is positively associated with work loss due to sickness and the association was stronger among those with higher wildfire smoke exposure. It also indicated that the current federal and state PM 2.5 standards (annual average of 12 µg/m 3 ) could be further strengthened to protect the health of the citizens of California., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Many filamentous fungi produce plant-polysaccharide-degrading enzymes (PPDE); however, the regulatory mechanism of this process is poorly understood. A Gal4-like transcription factor, CxrA, is essential for mycelial growth and PPDE production in Penicillium oxalicum. Its N-terminal region, CxrAΔ207-733 is required for the regulatory functions of whole CxrA, and contains a DNA-binding domain (CxrAΔ1-16&Δ59-733) and a methylated arginine (R) 94. Methylation of R94 is mediated by an arginine N-methyltransferase, PRMT2 and appears to induce dimerization of CxrAΔ1-60. Overexpression of prmt2 in P. oxalicum increases PPDE production by 41.4-95.1% during growth on Avicel, compared with the background strain Δku70;hphR+. Another arginine N-methyltransferase, PRMT3, appears to assist entry of CxrA into the nucleus, and interacts with CxrAΔ1-60 in vitro under Avicel induction. Deletion of prmt3 resulted in 67.0-149.7% enhanced PPDE production by P. oxalicum. These findings provide novel insights into the regulatory mechanism of fungal PPDE production., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Outdoor air pollution, including ozone (O 3 ) pollution, and childhood family environments may interact and impact asthma exacerbations in children. Previous epidemiology studies have primarily focused on stress in the home, rather than support, and whether psychosocial factors modify the association between pollution and health outcomes, rather than whether pollution exposure modifies associations between psychosocial factors and health outcomes., Methods: Data from the cross-sectional 2003 representative, population-based California Health Interview Survey were linked with air quality monitoring data on O 3 pollution from the California Air Resources Board. Adolescents (N = 209) ages 12-17 who reported an asthma diagnosis and lived within 5 mi of the nearest air monitoring station had linked O 3 data for a 12-month period preceding the survey interview date. Adolescents reported perceived available support from an adult at home and frequency of asthma symptoms., Results: In unadjusted models, for adolescents living in high O 3 pollution regions, greater perceived support was related to lower asthma symptom frequency. Follow-up analyses suggested that the most plausible interpretation of the interaction was that O 3 exposure modified the association between perceived support and symptom frequency. O 3  × perceived support interactions were not statistically significant after adjusting for covariates., Conclusions: These data provide preliminary evidence that the association between the lack of support in the home environment and worse asthma symptoms may be stronger in areas with higher O 3 exposure. Future work may benefit from incorporating personal pollution exposure assessments, comprehensive family environment assessments, and longitudinal follow-up of asthma exacerbations over time., (© 2022. The Author(s).)

Objective: To evaluate the effect of the transition from IMPACT, a disease-focused treatment program, to comprehensive health insurance under Medicaid through the Affordable Care Act (ACA) on general and prostate cancer-specific quality of life (QoL) on a cohort of previously uninsured low-income men. We hypothesize that general QoL would improve and prostate cancer-specific QoL would remain the same after the transition to comprehensive health insurance., Methods: We assessed and compared general QoL using the RAND SF-12v2™ (12-Item Short Form Survey, version 2) and prostate cancer-specific QoL using the UCLA PCI (Prostate Cancer Index) one year before, at, and one year after the transition between 30 men who transitioned to comprehensive insurance (newly insured/Medicaid group) and 54 men who remained in the prostate cancer program (uninsured/IMPACT group). We assessed the independent effects of Medicaid coverage on QoL outcomes using repeated-measures regression., Results: Our cohort was composed primarily of Hispanic men (82%). At transition, patient demographics and clinical characteristics were similar between the groups. General and prostate cancer-specific QoL did not differ between the groups and remained stable over time, Radical prostatectomy as primary treatment and shorter time since treatment were associated with worse urinary and sexual function across both groups and over all three time points., Conclusion: Those who transitioned to full-scope insurance and those who remained in the free prostate cancer-focused treatment program had stable general and prostate cancer-specific QoL. High-touch navigation aspects of a disease-focused program may have contributed to stability in outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: This study examines whether the "Emission Reduction Plan for Ports and Goods Movement" in California reduced air pollution exposures and emergency room visits among California Medicaid enrollees with asthma and/or chronic obstructive pulmonary disease., Method: We created a retrospective cohort of 5608 Medicaid enrollees from ten counties in California with data from 2004 to 2010. We grouped the patients into two groups: those living within 500 m of goods movement corridors (ports and truck-permitted freeways), and control areas (away from the busy truck or car permitted highways). We created annual air pollution surfaces for nitrogen dioxide and assigned them to enrollees' home addresses. We used a quasi-experimental design with a difference-in-differences method to examine changes before and after the policy for cohort beneficiaries in the two groups., Results: The reductions in nitrogen dioxide exposures and emergency room visits were greater for enrollees in goods movement corridors than those in control areas in post-policy years. We found that the goods movement actions were associated with 14.8% (95% CI, -24.0% to -4.4%; P = 0.006) and 11.8% (95% CI, -21.2% to -1.2%; P = 0.030) greater reduction in emergency room visits for the beneficiaries with asthma and chronic obstructive pulmonary disease, respectively, in the third year after California's emission reduction plan., Conclusion: These findings indicate remarkable health benefits via reduced emergency room visits from the significantly improved air quality due to public policy interventions for disadvantaged and susceptible populations., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Since 2016, California has implemented a series of policies, including prohibiting the sale of tobacco products and electronic cigarettes (e-cigarettes) to persons under 21, cigarette tax increase, and recreational marijuana legalization. The study aims to examine the use of cigarettes, e-cigarettes, and marijuana among young adults (ages 18-25) and their associations with other factors in the context of these policy changes., Methods: We used the data from the California Health Interview Survey (CHIS) 2017-2018 to compare the rates of using cigarettes, e-cigarettes, and marijuana separately or any use of the three. Using CHIS 2018 data, weighted logistic regression models were used to examine associations of using cigarettes, e-cigarettes, and marijuana separately or any use of these products/substance with demo-socioeconomic factors, psychological distress, and use of each product/substances., Results: Cigarette smoking remained flat while the use of e-cigarettes and marijuana escalated among young adults from 2017 to 2018. Using tobacco products increased the use of marijuana or vice versa among young adults. Severe psychological distress was significantly associated with cigarette use (adjusted odds ratio [AOR] = 4.06; 95% CI = 1.32, 12.55), marijuana use (AOR = 2.32; 95% CI = 1.10, 4.48), and any use (AOR = 4.11; 95% CI = 1.93, 8.77). Moderate psychological distress was also significantly associated with the use of these products/substance. Underage (ages 18-20) young adults had lower odds of using cigarettes than other young adults (ages 21-25)., Conclusions: Our findings highlight the importance of addressing the use of cigarettes, e-cigarettes, and marijuana simultaneously through policies to curtail tobacco and marijuana use among young adults., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background and Aims: We conducted a comprehensive analysis of the functional traits of leaves (leaflets) of cycads. The aim of this study was to clarify the functional divergence between the earlier origin Cycadaceae and the later differentiated Zamiaceae, and the differences in trait associations between cycads and angiosperms., Methods: We selected 20 Cycadaceae species and 21 Zamiaceae species from the same cycad garden in South China, and measured their leaf structure, economic traits, mechanical resistance (Fp) and leaf water potential at the turgor loss point (πtlp). In addition, we compiled a dataset of geographical distribution along with climatic variables for these cycad species, and some leaf traits of tropical-sub-tropical angiosperm woody species from the literature for comparison., Key Results: The results showed significantly contrasting leaf trait syndromes between the two families, with Zamiaceae species exhibiting thicker leaves, higher carbon investments and greater Fp than Cycadaceae species. Leaf thickness (LT) and πtlp were correlated with mean climatic variables in their native distribution ranges, indicating their evolutionary adaptation to environmental conditions. Compared with the leaves of angiosperms, the cycad leaves were thicker and tougher, and more tolerant to desiccation. Greater Fp was associated with a higher structural investment in both angiosperms and cycads; however, cycads showed lower Fp at a given leaf mass per area or LT than angiosperms. Enhancement of Fp led to more negative πtlp in angiosperms, but the opposite trend was observed in cycads., Conclusions: Our results reveal that variations in leaf traits of cycads are mainly influenced by taxonomy and the environment of their native range. We also demonstrate similar leaf functional associations in terms of economics, but different relationships with regard to mechanics and drought tolerance between cycads and angiosperms. This study expands our understanding of the ecological strategies and likely responses of cycads to future climate change., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Renal cell carcinoma (RCC) is a kidney cancer that is originated from the lined proximal convoluted tubule, and its major histological subtype is clear cell RCC (ccRCC). This study aimed to retrospectively analyze single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database, to explore the correlation among the evolution of tumor microenvironment (TME), clinical outcomes, and potential immunotherapeutic responses in combination with bulk RNA-seq data from The Cancer Genome Atlas (TCGA) database, and to construct a differentiation-related genes (DRG)-based prognostic risk signature (PRS) and a nomogram to predict the prognosis of ccRCC patients. First, scRNA-seq data of ccRCC samples were systematically analyzed, and three subsets with distinct differentiation trajectories were identified. Then, ccRCC samples from TCGA database were divided into four DRG-based molecular subtypes, and it was revealed that the molecular subtypes were significantly correlated with prognosis, clinicopathological features, TME, and the expression levels of immune checkpoint genes (ICGs). A DRG-based PRS was constructed, and it was an independent prognostic factor, which could well predict the prognosis of ccRCC patients. Finally, we constructed a prognostic nomogram based on the PRS and clinicopathological characteristics, which exhibited a high accuracy and a robust predictive performance. This study highlighted the significance of trajectory differentiation of ccRCC cells and TME evolution in predicting clinical outcomes and potential immunotherapeutic responses of ccRCC patients, and the nomogram provided an intuitive and accurate method for predicting the prognosis of such patients., (© 2022. The Author(s).)

Biogenic microvesicles (MVs) play a pivotal role in intercellular signal communication, thus initiating critical biological responses such as the proliferation of cancer cells, gene and protein transport, and chemo-drug resistance. In addition, they have been recognized as having great potential in drug delivery applications. However, the productivity of biologically produced MVs is not sufficient for clinical applications. In this study, synthetic poly(lactic-co-glycolic acid) (PLGA) MVs were prepared via a double emulsion method. The PLGA MVs had a biogenic MV-mimic vesicular structure with a hydrophilic core/surface and hydrophobic interior of the shell, showing great potential for drug delivery. We successfully embedded hydrophobic iron carbonyl (IC), a carbon monoxide (CO) donor, in the PLGA shell region, enabling the delivery of IC in an aqueous solution. Because of the intrinsic properties of PLGA, it was susceptible to temperature, and the MVs could easily collapse in a warm environment, leading to the decomposition of IC into CO. The in vitro result indicated that the cell viability of A549 lung carcinoma cells significantly decreased to 14% after treatment with IC-loaded PLGA MVs for 24 h, suggesting that these synthetic PLGA MVs constitute an excellent drug delivery platform.

Purpose: The aim of our study was to investigate the effect of breast cancer subtypes on the diagnostic value of axillary ultrasound for node status evaluation after neoadjuvant chemotherapy., Patients and Methods: Pathologic node-positive breast cancer patients underwent axillary ultrasound imaging after neoadjuvant chemotherapy were retrospectively reviewed. The enrolled patients were classified into four subtypes: Luminal A, Luminal B, human epidermal growth factor receptor 2-enriched and triple-negative. Ultrasound images of axillary nodes were reviewed and were evaluated as normal or abnormal and were associated with final pathologic results. Diagnostic value of axillary ultrasound was assessed in four subtypes based on sensitivity, specificity, positive predictive value and negative predictive value. The diagnostic value of axillary ultrasound as well as clinical and pathological characteristics was compared between four breast cancer subtypes using chi-square test or fisher's exact test., Result: Luminal A subtype had highest positive predictive value (92.1%), lowest sensitivity (43.8%) and lowest negative predictive value (11.8%). Triple-negative subtype had lowest positive predictive value (73.2%), highest sensitivity (76.9%) and highest negative predictive value (59.1%) (P < 0.05). Luminal B and human epidermal growth factor receptor 2-enriched subtypes had medium sensitivity, positive predictive value and negative predictive value., Conclusion: The diagnostic value of axillary ultrasound for node residue disease assessment after neoadjuvant chemotherapy is different between four breast cancer subtypes., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cell‑cell fusion is a dynamic biological phenomenon, which plays an important role in various physiological processes, such as tissue regeneration. Similarly, normal cells, particularly bone marrow‑derived cells (BMDCs), may attempt to fuse with cancer cells to rescue them. The rescue may fail, but the fused cells end up gaining the motility traits of BMDCs and become metastatic due to the resulting genomic instability. In fact, cell‑cell fusion was demonstrated to occur in vivo in cancer and was revealed to promote tumor metastasis. However, its existence and role may be underestimated, and has not been widely acknowledged. In the present review, the milestones in cell fusion research were highlighted, the evidence for cell‑cell fusion in vitro and in vivo in cancer was evaluated, and the current understanding of the molecular mechanisms by which cell‑cell fusion occurs was summarized, to emphasize their important role in tumor metastasis. The summary provided in the present review may promote further study into this process and result in novel discoveries of strategies for future treatment of tumor metastasis.

Given the relentless renewal ability of intestinal crypt-base stem cells, small intestine in the gastrointestinal (GI) tract is more vulnerable to radiation-induced disruption. Through promoting epithelial integrity and reducing intracellular reactive oxygen species (ROS) levels, hypoxia-inducible factors (HIFs) have been proved to exhibit radioprotective effects in the GI tract. Therefore, enhancing stability or transcriptional activity of HIFs might be a therapeutic strategy for developing radioprotectors. Factor inhibiting HIF (FIH or HIF-1AN) can hamper transcriptional capacity of HIF-1α via interacting with Asn803 in its C-terminal domain. Previously, we discovered promoting HIF-1α transcriptional activity in vitro by FIH inhibitor-N-oxalyl-D-phenylalanine (NOFD) exerts radioprotection on cells. However, the radioprotective effect of FIH inhibitor on the GI tract and its competing endogenous RNA (ceRNA) regulatory network from the FIH/HIF axis has never been addressed. Here we verified radioprotection of NOFD for the GI tract by an animal model and performed whole-transcriptome analysis to fully elucidate the radioprotective mechanism from the FIH/HIF axis against GI syndrome. We identified two novel circular RNAs (circRNAs) (circRNA&#95;2909 and circRNA&#95;0323) and two long non-coding RNAs (lncRNAs) (NONMMUT140549.1 and NONMMUT148249.1) that promote expression of HIF1A and NOS2 in the HIF-1 pathway by sponging microRNAs (miRNAs), especially mmu-miR-92a-1-5p. The de-repression of HIF-1α transcriptional capacity by inhibiting FIH proteomic activity suggests a new therapeutic strategy in alleviating radiation-induced GI syndrome., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Introduction: In 2006, the California Air Resources Board (CARB) and local air quality management districts implemented an Emission Reduction Plan for Ports and Goods Movement program (referred to hereinafter as GM policy actions) (CARB 2006). The GM policy actions comprise approximately 200 actions with an estimated investment value of $6 to $10 billion. These actions targeted the major sources and polluters related to goods movements, such as highways; ports and railyard trucks; ship fuel and shore power; cargo equipment; and locomotives. These actions aimed to reduce total statewide domestic GM emissions to 2001 levels or lower by the year 2010; to reduce the statewide diesel particulate matter (DPM) health risk from GM by 85% by the year 2020; and to reduce the nitrogen oxides (NO x ) emissions from international GM in the South Coast Air Basin by 30% from projected 2015 levels and 50% from projected 2020 levels. The years 2006 and 2007 marked an important milestone in starting to regulate GM polluters and adopting stricter standards for traffic-related air pollution., This project aimed to examine the impact of the GM policy actions on reductions in ambient air pollution and subsequent improvements in health outcomes of Medi-Cal fee-for-service (FFS) beneficiaries with chronic conditions in 10 counties in California. Specifically, we examined whether the GM policy actions reduced air pollution near GMC corridors more than in control areas. We subsequently assessed whether there were greater decreases in emergency room (ER) visits and hospitalizations for enrollees with chronic conditions who lived in the GM corridors (GMCs) than for those who lived in other areas., Methods: The study used a quasi-experimental design. We defined areas within 500 m of truck-permitted freeways and ports as GMCs. We further defined non-goods movement corridors (NGMCs) as locations within 500 m of truck-prohibited freeways or 300 m of a connecting roadway, and areas out of GMCs and NGMCs as controls (CTRLs). We defined years 2004-2007 as the pre-policy period and years 2008-2010 as the post-policy period. We developed linear mixed-effects land use regression models and created annual air pollution surfaces for nitrogen dioxide (NO 2 ), fine particulate matter (PM 2.5 ), and ozone (O 3 ) across California for years 2004-2010 at a spatial resolution of 30 m, then assigned them to enrollees' home addresses., We used a retrospective cohort of 23,000 California Medicaid (Medi-Cal) FFS adult beneficiaries living in 10 California counties with six years of data (September 1, 2004, to August 31, 2010). Cohort beneficiaries had at least one of four chronic conditions, including asthma, chronic obstructive pulmonary disease (COPD), diabetes, and heart disease., We used a difference-in-differences (DiD) model to assess whether air pollutant concentration and health care utilization (ER visits and hospitalizations) for cohort beneficiaries declined more for those living in intervention corridors (GMCs, NGMCs) than those living in CTRLs. All the models controlled for age, sex, language spoken, race/ethnicity, number of comorbidities in baseline years, county, time-varying health indicator variables, and several neighborhood variables., To facilitate interpretation, we calculated the DiD estimates in each of the three years after the policy intervention. The DiD was used to assess the causal impact of regulatory policy on reductions of air pollution, as well as for the improvements in health outcomes., We explored whether improvements in health outcomes were due to the air pollution reduction by using a multi- level mediation model, in which the effect of GM actions on health outcomes was mediated through the effect of actual air pollution reductions in the post-policy years. We used the Generalized Structural Equation Models for the estimation and combined the effects of NO 2 and PM 2.5 in the model. To further verify the causal inferences of the GM actions on reductions of exposures and improvements in health outcomes, we performed sensitivity analyses with propensity score weighting., Results: We observed statistically significant reductions in pollutant NO 2 and PM 2.5 concentrations for enrollees in all 10 counties. The enrollees in GMCs experienced greater reductions in NO 2 and PM 2.5 from the pre- to the post-policy periods than those in CTRLs. Greater reductions were also observed among beneficiaries living in NGMCs versus those in CTRLs, but those reductions were smaller than among beneficiaries living in GMCs. For O 3 concentrations, an opposite trend was observed., Furthermore, we observed significantly greater reductions in ER visits for patients with asthma and COPD living in GMCs than those in CTRLS in the post-policy years. For example, we saw in the DiD modeling results there were 170 fewer ER visits for 1,000 beneficiaries with asthma per year in GMCs if the regionwide trend in the CTRL group was considered not related to the GM policy. Similarly, among the beneficiaries with COPD, there were 180 fewer ER visits per 1,000 patients estimated in the GMCs for the third year after the implementation of the policy., We also observed greater reductions in ER visits among those with asthma, when comparing NGMCs with CTRLs, but reductions were smaller than comparisons between GMCs and CTRLs. The ER visits for those with COPD, diabetes, and the total sample in NGMCs also had downward trends in the post-policy year in comparison with those in CTRLs but the differences were not statistically significant; similar phenomena were also observed for the ER visits among those with diabetes and heart diseases and in the total sample when GMCs versus CTRLs and GMCs versus NGMCs were compared. Although hospitalizations also decreased more in GMCs than in NGMCs and more in NGMCs than in CTRLs in the post-policy period, results were not statistically significant., Using the mediation models, we observed 0.129 more reductions in the expected number of ER visits among individuals with asthma for a composite reduction in one unit NO 2 and one unit PM 2.5 (DiD = -0.129, P < 0.05) from the pre-policy years to the post-policy years. The reductions in NO 2 and PM 2.5 due to policy change estimated by the mediation model are essentially the same as shown in the respective DiD models. Mediation analyses suggested that the effects of GM policy interventions on health improvements were largely due to exposure reductions. Finally, sensitivity analyses with propensity scores produced similar DiD results., Conclusions: This project has produced empirical evidence that air pollution control actions reduced pollution exposures among disadvantaged and susceptible populations. More importantly, our findings suggest that the reductions in air pollution led to health outcome improvements among low-income people with chronic conditions. Our investigation also contributed to scientific methods for assessing the health effects of long-term, large-scale, and complex regulatory actions with routinely collected pollutants and medical claims data. Therefore, the results strongly support both short-term and long-term efforts to improve air quality for all members of society and future studies on the impact of air pollution control policies., (© 2021 Health Effects Institute. All rights reserved.)

The incidence of cathartic colon has been increasing, but satisfactory treatments are still lacking. In order to study the pathological mechanisms of the disorder and identify effective treatment methods, researchers have established different animal models of cathartic colon. This minireview briefly summarizes several common cathartic colon animal models, induced with anthraquinone laxatives such as rhubarb, total anthraquinone, rhein, and emodin, or induced with diphenylmethane laxatives such as phenolphthalein. The advantages and limitations of these models are evaluated and analyzed. We hope that this review will facilitate the selection of suitable models and improve relevant modeling methods. We anticipate the development of more convenient and stable models that can reflect the characteristics of cathartic colon in humans, and serve as useful tools for further studies., Competing Interests: Conflict-of-interest statement: There is no conflict of interest to report., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Over the past decade, researchers and policy-makers have become increasingly interested in regulatory and policy interventions to reduce air pollution concentrations and improve human health. Studies have typically relied on relatively sparse environmental monitoring data that lack the spatial resolution to assess small-area improvements in air quality and health. Few studies have integrated multiple types of measures of an air pollutant into one single modeling framework that combines spatially- and temporally-rich monitoring data. In this paper, we investigated the differential effects of California emissions reduction plan on reducing air pollution between those living in the goods movement corridors (GMC) that are within 500 m of major highways that serve as truck routes to those farther away or adjacent to routes that prohibit trucks. A mixed effects Deletion/Substitution/Addition (D/S/A) machine learning algorithm was developed to model annual pollutant concentrations of nitrogen dioxide (NO 2 ) by taking repeated measures into consideration and by integrating multiple types of NO 2 measurements, including those through government regulatory and research-oriented saturation monitoring into a single modeling framework. Difference-in-difference analysis was conducted to identify whether those living in GMC demonstrated statistically larger reductions in air pollution exposure. The mixed effects D/S/A machine learning modeling result indicated that GMC had 2 ppb greater reductions in NO 2 concentrations from pre- to post-policy period than far away areas. The difference-in-difference analysis demonstrated that the subjects living in GMC experienced statistically significant greater reductions in NO 2 exposure than those living in the far away areas. This study contributes to scientific knowledge by providing empirical evidence that improvements in air quality via the emissions reductions plan policies impacted traffic-related air pollutant concentrations and associated exposures most among low-income Californians with chronic conditions living in GMC. The identified differences in pollutant reductions across different location domains may be applicable to other states or other countries if similar policies are enacted., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the clinical significance of detecting serum level of miR-17 in patients with hepatitis B virus (HBV) induced liver fibrosis., Patients and Methods: A total of 200 HBV patients undergoing liver biopsy in Henan Provincial People's Hospital from June 2016 to December 2018, and 200 healthy subjects during the same period were included. Serum miR-17 level was detected by qRT-PCR. Multivariate Logistic regression analysis was conducted to evaluate independent risk factors of liver fibrosis in HBV patients. Meanwhile, ROC curves were used to assess the value of miR-17 in determining liver fibrosis severity of HBV patients., Results: 200 HBV patients were classified into 4 groups based on the severity of liver fibrosis, including 52 cases in S0-1, 47 cases in S2, 53 cases in S3, and 48 cases in S4. Serum level of miR-17 was lower in healthy subjects than that in HBV patients. In addition, the serum level of miR-17 was negatively correlated with liver fibrosis severity. The relative levels of aspartate aminotransferase (AST), HBV-DNA, albumin (ALB), platelets (PLT), aspartate aminotransferase-to-platelet ratio index (APRI) and miR-17 were the independent factors of advanced liver fibrosis in HBV patients. Serum level of miR-17 exerted a predictive potential in diagnosis of the severity of HBV-induced liver fibrosis., Conclusions: Serum miR-17 level is highly expressed in HBV patients, and negatively correlated with liver fibrosis severity, which could be utilized as a non-invasive hallmark assessing liver fibrosis severity in HBV patients.

Uncontrolled inflammatory response and subsequent cardiomyocytes loss (apoptosis and pyroptosis) are closely involved in sepsis-induced myocardial dysfunction. Our previous study has found that geniposide (GE) can protect the murine hearts against obesity-induced inflammation. However, the effect of GE on sepsis-related cardiac dysfunction is still unknown. Mice were exposed to lipopolysaccharide (LPS) to generate sepsis-induced myocardial dysfunction. And 50 mg/kg GE was used to treat mice for consecutive 7 days. Our results showed that GE treatment significantly improved survival rate and cardiac function, and suppressed myocardial inflammatory response, as well as myocardial loss in LPS-treated mice. Those effects of GE were largely abolished in NOD-like receptor protein 3 (NLRP3)-deficient mice. Further detection revealed that the inhibition of NLRP3 inflammasome activation depended on the reduction of p47phox by GE. GE treatment restored the phosphorylation and activity of AMP-activated protein kinase α (AMPKα) in the hearts of sepsis mice, and knockout of AMPKα abolished the protection of GE against reactive oxygen species (ROS) accumulation, NLRP3 inflammasome activation and cardiomyocytes loss in sepsis mice. In conclusion, our findings revealed that GE activated AMPKα to suppress myocardial ROS accumulation, thus blocking NLRP3 inflammasome-mediated cardiomyocyte apoptosis and pyroptosis and improving cardiac function in mice with sepsis., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Corosolic acid (CRA) is a pentacyclic triterpenoid isolated from Lagerstroemia speciosa. The aim of the present study was to determine whether CRA reduces cardiac remodelling following myocardial infarction (MI) and to elucidate the underlying mechanisms. C57BL/6J mice were randomly divided into control (PBS‑treated) or CRA‑treated groups. After 14 days of pre‑treatment, the mice were subjected to either sham surgery or permanent ligation of the left anterior descending artery. Following surgery, all animals were treated with PBS or CRA (10 or 20 mg/kg/day) for 4 weeks. After 4 weeks, echocardiographic, haemodynamic, gravimetric, histological and biochemical analyses were conducted. The results revealed that, upon MI, mice with CRA treatment exhibited decreased mortality rates, improved ventricular function and attenuated cardiac fibrosis compared with those in control mice. Furthermore, CRA treatment resulted in reduced oxidative stress, inflammation and apoptosis, as well as inhibited the transforming growth factor β1/Smad signalling pathway activation in cardiac tissue. In vitro studies further indicated that inhibition of AMP‑activated protein kinase α (AMPKα) reversed the protective effect of CRA. In conclusion, the study revealed that CRA attenuated MI‑induced cardiac fibrosis and dysfunction through modulation of inflammation and oxidative stress associated with AMPKα.

Aim: In this work, we explored the role of corosolic acid (CRA) during pressure overload-induced cardiac hypertrophy., Methods and Results: Cardiac hypertrophy was induced in mice by aortic banding. Four weeks post-surgery, CRA-treated mice developed blunted cardiac hypertrophy, fibrosis, and dysfunction, and showed increased LC3 II and p-AMPK expression. In line with the in vivo studies, CRA also inhibited the hypertrophic response induced by PE stimulation accompanying with increased LC3 II and p-AMPK expression. It was also found that CRA blunted cardiomyocyte hypertrophy and promoted autophagy in Angiotensin II (Ang II)-treated H9c2 cells. Moreover, to further verify whether CRA inhibits cardiac hypertrophy by the activation of autophagy, blockade of autophagy was achieved by CQ (an inhibitor of the fusion between autophagosomes and lysosomes) or 3-MA (an inhibitor of autophagosome formation). It was found that autophagy inhibition counteracts the protective effect of CRA on cardiac hypertrophy. Interestingly, AMPK knockdown with AMPKα2 siRNA-counteracted LC3 II expression increase and the hypertrophic response inhibition caused by CRA in PE-treated H9c2 cells., Conclusion: These results suggest that CRA may protect against cardiac hypertrophy through regulating AMPK-dependent autophagy., (© 2019 The Author(s).)

Background: Spinal cord infarction (SCI) is rarely caused by vertebral artery dissection (VAD), which is an important cause of posterior circulation stroke in young and middle-aged patients. We report the case of a middle-aged patient without obvious risk factors for atherosclerosis who had SCI from right VAD., Case Presentation: An otherwise healthy 40-year-old man presented with acute right-sided body weakness. Six days earlier, he had experienced posterior neck pain without obvious inducement. Neurologic examination revealed a right Brown-Séquard syndrome. Magnetic resonance imaging (MRI) of the head was normal. Further, cervical spine MRI showed spinal cord infarction (SCI) on the right at the C1-C3 level. Three-dimensional high-resolution MRI (3D HR-MRI) volumetric isotropic turbo spin echo acquisition (VISTA) scan showed evidence of vertebral artery dissection (VAD). The patient was significantly relieved of symptoms and demonstrated negative imaging findings after therapy with anticoagulation (AC) and antiplatelets (AP) for 3 months., Conclusions: The possibility of vertebral artery dissection (VAD) should be considered in the case of young and middle-aged patients without obvious risk factors for atherosclerosis. Furthermore the VISTA black blood sequence plays an important role in the pathological diagnosis of vertebral artery stenosis. Early correct diagnosis and active therapy are crucial to the prognosis.

Myricetin (Myr) is a common plant-derived polyphenol and is well recognized for its multiple activities including antioxidant, anti-inflammation, anticancer, and antidiabetes. Our previous studies indicated that Myr protected mouse heart from lipopolysaccharide and streptozocin-induced injuries. However, it remained to be unclear whether Myr could prevent mouse heart from pressure overload-induced pathological hypertrophy. Wild type (WT) and cardiac Nrf2 knockdown (Nrf2-KD) mice were subjected to aortic banding (AB) surgery and then administered with Myr (200 mg/kg/d) for 6 weeks. Myr significantly alleviated AB-induced cardiac hypertrophy, fibrosis, and cardiac dysfunction in both WT and Nrf2-KD mice. Myr also inhibited phenylephrine- (PE-) induced neonatal rat cardiomyocyte (NRCM) hypertrophy and hypertrophic markers' expression in vitro . Mechanically, Myr markedly increased Nrf2 activity, decreased NF- κ B activity, and inhibited TAK1/p38/JNK1/2 MAPK signaling in WT mouse hearts. We further demonstrated that Myr could inhibit TAK1/p38/JNK1/2 signaling via inhibiting Traf6 ubiquitination and its interaction with TAK1 after Nrf2 knockdown in NRCM. These results strongly suggested that Myr could attenuate pressure overload-induced pathological hypertrophy in vivo and PE-induced NRCM hypertrophy via enhancing Nrf2 activity and inhibiting TAK1/P38/JNK1/2 phosphorylation by regulating Traf6 ubiquitination. Thus, Myr might be a potential strategy for therapy or adjuvant therapy for malignant cardiac hypertrophy., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Hai-han Liao et al.)

We studied mycobionts from advanced seedlings and adult mycorrhizal roots of the terrestrial orchid Arundina graminifolia. Fungi were isolated, identified by ITS sequencing, and tested for their impact on seed germination, protocorm formation, and development of advanced seedlings (emergence of first leaf) in vitro. Among the six fungal species isolated, four were not standard orchid mycorrhizal fungi (Fusarium solani, Cylindrocarpon sp., Acremonium sp., and Phlebiopsis flavidoalba) and did not support germination beyond imbibition and greening of the seeds during a span of 35 days. Over the same time, one Tulasnella species isolated from adult mycorrhiza allowed protocorm formation but not further development. However, another Tulasnella species isolated from advanced seedlings facilitated development to the advanced seedling stage. Our results support (i) the inability of occasional orchid root colonizers to support late seed germination, and (ii) the growing literature showing that fungal associates can change over orchid development. Functionally, we show that mycorrhizal taxa isolated from advanced seedlings can be more efficient than those from adults in supporting germination in some species, leading to recommendations for ex situ orchid conservation.

A novel palladium-catalyzed decarbonylative annulation for the synthesis of phenanthridinones from phthalimides and arynes has been developed. This catalytic system tolerates a broad range of functional groups. Mechanistic experiments demonstrate that the Pd(ii) complex B is the key intermediate, which has been confirmed by X-ray crystallography for the first time.

Oxidative stress and cardiomyocyte apoptosis play critical roles in the development of doxorubicin- (DOX-) induced cardiotoxicity. Our previous study found that geniposide (GE) could inhibit cardiac oxidative stress and apoptosis of cardiomyocytes but its role in DOX-induced heart injury remains unknown. Our study is aimed at investigating whether GE could protect against DOX-induced heart injury. The mice were subjected to a single intraperitoneal injection of DOX (15 mg/kg) to induce cardiomyopathy model. To explore the protective effects, GE was orally given for 10 days. The morphological examination and biochemical analysis were used to evaluate the effects of GE. H9C2 cells were used to verify the protective role of GE in vitro. GE treatment alleviated heart dysfunction and attenuated cardiac oxidative stress and cell loss induced by DOX in vivo and in vitro. GE could activate AMP-activated protein kinase α (AMPK α ) in vivo and in vitro. Moreover, inhibition of AMPK α could abolish the protective effects of GE against DOX-induced oxidative stress and apoptosis. GE could protect against DOX-induced heart injury via activation of AMPK α . GE has therapeutic potential for the treatment of DOX cardiotoxicity.

Background: Fabry disease is rare, and the diagnosis is often delayed. Here, we describe a case of Fabry disease resulting in vasculopathy of the central nervous system. Magnetic resonance (MR) black-blood sequence (three-dimensional T1 volumetric isotropic turbo spin echo acquisition), with the unique advantage of imaging the vascular wall, facilitated a clear identification of the vasculopathy., Case Presentation: A 27-year-old man visited our hospital for the treatment of " double vision 6d." After a series of examinations, the patient was diagnosed with Fabry disease, which caused vasculopathy of the central nervous system. Subsequently, the patient was treated with corticosteroids and his symptoms were attenuated. Two months after the initial treatment, the initial lesion in the vascular vessel disappeared, however, a new lesion appeared. Similarly, four months after the initial treatment, although the previous lesion disappeared, a new lesion appeared., Conclusions: This case highlights that clinicians should use MR black-blood sequence scan in a timely manner in case of young patients with migratory lesions of brain. In case of detection of a vascular lesion in combination with other systemic lesions, the possibility of Fabry disease should be considered.

Radiation-induced damage to the mitochondrial macromolecules and electron transfer chain (ETC), causing the generation of primary and secondary reactive oxygen (ROS) species. The continuous ROS production after radiation will trigger cell oxidative stress and ROS-mediated nucleus apoptosis and autophagy signaling pathways. Scavenging radiation-induced ROS effectively can help mitochondria to maintain their physiological function and relief cells from oxidative stress. Nicotinamide is a critical endogenous antioxidant helping to neutralize ROS in vivo. In this study, we designed and synthetized a novel mitochondrial-targeted dihydronicotinamide (Mito-N) with the help of mitochondrial membrane potential to enter the mitochondria and scavenge ROS. According to experiment results, Mito-N significantly increased cell viability by 30.75% by neutralizing the accumulated ROS and resisting DNA strands breaks after irradiation. Furthermore, the mice survival rate also improved with the treatment of Mito-N, by effectively ameliorating the hematopoietic system infliction under lethal dose irradiation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

There has been mounting evidence for the beneficial effect of green space on mental health among adults, but studies on the same topics are lacking for teens in the US. This study aimed to fill in this research gap by utilizing data from California Health Interview Survey (CHIS) 2011-2014. A total of 81,102 households (composed of 4538 teens and 81,102 adults) were retained for main analyses. Surrounding greenness was assessed by the Normalized Difference Vegetation Index (NDVI) within varying buffers of home residence. Survey logistic regressions accounted for sampling weights and design were conducted to examine the effects of greenness on serious psychological distress (SPD), adjusted for major socio-demographic factors, neighborhood socioeconomic status (SES) and co-respondent's psychological distress level within the same household. An inter-quartile increment of NDVI in 350 m buffer predicted decreased odds of SPDs by 36% in teens (OR = 0.64, 95% CI = [0.46, 0.91]). Mediation analyses revealed that this association remained almost unchanged even after adjusting for social cohesion. The NDVI-SPD association of adults was found to be significant only in the older group (OR = 0.81, 95% CI = [0.68, 0.95]). This study is one of the first population-based US studies extending the epidemiological evidence for benefits of green space on mental health from adults to teens., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The long noncoding RNA (lncRNA) OTUD6B antisense RNA 1 (OTUD6B-AS1) is oriented in an antisense direction to the protein-coding gene OTUD6B on the opposite DNA strand. TCGA database data show that the expression of the lncRNA OTUD6B-AS1 is downregulated and that OTUD6B-AS1 acts as an antioncogene in a variety of tumors. However, the expression and biological functions of the lncRNA OTUD6B-AS1 are still unknown in tumors, including clear cell renal cell carcinoma (ccRCC)., Methods: The expression level of OTUD6B-AS1 was measured in 75 paired human ccRCC tissue and corresponding adjacent normal renal tissue samples. The correlations between the OTUD6B-AS1 expression level and clinicopathological features were evaluated using the chi-square test. The effects of OTUD6B-AS1 on ccRCC cells were determined via MTT assay, clone formation assay, transwell assay, and flow cytometry. Furthermore, the impact of OTUD6B-AS1 overexpression on the activation of the Wnt/β-catenin signaling pathway was investigated. Finally, ACHN cells with OTUD6B-AS1 overexpression were subcutaneously injected into nude mice to evaluate the influence of OTUD6B-AS1 on tumor growth in vivo., Results: In this study, we found that the expression of the lncRNA OTUD6B-AS1 was downregulated in ccRCC tissue samples and that patients with low OTUD6B-AS1 expression had shorter overall survival than patients with high OTUD6B-AS1 expression, which showed that the different expression level of OTUD6B-AS1 indirectly correlated with survival of patients. Lentivirus-mediated OTUD6B-AS1 overexpression significantly decreased the proliferation of ccRCC cells and promoted the apoptosis of the cells. Furthermore, OTUD6B-AS1 overexpression partly inhibited cell migration and invasion. The overexpression of OTUD6B-AS1 decreased the activity of the Wnt/β-catenin pathway and suppressed the expression of epithelial-to-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin and Snail) in ccRCC cells. In addition, compared with the parental ACHN cells, OTUD6B-AS1-overexpressing ACHN cells injected into nude mice exhibited decreased tumor growth in vivo., Conclusions: Taken together, our findings present a road map for targeting the newly identified lncRNA OTUD6B-AS1 to suppress ccRCC progression in cell lines, and these results elucidate a novel potential therapeutic target for ccRCC treatment.

Background: The effect of statin treatment on circulating coenzyme Q10 (CoQ10) has been studied in numerous randomized controlled trails (RCTs). However, whether statin treatment decreases circulating CoQ10 is still controversial., Methods: PubMed, EMBASE, and the Cochrane Library were searched to identify RCTs to investigate the effect of statin treatment on circulating CoQ10. We calculated the pooled standard mean difference (SMD) using a fixed effect model or random effect model to assess the effect of statin treatment on circulating CoQ10. The methodological quality of the studies was determined according to the Cochrane Handbook. Publication bias was evaluated by a funnel plot, the Egger regression test, and the Begg-Mazumdar correlation test., Results: Twelve RCTs with a total of 1776 participants were evaluated. Compared with placebo, statin treatment resulted in a reduction of circulating CoQ10 (SMD, - 2.12; 95% CI, - 3.40 to - 0.84; p = 0.001), which was not associated with the duration of statin treatment (Exp, 1.00; 95% CI, 0.97 to 1.03; p = 0.994). Subgroup analysis demonstrated that both lipophilic statins (SMD, - 1.91; 95% CI, - 3.62 to 0.2; p = 0.017) and hydrophilic statins (SMD, - 2.36; 95% CI, - 4.30 to - 0.42; p = 0.028) decreased circulating CoQ10, and no obvious difference was observed between the two groups (SMD, - 0.20; 95% CI, - 0.208 to 0.618; p = 0.320). In addition, both low-middle intensity statins (SMD, - 2.403; 95% CI, - 3.992 to - 0.813; p < 0.001) and high intensity statins (SMD, - 1.727; 95% CI, - 2.746 to - 0.709; p < 0.001) decreased circulating CoQ10. Meta-regression showed that the effect of statin on decreasing circulating CoQ10 was not closely associated with the duration of statin treatment (Exp, 1.00; 95% CI, 0.97 to 1.03; p = 0.994)., Conclusions: Statin treatment decreased circulating CoQ10 but was not associated with the statin solution, intensity, or treatment time. The findings of this study provide a potential mechanism for statin-associated muscle symptoms (SAMS) and suggest that CoQ10 supplementation may be a promising complementary approach for SAMS.

Whether aucubin could protect myocardial infarction- (MI-) induced cardiac remodeling is not clear. In this study, in a mouse model, cardiac remodeling was induced by left anterior descending coronary artery ligation surgery. Mice were intraperitoneally injected with aucubin (10 mg/kg) 3 days post-MI. Two weeks post-MI, mice in the aucubin treatment group showed decreased mortality, decreased infarct size, and improved cardiac function. Aucubin also decreased cardiac remodeling post-MI. Consistently, aucubin protected cardiomyocytes against hypoxic injury in vitro. Mechanistically, we found that aucubin inhibited the ASK1/JNK signaling. These effects were abolished by the JNK activator. Moreover, we found that the oxidative stress was attenuated in both in vivo aucubin-treated mice heart and in vitro-treated cardiomyocytes, which caused decreased thioredoxin (Trx) consumption, leading to ASK1 forming the inactive complex with Trx. Aucubin increased nNOS-derived NO production in vivo and vitro. The protective effects of aucubin were reversed by the NOS inhibitors L-NAME and L-VINO in vitro. Furthermore, nNOS knockout mice also reversed the protective effects of aucubin on cardiac remodeling. Taken together, aucubin protects against cardiac remodeling post-MI through activation of the nNOS/NO pathway, which subsequently attenuates the ROS production, increases Trx preservation, and leads to inhibition of the ASK1/JNK pathway.

The inflammatory response is involved in the pathogenesis of the most common types of heart disease. Sanguinarine (SAN) has various pharmacological properties such as anti-inflammatory, antioxidant, antibacterial, antitumor, and immune-enhancing properties. However, few studies have investigated the effects of SAN on lipopolysaccharide (LPS)-induced inflammatory and apoptotic responses in H9c2 cardiomyocytes. Therefore, in this study, H9c2 cells were co-treated with SAN and LPS, and the mRNA levels of pro-inflammation markers and the apoptosis rate were measured to clarify the effect of SAN on cardiac inflammation. The underlying mechanism was further investigated by detecting the activation of Toll-like receptor (TLR)4/nuclear factor-κB (NF-κB) signaling pathways. As a result, increased mRNA expression of interleukin (IL)-1β, IL-6, and TNFα induced by LPS was attenuated after SAN treatment; LPS-induced apoptosis of H9c2 cardiomyocytes and cleaved-caspase 8, 9, 3 were all significantly reduced by SAN. Further experiments showed that the beneficial effect of SAN on blocking the inflammation and apoptosis of H9c2 cardiomyocytes induced by LPS was associated with suppression of the TLR4/NF-κB signaling pathway. It was suggested that SAN suppressed the LPS-induced inflammation and apoptosis of H9c2 cardiomyocytes, which may be mediated by inhibition of the TLR4/NF-κB signaling pathway. Thus, SAN may be a feasible therapy to treat sepsis patients with cardiac dysfunction.

Background: Policies protecting children from exposure to secondhand smoke (SHS) may help prevent SHS-related negative health outcomes in children and discourage them from intending to smoke in the future. In this study, we assess the impact of California's 2007 smoke-free vehicle law on changes in middle and high school students' reported exposure to smoking in cars. Secondary aims included assessing the association of student-reported exposure to smoking in vehicles and lifetime asthma diagnosis and future intentions to smoke., Methods: Population-weighted data from the California Student Tobacco Survey and the National Youth Tobacco Survey were used to evaluate California and national trends, respectively. Weighted logistic regression models using California Student Tobacco Survey 2011 data assessed the association between the number of days of exposure to smoking in cars and student-reported lifetime asthma diagnosis as well as intention to smoke in the future., Results: The proportion of California students reporting exposure to smoking in cars in the last 7 days declined <1% annually from 2001 through 2005, but declined 12% annually from 2007 to 2011. National trends did not show comparable declines after 2006. Students reporting exposure to smoking in vehicles were more likely to report having ever been diagnosed with asthma and intending to smoke in the future than students who were not exposed to SHS., Conclusions: These findings support the legislative intent that public policies that are designed to protect children from exposure to smoking in vehicles will yield better adolescent health outcomes and a lower risk of future adolescent cigarette smoking., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Autophagy and poly(ADP-ribose) polymerase 1 (PARP-1) are activated and involved in a series of cell processes under oxidative stress, which is associated with pathogenesis of atherosclerosis. Research on their relationship under oxidative stress has been limited. In this study, we aimed to investigate the activation, relationship, and role of autophagy and PARP-1 in vascular smooth muscle cell (VSMC) death under oxidative stress. This study explored the signal molecule PARP-1 and autophagy in VSMCs using gene silencing and the hydrogen peroxide (H2O2)-stimulated oxidative stress model. We observed that H2O2 could induce autophagy in VSMCs, and the inhibition of autophagy could protect VSMCs against oxidative stress-mediated cell death. Meanwhile, PARP-1 could also be activated by H2O2. Additionally, we analysed the regulatory role of PARP-1 in oxidative stress-mediated autophagy and found that PARP-1 was a novel factor involved in the H2O2-induced autophagy via the AMPK-mTOR pathway. Finally, PARP-1 inhibition protected VSMCs against caspase-dependent apoptosis. These data suggested that PARP-1 played a critical role in H2O2-mediated autophagy and both of them were involved in apoptosis of VSMCs.

Computed tomography (CT) provides the primary diagnostic evidence for traumatic brain injury (TBI), but few positive traumatic findings are discovered in patients with mild TBI. In China, there are no existing criteria for selecting patients with mild TBI to undergo CT, and almost all of these patients undergo cranial CT in the emergency department. This retrospective study was performed to evaluate the necessity of cranial CT among patients with mild TBI, as well as the feasibility of 2 popular criteria (Canadian CT head rule [CCHR] and New Orleans Criteria [NOC]) in China. Patients with mild TBI who underwent cranial CT within 24 hours of the trauma were included in our institute. Two neurosurgeons reviewed the CT images independently to identify positive CT findings. The sensitivity and specificity of CCHR and NOC for positive CT findings related to TBI were analyzed. Finally, this study included 625 patients. Positive CT findings related to TBI were discovered in 13.12% (82/625) of these patients on cranial CT, and 6.88% (43/625) of them were admitted to the hospital for further management. Ultimately, 11 patients (1.76%, 11/625) underwent neurosurgery. In this study, the sensitivities of both the CCHR and NOC were 100%, but the specificity of CCHR was 43.36% and that of NOC was 33.12%. Based on our study, both CCHR and NOC have high sensitivity for the detection of positive CT findings related to head trauma in patients with mild TBI.

WD-40 repeat-containing protein MSI4 (FVE)/MSI4 plays important roles in determining flowering time in Arabidopsis. However, its function is unexplored in wheat. In the present study, coimmunoprecipitation and nanoscale liquid chromatography coupled to MS/MS were used to identify FVE in wheat (TaFVE)-interacting or associated proteins. Altogether 89 differentially expressed proteins showed the same downregulated expression trends as TaFVE in wheat line 5660M. Among them, 62 proteins were further predicted to be involved in the interaction network of TaFVE and 11 proteins have been shown to be potential TaFVE interactors based on curated databases and experimentally determined in other species by the STRING. Both yeast two-hybrid assay and bimolecular fluorescence complementation assay showed that histone deacetylase 6 and histone deacetylase 15 directly interacted with TaFVE. Multiple chromatin-remodelling proteins and polycomb group proteins were also identified and predicted to interact with TaFVE. These results showed that TaFVE directly interacted with multiple proteins to form multiple complexes to regulate spike developmental process, e.g. histone deacetylate, chromatin-remodelling and polycomb repressive complex 2 complexes. In addition, multiple flower development regulation factors (e.g. flowering locus K homology domain, flowering time control protein FPA, FY, flowering time control protein FCA, APETALA 1) involved in floral transition were also identified in the present study. Taken together, these results further elucidate the regulatory functions of TaFVE and help reveal the genetic mechanisms underlying wheat spike differentiation., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Two new platinum(II) complexes 7a and 7b with methyl hydrazinecarbodithioate derivatives of indolin-2-one have been prepared and characterized by single-crystal X-ray diffraction, NMR spectroscopy and mass spectrometry. Antiproliferative activity of the two complexes and their ligands 6a and 6b against HCT-116, MCF-7 and MDA-MB-231 cell lines was determined by the MTS assay. Complexes 7a and 7b exhibited stronger antiproliferative activity against three cell lines than compounds 6a and 6b (IC 50 , 1.89-5.60 versus 6.52-35.13 μM). Moreover, treatment of HCT-116 cells with the complexes resulted in an obvious sub-G1 peak by cell cycle profile analysis, and an increase of cleaved PARP1 and caspases 3, 7, and 9 by immunoblotting analysis. Live cell imaging showed that nucleus shrinkage and condensation started to appear when MCF-7 cells were treated with 7a for 8 h. Fluorescent spectrophotometric analysis revealed that the complexes physically associated with calf thymus DNA. Competitive DNA binding assays uncovered that the complexes non-covalently bind to DNA. Taken together, our results indicated that the two new platinum(II) complexes 7a and 7b non-covalently bind to DNA with high affinity and exhibit cytotoxicity against cancer cells by inducing apoptosis., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The matrix Gla (gamma-carboxyglutamic acid-rich) protein (MGP), a vitamin K-dependent and Gla-containing protein, is a calcification inhibitor that mainly functions in tissue calcification and mineralization. In this study, we obtained the complete cDNA sequence of MGP from the spinyhead croaker (Collichthys lucidus), which we named Cl-MGP. Cl-MGP was 923 bp long with a 384-bp open reading fragment that encoded 127 amino acids. The predicted MGP protein sequence contained a 19-residue hydrophobic signal peptide, suggesting that it possesses secretory characteristics. The Gla domain and the invariant unit ErraEtCedyspC, which has been identified in all known vitamin K-dependent vertebrate proteins, were highly conserved in Cl-MGP, suggesting that it uses the same mechanism to function as the known proteins. An alignment analysis revealed that Cl-MGP had the highest identity with Larimichthys crocea (93%), which had lost five amino acid residues in the C-terminal. A quantitative real-time polymerase chain reaction revealed that Cl-MGP expression was highest in the gill, followed by the cholecyst and spleen, with almost no expression in the blood, muscle, or testes. The high Cl-MGP expression in the gill is similar to that observed in other fish species, but the relatively high expression found in the cholecyst and spleen is not seen in all species. Future studies should investigate the tissue distributions of both mRNA and proteins in different species, in order to understand the function and evolution of MGP in different species.

Determining correlations between certain traits of economic importance constitutes an essential component of selective activities. In this study, our aim was to provide effective indicators for breeding programs of Lateolabrax maculatus, an important aquaculture species in China. We analyzed correlations between 20 morphometric traits and body weight, using correlation and path analyses. The results indicated that the correlations among all 21 traits were highly significant, with the highest correlation coefficient identified between total length and body weight. The path analysis indicated that total length (X 1 ), body width (X 5 ), distance from first dorsal fin origin to anal fin origin (X 10 ), snout length (X 16 ), eye diameter (X 17 ), eye cross (X 18 ), and slanting distance from snout tip to first dorsal fin origin (X 19 ) significantly affected body weight (Y) directly. The following multiple-regression equation was obtained using stepwise multiple-regression analysis: Y = -472.108 + 1.065X 1 + 7.728X 5 + 1.973X 10 - 7.024X 16 - 4.400X 17 - 3.338X 18 + 2.138X 19 , with an adjusted multiple-correlation coefficient of 0.947. Body width had the largest determinant coefficient, as well as the highest positive direct correlation with body weight. At the same time, high indirect effects with six other morphometric traits on L. maculatus body weight, through body width, were identified. Hence, body width could be a key factor that efficiently indicates significant effects on body weight in L. maculatus., Competing Interests: The authors declare no conflict of interest.