Solanesol is a noncyclic terpene alcohol composed of nine isoprene units and it mainly accumulates in solanaceous plants, especially tobacco (Nicotiana tabacum L.). Here, RNA-seq analyses of tobacco leaves, stems, and roots were used to identify solanesol biosynthesis genes. Six 1-deoxy-d-xylulose 5-phosphate synthase, two 1-deoxy-d-xylulose 5-phosphate reductoisomerase, two 2-C-methyl-d-erythritol 4-phosphate cytidylyltransferase, four 4-diphosphocytidyl-2-C-methyl-d-erythritol kinase, two 2-C-methyl-d-erythritol 2,4-cyclodiphosphate synthase, four 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase, two 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase, six isopentenyl diphosphate isomerase, and two solanesyl diphosphate synthase (SPS) genes were identified to be involved in solanesol biosynthesis. Furthermore, the two N. tabacum SPS (NtSPS1 and NtSPS2), which had two conserved aspartate-rich DDxxD domains, were highly homologous with SPS enzymes from other solanaceous plant species. In addition, the solanesol contents of three organs, and leaves from four growing stages, corresponded with the distribution of chlorophyll. Our findings provide a comprehensive evaluation of the correlation between the expression of different biosynthetic genes and the accumulation of solanesol in tobacco.

The Indian meal moth, Plodia interpunctella, poses a significant threat to global agricultural products. Although pheromone-based technologies show promise for P. interpunctella management, limitations like single-sex targeting necessitate exploring complementary strategies. Vegetable-based oils represent a potential alternative, but their efficacy, sex-specificity, and interaction with sex pheromones remain unclear. To answer these questions, we first examined attraction of P. interpunctella female and male adults to ten different vegetable oils, i.e., camellia, corn, olive, peanut, rapeseed, sesame, soybean, sunflower, walnut, and a blended oil (mixture of sunflower seed, rapeseed, soybean, peanut, and sesame oils), in the semi-field conditions. Sesame, olive, and blended oils demonstrated most attractive, capturing significantly more adults compared to other oils. We then evaluated effectiveness of these three attractive oils and their combinations with P. interpunctella sex pheromone in a grain warehouse. Traps baited with these oils captured significantly more females and males compared to control traps without attractants. However, sex pheromone addition did not improve male capture and significantly reduced female capture, suggesting an inhibitory effect. Our findings highlight the potential of blended, olive, or sesame oil trap alone as alternative monitoring and trapping tools for P. interpunctella, delivering novel insights into the development of efficient integrated pest management strategies for stored products.

: Tunnel instability and lining integrity are intimately tied to the creep properties of the surrounding rock. The acquisition of rock mass creep parameters is critical in ascertaining the appropriate timing for lining construction. Nevertheless, creep tests on rock specimens conducted in a controlled setting cannot be straightforwardly extrapolated to rock mass creep analysis. This study performs laboratory-based creep tests on mudstone samples and establishes the corresponding creep constitutive model. Integration of a Mohr-Coulomb element with the Burgers model in series serves to characterise the yield creep behaviour of the rock mass. Additionally, the research outlines a series of 100 orthogonal experiments utilising randomised creep parameters, and formulates a GA-BP neural network inversion model. Employing long-term deformation measurements from the crown and sidewalls of the project site, this study deduces the creep parameters of the mudstone in the investigated tunnel section and examines the prolonged deformation traits of the surrounding rock. Drawing on the deformation traits of the surrounding rock and the forces impacting the primary support and lining structures, this paper evaluates the earliest and latest viable lining casting periods and pinpoints an optimal timing interval for lining implementation. The methodologies employed herein can serve as a benchmark for analogous endeavors internationally.

Spermatogenesis is critical for insect reproduction and is regulated by many different genes. In this study, we found that Forkhead transcription factor Fd59a functions as a key factor in spermatogenesis of Drosophila melanogaster. Fd59a contains a conversed Forkhead domain, and it is clustered to the FoxD subfamily with other FoxD members from some insect and vertebrate species. Mutation in Fd59a caused swelling in the apical region of the testis. More importantly, only a few mature sperm were present in the seminal vesicle of Fd59a mutant flies compared to the control flies, and the fertility of Fd59a2/2 mutant males was significantly lower than that of the control flies. Immunofluorescence staining showed that the homeostasis of testis stem cell niche in Fd59a2/2 mutant and Fd59a RNAi flies was disrupted, and apoptosis of sperm bundles was increased. Furthermore, results from RNA-sequencing and qRT-PCR suggest that Fd59a can regulate expression of genes related to reproductive process and cell death. Taken together, our results indicated that Fd59a plays a key role in the spermatogenesis of Drosophila.

Large-scale hydrological modeling in China is challenging given the sparse meteorological stations and large uncertainties associated with atmospheric forcing data.Here we introduce the development and use of the China Meteorological Assimilation Driving Datasets for the SWAT model (CMADS) in the Heihe River Basin(HRB) for improving hydrologic modeling, by leveraging the datasets from the China Meteorological Administration Land Data Assimilation System (CLDAS)(including climate data from nearly 40000 area encryption stations, 2700 national automatic weather stations, FengYun (FY) 2 satellite and radar stations). CMADS uses the Space Time Multiscale Analysis System (STMAS) to fuse data based on ECWMF ambient field and ensure data accuracy. In addition, compared with CLDAS, CMADS includes relative humidity and climate data of varied resolutions to drive hydrological models such as the Soil and Water Assessment Tool (SWAT) model. Here, we compared climate data from CMADS, Climate Forecast System Reanalysis (CFSR) and traditional weather station (TWS) climate forcing data and evaluatedtheir applicability for driving large scale hydrologic modeling with SWAT. In general, CMADS has higher accuracy than CFRS when evaluated against observations at TWS; CMADS also provides spatially continuous climate field to drive distributed hydrologic models, which is an important advantage over TWS climate data, particular in regions with sparse weather stations. Therefore, SWAT model simulations driven with CMADS and TWS achieved similar performances in terms of monthly and daily stream flow simulations, and both of them outperformed CFRS. For example, for the three hydrological stations (Ying Luoxia, Qilian Mountain, and ZhaMasheke) in the HRB at the monthly and daily Nash-Sutcliffe efficiency ranges of 0.75-0.95 and 0.58-0.78, respectively, which are much higher than corresponding efficiency statistics achieved with CFSR (monthly: 0.32-0.49 and daily: 0.26 – 0.45). The CMADS dataset is available free of charge and is expected to a valuable addition to the existing climate reanalysis datasets for deriving distributed hydrologic modeling in China and other countries in East Asia.

MicroRNAs are small non-coding RNAs, which contribute to the regulation of many physiolog-ical and pathological processes. Conventionally, miRNAs perform their activity in the cyto-plasm, where they regulate gene expression by interacting in a sequence-specific manner with mature messenger RNAs. Recent studies point to the presence of mature miRNAs in the nucleus. This review summarizes current findings regarding the molecular activities of nuclear miRNAs. These molecules can regulate gene expression at the transcriptional level by directly binding DNA on the promoter or the enhancer of regulated genes. MiRNAs recruit to these regions dif-ferent protein complexes, resulting both in activation or repression of transcription, through a number of molecular mechanisms. Haematopoiesis is presented as a paradigmatic biological process whereby nuclear miRNAs possess a relevant regulatory role. Nuclear miRNAs may af-fect gene expression also acting on nuclear mRNA processing and on the biogenesis of miRNA themselves by regulating pri-miRNA maturation. Overall, nuclear miRNAs are biologically ac-tive molecules that can be critical for the fine tuning of gene expression and deserve further studies in a number of physiological and pathological conditions

Abstract: Background: In 2021, two randomized controlled trials (RCTs), TheraP and VISION, demonstrated that 177Lu-PSMA-617 as monotherapy was more effective for enhancing the decline of PSA than the comparator third-line treatments. Methods: Our review summarizes new RCTs that add to the use of radioligand therapy (RLT) for patients with high-risk prostate cancer (PCa). Results: Five past and present RCTs include 1139 patients. A RCT, ENZA-p, studied first-line treatment of patients with metastatic castration-resistant PCa (mCRPC). A combination of enzalutamide (ENZA) and 177Lu-PSMA-617 gave longer progression-free survival than ENZA as monotherapy. Other RCTs of patients with mCRPC, including the PSMAfore, and SPLASH trials, showed 177Lu-PSMA-617 as second-line treatment gave better progression-free survival than androgen receptor pathway inhibitors (combined p value 6 x 10-8). Conclusion: Patients with PCa may gain if they are given PSMA-RLT early in the treatment of PCa and as part of combination therapies.

Energy metabolism regulates the proliferation of stem cells by regulating energy production and the production of substrates through biosynthetic pathways. It is an important target for cell regulation and stem cell applications, and is crucial for determining the pluripotency and cell fate of stem cells. In this context, this article focuses on reviewing the latest research progress on the association between glucose metabolism, amino acid metabolism, fatty acid metabolism, and mitophagy with stem cell function, elucidating how key energy metabolism pathways affect stem cell function by regulating signal transduction and epigenetic modifications. In this review, we discuss the key factors affecting energy metabolism and their association with stem cell function. The integration of energy metabolism and stem cell fate regulation will open up a new path for future regenerative medicine practices.

Phosphorus deficiency highly interferes with plant growth and development. Plants respond to the persistent P deficiency by coordinating the expression of genes involved in the alleviation of the stress. Promoters of phosphate transporter genes are of great choice for the development of genetically modified plants with enhanced phosphate uptake abilities, which improve crop yields in phosphate-deficient soils. In our previous study, the sugarcane phosphate transporter PHT1;2 gene, showed a significantly high expression under salinity stress. In this study, the Erianthus arundinaceus EaPHT1;2 gene was isolated and characterized using various in-silico tools. The deduced 542 amino acid residues have 10 transmembrane domains, with a molecular weight and isoelectric point of 58.9 kDa and 9.80, respectively. They displayed 71–96% similarity with Arabidopsis thaliana, Zea mays, and Saccharum hybrid. To elucidate the function of the 5’ regulatory region, the 1.1kb promoter was isolated and validated in tobacco transgenics under Pi stress. The EaPHT1;2 promoter activity was detected using the β-glucuronidase (GUS) assay. While the EaPHT1;2 promoter showed 3 to 4.2-fold higher expression than the most widely used CaMV35S promoter. The 5’ deletion analysis with and without 5’UTR regions, revealed that a small size 374 bp fragment with the highest promoter activity among 5′ truncated fragments, which was 2.7 and 4.2 times higher than the well-used CaMV35S promoter under normal and Pi-deprivation conditions, respectively. The strong and short promoter of EaPHT1;2 with 374 bp showed significant expression in low Pi-stress conditions and it could be a valuable source for the development of stress-tolerant transgenic crops

The aim of the scoping review was to map out studies that compared the effect of smoking tobacco and smokeless tobacco on periodontal health. The review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) framework. The search for articles was conducted in five electronic databases namely: Scopus, CINAHL, Web of Science, Medline, and PubMed. The search yielded two eligible articles for full-text screening. The two studies were cross-sectional in design, conducted in India and they both used bivariate analysis for comparison of the effects of tobacco smoking and the use of smokeless tobacco on the health of the periodontium without adjusting for confounders. The two studies used 10 measures to assess the health of the periodontium namely: Periodontal probing depth, clinical attachment level, gingival index, and periodontal index, plaque index score, debris index score, calculus index score, gingival inflammation, bleeding on probing and pocket depth. Periodontal probing depth, periodontal index, calculus index score and pocket depth worse for tobacco smoking when compared with smokeless tobacco users. Both studies seem to concur on worse pocket depths for tobacco smokers than for users of smokeless tobacco.

On Feb. 6^th, 2020, FDA implemented the enforcement priorities against all flavored, cartridge-based e-cigarettes other than menthol and tobacco flavors. This ban undermined the products’ attraction to vapers, so e-cigarette manufacturers added flavorants of other attractive flavors into tobacco-flavored e-cigarettes and re-established attractions. Both the sales of e-cigarettes and posts on social media suggested that the manufacturers’ strategies are likely “successful”. The re-established attraction causes not only a public health issue, but also threats to the health of individual vapers. Research has shown an increase in toxicity associated with the flavorants commonly used in flavored e-cigarettes that are likely added in tobacco-flavored e-cigarettes based on tobacco-derived and synthetic tobacco free nicotine, and these other flavors are associated with higher clinical symptoms not often induced by only natural traditional tobacco flavors. The additional health risks posed by the flavorants are pronounced even without considering the interactions of toxicology of the different tobacco flavorants, and more research should be done to understand the health risks thoroughly and to take proper actions accordingly for regulation of these emerging products.

Trichoderma spp. are widely used in plant disease control as biocontrol agents. Inducing plant disease resistance is an important biocontrol mechanism of Trichoderma. It is of great significance to explore the factors involved in the surface recognition and interaction of Trichoderma with plants. Hydrophobin is a small molecular protein rich in cysteine in higher filamentous fungi and has been found to participate in the morphogenesis and interaction of fungi with other organisms. In this study, the type II hydrophobic protein-coding gene Thfb6 from T. harzianum TH33 was cloned and heterologously expressed in Escherichia coli BL21 (DE3). The purified recombinant protein Thfb6 induced a hypersensitive response in tobacco leaves, a burst of reactive oxygen species, and an accumulation of callose, phenolic substances, and lignin in tobacco, indicating that Thfb6 can induce an early defense reaction in tobacco. Thfb6 also enhanced the systemic resistance of tobacco against tobacco mosaic virus. The rate of lesion number reduction by treatment with Thfb6 could be up to 36.02%. Thfb6 increased the activity of tobacco defense-related enzymes, including phenylalanine ammonia-lyase (PAL), polyphenol oxidase, and peroxidase, which were all more than three times the control after 3–5 days post treatment of Thfb6. The transcription of resistance-related genes, including the PAL gene, non-expresser of pathogenesis-related gene1 (NPR1), and basic pathogenesis-related gene 1 (PR1-b), were upregulated after Thfb6 treatment. The relative expression levels of the PAL and NPR1 genes were highest on the third and fourth days after Thfb6 treatment, at 5.5 times and 8.3 times that of the control, respectively. The relative expression level of PR1 on the sixth day after Thfb6 treatment was 5.3 times that of the control. These results indicate that the improvement of defense-related enzyme activity and the induced expression of disease-resistance-related genes were the main mechanisms by which Thfb6 induced systemic resistance in tobacco.

Nowadays the relationship between planning land use and actual land use is not so clear in general. A lot of efforts have been put in the failures of regulation for the expansion of construction land. However, it still lacks an integrated approach to study the effectiveness of land use regulation in terms of different land use types. Furthermore, the existing evaluation of land use plan mainly focuses on a general level, a detailed research on the regulation effectiveness of each construction land use type is absent. Therefore, this research tries to evaluate regulation effectiveness of land use plan, which takes Cangwu country, Guangxi Province as an example. The finding by analysis is that the total area of construction land expansion was about 3494.73 ha, nearly 1.1 times of the plan quota. Moreover, the effectiveness differs greatly in various construction land use types. Town, industrial/mining sites can be well regulated through the quota of land use plan. While, the quota regulation system is not as effective for other type of construction land. Thus, we suggest to improve the regulation effectiveness of construction land through different plan instruments.

Tobacco Free Nicotine (TFN) Electronic Nicotine Delivery Systems (ENDS) are yet to be classified as tobacco products; consequently, there is ambiguity over whether Food and Drug Administration (FDA) regulatory authority can be extended to include TFN e-cigarettes. In recent years, a more significant number of e-cigarette companies have been manufacturing TFN-containing e-cigarettes and e-liquids to circumvent FDA regulations. While studies have shown that aerosols generated from tobacco-derived nicotine-containing e-cigarettes contain significant Reactive Oxygen Species (ROS) levels, no comparison studies have been conducted using TFN e-cigarettes. This study uses a single puff aerosol generator to aerosolize TFN and tobacco-derived nicotine-containing vape-products and subsequently involves semi-quantifying ROS generated by these vape products in H2O2 equivalents. We found that the differences between ROS levels generated from TFN and tobacco-derived nicotine-containing vape products vary by flavor. TFN tobacco flavors and fruit flavors are more toxic in terms of ROS generation than menthol/ice and drink/beverage flavored products using TFN. The type of salt nicotine used in vape products, TFN or tobacco-derived nicotine, impacts the level of ROS generated from flavored vape products. Thus, a better understanding of the type of salt nicotine used in e-cigarettes (tobacco-derived or synthetic), has modulating effect on lung oxidative stress.

Abstract: Transcription factors are crucial pre-transcriptional regulatory mechanisms that can modulate the expression of downstream genes by binding to their promoter regions. DOF (DNA binding with One Finger) proteins are a unique class of transcription factors with extensive roles in plant growth and development. Our previous research indicated a decrease in iron content in chlorotic bamboo leaves. However, to our knowledge, genes related to iron metabolism pathways in bamboo species have not yet been studied. Therefore, in the current study, we identified iron metabolism-related (IMR) genes in bamboo and determined the transcription factors that significantly influence them. Among these, DOFs were found to have widespread effects and potentially significant impacts on their expression. We identified specific DOF members in Dendrocalamus latiflorus with binding abilities through homology with Arabidopsis DOF proteins, and established connections between some of these members and IMR genes using RNA-seq data. Additionally, molecular docking confirmed the binding interactions between these DlDOFs and the DOF binding sites in the promoter regions of IMR genes. The co-expression relationship between the two gene sets was further validated using q-PCR experiments. This study paves the way for research into iron metabolism pathways in bamboo and lays the foundation for understanding the role of DOF transcription factors in D. latiflorus.

Background: Exposure to environmental tobacco smoke (ETS) presents substantial health risks for pregnant women and newborn infants. Measurements of ETS include invasive and expensive biochemical tests as well as less invasive and lower-cost self-reported exposure and avoidance measures. Better understanding of self-report measures will help to select ETS assessments for evaluation. Methods: This analysis was conducted within the context of a tailored video intervention to reduce tobacco smoking and ETS exposure during pregnancy and after delivery, in the control group sample of 147 nonsmoking women. Measurements of salivary cotinine concentration, self-reported ETS exposure and avoidance behaviors were captured at 32 weeks gestation and 6 months postpartum. Results: Salivary cotinine concentration was significantly related to ETS avoidance among pregnant nonsmokers at 32 weeks gestation, but not ETS exposure. At 6 months postpartum, both the reported ETS exposure of the infant and maternal avoidance behaviors to reduce her infant’s exposure were associated with the infant’s salivary cotinine concentration. At 32 weeks gestation and 6 months postpartum, avoidance behaviors decreased as exposure increased. Discussion: This study suggests that for nonsmoking women during pregnancy, report of tobacco smoke avoidance is more valid than report of exposure. After delivery, self-reported ETS exposure or avoidance are associated with each other and biochemical measurement of salivary cotinine. These results provide researchers and clinicians with evidence to support inclusion of avoidance behaviors in the selection of ETS measure.

Duke University was founded in 1930 primarily due to funds generated from James B. Duke’s tobacco business. Duke achieved great financial wealth primarily due to the early application of machine rolled cigarettes, as opposed to hand rolled. This early adoption of technology allowed Duke Tobacco to out-produce other companies still selling hand rolled cigarettes. By making smoking more inexpensive and easier than pipe smoking, the cigarette formed the foundation for nicotine addiction in the 1900s, generating huge profits for the tobacco industry. At the time Duke University was founded, little was known about the connection between nicotine, cigarettes, and respiratory diseases such as emphysema and lung cancer. Through James Duke’s philanthropy, the devastating harm from cigarettes has been mitigated in part through the founding of one of the world’s most prominent medical centers and research universities.

The p53 tumor suppressor protein shows antiviral activity. The replication of viruses is also antagonized by interferons (IFNs) – cytokines, which control immunity genes by the STAT transcription factors. The best studied interferons belong to type I (e.g. IFNα) and type II (IFNγ) groups. IFNα and IFNγ both induce activating phosphorylation of STAT1 on Tyr701. Previously, we noticed that p53 activates SOCS1, which is a negative regulator of STAT1 phosphorylation. Thus, we hypothesized that p53 by activating SOCS1 expression reduces phosphorylation of STAT1 and attenuates activation of genes stimulated either by IFNα or IFNγ. To test this hypothesis, we exposed p53-proficient and p53-deficient cells to strong p53 activators, and either to IFNα or IFNγ. Subsequently, we estimated the phosphorylation status of STAT1 and the expression of genes regulated by either of these cytokines. Strong activation of p53 reduced the phosphorylation of STAT1 on Tyr701, however surprisingly it did not lead to reduced expression of most tested interferon-stimulated genes. On contrary, p53 and IFNγ synergized in the activation of CASP1, IFIT1 and IFIT3 genes. We conclude that the interactions between p53 and interferon-activated pathways are more complicated than initially expected, but the apparent cooperation between p53 and IFNγ deserves further studies.

Smokeless tobacco (ST) products vary significantly in their oral carcinogenicity. Much is known about the differences in chemical, but not bacterial, constituents of these products. In this study, we explore the composition and function of the bacteriome in ST products from 4 countries using q-PCR and 16S rRNA-based next generation sequencing. The bacterial load (16S rRNA copies/gram) was lowest in Swedish snus (3.4E+6) and highest in Yemeni shammah (6.6E+11). A total of 491 species-level taxa, many of which are potentially novel, belonging to 178 genera and 11 phyla were identified. Species richness and diversity were highest for Swedish snus and lowest for Yemeni shammah. Bacillus, Paenibacillus, and Oceanobacillus spp. were the most abundant in American snuff; species of Pseudomonas, Massilia, Propionibacterium, Puniceispirillum and Gloeothece predominated in Swedish snus. In Sudanese toombak, Facklamia, Desemzia, Atopostipes and Lysinibacillus spp. accounted for the majority of the bacteriome. Yemeni shammah exclusively contained Bacillus spp. PICRUSt functional prediction showed that genes encoding cadmium/zinc and nickel transport systems were enriched in the presumptively “high carcinogenicity” products. The bacteriome of ST products thus differed qualitatively, quantitatively and functionally. The relevance of these differences, particularly with respect to nickel and cadmium, to oral carcinogenesis warrants further investigation.

The positional cloning of single nucleotide polymorphisms (SNPs) of the neutrophil cytosolic factor 1 (Ncf1) gene, advocating that a low oxidative burst drives autoimmune disease, demands an understanding of the underlying molecular causes. A cellular target could be T cells, which have been shown to be regulated by reactive oxygen species (ROS). However, the pathways by which ROS mediate T cell signaling remain unclear. The adaptor molecule linker for activation of T cells (LAT) is essential for coupling T cell receptor-mediated antigen recognition to downstream responses, and it contains several cysteine residues that have previously been suggested to be involved in redox regulation. To address the possibility that ROS regulate T cell-dependent inflammation through LAT, we established a mouse strain with cysteine-to-serine mutations at positions 120 and 172 (LATSS). We found that redox regulation of LAT through C120 and C172 mediate its localization and phosphorylation. LATSS mice had reduced numbers of double-positive thymocytes and naïve peripheral T cells. Importantly, redox insensitivity of LAT enhanced T cell-dependent autoimmune inflammation in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). This effect was reversed on an NCF1-mutated (NCF1m1j), ROS-deficient, background. Overall, our data shows that LAT is redox-regulated, acts to repress T cell activation, and is targeted by ROS induced by NCF1 in antigen-presenting cells (APCs).

Promoting green development has become an important way to optimize the ecological and economic structure and promote sustainable development. The Yangtze River Economic Belt is an important economic corridor in China, and it remains to be examined whether the implementation of environmental regulations has enhanced the green total factor productivity (GTFP) of cities. This paper calculates the green total factor productivity of 107 cities within the Yangtze River Economic Belt by using the super-efficient SBM model and the GML index with Chinese city panel data from 2007-2019 and measures the intensity of environmental regulations through textual analysis. The bidirectional fixed-effects model constructed in this paper suggests an inverted U-shaped relationship between environmental regulation and GTFP, which is confirmed by a series of robustness tests. Green technology innovation and advanced industrial structure play a mechanism role in this. In regions with lower levels of green technology and industrial structure, the inverted U-shaped relationship between environmental regulation and green total factor productivity is more significant. In addition, the phenomenon of GTFP rising and then falling because of environmental regulation is more obvious in cities in the middle and upper reaches of the Yangtze River and outside the urban agglomerations. Therefore, when formulating environmental regulation policies, it is necessary to balance the relationship between economic development and environmental protection and harmonize the environment and economic development of the entire Yangtze River Basin.

Tobacco smoke is an environmental mixture including polycyclic aromatic hydrocarbons and may interfere in endocrine system as an EDC in aging. Thus, we performed a molecular epidemiological approach with in-depth biological monitoring of combustible cigarette smoking among adolescents and adults in South Korea (N=620) with exposure biomarkers, i.e., exhaled CO, urinary cotinine, t,t-muconic acid (TTMA), malondialdehyde (MDA), and obtained information of their lifestyle and tobacco addiction status. We also diagnosed the genetic polymorphisms on the 96 SNPs for tobacco-metabolism, -addiction, and expression differences and compared mtDNA abnormalities in buccal and blood cells. As results, there were positive associations among the above tobacco exposure biomarkers. Man or youth smokers showed high frequency in some of mtDNA alteration, such as ‘SNPs for inconsistent bases between buccal and blood cells’. Among the SNPs, the polymorphisms on SULT1A1, DRD2, and ADH1B were related to multi-exposure biomarkers. Interestingly, youth showed similar levels of urinary TTMA and MDA to adults, although their pack-year was approx. 1/6 volume of that of adults. We also observed the negative association between urinary MDA levels and the growth rate in the adolescents (p<0.05). In conclusion, the present biological monitoring provides high susceptible population, i.e., adolescents rather than adults, and reliable genetic factors affecting tobacco exposure. The inferred environment-gene-gene interaction suggests tobacco smoking accelerats aging in adolescents as an EDC.

Fungi are rich sources of secondary metabolites of agrochemical, pharmaceutical and food importances, such as mycotoxins, antibiotics and antitumor agents. Secondary metabolites play vital roles in fungal pathogenesis, growth and development, oxidative status modulation, and adaptation/resistance to various environmental stresses. LaeA contains an S-adenosylmethionine binding site and displays methyltransferase activity. The members of velvet proteins include VeA, VelB, VelC, VelD and VosA, for each member with a velvet domain. LaeA and velvet proteins can form multimeric complexes such as VosA-VelB and VelB-VeA-LaeA. They belong to global regulators and are mainly impacted by light. One of their most important functions is to regulate gene expression that are responsible for secondary metabolite biosynthesis. The aim of this mini-review is to represent the newest cognition on the biosynthetic regulation of mycotoxins and other fungal secondary metabolites by LaeA and velvet proteins. In most cases, LaeA and velvet proteins positively regulated production of fungal secondary metabolites. The regulated fungal species mainly belong to the toxigenic fungi from the genera of Alternaria, Aspergillus, Botrytis, Fusarium, Magnaporthe, Monascus, and Penicillium for the production of mycotoxins. We can control secondary metabolite production to inhibit the production of harmful mycotoxins while promoting the production of useful metabolites by global regulation of LaeA and velvet proteins in fungi. Furthermore, the regulation by LaeA and velvet proteins should be a practical strategy in activating silent biosynthetic gene clusters (BGCs) in fungi to obtain previously undiscovered metabolites.

This article explores the significant parallels between big tobacco companies and major social networking sites regarding their influence on public health and society. While acknowledging the fundamental differences in their products and services, the paper scrutinises both industries through five primary lenses: addiction, misinformation, lack of regulation, harm to public health, and youth targeting. Both industries exhibit addictive characteristics, have faced criticism for the spread of misinformation, operate with limited regulation and transparency, and have raised concerns about targeting young demographics. Moreover, the potential harm to public health is a significant concern, with tobacco leading to well-established physical health issues. At the same time, excessive social media use has been linked to psychological harm, particularly among young users. The comparison underscores the necessity for greater regulation and oversight of social media companies, highlighting the urgent need for more comprehensive policies to mitigate potential harm and safeguard public health in the digital age.

Measuring the impact of land use regulation on the land market involves identifying and classifying relevant impact factors related to the land market. The objective of this study was to identify land market impact factors in the context of the introduction of land use regulation in Nepal. A desktop review was carried out to identify preliminary set of impact factors, which were reclassified through intuitive analysis based on the degree of thematic closeness. Perspective-based impact factors were identified through the qualitative analysis of primary data collected through semi-structured interviews with the Nepalese land market stakeholders. These independently derived impact factors were compared with the desktop literature review impact factors resulting in fourteen land market impact factors across four dimensions, including transaction cost, valuation, mortgage availability, taxation, and compensation across the economic dimension; lot size, subdivision restrictions, and coordination across the institutional dimension; awareness, expectation and proximity across the social dimension; and risk reduction, quality of residential land, and suitability of zoning classification across the environmental dimension. There was significant overlap and commonality across factors identified from both the literature review and semi-structured interviews. The land market impact factors determined in the study may be adapted and generalized across other countries and could be utilized to better understand the impacts of land policy decisions on urban planning and development. Further research is recommended on the process to operationalize the use of these factors to quantify the impact of land use regulation on different land markets.

Background: Prior to the federal law passed in late 2019, many states passed an increased age of sale law prohibiting youth under age 21 (or Tobacco 21) from purchasing tobacco products and e-cigarettes. Although previous research has documented tobacco retail sales violations, fewer studies have examined age verification and illegal tobacco sales in the context of Tobacco 21 or in repeated purchase attempts in various settings. Methods: In this study conducted between 2019 and 2022, buyers aged 18 to 20 years made repeated unsupervised purchase attempts of cigarettes, cigars, e-cigarettes, tobacco-free nicotine pouches and/or smokeless tobacco in store visits to over 180 tobacco or vape retailers in New Jersey, New York City, and Pitt County, North Carolina. Buyers documented whether they were asked for identification and whether they were able to successfully purchase a tobacco or nicotine product at each visit. Results: The primary outcome will be the percent of retailers that checked buyers’ identification at store visits and the precent of visits that resulted in a successful underage tobacco product purchase. We will aim to compare the results across time periods and study sites while controlling for other factors (including repeated visits). Conclusion: These results will be beneficial to designing compliance check inspections and/or interventions that reduce youth access to tobacco.

Providing data on usage patterns is key to assessing the reduced-risk potential of novel tobacco and nicotine products at a population level. We performed a nationwide cross-sectional survey of the general population in Japan to assess usage patterns after the introduction of tobacco heating products (THPs). Eligible participants were Japanese residents, aged 20 years or older who consented to complete the survey. Individuals living in institutions were excluded. A three-stage probability sampling method was applied that was geographically stratified by street blocks proportionate to population density. Respondents self-reported patterns of product use and reasons for THP use. Complete responses were available from 5,306 individuals, of whom 933.5 (17.6%) were current users, 984.2 (18.5%) were former users and 3388.4 (63.9%) were never users of tobacco products. Cigarettes were used by 14.6% of current tobacco product users and THPs by 5.3%. Cigarettes and THPs were used exclusively by 64.5% and 12.2%, respectively, and both were used by 12.7%. The most common reasons reported for THP use were perceived reduction in harm to self and others compared to cigarettes. While the prevalence of cigarette use in Japan is decreasing, THPs seem to be increasingly used as long-term alternatives to cigarette smoking.

The additional sex combs-like (ASXL) family, a mammalian homolog of the additional sex combs (Asx) of Drosophila, has been implicated in transcriptional regulation via chromatin modifications. Abnormal expression of ASXL family genes leads to myelodysplastic syndromes and various types of leukemia. De novo mutation of these genes also causes developmental disorders. Genes in this family and neighbor genes are evolutionary conserved in humans and mice. This review provides a comprehensive summary of epigenetic regulations associated with ASXL family genes. Their expression is commonly regulated by DNA methylation at CpG islands preceding transcription starting sites. Their proteins primarily engage in histone tail modifications through interactions with chromatin regulators (PRC2, trithorax complex, PR-DUB, SRC1, HP1α, and BET proteins), and with transcription factors, including nuclear hormone receptors (RAR, PPAR, ER, and LXR). Recently, non-coding RNAs have been identified following mutations in the ASXL1 or ASXL3 gene, along with circular ASXLs and microRNAs that regulate ASXL1 expression. The diverse epigenetic regulations linked to ASXL family genes collectively contribute to tumor suppression and developmental processes. Our understanding of ASXL-regulated epigenetics may provide insights into the development of therapeutic epigenetic drugs.

The retinoblastoma (RB) transcriptional corepressor 1 (RB1) is a critical tumor suppressor gene, governing diverse cellular processes implicated in cancer biology. Dysregulation or deletion in RB1 contributes to the development and progression of various cancers, making it a prime target for therapeutic intervention. RB1's canonical function in cell cycle control and DNA repair mechanisms underscores its significance in restraining aberrant cell growth and maintaining genomic stability. Understanding the complex interplay between RB1 and cellular pathways is beneficial to fully elucidate its tumor-suppressive role across different cancer types and for therapeutic development. As a result, investigating vulnerabilities arising from RB1 deletion-associated mechanisms offers promising avenues for targeted therapy. Recently, several findings highlighted multiple methods as a promising strategy for combating tumor growth driven by RB1 loss, offering potential clinical benefits in various cancer types. This review summarizes the multifaceted role of RB1 in cancer biology and its implications for targeted therapy.

Flavonoids are major secondary metabolites in plants, which play important roles in maintaining the cellular redox balance in cells. Chalcone synthase (CHS) is the key enzyme in the flavonoids biosynthesis pathway, and has been proved to monitor the changes to drought stress tolerance. In this work, we overexpressed a CHS gene in tobacco (Nicotiana tabacum). The transgenic tobacco plants were more tolerant than the control plants to drought stress. The transcription levels of the key genes involved in the flavonoids pathway and the contents of seven flavonoids were also significantly raised in the transgenic tobacco plants. In addition, overexpression of the CHS gene lead to a lower concentration of the oxidative stress product malondialdehyde. Overall, the NtCHS gene studied in this work was considered as a candidate gene for genetic engineering to enhance drought tolerance of plants and improve response to oxidative stress.

mRNA-lipid nanoparticle (LNP) medicinal products can be considered a platform technology because the development process is similar for different diseases and conditions, with similar noncoding mRNA sequences and lipid nanoparticles and essentially unchanged manufacturing and analytical methods utilised often for different products. It is critical not to lose the momentum built using the platform approach during the development, regulatory approval and rollout of vaccines for SARS-CoV-2 and its variants. This Review proposes a set of modifications to existing regulatory requirements for mRNA products, based on a platform perspective for quality, manufacturing, preclinical and clinical data. For the first time, we address development and potential regulatory requirements when the mRNA sequences and LNP composition vary in different products as well. In addition, we propose considerations for self-amplifying mRNA, individualised oncology mRNA products and mRNA therapeutics. Providing a predictable development pathway for academic and commercial groups, so they can know in detail what product characterisation and data are required to develop a dossier for regulatory submission, has many potential benefits. These include reduced development and regulatory costs; faster consumer/patient access and more agile development of products in the face of pandemics; and for rare diseases where alternatives may not exist or to increase survival and the quality of life in cancer patients. Therefore, achieving consensus around platform approaches is both urgent and important. This approach with mRNA can be a template for similar platform frameworks for other therapeutics and vaccines to enable more efficient development and regulatory review.

Cysteine and its derivatives, including H2S, can influence bacterial virulence and sensitivity to antibiotics. In minimal sulfate media, H2S is generated under stress to prevent excess cysteine and, together with incorporation into glutathione and export into the medium, is a mechanism of cysteine homeostasis. Here, we studied the features of cysteine homeostasis in LB medium, where the main source of sulfur is cystine, whose import can create excess cysteine inside cells. We used mutants in the mechanisms of cysteine homeostasis and a set of microbiological and biochemical methods, including real-time monitoring of sulfide and oxygen, determination of cysteine and glutathione, and expression of the Fur, OxyR, and SOS regulons genes. During normal growth, the parental strain generated H2S when switching respiration to another substrate. The mutations affected the onset time, intensity and duration of H2S production, cysteine and glutathione levels, bacterial growth and respiration rates, and induction of defense systems. Exposure to chloramphenicol and high doses of ciprofloxacin increased cysteine content and GSH synthesis. A high inverse relationship between log CFU/ml and bacterial growth rate before ciprofloxacin addition was revealed. The study points to the important role of maintaining cysteine homeostasis during normal growth and antibiotic exposure in LB medium.

The paper examines the various uncertainties encountered in high-frequency trading (HFT) environments and delves into the multiple challenges faced by HFT firms in navigating the Dodd-Frank Wall Street Reform and Consumer Protection Act (referred to as the "Dodd-Frank Act"), particularly during the initial stages of its enactment. These challenges include the ambiguity surrounding the definition of HFT, the lack of clarity regarding regulatory requirements and boundaries, inconsistencies in enforcement resulting from deviations in understanding the content, and the absence of detailed descriptions of the Act’s provisions. These hurdles significantly impact not only the daily operations of HFT firms but also pose higher demands on their long-term strategic planning and risk management. Drawing upon the Data, Information, Knowledge, Wisdom, and Purpose (DIKWP) model, this study employs an innovative analytical framework. Through the comprehensive application of conceptual space, cognitive space, and semantic space, it provides a systematic methodology for identifying and analyzing the aforementioned issues. This approach not only aids firms in better comprehending and adhering to complex regulatory requirements but also enables them to explore new business opportunities and competitive advantages while ensuring compliance.

Gene regulation is vital for cellular function and homeostasis, involving diverse mechanisms controlling specific gene products and contributing to tissue-specific gene expression. Dysregulation leads to diseases, emphasizing the need for understanding these mechanisms. Non-coding regions, notably enhancers and super-enhancers (SEs), act as crucial gene regulators, orchestrating transcriptional activity via transcription factors (TFs). SEs, with high activity, are pivotal in cell identity and disease progression. Current computational approaches focus on individual regulators like TFs and miRNAs, neglecting SE interactions. We emphasize incorporating SEs into models to enhance understanding. Experimental studies have recently linked miRNAs and TFs to SEs. Chromatin immunoprecipitation followed by sequencing (ChIP-Seq) provides valuable SE information. In this review, we categorize computational methods leveraging TF and miRNA data into three areas and explore challenges integrating enhancers/SEs. These include unraveling indirect regulatory networks, identifying network motifs, and enriching pathway identification by dissecting gene regulators, including SEs. We hypothesize that addressing these challenges will enhance our understanding of gene regulation, aiding in identifying therapeutic targets and disease biomarkers. We believe that understanding the role of ChIP-Seq data in predicting the effect of miRNA on gene regulation is crucial to construct statistical/computational model that would tackle these challenges.

The purpose of this review is to elucidate the actual threat of the most prevalent mycotoxins in agricultural commodities and human/animal food/feed for appearance of foodborne ailments and diseases. The underestimated hazard of joint mycotoxin uptake of animals or humans is critically discussed with regards to synergistic or additive interaction between some target mycotoxins. The real toxicity of target mycotoxin combinations as it happens in practice is evaluated and possible lower limit values or control measures are suggested in such cases. Some critical points in adequate risk assessment, hygiene control and regulation of mycotoxns are discussed. The efficiency of current mycotoxin regulations and control measures is evaluated in regards to human/animal health hazard. The risk assessment in the case of multiple mycotoxin exposure of humans/animals via the food/feed or agricultural commodities is evaluated and some suggestions are proposed in such cases. Appropriate control measures and food safety issues throughout the food supply chain are proposed in order to prevent target foodborne diseases. Some preventive measures and possible veterinary hygiene control or risk assessment are proposed in some practical cases of foodborne diseases for preventing mycotoxin contamination of animal products designed for human consumption and to avoid possible public health issues.

Introduction: Young adults are the second largest segment of the immigrant population in the United States (US). Given recent trends in later age of initiation of tobacco use, we examined variation in use of tobacco products by nativity status for this population group. Methods: Our study included young adults 18-30 years of age sampled in the National Health Interview Survey (2015-2019), a nationally representative sample of the US population. We calculated prevalence of use of any and 2 or more tobacco products (cigarettes, cigars, pipes, e-cigarettes, and smokeless tobacco) for foreign-born (n=3,096) and US-born (n=6,811) young adults. Logistic regression models adjusted for age, sex, race-ethnicity, education, and poverty, while accounting for the complex survey design. Results: Foreign-born young adults were significantly less likely to use any tobacco product (Cigarette = 7.3% vs 10.7%; Cigar= 1.8% vs 4.8%; E-cigarette= 2.3% vs 4.5%, respectively; p<0.01) or poly tobacco use (1.9% vs. 4.2%; p<0.01) than US-born young adults. Adjusted regression models showed lower odds of poly tobacco use among the foreign-born than their US-born counterparts (Odds Ratio = 0.41, (95% Confidence Interval: 0.26-0.63)). Conclusion: Findings highlight the importance of targeted interventions by nativity status and further tobacco prevention efforts needed for the US-born.

This paper argues that popular misrepresentation of the nature of AI has important consequences concerning how it should be regulated. Viewing AI as something that exists in itself, rather than as a set of cognitive technologies whose characteristics – physical, cognitive, and systemic – are quite different from ours (and at times from each other) leads to inefficient approaches to regulation. It limits our ability to anticipate the consequences of its foreseeable developments and social diffusion. It undermines attempts to protect ourselves from the social and political dangers it presents. After a short introduction, section 2 retraces rapidly the history of the idea that intelligence is essentially a quality, one that AI shares with human intelligence and that this resemblance trumps the differences that exist between artificial and natural cognitive systems. Section 3 reviews two approaches to the dangers of AI that reflect the illusion that AI exists in itself. Section 4 turns to the proper understanding of regulations and what is their main goal and purpose. Section 5 analyses three central characteristics of artificial cognitive systems which section six compares with corresponding characteristics of natural cognitive systems. Finally, section 7 draws some conclusions regarding how we should regulate artificial intelligence.

Mitochondria are semiautonomous organelles, which are pivotal for the energy metabolism of eukaryotic cells. These organelles contain their own genetic system (mtDNA, mitogenome) that encodes to some structural RNAs and organellar proteins. The biogenesis and function of mitochondria is tightly regulated by nuclear-encoded protein cofactors. The mtDNAs of land plants are characteristically large, with a complex mode of gene organization and expression, in particularly at the post-transcriptional level. To become functional, the primary organellar transcripts undergo extensive maturation steps, which include endo- and exo-nucleolytic cleavage, RNA-base editing, and both ‘cis’- and ‘trans’-splicing events. These essential processing steps rely on the activities of a large set of nuclear-encoded factors. Among these, the RNA helicases serve as key players in organellar (mt-)RNA metabolism. This review summarizes the important roles played by these factors in regulating the highly dynamic processes of transcription, RNA processing, and translation within the mitochondria of land plants. We further discuss recent advancements in understanding how dysregulation of mitochondrial RNA helicases affects the organellar gene expression, respiratory functions, and hence the growth, development and physiology of land plants.

In order to obtain stable and reliable configuration transformation ability, reliability optimization design is regarded as an effective way to reduce the probability of kinematic function failure for the constrained metamorphic mechanism. Based on the structural composition principle of multi-configuration source metamorphic mechanism that can operate in an under-actuated state, the modularized calculation methods are established for the force analysis of augmented Assur groups including metamorphic kinematic joints. According to the equivalent resistance gradient model of metamorphic mechanisms, with considering the uncertainties in the link dimensions, masses, and compliance parameters et al, a probabilistic evaluation method for describing the configuration transformation ability of the constrained metamorphic mechanism is established. Based on reliability evaluation and reliability sensitivity analysis, a reliability optimization design method for improving the configuration transformation ability is proposed, and then the optimization design is carried out for tolerances of random variables focusing on those structural parameters with higher reliability sensitivity, so that the optimized results can satisfy the requirements of both reliability and economic simultaneously. Finally, the feasibility and effectiveness of the proposed method is verified by the illustration of a paper folding metamorphic mechanism. The research provides the foundation of reliability design of metamorphic mechanisms to obtain the high-probability repeated execution ability of configuration transformation, it also has theoretical and practical significance to promote the engineering application of metamorphic mechanisms.

Global climate change, particularly rising sea surface temperatures, profoundly impacts coral ecosystems, disrupting reproduction synchrony, symbiotic relationships with algae from the Symbiodiniceae family, and causing widespread bleaching and mortality among coral populations.  Oculina patagonica, a temperate scleractinian coral dominant in Mediterranean coastal waters, tolerates an annual temperature range of 10- 31°C. Moreover, in the past three decades, sea surface temperatures have rapidly risen in the Eastern Mediterranean Sea. O. patagonica offers insight into evolutionary adaptation to rapid environmental changes. This study investigated the effects of temperature changes on O. patagonica reproductive development, synchrony, and thermal sensitivity. Monthly monitoring of O. patagonica colonies for a year reveals no disruption in gonad development compared to previous studies, suggesting an unaffected sexual reproduction capacity. Thermal performance

Smoking has been established as a major risk factor for developing oral squamous cell carcinoma (OSCC), but less attention has been paid to the effects of smokeless tobacco products. Our objective is to identify potential biomarkers to distinguish the biological effects of combustible tobacco products from those of non-combustible using oral cell lines. Normal human gingival epithelial cells (HGEC), non-metastatic (101A) and metastatic (101B) OSCC cell lines were exposed to different tobacco product preparations (TPPs) including cigarette smoke total particulate matter (TPM), whole-smoke conditioned media (WS-CM), smokeless tobacco extract in complete artificial saliva (STE), or nicotine (NIC) alone. We performed microarray-based gene expression profiling and found 3456 probe sets from 101A, 1432 probe sets from 101B, and 2717 probe sets from HGEC to be differentially expressed. Gene Set Enrichment Analysis (GSEA) revealed xenobiotic metabolism and steroid biosynthesis were the top two pathways that were upregulated by combustible but not by non-combustible TPPs. Notably, aldo-keto reductase genes, AKR1C1 and AKR1C2, were the core genes in the top enriched pathways and were statistically upregulated more than 8 fold by combustible TPPs. Our qRT-PCR results statistically support AKR1C1 as a potential biomarker for differentiating the biological effects of combustible from non-combustible tobacco products.

Cigar stacking fermentation is a key step in tobacco aroma enhancement and miscellaneous gas reduction, which both have a great influence on increasing cigar flavor and improving industrial availability. To analyze the effect of cigar tobacco leaf (CTLs) microbial community structure on volatiles during cigar stacking fermentation, this study used multi-omics technology to reveal the changes in microbial community structure and volatiles of different cigar varieties during stacking fermentation, in addition to exploring the interaction mechanism of microbiome and volatiles. The results showed that the dominant microbial compositions of different CTL varieties during stacking fermentation were similar, which included Staphylococcus, Corynebacterium 1, Aerococcus, and Aspergillus. These dominant microbes mainly affected the microbial community structure and characteristic microorganisms of CTLs through microbial interactions, thereby influencing the transformation of volatiles. Characteristic microorganisms of different CTLs varieties such as Trichothecium, Trichosporon, Thioalkalicoccus and Jeotgalicoccus, were found to posively correlate with characteristic volatiles like megastigmatrienone 4, pyrazine, tetramethyl-, geranyl acetone, and 2-undecanone, 6,10-dimethyl-, respectively. This in turn affected the aroma and sensory quality of the CTLs. This study provides theoretical support for the analysis of the mechanism of microorganisms on volatiles and aroma, and development of microbial agents during cigar stacking fermentation.

The signaling complex around voltage-gated sodium (Nav) channels includes accessory proteins and kinases crucial for regulating neuronal firing. Previous studies showed that one such kinase, WEE1—critical to the cell cycle—selectively modulates Nav1.2 channel activity through the accessory protein fibroblast growth factor 14 (FGF14). Here, we tested whether WEE1 exhibits crosstalk with the AKT/GSK3 pathway for coordinated regulation of FGF14/Nav1.2 channel complex assembly and function. Using the in-cell split luciferase complementation assay (LCA), we found that the WEE1 inhibitor II and GSK3 inhibitor XIII reduce FGF14/Nav1.2 complex formation, while the AKT inhibitor triciribine increases it. However, combining WEE1 inhibitor II with either one of the other two inhibitors abolished its effect on FGF14/Nav1.2 complex formation. Whole-cell voltage-clamp recordings of sodium currents (INa) in HEK293 cells co-expressing Nav1.2 channels and FGF14-GFP showed that WEE1 inhibitor II significantly suppresses peak INa density, both alone and in the presence of triciribine or GSK3 inhibitor XIII, despite the latter inhibitors’ opposite effects on INa. Additionally, WEE1 inhibitor II slowed the tau of fast inactivation, and caused depolarizing shifts in the voltage dependence of activation and inactivation. These phenotypes either prevailed or were additive when combined with triciribine but were outcompeted when both WEE1 inhibitor II and GSK3 inhibitor XIII were present. Concerted regulation by WEE1 inhibitor II, triciribine and GSK3 inhibitor XIII were also observed on long-term inactivation and use-dependence of Nav1.2 currents. Overall, these findings suggest a complex role for WEE1 kinase—in concert with the AKT/GSK3 pathway—in regulating the Nav1.2 channelosome.

Few data are available on the health impact of tobacco heating products (THPs) at the population level. We used systems dynamics modelling to estimate effects in the established THP market in Japan. We projected effects of THP use in overall mortality up to 2100 and compare those projections against a baseline scenario based on smoking rates pre-THP launch, i.e., smoking only. The model was informed using data from publicly available sources and the literature, including population size, yearly deaths and smoking prevalence with initialisation year (2004) and, births and migration from 2004 to 2065. Transitions between products were estimated from cross-sectional population surveys in Japan. Potential life-years saved with the introduction of THPs was 13 million by 2100 compared with smoking only. In worst-case scenario, population health gains would be seen with THPs risk 10–50% lower risk than smoking. Assuming equal risk for dual use and smoking, THP risk would need to be at least 10% lower than smoking to achieve a population health benefit by 2100. In credible scenarios, substantial population health gains will follow the introduction of THPs in Japan in a relatively short time frame.

The draconian regulation required by the inherent instability of cognitive phenomena -- gene expression, immune function, cancer suppression, wound healing, animal consciousness, machine intelligence, network stabilization, institutional cognition, and their many and varied composites -- can be viewed through the lens of the asymptotic limit theorems of both information and control theories. Here, we explore the dynamics and sometimes highly punctuated failures of the regulation of cognition under increasing `noise'. The approach parallels, and indeed generalizes, the Data Rate Theorem of control theory, extending the theorem's requirement of a minimum channel capacity necessary for stabilization of an inherently unstable system. Various models are explored across different basic underlying probability distributions characteristic of the system under study, and across different hierarchical scales, finding the addition of adaptive -- learned -- regulation greatly extends the reach of innate -- e.g., AI-driven or otherwise pre-programmed -- regulation. This work points toward the construction of new statistical tools for the analysis of observational and empirical data across a wide spectrum of inherent pathologies and adversarial challenges afflicting a wide variety of cognitive processes.

Purpose. This paper aims to present a unique perspective that emphasizes the intricate interplay between energy, dietary proteins, and amino acid composition, underscoring their mutual dependence for health-related considerations. Energy and protein synthesis are fundamental to biological processes, crucial for the sustenance of life and growth of organisms. Methods and Results. We explore the intricate relationship between energy metabolism, protein synthesis, regulatory mechanisms, protein sources, amino acid availability, and autophagy, in order to elucidate how these elements collectively maintain cellular homeostasis. We underscore the vital role this dynamic interplay has in preserving cell life. Conclusion. A deeper understanding of the link between energy and protein synthesis is essential to comprehend fundamental cellular processes. This insight could have wide-ranging impact in several medical fields, such as nutrition, metabolism, and disease management.

ETS exposure has been shown as an important environmental risk factor in vulnerable population groups. The aim of the project is to analyze the relationships among the ETS and behavior and health in 6−15-year-old children in Slovakia. The status of physical and mental health of children in relation to exposure to tobacco smoke was examined in the representative group of 1478 school children. The methods used, included anonymous questionnaires filled in by parents, Columbia Impairment Scale (CIS), Behavior Problem Index (BPI) and anthropometry. The prevalence of passive smoking is the highest in the capital (27%) and southern cities. Significant relationships have been confirmed between ETS and the age, socio-economic status, the incompleteness of the family, the level of mother's education and the significantly higher prevalence of respiratory diseases (26.7%).The relationships of ETS with emotional (CIS scores ≥16) and behavioral functions (BPI score ≥14) were significant in children exposed to mother‘s and father‘s smoking at home. In the multivariate analysis this association was not significant; the factors such as income and completeness of the family were dominant. The results confirmed the impact of ETS and social factors on health state and health behavior and could be the argumentation for legislative changes.

Neuronal cells are believed to rely on autophagy to maintain cellular homeostasis. Nevertheless, autophagy may be a therapeutic target for neurodegenerative diseases because of the role it plays in neuronal cell death. Despite Beclin 1 association with autophagy and apoptosis, the molecular mechanisms that underlie Tau-induced vesicular pathology and Tau protein aggregates in humans remain poorly understood. Here, we set out to examine the role of three genes-ATG14L, Beclin 1 and VPS34- in autophagy nucleation failure-associated Tau disorders in fruit fly models. We found that either reduced ATG14L levels improve neuronal outcomes, or transgenic expression of ATG6/Beclin 1 greatly reduced age-dependent neurodegeneration and Tau pathology; whereas, the loss of Beclin 1 exacerbated these effects. Prior to p-Tau accumulation, the neuronal Beclin 1 network is critical for reducing p-Tau accumulation, indicating that the loss of Beclin 1 causes Tau pathology and neurodegeneration. As neurodegeneration progressed, glial cells showed an upregulation of vesicular Beclin 1 immunoreactivities. The reduced VPS34 also resulted in p-Tau accumulation, suggesting that neurons require both Beclin 1 and VPS34 to reduce p-Tau accumulation. Our results provide mechanistic insight into the molecular pathways that cause age-dependent Tau pathology and neurodegeneration due to an excess of autophagy nucleation processes and autophagy activity, and we derive novel inferences on the therapeutic possibilities of rebalanced Beclin 1 network by reducing autophagic specific nucleation component of ATG14L.

This study aimed to investigate the relationship between sleep duration, dementia severity, age, and ANS regulation. This cross-sectional pilot study included 27 older patients with probable Alzheimer’s disease, hospitalized at a psychiatric center. We measured heart rate variability to assess ANS regulation at night, evaluated dementia severity using the Clinical Dementia Rating scale, and obtained sleep duration data from sleep diaries maintained by psychiatric nurses. The data were analyzed using repeated-measures generalized linear models with age, sex, dementia severity, and medication (antipsychotics) as covariates. A sleep duration of 7–8 h per night was associated with better ANS regulation than other sleep durations, as indicated by sympathovagal balance (p = 0.005). ANS dysregulation was characterized by a 20.7% increase in sympathetic nervous system activity and a 14.8% decrease in parasympathetic nervous system (PSNS) activity. We found a significant correlation between dementia severity and PSNS activity (p = 0.04) and observed an inverted U-shaped association between sleep duration and ANS regulation. This pilot study demonstrated that a sleep duration of 7–8 h per night may be critical in maintaining optimal ANS regulation. Bidirectional associations between sleep duration, inadequate sleep duration, aging, and ANS regulation warrant further investigation.

Rapidly and accurately extracting tobacco plant information can facilitate tobacco planting man-agement, precise fertilization and yield prediction. In karst plateau of southern China, tobacco plant identification is affected by large ground undulations, fragmented planting areas, complex and diverse habitats and uneven plant growth. This study took a tobacco planting area in Gui-zhou Province as the research object and used DJI UAVs to collect UAV visible light images. Considering plot fragmentation, plant size, presence of weeds and shadow masking, this area was classified into eight habitats. The datasets of different habitats were constructed to train the U-Net model. The results show that (1) the overall precision, recall, F1-score and IOU of tobacco plant information extraction were 0.68, 0.85, 0.75 and 0.60, respectively. (2) The precision was the highest for the subsurface-fragmented and weed-free habitat and the lowest for the smooth-tectonics and weed-infested habitat. (3) The weed-infested habitat with smaller tobacco plants can cause blurred images, reducing the plant identification accuracy. This study verified the feasibility of the U-Net model for tobacco single-plant identification in complex habitats. Decomposing complex habitats to establish the sample set method is a new attempt to improve crop identification in complex habitats in karst mountainous areas.

More than two-thirds of death in developing countries are due to non-communicable diseases (NCDs), and tobacco is a leading risk factor. Among different socio-demographic factors, occupation and its corelates have impact on use of smokeless tobacco (SLT) and the evidence in India is limited. The objectives of this study are to find out the overall preva-lence of SLT use and its pattern of association with various occupation and associated variables. Methods: This study used data from Longitudinal Ageing Study in India (LASI) wave 1. Current and ever users of SLT are taken into consideration as target population. For the data analysis, survey-weighted tools have been applied for descriptive statistics and multivariable logistic re-gression model. The weighted data analysis has been done using R. Results and Discussion: From the sample size of 65561, 38% have ever used either smoking or SLT, of them, 40 % use to-bacco in smoke form, 51 % use SLT and 9 % take both. At the population level, 22.8% and 20.4% are ever and current users of SLT respectively. Type, place, and workload in the occupation found to be significantly associated with SLT use. Workplace tobacco-cessation-policy for infor-mal-workers is required to manage this issue.

Background: The study aimed to investigate the association between environmental tobacco smoke exposure and the risk of wheezing among rural and urban preschool children in Mpumalanga province, South Africa, an area associated with poor air quality. Methods: In this study, parents/caregivers of preschool children (n=3145) completed a modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Data were analysed using multiple logistic regression models. Results: The overall prevalence of Wheeze ever was 15.14%, with a higher prevalence in urban pre-schoolers than rural pre-schoolers (20.71% vs 13.30 %, P<0.000). Moreover, the total prevalence of asthma ever was 2.34%. The prevalence was greater in urban pre-schoolers than in rural pre-schoolers (3.92% vs 1.81%, P<0.001). In the final adjusted model, both urban and rural area children who lived with one or more people who smoked in the same household (WE: OR 1.44, 95% CI 1.11-1.86) (CW: OR 2.09, 95% CI 1.38-3.16) and (AE: OR 2.49, 95% CI 1.12-5.54) were found to have an increased likelihood of having Wheeze Ever, Current Wheeze and Asthma Ever as compared to those who lived with non-smokers. Conclusions: The implementation of smoking limits and prohibition is crucial in areas that are frequented or utilized by children. Hence, it is imperative for healthcare providers to actively champion the rights of those who do not smoke within the society, while also endorsing legislative measures aimed at curtailing the extent of tobacco smoke exposure.

This review deals with the developmental origins of extraocular, jaw and laryngeal muscles, the expression, regulation and functional significance of myosin heavy chains (MyHCs) they express and changes in MyHC expression during phylogeny. Myogenic progenitors from mesoderm in the prechordal plate and branchial arches specify craniofacial muscle allotypes with different repertoires for MyHC expression. To cope with very complex eye movements, extraocular muscles express 11 MyHCs, ranging from the superfast extraocular MyHC to the slowest, non-muscle MyHC IIB. They have distinct global and orbital layers, singly- and multiply-innervated fibres, longitudinal MyHC variations, and palisade endings that mediate axon reflexes. Jaw-closing muscles express the high-force masticatory MyHC, cardiac or limb MyHCs depending on the appropriateness for the acquisition and mastication of their food. Laryngeal muscles express extraocular and limb muscle MyHCs but shift towards slower MyHCs in large animals. During postnatal development, MyHC expression of craniofacial muscles is subject to neural and hormonal modulation. The primary and secondary myotubes of developing EOMs are postulated to induce, via different retrogradely transported neurotrophins, the rich diversity of neural impulse patterns that regulate the specific MyHCs they express. Thyroid hormone shifts 2A MyHC towards 2B in jaw, laryngeal muscles and possibly extraocular muscles.

Hepatitis B virus (HBV) is the dominant risk factor for hepatocellular carcinoma (HCC). HBV X protein (HBx) plays crucial roles in HCC carcinogenesis. HBx interferes with several signaling pathways including Notch1 pathway in HCC. In our study, we found that Notch1 was highly expressed in HCC especially in large HCC. Notch1 and HBx co-localized in HCC and their levels were positively correlated with each other. Notch1 expression was more elevated in HepG2.2.15 than that in HepG2. HBx activated Notch1 pathway in HepG2.2.15. Repression of HBx and Notch1 pathway attenuated the growth of HepG2.2.15. Notch1, ERK and AKT pathways were inhibited after a γ-secretase inhibitor treatment. Dual-specificity phosphatase 1 (DUSP1) and phosphatase and tensin homolog (PTEN) were up-regulated after the γ-secretase inhibitor treatment and Hes1 inhibition. Luciferase reporter assays showed that Hes1 repressed the promoters of DUSP1 and PTEN and this was reverted by γ-secretase inhibitor treatment. Western blotting demonstrated that DUSP1 dephosphorylated pERK and PTEN dephosphorylated pAKT. Collectively, we reported a link among HBx, Notch1 pathway, DUSP1/PTEN, and ERK/AKT pathways, which influenced HCC cell survival and could be a therapeutic target for HCC.

Indian tobacco farm laborers are primarily women and children working for very low wages. The aim of this study was to explore occupational and reproductive health challenges faced by women tobacco farm labors in Mysore District, India. We conducted interview and six focus group discussions among 41 women tobacco farm laborers. Codes and themes were generated based on deductive and inductive approaches using the socio-ecological model. Participants reported symptoms of green tobacco sickness including headaches, back pain, gastric problems, weakness, and allergies during menstruation, pre-natal, and post-natal periods. Participants had poor awareness about the health effects of tobacco farming and there were gender inequalities in wages and use of personal protective equipment. Participants received support from family and commu-nity health workers during their pregnancy and post-natal period. Women reported wanting ma-ternity benefits from the tobacco board, monetary support, and nutritional supplements. There is a need for health education about the environmental dangers of tobacco among farm laborers, and more supportive policies for women farmworkers during pregnancy and post-natal periods.

RNA transcripts play a crucial role as witnesses of gene expression health. Identifying disruptive short sequences in RNA transcription and regulation is essential for potentially treating diseases. Let’s delve into the mathematical intricacies of these sequences. We’ve previously devised a mathematical approach for defining a “healthy” sequence (10.14218/GE.2023.00079). This sequence is characterized by having at most four distinct nucleotides (denoted as nt≤4). It serves as the generator of a group denoted as fp. The desired properties of this sequence are as follows: fp should be close to a free group of rank nt−1, it must be aperiodic, fp should not have isolated singularities within its SL2(C) character variety (specifically within the corresponding Groebner basis). Now, let’s explore the concept of singularities. There are cubic surfaces associated with the character variety of a four-punctured sphere denoted as S24. When we encounter these singularities, we find ourselves dealing with some algebraic solutions of a dynamical second-order differential (and transcendental) equation known as the Painlevé VI equation (10.3390/dynamics4010001). In certain cases, S24 degenerates, in the sense that two punctures collapse, resulting in a “wild” dynamics governed by the Painlevé equations of an index lower than VI. In our paper, we provide examples of these fascinating mathematical structures within the context of miRNAs. Specifically, we find a clear relationship between decorated character varieties of Painlevé equations and the character variety calculated from the seed of oncomirs. These findings should find applications in cancer research.

Reactive oxygen species (ROS), which were originally classified as exclusively deleterious compounds, have gained increasing interest in the recent years given their action as bona fide signalling molecules. The main target of ROS action is the reversible oxidation of cysteines, leading to the formation of disulfide bonds, which modulate protein conformation and activity. ROS endowed with signalling properties are mainly produced by NADPH oxidases at the plasma membrane, but their action also involves a complex machinery of multiple redox-sensitive protein families that differs in their subcellular localization and their activity. Given that the levels and distribution of ROS are highly dynamic in part due to their limited stability, the development of various fluorescent ROS sensors, some of which are quantitative (ratiometric), represents a clear breakthrough in the field and have been adapted to both ex vivo and in vivo applications. The physiological implication of ROS signalling will be presented mainly in the frame of morphogenetics processes, embryogenesis, regeneration, and stem cell differentiation. Gain and loss of function as well as pharmacological strategies have demonstrated the wide but specific requirement of ROS signalling at multiple stages of these processes and its intricate relationship with other well-known signalling pathways.

Several recent studies have indicated that miR-30a plays critical roles in various biological processes and diseases. However, the mechanism of miR-30a participation in the regulation of idiopathic pulmonary fibrosis (IPF) is ambiguous. Our previous study demonstrated that miR-30a may function as a novel therapeutic target for lung fibrosis by blocking mitochondrial fission, which is dependent on dynamin-related protein-1 (Drp-1). However, the regulatory mechanism between miR-30a and Drp-1 has yet to be investigated. In addition, whether miR-30a can act as a potential therapeutic has not been verified in vivo. In this study, the miR-30a expression in IPF patients was evaluated. Computational analysis and a dual luciferase reporter system assay were used to identify the target gene of miR-30a, and cell transfection was used to confirm this relationship. Ten-eleven translocation 1 (TET1) was validated as a direct target of miR-30a, and the transfection of miR-30a mimic/inhibitor significantly reduced/increased the expression of TET1 protein. Further experiment verified that the interference on TET1(siRNA) could inhibit the hydroxymethlation of the Drp-1 promoter. Finally, miR-30a agomir was designed and applied to identify and validate the therapeutic effect of miR-30a in vivo. Our study demonstrated that miR-30a could inhibit the TET1 expression by base pairing with complementary sites in the 3′ untranslated region to regulate the hydroxymethlation of the Drp-1 promoter. Furthermore, miR-30a could act as a potential therapeutic target for IPF.

To elucidate the function of the cold resistance regulatory gene FmNAC1 from Fraxinus mandshurica, this study identified the role that the overexpression of the FmNAC1 gene plays in tobacco growth and cold stress regulation. The cloned FmNAC1 gene from F. mandshurica is 891 bp in length and encodes 296 amino acids. Our subcellular localization analysis confirmed that FmNAC1 is primarily located in the nucleus and functions as a transcription factor. FmNAC1 is responsive to cold and NaCl stress, as well as to the induction of IAA, GA, and ABA hormone signals. To further elucidate its function in cold resistance, four transgenic tobacco lines of FmNAC1 overexpression（FmNAC1-OE）were generated through tissue culture after the agrobacterium-mediated transformation of wild-type (WT) tobacco. These FmNAC1-OE plants exhibited accelerated growth after transplantation. When exposed to low-temperature conditions at -5°C for 24 hours, the rates of wilting and yellowing of the FmNAC1-OE plants were significantly lower than those of the WT tobacco plants. Additionally, the membrane integrity, osmotic regulation, and reactive oxygen species (ROS)-scavenging abilities of the FmNAC1-OE tobacco lines were better than those of the WT plants, indicating the potential of the FmNAC1 gene to improve plant cold resistance. The gene expression results further revealed that the FmNAC1 transcription factor exhibits regulatory interactions with growth-related genes such as IAA and AUX1; cold resistance-related genes such as ICE, DREB, and CBF1; and genes involved in the clearance of reactive oxygen species (ROS), such as CAT and SOD. All of this evidence shows that the FmNAC1 transcription factor from F. mandshurica plays a key role in contributing to the enhancement of growth, cold resistance, and ROS clearance in transgenic tobacco plants.

Inflammasomes are multimolecular complexes with potent inflammatory activity. As such, their activity is tightly regulated at the transcriptional and post-transcriptional levels. In this review, we present the transcriptional regulation of inflammasome genes from sensors (e.g NLRP3) to substrates (e.g. IL-1β). Lineage-determining transcription factors shape inflammasome responses in different cell types with profound consequences on the responsiveness to inflammasome-activating stimuli. Pro-inflammatory signals (sterile or microbial) have a key transcriptional impact on inflammasome genes, which is largely mediated by NF-κB and, that translates into higher antimicrobial immune responses. Furthermore, diverse intrinsic (e.g. circadian clock, metabolites) or extrinsic (e.g. xenobiotics) signals are integrated by signal-dependent transcription factors and chromatin structure changes to modulate transcriptionally inflammasome responses. Finally, anti-inflammatory signals (e.g. IL-10) counterbalance inflammasome genes induction to limit deleterious inflammation. Transcriptional regulations thus appear as the first line of inflammasome regulation to raise the defense level in front of stress and infections but also to limit excessive or chronic inflammation.

The South African government introduced a nationwide lockdown in March 2020 to mitigate the spread of Covid-19. Among other restrictions, the government banned the sale of tobacco products, which lasted for nearly five months. We performed a Google search using the keywords smok*, puff*, lockdown, tobacco, and cigarette*, for articles published in English from 23 March 2020to 18 December 2020 and analysed 441 online media articles. We identified the main arguments made by proponents and opponents of the tobacco sales ban, which were categorised into themes. Three themes were prominent: medical, legal, and economic/financial. Legal aspects were covered in 48% of articles, followed by economic (34%), and medical aspects (18%). The media was generally ambivalent about the tobacco sales ban during the first five weeks of lockdown. Sentiment then turned against the ban. because the medical rationale was not well communicated by the government, there was limited empirical evidence of a link between smoking and contracting Covid-19, and the sales ban was ineffective, since most smokers still purchased cigarettes. Policy framing in the media plays an important role in how the public receives the policy. Any future tobacco control policy intervention should be well-considered and appropriate cessation support services offered.

In current severe global emergency situation of 2019-nCov outbreak, it is imperative to identify vulnerable and susceptible groups for effective protection and care. Recently, studies found that 2019-nCov and SARS-nCov share the same receptor, ACE2. In this study, we analyzed five large-scale bulk transcriptomic datasets of normal lung tissue and two single-cell transcriptomic datasets to investigate the disparities related to race, age, gender and smoking status in ACE2 gene expression and its distribution among cell types. We didn’t find significant disparities in ACE2 gene expression between racial groups (Asian vs Caucasian), age groups (>60 vs <60) or gender groups (male vs female). However, we observed significantly higher ACE2 gene expression in former smoker’s lung compared to non-smoker’s lung. Also, we found higher ACE2 gene expression in Asian current smokers compared to non-smokers but not in Caucasian current smokers, which may indicate an existence of gene-smoking interaction. In addition, we found that ACE2 gene is expressed in specific cell types related to smoking history and location. In bronchial epithelium, ACE2 is actively expressed in goblet cells of current smokers and club cells of non-smokers. In alveoli, ACE2 is actively expressed in remodelled AT2 cells of former smokers. Together, this study indicates that smokers especially former smokers may be more susceptible to 2019-nCov and have infection paths different with non-smokers. Thus, smoking history may provide valuable information in identifying susceptible population and standardizing treatment regimen.

Arthropods, the most abundant group in ecosystems, play crucial roles in human production. Soil physicochemical properties reflect soil health and are linked to arthropods through cascading effects. Gravel-sand mulching, commonly practiced in dry farming regions, initially aids in water retention and temperature regulation. However, long-term cultivation can lead to land degradation and habitat fragmentation. This study aimed to investigate field systems using multiple comparison, linear, and nonlinear correlation analyses to explore the effects of different tillage durations on soil properties and arthropod diversity under gravel-sand mulching. Results indicate that arthro-pod diversity was lower while the fields maintained better soil fertility than the desert steppe. Both soil fertility and arthropod diversity declined significantly with increased years of cultivation. Mantel tests revealed no significant response of desert steppe arthropods to the altered soil properties of gravel-sand mulched fields. However, the Generalized Additive Model analysis indicated significant linear correlations between arthropod occurrence and total nitrogen (positive), available phosphorus, and water content (negative). Arthropod abundance showed significant nonlinear correlations with total potassium, alkali hydrolyzable nitrogen, and organic matter (OM), with OM changes having the most pronounced impact. Thus, gravel-sand mulching can maintain soil fertility over time but at the expense of local arthropod diversity.

In tobacco plants, symbiont endophytic fungi are widely distributed in all tissues where they play important roles. It is therefore important to determine the species distribution and characteristics of endophytic fungi in tobacco. Here, two parasitic fungi Leptosphaerulina chartarum and Curvularia trifolii were isolated and identified from normal tobacco tissue. We sequenced the mitogenomes of these two species and analysed their features, gene content, and evolutionary histories. The L. chartarum and C. trifolii mitochondrial genomes were 68,926 bp and 59,100 bp long circular molecules with average GC contents of 28.60% and 29.31%, respectively. The L. chartarum mitogenome contained 36 protein coding genes, 26 tRNA genes, and 2 rRNA genes (rrnL and rrnS), which were located on both strands. The C. trifolii mitogenome contained 26 protein coding genes, 29 tRNA genes, and 2 rRNA genes (rrnL and rrnS). The L. chartarum 26 tRNAs ranged from 70 bp to 84 bp in length, whereas the 29 tRNAs in C. trifolii ranged from 71 bp to 85 bp. L. chartarum and C. trifolii mtDNAs had an identical mitochondrial gene order and orientation and were phylogenetically identified as sisters. These data therefore provide an understanding of the gene content and evolutionary history of species within Pleosporales.

The purpose of this study was to identify different adolescent profiles identified by their use tobacco/alcohol and violent behavior repertoires as well as to analyze the extent to which they show impulsivity traits. Participants were selected by cluster random sampling. There was a total of 822 high school students in the sample aged 13 to 18 years with a mean of 14.84 (SD=.87). A cluster analysis with the following variables was done to form the groups: Use of tobacco, Use of alcohol, Physical aggression, Verbal aggression, Anger and Hostility. Three groups of adolescents resulted from these five variables. The multivariate comparison demonstrated the existence of significant between-group differences, and individual analysis for each of the dependent variables (impulsivity dimensions) showed that the relationship was statistically significant in all cases. In conclusion, analysis of factors possibly associated with adolescent’s risk behavior makes possible and orients intervention in different stages of development for sustainable consumption in adolescents.

Several studies suggests that ghrelin (GHRL) has neurobiological effects that extend beyond control of food intake. Our previous results confirmed that GHRL modulates the secretory activity of the pineal gland (PG) through nocturnal melatonin (MEL) secretion in sheep, the seasonally reproductive animals. Here we investigated the effects of GHRL (10 ng/ml) on the expression of enzymes limiting synthesis of MEL, including tryptophan 5-hydroxylase 1 (TPH1), serotonin N-acetyltransferase (AA-NAT) and its phosphorylated form p31T-AA-NAT in sheep PG explants (n = 72) during the 4-hour incubation in a gas-liquid interface, at a short (SD) and long (LD) photoperiods. After each hour of incubation selected explants were frozen in liquid nitrogen and stored at -80°C for subsequent analysis (real-time PCR, western-blotting, ELISA). Results show that GHRL regulates nightly MEL secretion in a TPH1-independent manner. The factor modulating GHRL activity was photoperiod. During SD photoperiod GHRL significantly reduced the expression of p31T-AA-NAT, AA-NAT and inhibited MEL secretion from PG explants. Whereas, during LD photoperiod no effect of GHRL on MEL secretion and expression of examined enzymes was noted. Studies indicate that GHRL directly affects PG under in vitro conditions and causes MEL secretion in animals which exhibit seasonality in reproductive and metabolic processes.

Sepsis is an inflammatory disorder caused by the host’s dysfunctional response to infection. Septic patients present diverse clinical characteristics, and in the recent years it has been the main cause of death in intensive care units (ICU). Aquaporins, membrane proteins with role in water transportation, have been reported to participate in numerous biological processes. Their role in sepsis progression has been studied extensively. This review aims to examine recent literature on aquaporin expression and regulation in clinical sepsis, as well as established experimental models of sepsis. We will present how sepsis affects aquaporin expression at the molecular and protein level. Moreover, we will delve into the importance of aquaporin regulation at the transcriptional, post-transcriptional, translational, and post-translational level in sepsis, by presenting data on aquaporin regulation by non-coding RNAs and selected chemical molecules. Finally, we will focus on the importance of aquaporin single nucleotide polymorphisms in the setting of sepsis.

Artificial intelligence (AI) systems are poised to become deeply integrated into society. If developed responsibly, AI has potential to benefit humanity immensely. However, it also poses a range of risks, including risks of catastrophic accidents. It is crucial that we develop oversight mechanisms that prevent harm. This article outlines a framework for evaluating and auditing AI to provide assurance of responsible development and deployment, focusing on catastrophic risks. We argue that responsible AI development requires comprehensive auditing that is proportional to AI systems’ capabilities and available affordances. This framework offers recommendations toward that goal and may be useful in the design of AI auditing and governance regimes.

Pancreatic neuroendocrine tumors (PNETs) are characterized by dysregulated signaling pathways that are crucial for tumor formation and progression. The efficacy of traditional therapies is limited, particularly in treatment of PNETs at advanced stage. Epigenetic alterations profoundly impact the activity of signaling pathways in cancer development, offering potential opportunities for drug development. There is currently a lack of extensive research on epigenetic regulation in PNETs. To fill this gap, we first summarize major signaling events which are involved in PNET development. Then, we discuss the epigenetic regulation of these signaling pathways in the context of both PNET and commonly occurring, and therefore more extensively studied, malignancies. Finally, we will offer perspective on the future research direction of PNET epigenome and its potential applications in patient care.

The nervous system is composed of neurons, which conduct the signals, and glial cells that provide metabolic and functional support and protection to neurons. An important component of the nervous system is the myelin sheath, an insulating layer around the nerves of the brain and spinal cord, which allows a fast and efficient nerve conduction and therefore the proper transmission of signal to all tissues and organs. Myelin is made of protein and fatty substances and gives protection for the propagation of the electrical impulse. Myelin alterations determine the onset of several neuropathies as the electrical signal can be slowed or stopped. Myelin is formed by oligodendrocytes in the central nervous system (CNS) and by Schwann cells in the peripheral nervous system (PNS). Differences in myelination in the CNS and PNS have been found and molecules involved in membrane trafficking such as SNAREs and rabs have been proved to contribute to several aspects regarding the formation of myelin or dysmyelination. Here, I will describe the role of these proteins in regulating membrane trafficking and nerve conduction, myelin biogenesis and maintenance.

Transcription factors (TFs) and microRNAs (miRNAs) are co-actors in genome-scale decoding and regulatory networks, often targeting common genes. In this paper, we describe the algebraic geometry of both TFs and miRNAs thanks to group theory. In TFs, the generator of the group is a DNA-binding domain while, in miRNAs, the generator is the seed of the sequence. For such a generated (infinite) group $\pi$, we compute the $SL(2,\mathbb{C})$ character variety, where $SL(2,\mathbb{C})$ is simultaneously a \lq space-time' (a Lorentz group) and a \lq quantum' (a spin) group. A noteworthy result of our approach is to recognize that optimal regulation occurs when $\pi$ looks like a free group $F_r$ ($r =1$ to $3$) in the cardinality sequence of its subgroups, a result obtained in our previous papers. A non free group structure features a potential disease. A second noteworthy result is about the structure of the Groebner basis $\mathcal{G}$ of the variety. A surface with simple singularities (like the well known Cayley cubic) within $\mathcal{G}$ is a signature of a potential disease even when $G$ looks like a free group $F_r$ in its structure of subgroups. Our methods apply to groups with a generating sequence made of two to four distinct DNA/RNA bases in $\{A,T/U,G,C\}$. Several human TFs and miRNAs are investigated in detail thanks to our approach.

Past public health crises (e.g. tobacco, alcohol, opioids, cholera, HIV, lead, pollution, venereal disease, even COVID-19) have been met with interventions targeted both at the individual and all of society. While the healthcare community is very aware that the global pandemic of non-communicable diseases (NCD’s) has its origins in our Western ultraprocessed food diet, society has been slow to initiate any interventions other than public education, which has been ineffective, in part due to food industry interference. This article provides the rationale for such public health interventions, by compiling the evidence that added sugar, and by proxy the ultraprocessed food category, meets the four criteria set by the public health community as necessary and sufficient for regulation — addiction, toxicity, ubiquity, and externalities (how does your consumption affect me?). To its credit, some countries have recently heeded this science and have instituted sugar taxation policies to help ameliorate NCD’s within their borders. This article also supplies scientific counters to food industry talking points, in order to guide both scientists and policy makers in instituting further appropriate public health measures to quell this pandemic.

RNA epigenetics is perhaps the most recent aspect of interest for translational epigeneticists. RNA modifications create such an extensive network of epigenetically driven combination whose role in physiology and pathophysiology is still far from being elucidated. Not surprisingly, some of the players determining changes into RNA structure are in common with those involved in DNA and chromatin structure regulation, while other molecules seem very specific to RNA. It is envisaged, then, that new small molecules, acting selectively on RNA epigenetic changes, will be reported soon, opening new therapeutic interventions based on the correction of the RNA epigenetic landscape. In this review, we shall summarize some aspects of RNA epigenetics limited to those in which the potential clinical translatability to cardiovascular disease is emerging.

Background: There is considerable evidence to support the association between environmental tobacco smoke (ETS) exposure and children’s burden of disease. However, literature on the health outcomes of prenatal ETS exposure among Chinese children has not yet been comprehensively reviewed. Objective: This systematic scoping review examines the currently available evidence and identifies gaps for further research on the health consequences of prenatal ETS exposure among Chinese children. Methods: Following the JBI scoping review methodological framework, we conducted a computer-aid search of three electronic databases-- PubMed, EBSCOhost, and ProQuest to include studies from January 2011 to May 2023 that addressed the health outcomes of Chinese children whose mothers were exposed to ETS at any stage of the pregnancy. Further, a methodological quality assessment of the selected articles was conducted, using JBI Critical Appraisal Checklists. Results: A total of 30 articles were reviewed, including eleven high-quality studies and nineteen moderate-quality studies. Five main themes, including hypertension, foetal and children’s development, behavioural disorders, respiratory outcomes, and other health outcomes. Majority of studies showed positive link between prenatal ETS exposure and increase risk of preterm birth, and moderately, foetal growth restriction. Few studies explored other potential adverse outcome of ETS, including hypertension, respiratory morbidity, lung function and asthma in their children. Conclusion: The current available evidence on prenatal ETS exposure in Chinese children has unveiled a wide range of health outcomes, including preterm birth, foetal development, behavioural disorders and much more. However, Chinese studies in this area are still lacking and a gap still exists in relation to the strength of association between prenatal ETS exposure and some health risks. Efficient anti-smoking policies and smoking cessation programs should be developed to promote maternal and child health. Further research is also needed to provide better evidence in this field.

The prolonged exposure to nicotine and the development of nicotine dependence have significant implications for cancer risk. Tobacco use, driven by nicotine addiction, is a major contributing factor to the development of various types of cancer. Smoking tobacco, in particular, has been strongly associated with an increased risk of lung cancer, as well as other malignancies. The harmful chemicals present in tobacco products, including carcinogens, can cause DNA damage and promote the initiation and progression of cancerous cells. This article presents a comprehensive literature review on the neurobiology of nicotine dependence and its implications for tobacco use treatment. Nicotine dependence is a complex phenomenon involving various neurobiological mechanisms. When nicotine enters the body, it binds to nicotinic acetylcholine receptors in the brain's reward circuitry, triggering the release of neurotransmitters like dopamine, serotonin, and norepinephrine. Over time, repeated nicotine exposure leads to neuroadaptive changes in the brain, resulting in increased motivation to seek and use the drug. Understanding the neurobiology of nicotine dependence is crucial for developing effective treatment strategies. Pharmacological interventions, such as nicotine replacement therapy and medications like bupropion and varenicline, can help individuals manage cravings and withdrawal symptoms. Additionally, behavioral therapies and counseling play a vital role in enhancing self-efficacy and providing support for smoking cessation efforts. By reviewing the existing literature, this article sheds light on the intricate neural pathways and processes involved in nicotine addiction. It emphasizes the importance of a multidimensional approach that combines pharmacological treatments and behavioral interventions to address the physiological and psychological aspects of nicotine dependence. This knowledge can inform the development of more targeted and personalized treatment approaches to help individuals overcome tobacco addiction and improve their chances of successful smoking cessation.

The use of alcohol and tobacco is related to several variables which act as risk or protective factors, depending on the circumstances. The objectives of this study were to analyze the relationship between emotional intelligence, resilience and family functioning in adolescent use of alcohol and tobacco and to find emotional profiles for their use considering self-concept. The sample was made up of 317 high school students aged 13 to 18 who filled out the Brief Emotional Intelligence Inventory, the Resilience Scale for Adolescents, the APGAR Scale, the Alcohol Expectancy Questionnaire - Adolescents and the Five-Factor Self-Concept Questionnaire. The results revealed that emotional intelligence and resilience, specifically, stress management and family cohesion were significant in the group of nonusers. Family functioning acts as a predictor factor for onset of use of tobacco and alcohol. Positive expectancies about drinking alcohol were found to be a risk factor and the intrapersonal factor to be protective. Both stress management and family cohesion were protective factors against smoking. Furthermore, cluster analysis revealed emotional profiles for users of both substances based on self-concept. Finally, the importance of the direction of the relationship between the variables studied for intervention in this problem should be mentioned. Responsible use by improving adolescent decision-making is one of the results expected from this type of intervention.

Health communication has been highlighted as a cost-effective preventive intervention in Africa where prevalence of tobacco use is still relatively low compared to other World Health Organization (WHO) regions. This scoping review aims to examine tobacco control health communication interventions in Africa. The review was guided by the PRISMA-ScR checklist. Data was extracted from twenty peer-reviewed papers, WHO Global Health Observatory on Anti-tobacco mass media campaigns for 54 African countries, and six WHO Framework Convention on Tobacco Control reports on Article 12. Data extraction informed by JBI data extraction questions was used for peer review studies while a pre-determined template was used for the other sources. Narrative data synthesis informed by the JBI manual for evidence synthesis was employed. Lack of research that comprehensively address all areas of health communication and Inconsistent use of health communication campaigns was identified. Only an average of 6 countries had ever implemented effective mass media campaigns in a decade while an average of 33 countries consistently failed to conduct campaigns that lasted more than 3 weeks. Although the involvement of key populations was clearly vital to ensure content relevance and message clarity; a lack of health communication informed by young people was observed as they rarely participated in key decision-making despite reportedly being targets of interventions. Clear health communication for tobacco use prevention informed by young people is lacking in African countries. Active participation of young people in developing targeted campaigns is needed to facilitate content relevance and comprehension to ultimately contribute to tobacco use prevention.

Soluble chaperones residing in the endoplasmic reticulum (ER) play vitally important roles in folding and quality control of newly synthesized proteins that transiently pass through the ER en route to their final destinations. These soluble residents of the ER are themselves endowed with an ER retrieval signal that enables the cell to bring the escaped residents back from the Golgi. Here, by using purified proteins, we showed that Nicotiana tabacum phytaspase, a plant aspartate-specific protease, introduces two breaks at the C-terminus of the N. tabacum ER resident calreticulin-3. These cleavages resulted in removal of either a dipeptide or a hexapeptide from the C-terminus of calreticulin-3 encompassing part or all of the ER retrieval signal. Consistently, expression of the calreticulin-3 derivative mimicking the phytaspase cleavage product in Nicotiana benthamiana cells demonstrated loss of the ER accumulation of the protein. Notably, upon its escape from the ER, calreticulin-3 was further processed by an unknown protease(s) to generate the free N-terminal (N) domain of calreticulin-3, which was ultimately secreted into the apoplast. Our study thus identified a specific proteolytic enzyme capable of precise detachment of the ER retrieval signal from a plant ER resident protein, with implications for the further fate of the escaped resident.

Telomeres – special DNA-protein structures at the ends of linear eukaryotic chromosomes define the proliferation potential of cells. Extremely short telomeres promote DNA damage response and cell death to eliminate cells potentially accumulated mutations after multiple divisions. However, telomere elongation is associated with increased proliferative potential of special types of cells, such as stem and germ cells, permanently, and is activated temporally in processes of activation of immune response, regeneration processes. Activation of mechanisms of telomere lengthening coupled with increased proliferation and with requirements of cells in energy and building resourses. To obtain necessary nutrients cells stimulate metabolism by switching of oxidative phosphorylation program to glycolysis. In this review we focused on the interconnection of metabolism program and telomere lengthening mechanisms known for the situation of the programmed activation of proliferation such as germ cells maturation, early embryonic development program and immune response activation. Here, we propose that it is possible to reprogram metabolism in order to regulate the telomere length, proliferative activity of cells that may be important for the development of approaches to regeneration, immune response modulation and cancer therapy and further investigations in this area are necessary to improve the understanding and manipulating of molecular mechanisms used for regulation of proliferation.

The purpose of this article was to check the effects on health of various types of physical activities, diet, BMI, smoking and alcohol consumption and their interrelationships with control for age, sex and level of education. The study was based on epidemiological data (9617 participants from 19 to 81 years old for whom we have health indicators over a period of 11 years) together with questionnaires about diet, alcohol, tobacco and the frequency of different types of physical activities. Descriptive statistics and non-parametric correlational analysis of epidemiological data was performed with use of SPSS v.19. Our results indicate the existence of the significant relationship between leading a healthy life style (type of physical activities, limitations of fats consume and weight maintenance). However, the different categories of physical activities were analysed separately and showed slight differences on health indicators impacts. Our findings confirm that leading a healthy life style (all types of physical activities, limitations of fats consume and weight maintenance) is an important issue since it has a significant relationship with physical and mental health indicators, but outdoor physical activities and practicing sport in group have shown slightly higher impact on health.

The increase in tobacco production while ameliorating the condition of the participant households has caused challenges to stakeholders particularly those in the governance of forest resources upon which the sector is hinged. Massive deforestation has proceeded at an alarmingly high level, in a way that threatens the long term viability of the tobacco sector and sustainability of natural forest resources. The entrance of previously disadvantaged majority into the once minority-dominated tobacco sector (and economy) in a quest to improving their livelihoods, is driving forest landscape changes that pose inherent environmental challenges including climate change. This article adopts institutional and landscape approaches to explore and explain the drivers, nexus and implications of smallholder tobacco as a livelihood strategy to the forest landscape changes and the subsequent imperative for governance of the sustainable utilization of forest resources in Zimbabwe. Drawing on documentary evidence the paper concludes that this situation poses a dilemma to forest and livelihood policies, hence the need to examine new institutional and livelihood initiatives.

Cotton fiber, a crucial and sustainable resource for global textile production, undergoes a complex five-stage developmental process, encompassing initiation, elongation, transition, secondary cell wall biosynthesis, and maturation. These elongated single-cell fibers originate from the outer ovule epidermis. The development of cotton fibers involves intricate changes in gene expression and physiological processes, resulting in a nearly pure cellulose product vital for the global cotton industry. Decoding genes associated with fiber development enhances our understanding of cotton fiber mechanisms and facilitates the cultivation of varieties with enhanced quality. In recent decades, advanced omics approaches, including genomics, transcriptomics, and proteomics, have played a pivotal role in identifying genes and gene products linked to cotton fiber development, including the MYB transcription factor family which coordinates cotton fiber development. Molecular studies have revealed transcription factors like MYB, WRKY, Homeodomain Leucine Zipper (HD-ZIP) and basic Helix-Loop-Helix (bHLH) influencing fiber initiation and elongation. The intricate interplay of phytohormones like auxin, gibberellic acid (GA), brassinosteroid (BR), jasmonic acid (JA), ethylene, abscisic acid (ABA), and cytokinin is explored, providing a comprehensive perspective on shaping cotton fibers. Numerous candidate genes and cellular processes affecting various aspects of fiber development hold promise for genetic engineering or marker-assisted breeding to improve fiber quality. This review presents a comprehensive overview of key achievements in cotton molecular biology, with a specific emphasis on recent advancements in understanding transcription factors and phytohormones involved in cotton fiber initiation and elongation.

In numerous instances, the fate of a single cell not only represents its peculiar outcome but also contributes to the overall status of an organism. In turn, cell division cycle and its control strongly influence cell destiny playing a critical role in targeting it towards a specific phenotype. Several factors participate to the control of growth and among them p27 and p57, two proteins modulating various transitions of cell cycle, appear to play key functions. In this review, the major features of p27 and p57 will be described, focusing in particular on their recently identified roles not directly correlated to cell cycle modulation. Then, their possible role as molecular effectors of polyphenols activities are discussed. Polyphenols represent a large family of natural bioactive molecules that have been demonstrated to play promising protective activities against several human diseases. Their use has also been proposed in association with classical therapies for ameliorating their clinical effects and for diminishing their negative side activities. The importance of p27 and p57 in polyphenol cellular effects will be discussed with the aim of identifying novel therapeutic strategies for the treatment of important human diseases, such as cancers, characterized by an altered control of growth.

This paper utilizes dynamic panel threshold technology to conduct a nonlinear test on the direct effect between environmental regulation and economic fluctuations and the effect of industrial structure upgrading by taking 35 industrial sectors in China from 2003 to 2016 . The research has found that there is an inverted "U" relationship between environmental regulation and economic fluctuations, with the enhancement of environmental regulations, the economic fluctuation increases first and then decreases. The cross-terms of environmental regulation and industrial structure rationalization or industrial structure upgrading are significantly negative, which indicates that the enhancement of environmental regulation is conducive to promoting industrial structure upgrading and reducing the economic fluctuations. While the rationalization factors of industrial structure and advanced industrial structure are significantly negative, indicating that both forms of industrial structure upgrading are conducive to reducing the economic fluctuations. Environmental regulation has technical innovation thresholds for industrial structure upgrading and economic fluctuations, but there are no human capital or FDI thresholds. In the rationalization model of industrial structure, there is a nonlinear "U" relationship between environmental regulation and economic fluctuations when the proportion of scientific research expenditure is more than 1.35%. With the enhancement of environmental regulation, the economic fluctuation reduces first and then increases, and the corresponding inflection point value is 2.398% of the environmental regulation level. At the same time, the environmental regulation can indirectly reduce economic fluctuations by pushing down the industrial structure upgrades. In the advanced model of industrial structure, there is a “U” relationship between environmental regulation and economic fluctuation when the proportion of scientific research expenditure is greater than 1.26%. With continuous enhancement of environmental regulation, the economic fluctuation reduces first and then increases. The corresponding inflection point value is 1.78% of the environmental regulation level, and environmental regulation can indirectly reduce economic fluctuations by promoting the industrial structure at the same time.

This study investigated the influence and interaction of tobacco promotional and control information with adolescents’ current smoking and smoking susceptibility. 12,278 students were recruited from junior, senior and vocational high schools located in Shanghai, China. The exposure to tobacco promotional and control message of participants over the past 30 days were examined, as well as current smoking and never smokers’ initiation susceptibility. Complex sample analysis was applied. Descriptive and multivariate logistic regressions were conducted. 89.3% and 91.5% of adolescents investigated were exposed to tobacco promotional and control message respectively, which separately increased and decreased the risk of current smoking and never-smokers’ smoking susceptibility, especially among males and junior high school students. The risk changed in consistency with the exposure level（P_trend < 0.001）. Tobacco control message seemed to mitigate the influence of tobacco promotions in the risk of both current smoking (OR = 0.64, 95%CI: 0.41–0.99) and smoking susceptibility (OR = 0.65, 95%CI: 0.46–0.93). Tobacco-related message exposure was highly prevalent and associated with youth smoking risk and smoking susceptibility. It is important to enhance the comprehensiveness and enforcement of promotion bans. Given the improvement of tobacco control message on smoking risk brought by tobacco promotions, the publicity and dissemination of tobacco control information need to be consistently strengthened.

The popularity of electronic cigarettes in the United States and around the world has led to a startling rise in youth nicotine use. The Juul e-cigarette was introduced in the U.S. market in 2015 and had captured approximately 13% of the U.S. market by 2017. Unlike many other contemporary electronic cigarette companies, the founders behind the Juul® e-cigarette approached their product launch like a traditional high-tech start-up company, not like a tobacco company. This article presents a case study of Juul’s corporate and product development history in the context of US regulatory actions. The objective of this article is to demonstrate the value of government-curated archives as leading indicators which can (a) provide insight into emergent technologies and (b) inform emergent regulatory science research questions. A variety of sources were used to gather data about the Juul e-cigarette and the corporations that surround it. Sources included government agencies, published academic literature, non-profit organizations, corporate and retail websites, and the popular press. Data was disambiguated, authenticated, and categorized prior to being placed on a timeline of events. A timeline of four significant milestones, nineteen corporate filings and events, twelve US regulatory actions, sixty four patent applications, eighty seven trademark applications, twenty three design patents and thirty two utility patents related to Juul Labs and its associates is presented spanning the years 2004 thought 2020. This work demonstrates the probative value of findings from patent, trademark, and SEC filing literature in establishing a premise for emergent regulatory science research questions which may not yet be supported by traditional archival research literature. The methods presented here can be used to identify key aspects of emerging technologies before products actually enter the market, this shifting policy formulation and problem identification from a paradigm of being reactive in favor of becoming proactive. Such a proactive approach may permit anticipatory regulatory science research and ultimately shorten the elapsed time between market technology innovation and regulatory response.

Lung adenocarcinoma (LUAD) is the most common lung cancers, which accounts for about 35%-40% of all lung cancer patients. Despite therapeutic advancements in recent years, the overall survival time of the LUAD patients still remain poor, especially KRAS mutant LUAD. Therefore, it is necessary to further explore novel targets and drugs to improve the prognosis of LUAD. Ferroptosis, an iron-dependent regulated cell death (RCD）caused by lipid peroxidation, has attracted much attention recently as an alternative target for apoptosis in LUAD therapy. Ferroptosis has been found closely related with LUAD, at its every stage, including initiation, proliferation and progression. In this review, we will provide a comprehensive overview on ferroptosis mechanisms, it’s regulation in LUAD, and application of targeting ferroptosis for LUAD therapy.

MicroRNA plays a critical role in regulating gene expression post-transcriptionally. Variations in mature microRNA sequences, known as isomiRs, arise from imprecise cleavage and nucleotide substitution or addition. These isomiRs can target different mRNAs or compete with their canonical counterparts, thereby expanding the scope of miRNA post-transcriptional regulation. Our study investigated the relationship between cis-acting single nucleotide polymorphisms (SNPs) in precursor miRNA regions and isomiR composition, represented by the ratio of a specific 5’-isomiR subtype to all isomiRs identified for a particular mature miRNA. Significant associations between 95 SNP-isomiR pairs were identified. Of note, rs6505162 was significantly associated with both 5’-extension of hsa-miR-423-3p and 5’-trimming of hsa-miR-423-5p. Comparison of breast cancer and normal samples revealed that expression of both isomiRs was significantly higher in tumors than in normal tissues. This study sheds light on the genetic regulation of isomiR maturation and advances our understanding of post-transcriptional regulation by microRNA.

Animal communication signals are regulated by multiple hormonal axes that ensure appropriate signal targeting, timing, and information content. The regulatory roles of steroid hormones and many peptide hormones are well understood and documented across a wide range of vertebrate taxa. Two recent studies have reported a novel function for leptin, a peptide hormone central to energy balance regulation: regulating communication signals of weakly electric fish and singing mice. With only limited evidence available at this time, a key question is just how widespread leptinergic regulation of communication signals is within and across taxa. A second important question is what features of communication signals are subject to leptinergic regulation. Here we consider the functional significance of leptinergic regulation of animal communication signals in the context of both direct and indirect signal metabolic costs. Direct costs arise from metabolic investment in signal production, while indirect costs arise from the predation and social conflict consequences of the signal’s information content. We propose a preliminary conceptual framework for predicting which species will exhibit leptinergic regulation of their communication signals and which signal features leptin will regulate. This framework suggests a number of directly testable predictions within and across taxa. Accounting for additional factors such as life history and reproductive strategies will likely require modification or elaboration of this model.

The gastrointestinal tract contains multiple types of immune cells that maintain the balance between tolerance and activation at the first line of host defense facing non-self antigens, including dietary antigens, commensal bacteria, and sometimes unexpected pathogens. Maintaining homeostasis at the gastrointestinal tract requires stringent regulation of the immune responses against various environmental conditions. Diet can be converted into gut metabolites which have unique functional activities through host as well as microbial enzymatic activities. Accumulating evidences demonstrate that gastrointestinal metabolites have significant impacts on the regulation of intestinal immunity and further integrate immune response of distal mucosal tissue. Metabolites, especially derived from microbiota, regulate immune cell functions by various ways including recognition and activation of cell surface receptors, controlling of gene expression by epigenetic regulation and integration of cellular metabolism. These mucosal immune regulations are key to understand underlying mechanism for the development of gastrointestinal disorders. Here, we review the recent advancement of our understanding on the role of gut metabolites in the regulation of gastrointestinal immunity with highlighting the cellular and molecular regulatory mechanisms by macronutrients-derived metabolites.

The first group to build artificial general intelligence or AGI stands to gain a significant strategic and market advantage over competitors, so companies, universities, militaries, and other actors have strong incentives to race to build AGI first. An AGI race would be dangerous, though, because it would prioritize capabilities over safety and increase the risk of existential catastrophe. A self-regulatory organization (SRO) for AGI may be able to change incentives to favor safety over capabilities and encourage cooperation rather than racing.

Oil-Gan, also known as emblica, is the fruit of the genus Phyllanthus emblica L. The fruits of these trees are high in nutrients and have excellent effects on health care and development values. There are many methods for the management of diabetic nephropathy (DN). However, there is a lack of effective drugs for treating DN from throughout the disease course. The primary aim of this study was to examine the protective effects (including urine analyses, the measurement of inflammatory cytokine levels, and histological examination) and mechanisms of action of an ethyl acetate extract of P. emblica (EPE) on db/db mice, an animal model of diabetic nephropathy, as well as a secondary aim of examining the expression levels of protein kinase Cα (PKCα) in the kidney and its downregulation of vascular endothelial growth factor (VEGF) and fibrosis gene transforming growth factor-β1 (TGF-β1) by Western blot analyses. Eight db/m C57BLKS/J mice were used as the control group. Forty db/db mice were randomly divided into five groups. Treatments included vehicle, EPE1, EPE2, EPE3 (at doses of 100, 200, or 400 mg/kg EPE), or the comparative drug aminoguanidine for 8 weeks. After 8 weeks of treatment, blood samples were collected for analyses of blood glucose, insulin, and HbA1c levels, and pancreatic and kidney tissues were dissected for histological analyses. The present study indicated that the administration of EPE to db/db mice effectively controlled hyperglycemia and hyperinsulinemia by markedly lowering blood glucose, insulin, and glycosylated HbA1c levels. Administration of EPE to db/db mice decreased the levels of BUN and creatinine both in blood and urine and reduced urinary albumin excretion and the albumin creatine ratio (UACR) in urine. Moreover, EPE treatment decreased the blood levels of inflammatory cytokines, including kidney injury molecule-1 (KIM-1), C-reactive protein (CRP), and NLR family pyrin domain containing (NLRP3). Our findings showed that EPE not only had antihyperglycemic effects but also improved renal function in db/db mice. Histological examination of the kidney by immunohistochemistry indicated that EPE can improve kidney function by ameliorating glomerular morphological damage following glomerular injury; alleviating proteinuria by upregulating the expression of nephrin, a biomarker of early glomerular damage; and inhibiting glomerular expansion and tubular fibrosis. Moreover, the administration of EPE to db/db mice increased the expression levels of p- PKCα/t-PKCα but decreased the expression levels of VEGF and renal fibrosis biomarkers (TGF-β1, collagen IV, p-Smad2, p-Smad3, and Smad4), as shown by Western blot analyses. These results implied that EPE as a supplement has a protective effect against renal dysfunction through the amelioration of insulin resistance as well as the suppression of nephritis and fibrosis in a DN model.

The purpose of this original study is to critically analyze the emergence and development of the national models of financial regulation; international standards and codes; regional and national financial regulation and supervision (the case of UK, USA, Sweden, EU and Finland). The research raises both academic and regulatory concerns. It aims at shaping changes (innovations) in the supervisory practices of national and international regulators in response to new developments in FinTech markets, digital products, financial instruments and risks. Secondly, it will stimulate more systematic work on regulatory databases, registration and reporting procedures in various economies in different financial markets. The author identifies five main systems of national financial regulatory markets: the multi-tiered, multi-agency US system; the Twin Peaks model (UK); the mega-regulatory model (Sweden). There is a thorough review of international standards and institutions that work for the stability of financial systems. The analysis of regional and national systems of financial regulation and supervision is based on the examples of the EU and Finnish institutions. National macro and microeconomic regulation and supervision have been examined with a focus on the US Federal Reserve and the US Treasury. National and international regulatory institutions have been evolving along several lines. First, minimum capital and credit risk requirements for banks (80s of the 20th century) are complemented in the 21st century by buffer reserves, liquidity and leverage standards. Second, regulation focuses on ensuring the sustainability of the national economy. The regulatory focus is on ensuring the sustainability of national and global financial systems. Third, there is an increase in the number of supervised institutions. Fourth, there is a division of functions between central banks (macroeconomic regulation) and one or two mega-regulators (microeconomic regulation and supervision). Fifth, there is a division of labour between the international financial institutions (BIS, IMF, WB) and national regulators. Sixth, the focus is on protecting consumers and investors, and countering money laundering and the financing of terrorism. Seventh, there is an understanding for a common approach by central banks to new financial technologies and cybersecurity.

Pattern recognition receptors such as nucleotide-binding oligomerization domain (NOD)-containing protein receptors (NLRs) and the pyrin and HIN domain (PYHIN) receptors initiate the inflammatory response following cell stress or pathogenic challenge. When activated some of these receptors oligomerize to form the structural backbone of a signalling platform known as the inflammasome. The inflammasome promotes the activation of caspase-1 and the maturation of the proinflammatory cytokines, interleukin (IL)-1β and IL-18. In the gut dysregulation of the inflammasome complex is thought to be a contributing factor in the development of inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD). The importance of inflammasomes to intestinal health has been emphasized by various inflammasome deficient mice in dextran sulphate sodium (DSS) models of intestinal inflammation and by the identification of novel potential candidate genes in population based human studies. In this review we summarise the most recent finding with regard to formation, sensing and regulation of the inflammasome complex and highlight their importance in maintaining intestinal health.

This review focuses on the regulation and modulation of human DNA polymerase δ (Pol δ). The emphasis is on mechanisms that regulate the activity and properties of Pol δ in DNA repair and replication. The areas covered are the degradation of the p12 subunit of Pol δ, which converts it from a heterotetramer (Pol δ4) to a heterotrimer (Pol δ3), in response to DNA damage and also during the cell cycle. The biochemical mechanisms that lead to degradation of p12 are reviewed, as well as the properties of Pol δ4 and Pol δ3 that provide insights into their functions in DNA replication and repair. The second focus of the review involves the functions of two Pol δ binding proteins, PDIP46 and PDIP38, both of which are multi-functional proteins. PDIP46 is a novel activator of Pol δ4, and the impact of this function is discussed in relation to its potential roles in DNA replication. Several new models for the roles of Pol δ3 and Pol δ4 in leading and lagging strand DNA synthesis that integrate a role for PDIP46 are presented. PDIP38 has multiple cellular localizations including the mitochondria, the splicesosomes and the nucleus. It has been implicated in a number of cellular functions, including the regulation of specialized DNA polymerases, mitosis, the DNA damage response, Mdm2 alternative splicing and the regulation of the Nox4 NADPH oxidase.

Background: Inflammasomes recognize cytosolic danger signals, including pathogens, and subsequently induce the secretion of pro-inflammatory cytokines, such as interleukin (IL)-1β. Studying inflammasomes in the red fox (Vulpes vulpes) is crucial from a wildlife veterinary and public health perspective, as it can be used to help control and prevent the transmission of zoonotic pathogens. The understanding of how diversity in inflammasomes across species affects pathogen carriage in the red fox is still limited. Methods: We investigated the activation and intracellular mechanisms of three inflammasomes (NLRP3, AIM2, and NLRC4) in fox peripheral blood mononuclear cells (PBMCs), using established triggers and inhibitors derived from humans and mice. Results: Fox PBMCs exhibited normal activation and induction of IL-1β secretion in response to representative inflammasome triggers (ATP and nigericin for NLRP3, dsDNA for AIM2, flagellin for NLRC4). However, in inhibitor studies, MCC950, a selective NLRP3 inhibitor, suppressed IL-1β secretion mediated by the fox AIM2 and NLRC4 inflammasomes. Conclusions: These findings suggest that NLRP3 may have a common role in dsDNA- and flagellin-mediated inflammasome activation in the red fox. In conclusion, this fox inflammasome biology can be applied to the control of zoonotic infections and the treatment of inflammasome-mediated diseases in the red fox.

This review provides an overview of the current understanding of the neural systems involved in regulating wakefulness, non-rapid eye movement sleep (NREMS), and rapid eye movement sleep (REMS) in mammals. Specifically, we focus on the anatomical connections between the subiculum, a component of the hippocampal formation, and the regions responsible for regulating the sleep-wake cycle. The subiculum exhibits direct connections with key areas involved in sleep regulation, such as the lateral hypothalamus, tuberomammillary nucleus, basal forebrain, ventrolateral preoptic nucleus, ventrolateral tegmental area, and suprachiasmatic nucleus. Additionally, second-order projections from the subiculum are received by the laterodorsal tegmental nucleus and locus coeruleus, suggesting potential involvement of the subiculum in the regulation of circadian rhythms, particularly the circadian sleep-wake cycle. We also discuss alterations in the subiculum observed in individuals with sleep disorders and sleep-deprived mice, underscoring the significance of investigating neuronal communication between the subiculum and pathways promoting both sleep and wakefulness.

Metabolic changes are an important component of tumor cell progression. Tumor cells adapt to environmental stresses via changes to carbohydrate and lipid metabolism. Autophagy, a physiological process in mammalian cells that digests damaged organelles and misfolded proteins via lysosomal degradation is closely associated with metabolism in mammalian cells acting as a meter of cellular ATP levels. In this review, we discuss the changes in glycolytic and lipid biosynthetic pathways in mammalian cells and their impact on carcinogenesis via the autophagy pathway. Also, we discuss the impact of these metabolic pathways on autophagy in lung cancer.

Mycotoxins are deleterious fungal secondary metabolites that contaminate food and feed, thereby creating concerns regarding food safety. Common fungal genera can easily proliferate in Indian tropical and sub-tropical conditions, and scientific attention is warranted to curb its growth. To address this, two nodal governmental agencies, namely the Agricultural and Processed Food Products Export Development Authority (APEDA) and Food Safety and Standards Authority of India (FSSAI), have developed and implemented analytical methods and quality control procedures to monitor mycotoxin levels in a range of food matrices and assess risks to human health over the past two decades. However, comprehensive information on such advancements in mycotoxin testing and issues in implementing these regulations is inadequately covered in recent literature. The aim of this review is thus to uphold a systematic picture of the role played by the FSSAI and APEDA for mycotoxin control at the domestic level and for the promotion of international trade along with certain challenges in dealing with mycotoxin monitoring. Additionally, it unfolds various regulatory concerns regarding mycotoxin mitigation in India. Overall, it provides valuable insights to the Indian farming community, food supply chain stakeholders, and researchers about India’s success story in arresting mycotoxins throughout the food supply chain.

The global trend towards increased demand for organic food, greener environments, and the integration of biological control agents into pest management strategies has greatly enhanced the need for biological pesticides (biopesticides). Biopesticides are generally environmentally friendly and are made from micro-organisms or other natural substances. Despite their great potential, relatively few have been registered and commercialised in Nigeria compared to other African countries such as South Africa and Kenya. Biological active agents are so diverse such that ap-plying the same safety standards or environmental conditions to all of them is almost impossible. A review of risk assessment processes and comparative assessments of Nigeria's biopesticide regulations with other developing African countries and developed regions was conducted. Prolonged field testing, lack of bridged risk assessments and technical checklists have been identified as key factors hampering the timely development and commercialisation of biopesti-cides in Nigeria. Recommendations on necessary changes to the existing Nigeria biopesticide regulations have been made. Risk assessment matrices for microbial and biochemical biopesti-cides and a scientific/technical checklist have also been developed. Harmonisation and data ex-change among other countries in the region will also enhance the advancement of scientific and technical knowledge for sustainable regulation and cross-border trade.