Cinnamate 4-hydroxylase (C4H) is a cytochrome P450-dependent monooxygenase enzyme that catalyzes a key step in phenylpropanoid metabolism in plants. However, there is very limited information on the function of C4H in medicinal plants. In the present study, the C4H gene from the Ferula pseudalliacea genome (named FpC4H) was cloned and characterized. In addition, the expression levels of FpC4H in the roots, stems, leaves, flowers and seeds were investigated via real-time PCR. FpC4H showed the most similarity with C4H proteins from Daucus carota. The results predicted that FpC4H, as well as its orthologs, is an unstable and hydrophilic protein. A high genetic distance was observed between FpC4H and C4H from monocots based on evolutionary analysis. Moreover, a variable region related to the variable function of C4H was detected in conserved domain region of C4H proteins. Protein structure analysis revealed that isoleucine and leucine residues are frequently present in the binding region of FpC4H, and two ion binding regions, cysteine258 and asparagine217, were identified in the 3D structure of FpC4H. Expression analysis revealed that the FpC4H gene is expressed in all organs of F. pseudallicea. A low expression level of FpC4H was recorded in leaves, and a high expression level was observed in flower tissues. Based on the expression profile, FpC4H seems to be linked to a high content of phenolic compounds in flowers.

Two putative boar pheromones (Androstenone and Androstenol) were discovered in endangered mouse deer during captive breeding program. This study further examined the molecular characteristics, pheromone synthesis pathway, and the functional role of these pheromones in reproduction of mouse deer. CYP17A1 and CYB5 genes were cloned and expressed in HEK-293, COS-7 cell lines and gonads of mouse deer to investigate CYP17A1 gene’s andien-β-synthase activity towards synthesis of sex pheromones in mouse deer. An enzyme immunoassay was also developed and standardized to measure the fecal androstenone during reproductive cycles of mouse deer. Results showed that mouse deer’s CYP17A1 gene possesses andien-β-synthase activity and could transform pregnenolone into 5,16-androstadien-3β-ol. The expression of CYP17A1 gene upregulated in the testis and ovary, compared to other tissues in mouse deer. Significantly elevated pheromones and estrogens were recorded prior to delivery and postpartum estrus / mating in mouse deer. Further, there were weak correlations between fecal pheromones and estrogens/ androgens in mouse deer during breeding season. The findings suggest that the boar pheromones might play a direct role in the reproductive activities of mouse deer which might be used for breeding of mouse deer elsewhere.

Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder that can diminish the quality of life of both children and adults in academic, occupational, and social contexts. The kynurenine pathway (KP) contains a set of enzymatic reactions involved in tryptophan (TRP) degradation. It is known to be associated with the risk of developing ADHD. This review will address the KP and underlying mechanism of inflammation in ADHD. Potential inflammatory biomarkers reported in the most recent studies are summarized. Although a strong neuroimmunological basis has been established due to advances of recent neurobiological research, the pathophysiology of ADHD remains unclear.

The accumulation of foam cells in arterial intima and the accompanied chronic inflammation are considered major causes of neoatherosclerosis and restenosis. However, both the underlying mechanism and effective treatment for the disease are yet to be uncovered. In this study, we combined transcriptome profiling of restenosis artery tissue and bioinformatic analysis to reveal that NLRP3 inflammasome is markedly upregulated in restenosis and that several restenosis re-lated DEGs are also targets of mulberry extract, a natural dietary supplement used in traditional Chinese medicine to improve liver vitality. Further pathway enrichment analysis identified MAPK signaling pathway to be involved in the inflammatory response of foam cells. Consistently, immunofluorescence microscopy shows co-localization of NLRP3 with CD68+ macrophages. We then evaluated the efficacy of mulberry extract in inhibiting both the formation of foam cells and their inflammatory response. We demonstrated that mulberry extract suppresses the formation of ox-LDL induced foam cells, possibly by upregulating the cholesterol efflux genes ABCA1 and ABCG1 to inhibit intracellular lipid accumulation. In addition, mulberry extract dampens NLRP3 inflammasome activation by stressing the MAPK signaling pathway. Collectively, our mecha-nistic and functional studies unveil the therapeutic value of mulberry extract in neoatherosclerosis and restenosis treatment by regulating lipid metabolism and inflammatory response of foam cells.

Diabetes mellitus is a heterogeneous disease of complex etiology and pathogenesis. Hyperglycemia leads to many serious complications, but also directly initiates the process of β cell apoptosis. A potential strategy for the preservation of pancreatic β cells in diabetes may be to inhibit the implementation of pro-apoptotic pathways or to enhance the action of pancreatic protective factors. The HIPPO signaling pathway is proposed and selected as a target to manipulate the activity of its core proteins in therapy - basic research. MST1 and LATS2 as major upstream signaling kinases of the Hippo pathway are considered as target candidates for pharmacologically induced tissue regeneration and inhibition of apoptosis. Manipulating the activity of components of the HiPPO pathway offers a wide range of possibilities, and thus is a potential tool in the treatment of diabetes and the regeneration of β cells. Therefore, it is important to fully understand the processes involved in apoptosis in diabetic states and to fully characterize the role of this pathway in diabetes. Therapy consisting in slowing down or stopping the mechanisms of apoptosis may be an important direction of diabetes treatment shortly.

The genetic heterogeneity of autism has stymied the search for causes and cures. Whole-genomic studies on large numbers of families have helped identify combinations of inherited and de novo signal. In the present work, we re-analyze DNA microarrays using a novel strategy that takes prior knowledge of genetic relationships into account and that was designed to boost signal important to our understanding of the molecular basis of autism. Our strategy was designed to identify significant genomic variation within a priori defined biological concepts and improves signal detection while lessening the severity of multiple test correction seen in standard analysis of genome-wide association data. Upon application of our approach using 3,244 biological concepts, we detected genomic variation in 68 biological concepts with significant association to autism in comparison to family-based controls. These concepts clustered naturally into a total of 19 classes, principally including cell adhesion, cancer, and immune response. The top-ranking concepts contained high percentages of genes already suspected to play roles in autism or in a related neurological disorder. In addition, many of the sets associated with autism at the DNA level also proved to be predictive of changes in gene expression within a separate population of autistic cases, suggesting that the signature of genomic variation may also be detectable in blood-based transcriptional profiles. This cross-validation with gene expression data from individuals with autism coupled with the enrichment within autism-related neurological disorders supported the possibility that the mutations play important roles in the onset of autism and should be given priority for further study. Our work provides new leads into the genetic underpinnings of autism and highlights the importance of reanalysis of genomic studies of complex disease using prior knowledge of genetic organization.

Oral cancer is a major public health burden worldwide. The lack of biomarkers for early diagnosis has increased the difficulty in managing this disease. Recent studies have reported that neutrophil gelatinase-associated lipocalin (NGAL), a secreted glycoprotein, is upregulated in various tumors. In our study we found that NGAL was significantly downregulated in primary malignant and metastatic tissues of oral cancer compared to normal tissues. The downregulation of NGAL was strongly correlated with the degree of differentiation and stage (I-IV), and can serve as a prognostic biomarker for oral cancer. Tobacco carcinogens were also found to be involved in the downregulation of NGAL. Mechanistic studies revealed that knockdown of NGAL increased oral cancer cell proliferation, survival, and migration, and also induced resistance against cisplatin. Silencing of NGAL activated mTOR signaling and reduced autophagy by the LKB1-AMPK-p53-Redd1 signaling axis. Moreover, cyclin-D1, Bcl-2, and MMP-9 were upregulated, and caspase-9 was downregulated, suggesting that silencing of NGAL increases oral cancer cell proliferation, survival, and migration. Thus, from our study it is evident that downregulation of NGAL activates the mTOR pathway and helps in the progression of oral cancer.

Furazolidone (FZD) is a synthetic nitrofuran with the antiprotozoal and antibacterial activity. The proper mechanism of FZD induced toxicity is still unclear. This study aimed to investigate the protective effect of curcumin on FZD induced oxidative stress, DNA injury and apoptosis in human hepatocyte L02 cells. The results showed that curcumin treatment significantly ameliorated FZD induced cytotoxicity, characterized by decreasing the production of reactive oxygen species (ROS) and malondialdehyde, as well as increasing superoxide dismutase, catalase activities and glutathione contents. Moreover, curcumin pretreatment significantly inhibited FZD induced the loss of mitochondrial membrane potential, the activation caspase-9 and -3 and apoptosis. Comet assay showed that curcumin attenuated FZD induced DNA injury in a dose-dependent manner. Correspondingly, curcumin markedly reversed the up-regulation of p53, Bax, caspase-9 and -3 mRNA expressions and the down-regulation of Bcl-2 mRNA (all p<0.05 or 0.01). These results reveal that curcumin protects against FZD induced oxidative stress, DNA injury and cell apoptosis via inhibiting oxidative stress and mitochondrial pathway, which may be attributed to ROS scavenging and anti-oxidative ability of curcumin. Importantly, our study highlights that curcumin may be a potential way to prevent FZD-mediated oxidative DNA injury and apoptosis in human or animals.

We profiled the transcriptomes of primary mouse cortical astrocytes cultured alone or co-cultured with immortalized precursor oligodendrocytes. The experimental set-up (insert systems) prevented formation of gap junction channels but allowed free exchange of the two culture media. The study complements our previously published reports that the genomic fabrics of major functional pathways in oligodendrocytes are substantially remodeled by the proximity of non-touching astrocytes. Here, we present new analysis indicating that the transcriptomic landscape of astrocytes likewise changes significantly in the proximity of non-touching oligodendrocytes. The research was stimulated by the reported transcriptomic similarity between the brains of Cx43KO and Cx32KO mice, both substantially different from that of the Cx36KO mice. Since the three connexins are expressed in different cell types (Cx43 in astrocytes, Cx32 in oligodendrocytes and Cx36 in neurons), altogether these findings support the idea of a “panglial transcriptomic syncytium” in the mouse brain. Going further, our results suggest that integration in a heterocellular tissue modulates not only the expression profile but also the expression control and networking of the genes in each cell phenotype.

Antimalarial drug resistance has become a real public health problem despite WHO measures. New sequencing technologies make it possible to investigate genomic variations associated with resistant phenotypes at the genome-wide scale. Based on the use of hemisynthetic nanopores, the PromethION technology from Oxford Nanopore Technologies can produce long-read sequences, in contrast to previous short-read technologies used as gold-standard to sequence Plasmodium. Two clones of P.falciparum (Pf3D7 and PfW2) were sequenced in long-read using the PromethION sequencer from Oxford Nanopore Technologies without genomic amplification. This made it possible to create a processing analysis pipeline for human Plasmodium with ONT Fastq only. De novo assembly revealed N50 lengths of 18,488 kb and 17,502 kb for the Pf3D7 and PfW2, respectively. The genome size was estimated at 23,235,407 base pairs for the Pf3D7 clone and 21,712,038 base pairs for the PfW2 clone. The average genome coverage depth was estimated at 787X and 653X for the Pf3D7 and PfW2 clones, respectively. This study proposes an assembly processing pipeline for the human Plasmodium genome using software’s adapted to large ONT data and the high AT percentage of Plasmodium. This search provides all the parameters, which have been optimized, for use with the software selected in the pipeline.

This study aims to explore methods for automating the replication of correlated portfolios across shares using various algorithms. The goal is to select one algorithm for implementation in a visualization tool that will facilitate portfolio building. The dynamics of the stock market provide a comprehensive view of the global economy, acting as a catalyst for stakeholders to participate and benefit various sectors financially, primarily through investments in companies that yield returns and contribute to the economy. The evaluation and comparison of these algorithms are crucial for making well-informed decisions regarding the core objectives of the study. Ultimately, a determination will be made as to whether the program can effectively analyse data from Yahoo finance to provide a quick overview of the financial market state of companies in the S&P 500 US stock prices.

Porphyromonas gingivalis is the major pathogenic bacteria found in the subgingival plaque of patients with periodontitis, leading to neuroinflammation. The bacteria destroy periodontal tissue through its virulence factors which are retained in the bacteria’s outer membrane vesicles (OMV). The purpose of this study was to determine the real time effect of intraperitoneal in-jection of P. gingivalis OMV on the production and expression of inflammatory markers as well as histopathological changes in the central nervous system (CNS) of adult zebrafish. Fol-lowing the LD50 (21 µg of OMV), the zebrafish were injected intraperitoneally with 18 µg of OMV and control group with normal saline at 7 different time points. Brains of experimental zebrafish were dissected at desired time points for colorimetric assays, ELISA and histology. This study discovered that nitric oxide and PGE2 were significantly increased at 45 minutes while IL-1β and IL-6 were expressed at subsequent 12- and 24-hours. respectively. Histopatho-logical changes such as blood coagulation, astrocytosis, oedema, spongiosis, and necrosis were also observed between 6- and 24-hours. The two apoptotic enzymes, caspases 3 and 9 were not expressed at any time point. In summary, the OMV induced neuroinflammatory responses and histopathological changes in adult zebrafish were time point dependent

Aluminum (Al) toxicity and low phosphorus availability (LP) are the top two co-existing edaphic constraints limiting agriculture productivity in acid soils. Plants have evolved versatile mechanisms to cope with the two stresses alone or simultaneously. However, the specific and common molecular mechanisms, especially those on flavonoids and carbohydrate metabolism, are still unclear. Laboratory studies were conducted on two wheat genotypes, Fielder (Al-tolerant and P-efficient) and Ardito (Al-sensitive and P-inefficient), exposed to 50 μM Al and 2 μM Pi (LP) in hydroponic solutions. After 4 days of stress, wheat roots were analyzed via transcriptomic and targeted metabolomic techniques. A total of 2296 differentially expressed genes (DEGs, 1535 up and 761 down) under Al and 3029 DEGs (1591 up and 1438 down) under LP were identified in Fielder. Similarly, 4404 DEGs (3191 up and 1213 down) under Al and 1430 DEGs (1176 up and 254 down) under LP were identified in Ardito. The GO annotation analysis results that 4079 DEGs annotated to the metabolic processes term. These DEGs were significantly enriched in the phenylpropanoid, flavonoid, flavone and flavonol biosynthesis, and carbohydrate metabolism pathways by performing the KEGG enrichment analysis. The targeted metabolome analysis detected 19 flavonoids and 15 carbohydrate components in Fielder and Ardito under Al and LP. More responsive genes and metabolites were involved in flavonoid metabolism under LP than Al in the Fielder, while an opposite trend in the Ardito. In the carbohydrate metabolism pathway, the genes and metabolites were higher in Fielder than in Ardito. The combined transcriptome and metabolome analysis revealed that the flavonoid and carbohydrate genes and metabolites differed between Fielder and Ardito under Al and LP, which may be an important reason for Fielder’s high Al and LP resistance. The results of this study lay a foundation for pyramiding genes and breeding multi-resistance varieties.

Flexible capacity applications demands to large energy storage density and high breakdown electric field strength of flexible films. Here, P(VDF-HFP) with ultra-thin Al2O3 nanosheets composite films were designed and fabricated through an electrospinning process followed by hot-pressing in sandwich structured. The results show that the insulating ultra-thin Al2O3 nanosheets and the sandwich structure can enhance the composites' breakdown field (by 24.8%) and energy density (by 30.6%) remarkedly to P(VDF-HFP) polymer matrix. An energy density of 23.5 J/cm3 at the ultrahigh breakdown field of 740kV/mm can be therefore realized. Insulating test and phase-field simulation results reveal that ultra-thin nanosheets insulating buffer layers can reduce the leakage current in composites, thus it effects the electric field spatial distribution to enhance breakdown strength. Our research provides a feasible method to increase the breakdown strength of ferroelectric polymers, which is comparable to those of non-ferroelectric polymers.

The role of biomarkers in the diagnosis of inflammatory bowel disease is not fully characterized. C-reactive protein has a short half-life and elevates quickly after the onset of an inflammatory process, the performance is better in Crohn’s disease than in ulcerative colitis. Erythrocyte sedimentation rate is easy to determine, widely available, and cheap but the long half-life the influence of age, anemia, smoking, and drugs limit its usefulness. Fecal markers have good specificity, but suboptimal accuracy. Microbial antibodies and novel immunological markers show promise but need further evidence before entering clinical practice. Proteomic methods could represent the dawn of a new era of stool protein/peptide biomarker panels able to select patients at risk of inflammatory bowel disease.

Background: Hypovitaminosis D is a public health problem due to its implications for various diseases. Vitamin D has numerous functions, such as modulating the metabolism of some cellular tissues, and is expressed through the VDR gene that may influence gene expression modulation, which plays an important role in vitamin D metabolism. Objective: To evaluate the effect of the genotypes of single nucleotide polymorphism (SNP) BsmI of the vitamin D receptor (VDR) gene on VDR, SOD2, and CYP24A1 gene expression in individuals with low serum vitamin D levels. Methods: This was a cross-sectional analytical study. Individuals were invited to participate and, after signing the informed consent form, answered a structured questionnaire with identification data. Blood was collected for biochemical analysis, and vitamin D was measured by chemiluminescence; BsmI polymorphism was determined using real-time polymerase chain reaction (PCR) assays with TaqMan allelic discrimination, and gene expression was conducted by qRT-PCR using QuantiFast SYBR® Green PCR Master Mix. Data were analyzed using the SPSS 20.0 software, and differences were considered significant at p&lt;0.05. Results: 98 individuals with vitamin D ≤20 ng/dL were evaluated, and the SNP BsmI of the VDR gene showed CYP24A1 overexpression and low SOD2 expression. Conclusion: SNP Bsm I of the VDR gene can modulate the expression of the genes evaluated without interfering with serum levels.

The multidrug efflux transporter ABCB1 is clinically important for drug absorption and distribution and can be a determinant of chemotherapy failure. Recent structure data shows that three glutamines donate hydrogen bonds to co-ordinate taxol in the drug binding pocket. This is consistent with earlier drug structure-activity relationships that implicated the importance of hydrogen bonds in drug recognition by ABCB1. By replacing the glutamines with alanines we have tested whether any or all of Q347, Q725 and Q990 are important for the transport of three different drug classes. Flow cytometric transport assays show that Q347A and Q990A act synergistically to reduce transport of Calcein-AM, BODIPY-verapamil and OREGON GREEN-taxol bisacetate but the magnitude of the effect was dependent on the test drug and no combination of mutations completely abrogated function. Surprisingly, Q725A mutants generally improved transport of Calcein-AM and BODIPY-verapamil, suggesting that engagement of the wild-type Q725 in a hydrogen bond is inhibitory for the transport mechanism. To test transport of unmodified taxol, stable expression of Q347/725A and the triple mutant was engineered and shown to confer equivalent resistance to the drug as the wild-type transporter, further indicating that none of these potential hydrogen bonds between transporter and transport substrate are critical for function of ABCB1. The implications of the data for plasticity of the drug binding pocket are discussed.

During their complex life cycles, the Apicomplexan parasites, Plasmodium falciparum and Toxoplasma gondii employ several genetic switches to regulate their gene expression. One such switch is mediated at the level of translation through upstream Open Reading Frames (uORFs). As uORFs are found in the upstream regions of a majority of genes in both the parasites, it is essential that their roles in translational regulation be appreciated to a greater extent. This review provides a comprehensive summary of studies that show uORF-mediated gene regulation in these parasites and highlights examples of clinically and physiologically relevant proteins that exhibit uORF-mediated regulation. In addition to these examples, several studies that use bioinformatics, transcriptomics, proteomics, and ribosome profiling also indicate the possibility of widespread translational regulation by uORFs. Further analysis of genome-wide datasets will reveal novel genes involved in key biological pathways such as cell-cycle progression, stress-response, and pathogenicity. The cumulative evidence from studies presented in this review suggests that uORFs will play crucial roles in regulating gene expression during clinical disease caused by these important human pathogens.

It was once thought that high QoS (Quality of Service) performance solves recurrent problems of low-quality multimedia services. Since then, solutions have been proposed to ensure a high level of QoE (Quality of Experience). In this document, the authors attempt to outline their understanding of an accurate meaning of quality of multimedia services. Starting from QoS and passing through generalised QoE, the authors focus on aspects of subjective and objective quality modelling and optimisation of visual performance for TRV (Target Recognition Video) applications (such as video surveillance), outlining the path of ITU-T standardisation in this area. The authors revised the ITU-T Recommendation P.912 to reflect improved subjective test techniques developed since this Recommendation was approved. The authors also attempt to predict at least some existing errors of reasoning, which are likely to become evident for the industry in the next decade.

Prediction and early detection of atrial fibrillation (AF) remain a permanent challenge in everyday practice. Timely identification of an increased risk for AF episodes (which are frequently asymptomatic) is essential in the primary and secondary prevention of cardioembolic events. One of the noninvasive modalities of AF prediction is represented by the electrocardiographic P-wave analysis. This includes the study and diagnosis of interatrial conduction block (Bachmann`s bundle block). Bayés’ Syndrome (named after its first descriptor) denotes the association between interatrial conduction defect and supraventricular arrhythmias (mainly AF) predisposing to cardioembolic events. Our short review presents an update of the most important data concerning this syndrome: brief history, main ECG features, pathophysiological background and clinical implications.

SARS-CoV-2 infections underlie the current Coronavirus disease (COVID-19) pandemic and are causative for a high death toll particularly among elderly subjects and those with comorbidities. Selenium (Se) is an essential trace element of high importance for human health and particularly for a well-balanced immune response. Mortality risk from severe disease like sepsis or polytrauma is inversely related to Se status. We hypothesized that this relation also applies to COVID-19. Serum samples (n=166) from COVID-19 patients (n=33) were collected consecutively and analysed for total Se by X-ray fluorescence and selenoprotein P (SELENOP) by a validated ELISA. Both biomarkers showed the expected strong correlation (r=0.7758, p<0.001), pointing to an insufficient Se status for optimal selenoprotein expression. In comparison to reference data from a European cross sectional analysis (EPIC, n=1915), the patients showed a pronounced deficit in total serum Se (mean±SD, 50.8±15.7 vs. 84.4±23.4 µg/L) and SELENOP (3.0±1.4 vs. 4.3±1.0 mg/L). A Se status below the 2.5th percentile of the reference population, i.e., [Se] < 45.7 µg/L and [SELENOP] < 2.56 mg/L was present in 43.4% and 39.2% of COVID samples, respectively. The Se status was significantly higher in samples from surviving COVID patients as compared to non-survivors (Se; 53.3±16.2 vs. 40.8±8.1 µg/L, SELENOP; 3.3±1.3 vs. 2.1±0.9 mg/L). We conclude that Se status analysis in COVID patients provides diagnostic information. However, causality remains unknown due to the observational nature of this study. Nevertheless, the findings strengthen the notion on a relevant role of Se for COVID convalescence, and support the discussion on adjuvant Se supplementation in severely diseased and Se-deficient patients.

P-glycoprotein (Pgp) determines resistance to a broad spectrum of drugs in glioblastoma multiforme (GB) because it is highly expressed in GB stem cells and in brain-blood barrier (BBB), the peculiar endothelium surrounding brain. Inhibiting Pgp activity in BBB and GB is still an open challenge. Here, we tested the efficacy of a small library of tetrahydroisoquinoline derivatives with an EC₅₀ for Pgp < 50 nM, in primary human BBB cells and in patients-derived GB, from which we isolated differentiated/adherent cells (AC, i.e. Pgp-negative/doxorubicin-sensitive cells) and stem cells (neurospheres, NS, i.e. Pgp-positive/doxorubicin-resistant cells). At 1 nM, 3 compounds increased the delivery of doxorubicin, a typical substrate of Pgp, across BBB monolayer, without altering expression and activity of other transporters. The compounds increased the drug accumulation within NS, restoring necrosis, apoptosis and reduction in cell viability induced by doxorubicin. In co-culture systems, the compounds added to the luminal face of BBB increased the delivery of doxorubicin to NS growing under BBB and rescued the drug’s cytotoxicity. Our work identified new ligands of Pgp active at low nanomolar concentrations, that effectively reduce Pgp activity in BBB and GB, and can improve chemotherapy efficacy in this tumor.

Possibilities of utilization of two frequencies synthetic aperture radar (SAR) operating simultaneously in P-band and S or L-band are considered. Advantages of such system are shown. They are caused by improvement of data interpretation and by decrease of ionosphere influence. Tasks of surface and subsurface sensing by the complex SAR were under investigation for vegetation, soil covers are given. As an example, the investigation results of coniferous forest areas backscattering by the spaceborne P-band SAR together with L-band SAR in the September-February period are presented. Studies have shown that the joint use of the results in L and P bands offer unique opportunities to explore the effects of changes in the backscattering properties of forest surfaces.

In winter 2008-2009, Lake Occhito, a strategic multiple-uses reservoir in South Italy, was affected by an extraordinary Planktothrix rubescens bloom. P. rubescens is a filamentous potentially toxic cyanobacterium which has recently colonized many environments in Europe. A number of studies is currently available on the use of remote sensing techniques to monitor different fresh water cyanobacteria species. By contrast no specific applications are available on the remote sensing monitoring of P. rubescens. In this paper we present a specific algorithm, based on Water Leaving Reflectances (WLR) from MERIS data, atmospherically corrected using the Aerosol Optical Thickness (AOT) retrieved by MODIS data, to detect P. rubescens blooms. The high accuracy in AOT data, provided by MOD09 surface reflectance product, at 1km spatial resolution, allowed obtaining a good correlation between the WLR and the P. rubescens chlorophyll-a concentrations measured in the field, through multiple stations fluorometric profiles. A modified Normalized Difference Chlorophyll index (NDCI) algorithm is presented. The performance of the proposed algorithm has been successfully compared with other specific algorithms for turbid productive waters. We demonstrated how important is to verify the spectral behaviour of bio-optical parameters in order to develop an ad hoc algorithm that better performs with respect to standard algorithms.

In this paper, we establish some inequalities bounding the ratio Г_p,k(x)/Г_p,k(y), where Г_p,k(.) is the (p,k)-analogue of the Gamma function. Consequently, some previous results are recovered from the obtained results.

In this data deposit, I describe a dataset that is the result of content mining 167,318 published articles for statistical test results. As a result of this content mining, 688,112 results from 50,845 articles were extracted. In order to provide a comprehensive set of data, the statistical results are supplemented with metadata from the article they originate from. The dataset is provided in a comma separated file (CSV) in long-format. For each of the 688,112 results, 20 variables are included, of which seven are article metadata and 13 pertain to the individual statistical results (e.g., reported and recalculated p-value). A five-pronged approach was taken to generate the dataset: (i) collect journal lists, (ii) spider journal pages for articles, (iii) download articles, (iv) add article metadata, and (v) mine articles for statistical results.

In the present study, we introduce the two dimensional Chlodovsky type Bernstein operators based on (p, q)−integer. We examine approximation properties of our new operator by the help of Korovkin-type theorem. Further, we present the local approximation properties and establish the rates of convergence by means of the modulus of continuity and the Lipschitz type maximal function. Also, we give a Voronovskaja type theorem for this operators. And, we investigate weighted approximation properties of these operators and estimate rate of convergence in the same space. Finally, with the help of Maple, illustrative graphics show the rate of convergence of these operators to certain functions . The optimization of approximation speeds by operators during system control provides significant improvements in stability and performance. As a result, the control and modeling of dynamic systems become more efficient and effective through innovative methods. These advancements in the fields of modeling fractional differential equations and control theory offer substantial benefits to both modeling and optimization processes, expanding the range of applications in these areas.

Triple negative breast cancer (TNBC) is associated with a generally poor prognosis due to its highly aggressive and metastatic nature, lack of targetable receptors, as well as the frequent development of resistance to chemotherapy. We previously reported that AU1, a small molecule developed as an inhibitor of BPTF (bromodomain PHD finger containing transcription factor), was capable of sensitizing preclinical models of triple negative breast cancer to chemotherapy, in part via the promotion of autophagy. In studies reported here, we identify an additional property of this compound, specifically that sensitization is associated with inhibition of the P-glycoprotein efflux pump. In silico molecular docking studies indicate that AU1 binds to active regions of the efflux pump, in a manner consistent with inhibition of pump function. This work identifies a novel chemical structure that can influence multidrug efflux, an established mechanism of drug resistance in triple negative breast cancer, that has not yet been successfully addressed by clinical efforts.

We prove the continuous non-Archimedean (resp. p-adic) Banach space and Hilbert space versions of non-Archimedean (resp. p-adic) Welch bounds proved by M. Krishna. We formulate continuous non-Archimedean and p-adic functional Zauner conjectures.

We prove the non-Archimedean (resp. p-adic) Banach space version of non-Archimedean (resp. p-adic) Welch bounds recently obtained by M. Krishna. More precisely, we prove following results. \begin{enumerate}[\upshape(i)] \item Let $\mathbb{K}$ be a non-Archimedean (complete) valued field satisfying $\left|\sum_{j=1}^{n}\lambda_j^2\right|=\max_{1\leq j \leq n}|\lambda_j|^2$ for all $ \lambda_j \in \mathbb{K}, 1\leq j \leq n$, for all $n \in \mathbb{N}.$ Let $\mathcal{X}$ be a $d$-dimensional non-Archimedean Banach space over $\mathbb{K}$. If $\{\tau_j\}_{j=1}^n$ is any collection in $\mathcal{X}$ and $\{f_j\}_{j=1}^n$ is any collection in $\mathcal{X}^*$ (dual of $\mathcal{X}$) satisfying $f_j(\tau_j) =1$ for all $1\leq j \leq n$ and the operator $S_{f, \tau} : \text{Sym}^m(\mathcal{X})\ni x \mapsto \sum_{j=1}^nf_j^{\otimes m}(x)\tau_j^{\otimes m} \in \text{Sym}^m(\mathcal{X})$, is diagonalizable, then \begin{align}\label{NONFUNCTIONALWELCH} \max_{1\leq j,k \leq n, j \neq k}\{|n|, |f_j(\tau_k)f_k(\tau_j)|^{m} \}\geq \frac{|n|^2}{\left|{d+m-1 \choose m}\right| }. \end{align} We call Inequality (\ref{NONFUNCTIONALWELCH}) as non-Archimedean functional Welch bounds. \item For a prime $p$, let $\mathbb{Q}_p$ be the p-adic number field. Let $\mathcal{X}$ be a $d$-dimensional p-adic Banach space over $\mathbb{Q}_p$. If $\{\tau_j\}_{j=1}^n$ is any collection in $\mathcal{X}$ and $\{f_j\}_{j=1}^n$ is any collection in $\mathcal{X}^*$ (dual of $\mathcal{X}$) satisfying $f_j(\tau_j) =1$ for all $1\leq j \leq n$ and there exists $b \in \mathbb{Q}_p$ such that $ \sum_{j=1}^{n}f_j^{\otimes m}(x) \tau_j^{\otimes m} =bx$ for all $ x \in \text{Sym}^m(\mathcal{X}),$ then \begin{align}\label{PADICFUNCTIONALWELCH} \max_{1\leq j,k \leq n, j \neq k}\{|n|, |f_j(\tau_k)f_k(\tau_j)|^{m} \}\geq \frac{|n|^2}{\left|{d+m-1 \choose m}\right| }. \end{align} We call Inequality (\ref{PADICFUNCTIONALWELCH}) as p-adic functional Welch bounds. \end{enumerate} We formulate non-Archimedean functional and p-adic functional Zauner conjectures.

Genomic sequencing of Alternaria oxytropis OW 7.8 isolated from Oxytropis glabra was performed, the swnK gene was cloned and knocked out firstly. The colony morphology of ΔswnK-ACP differed from that of A. oxytropis OW 7.8, appearing milky white or pale yellow, with irregular shapes and a slower growth rate. SW was not detected in ΔswnK-ACP, indicating that the swnK gene promotes SW synthesis in A. oxytropis OW 7.8. 8 differentially expressed genes (DEGs) and 7 differentially expressed metabolites (DEMs) closely associated with SW biosynthesis were identified in the transcriptome and metabolome analysis of A. oxytropis OW 7.8 and ΔswnK-ACP. The SW biosynthesis pathway in A. oxytropis OW 7.8 was predicted and refined. These results may lay foundation of in-depth analysis of the molecular mechanisms and metabolic pathway of SW synthesis in fungi, and provide reference for future control of SW in locoweed, which would benefit the development of grassland animal husbandry and the sustainable use of grassland ecosystem.

Background: Before the COVID-19 outbreak, food microbiology was crucial in identifying and preventing foodborne pathogens like Salmonella and E. coli. The pandemic underscored the importance of this discipline, highlighting the need for enhanced surveillance and microbiological control in the food chain to prevent future global public health threats. This research aimed to advance knowledge management in Bioeconomy, focusing on Eco-Intensification and biotechnology applications that directly affect food microbiology, especially in the context of the COVID-19 crisis. Methodology: The study involved a comprehensive literature review grounded in the epistemological principles of Bioeconomy, utilizing the Bibliometric Scopus database. This approach facilitated the exploration of the development of eco-intensification and biotechnology applications within food safety and nutrition microbiology. Results: The findings emphasize the importance of understanding the social and economic impacts of microbiological activities in food intake through a Bioeconomy lens. The research highlights the need for integrating microbiological insights into broader bioeconomic frameworks to address food safety and sustainability challenges effectively. Conclusion: Recommendations are provided for decision-makers to enhance public health agendas from a bioeconomic perspective. These recommendations aim to strengthen the focus on Bioeconomy and improve the management of interactions between food microbiology and the challenges exacerbated by the COVID-19 pandemic.

Gestational Diabetes Mellitus (GDMs) is worldly wide pregnancy complication. Gestational Diabetes can significantly impact the fetus development. However, the effects of high glucose on embryological development post-fertilization are yet to be researched. Danio rerio embryos are great model to study the embryonic development. In this study, the effects on embryological (morphological and genetic) development were examined in the presence of a high glucose environment that mimic the developing fetus in pregnant women with GMD. Fertilized Zebrafish embryos were treated with normal media and high glucose for 5 days from 3 hours post-fertilization(hpf) to 96hpf respectively as control and experimental groups. Morphological changes are recorded with Microscope images. Hatch rate and heart rate are compared between groups in set up time points. RNA-Seq is performed to examine the gene changes in experimental group. Glucose delayed the zebrafish embryo development by slowing the hatch rate about 24 hours. The brain, heart, and tail started showing morphology smaller in the glucose group compared to the control group at 24 hpf. Heart rate is faster in the glucose group compared to the control group on day 2 and 3 with a statistically significant difference. Among zebrafish whole genome, the significantly changed genes are 556 genes up-regulated and 1118 genes down-regulated respectively in high glucose group. The metabolic and Wnt pathways are altered under high glucose condition. These conditions contribute to significant physiological differences that may provide insight on functionality post-embryological development.

L-cysteine, a precursor of essential components for plant growth, is synthesized by the cysteine synthase complex, which includes O-acetylserine(thiol) lyase (OAS-TL) and serine acetyltrans-ferase. In this work, we investigated how S-benzyl-L-cysteine (SBC), an OAS-TL inhibitor, affects the growth, photosynthesis, and oxidative stress of Ipomoea grandifolia plants. SBC impaired gas exchange and chlorophyll a fluorescence, indicating damage that compromised photosynthesis and reduced plant growth. Important parameters such as light-saturated net photosynthetic rate (PNmax), light saturation point (LSP), maximum carboxylation rate of Rubisco (Vcmax), electron transport rate (J), and triose phosphate utilization (TPU) decreased as a result. The quantum yield of photosystem II photochemistry (ϕPSII) and the electron transport rate through PSII (ETR) also decreased, as did the stomatal conductance (gs) and the photochemical quenching coefficient (qP). Additionally, SBC decreased the maximum fluorescence yield (Fm), variable fluorescence (Fv), and chlorophyll index, indicating possible damage to the photosynthetic apparatus. SBC triggered oxidative stress by increasing reactive oxygen species, malondialdehyde, and conjugated dienes. We hypothesize that dysfunctions in the sulfur-containing components of the photosynthetic electron transport chain, such as the cytochrome b6f complex, ferredoxin, and iron-sulfur (Fe-S) centers are the cause of these effects, which ultimately reduce the efficiency of electron transport and hinder photosynthesis in I. grandifolia plants. In short, our findings suggest that targeting OAS-TL with inhibitors such as SBC could be a promising strategy for the development of novel herbicides.

Lirianthe delavayi has valuable ornamental and medicinal value, is an important economic tree, and has a long history of cultivation. As important regulatory molecules, miRNAs are involved in important physiological processes, such as the plant stress response, organ morphogenesis, hormone secretion, and signaling. In this study, based on miRNA sequencing analysis of wild and cultivated Lirianthe delavayi, we explored the differences in posttranscriptional regulation during the cultivation of Lirianthe delavayi from the aspect of miRNA molecular regulation. The results revealed the following: 1. A total of 365 miRNAs were sequenced and identified, and their first bases had obvious uracil (U) base preferences. Among them, 242 miRNAs were classified into 32 miRNA families; 2. Analysis of miRNA expression differences revealed that 39 miRNAs had significant expression differences between wild and cultivated populations; 3. Bioinformatics target gene prediction and target gene enrichment analysis of significantly differentially expressed miRNAs revealed that the target genes were significantly enriched in plant‒pathogen interactions, sphingolipid metabolism, defense responses, and ADP binding. 4. The plant‒pathogen interaction pathway involves seven differentially expressed miRNAs and 30 miRNA‒target gene regulatory pairs, which are involved mainly in pathogen signature molecule recognition and binding, signal transduction, and the regulation of disease resistance molecules or gene expression; Ath-MIR169g-p3_2ss7AG19GA, ath-MIR169g-p5_2ss7AG19GA, and ath-miR408-3p_L-3 are expressed only in wild population, and it is hypothesized that the domestication process from wild to cultivation species may be accompanied by the loss of disease resistance-related miRNAs. This study provides a reference for exploring the posttranscriptional-level regulatory mechanisms of adaptive changes in Lirianthe delavayi from wild to cultivated.

A proof is given showing the Collatz Conjecture is true for all positive integers. The proof was possible once the perspective of the proof was changed from looking at the pattern of the positive integers to looking at the conjecture rules. The conjecture rule for even numbers organizes all positive integers into unique sets and the rule for odd numbers interconnects the unique sets into dendritic pathways to “1.” Infinite loops, other than the minor 4-2-1 loop after reaching “1,” and pathways to infinity are shown to be mathematically impossible. The proof predicted a general equation that shows all positive integers ultimately reach a final value of “1," and calculates the values and locations of the odd positive integers during the iterations for each tested positive integer.

Abstract: Lung cancer, characterized by its heterogeneity, presents a significant challenge in ther-apeutic management, primarily due to the development of resistance to conventional drugs. This resistance is often compounded by the tumour’s ability to reprogram its metabolic pathways, a survival strategy that enables cancer cells to thrive in adverse conditions. This review article ex-plores the complex link between drug resistance and metabolic reprogramming in lung cancer, offering a detailed analysis of the molecular mechanisms and treatment strategies. It emphasizes the interplay between drug resistance and changes in metabolic pathways, crucial for developing effective lung cancer therapies. The review examines the impact of current treatments on metabolic pathways and the significance of considering metabolic factors to combat drug resistance. It highlights the different challenges and metabolic alterations in non-small cell lung cancer and small cell lung cancer, underlining the need for subtype-specific treatments. Key signalling pathways, including PI3K/AKT/mTOR, MAPK, and AMPK, have been discussed for their roles in promoting drug resistance and metabolic changes, alongside the complex regulatory networks involved. The article evaluates emerging treatments targeting metabolism, such as metabolic inhibitors, dietary management, and combination therapies, assessing their potential and challenges. It concludes with insights into the role of precision medicine and metabolic biomarkers in crafting personalized lung cancer treatments, advocating for metabolic targeting as a promising approach to enhance treatment efficacy and overcome drug resistance. The review underscores ongoing advancements and hurdles in integrating metabolic considerations into lung cancer therapy strategies.

The shikimate pathway is crucial for the biosynthesis of aromatic amino acids in plants and represents a promising target for developing new herbicides. This work aimed to identify inhibitors of shikimate dehydrogenase (SDH), a key enzyme of the shikimate pathway that catalyzes the conversion of 3-dehydroshikimate to shikimate. Virtual screening and molecular docking were performed on the SDH active site of Arabidopsis thaliana (AtSDH), and 6-nitroquinazoline-2,4-diol (NQD) was identified as a potential inhibitor. In vitro assays showed that NQD decreased the activity of AtSDH by reducing Vmax while keeping KM unchanged, indicating noncompetitive inhibition. In vivo, hydroponic experiments revealed that NQD reduced the root length of soybean and maize. Additionally, NQD increased the total protein content and certain amino acids. Soybean roots uptake NQD more efficiently than maize roots. Furthermore, NQD reduced shikimate accumulation in glyphosate-treated soybean roots, suggesting its potential to restrict the flow of metabolites along the shikimate pathway in soybean. Simultaneous treatment of maize seedlings with glyphosate and NQD accumulated gallic acid in the roots, indicating that NQD inhibits SDH in vivo. Overall, the data indicate that NQD inhibits SDH both in vitro and in vivo, providing valuable insights into the potential development of herbicides targeting SDH.

A prior investigation revealed that a lack of Zinc (Zn) could hinder the intestinal cell proliferation in broiler chickens; however, the mechanisms responsible for this effect remain unclear. We aimed to investigate the possible mechanisms of dietary Zn deficiency in inhibiting the jejunal cell proliferation of broilers. For this study, a total of 112 chickens (21 d old) were randomly divided into two treatments (n = 7, 8 chickens per replicate cage): control (CON) and Zn deficiency groups. The duration of feeding was 21 d. Chickens in the CON group were provided with a basal diet containing an extra addition of 40 mg Zn/kg in the form of Zn sulfate, whereas chickens in the Zn deficiency group were given the basal diet with no Zn supplementation. The results indicated that, in comparison to the CON, Zn deficiency increased (P < 0.05) duodenal and jejunal crypt depth (CD) of broilers on d 28 and jejunal and ileal CD on d 35, and decreased (P < 0.05) duodenal, jejunal and ileal villus height/crypt depth (VH/CD) on d 28 and jejunal VH, jejunal and ileal villus surface area and VH/CD on d 35. Furthermore, Zn deficiency decreased (P < 0.0001) the amount of proliferating cell nuclear antigen positive cells, and down-regulated (P < 0.01) mRNA or protein expression levels of phosphatidylinositol 3-kinase (PI3K), phosphorylated PI3K, phosphorylated serine threonine kinase (AKT), phosphorylated mechanistic target of rapamycin (mTOR), G protein-coupled receptor 39 (GPR39), and extracellular regulated protein kinase, but up-regulated (P < 0.05) mRNA or protein expression levels of P38 mitogen activated protein kinase, c-jun N-terminal kinase (JNK) 1 and JNK2 and phosphorylated Protein Kinase C in the jejunum of broilers on d 42. It was concluded that dietary Zn deficiency inhibited the cell proliferation possibly via GPR39-mediated suppression of PI3K/AKT/mTOR signaling pathway in the jejunum of broilers.

Chrysin, a flavonoid compound, has attracted interest as a therapeutic agent due to its anti-inflammatory, antidiabetic, antidepressant, and particularly its anticancer properties. Although studies have presented findings regarding the anticancer properties of chrysin, research on its molecular mechanisms of action remains largely insufficient. This research aimed to deeply investigate chrysin's effects on the breast cancer cell line, MDA-MB-231, in terms of proliferation, invasion, colony formation, and apoptosis. The XTT test results confirmed chrysin's cytotoxic effect on MDA-MB-231 cells, indicating a 48-hour IC50 value of 115.77 µM. Chrysin induced apoptosis in cells, as evidenced by Annexin V assay, and also reduced their colony-forming and invasion. Gene expression analyses showed elevated levels of APC, AXIN1, AXIN2, GSK3A, GSK3B, CK1α, CTNNB1, as well as apoptosis-related genes CASP3, -7, -9, and BAX. This increase was corroborated by the observed rise in protein levels of caspase 3/7 and GSK3B. Moreover, molecular docking results showed that chrysin interacted with genes in the WNT/β-catenin pathway and exhibited drug-like ADME properties. In conclusion, chrysin exhibits potential anticancer effects against MDA-MB-231 cells. It is hoped that these findings will advance preclinical and clinical studies on chrysin's potential in breast cancer treatment.

The application of melatonin (MT) has been shown to improve the quality during the storage of fruits and vegetables. The primary objective of this study is to investigate the effects of MT on the quality of fresh-cut Gastrodia elata during low temperature (4°C) storage. The results indicate that MT treatment could suppress the respiratory rate and malondialdehyde content of fresh-cut G. elata, while also slowing down the decline in total acidity and total soluble solids. The treatment with MT reduced the superoxide anions and hydrogen peroxide production, inhibited the activity and expression of peroxidase and polyphenol oxidase. Additionally, it led to increased activity and expression of antioxidant-related enzymes, including superoxide dismutase, catalase, ascorbate peroxidase, glutathione reductase, monodehydroascorbate reductase, and dehydroascorbate reductase, while also resulted in elevated levels of ascorbic acid and glutathione. Furthermore, the treatment with MT induced an increase in total phenolic and flavonoid content of fresh-cut G. elata and enhanced the activity and expression of key enzymes involved in phenylpropanoid pathway (phenylalanine ammonia-lyase, cinnamate-4-hydroxylase, 4-coumarate: CoA ligase). In summary, MT enhances the antioxidant capacity by activating both ROS metabolism and phenylpropanoid pathway, thus maintaining the quality of fresh cut G. elata.

Bone Morphogenetic Proteins (BMPs) are a group of structurally and functionally related signaling molecules that comprise a subfamily, belonging to the TGF-β superfamily. Most BMPs play roles in the regulation of embryonic development, stem cell differentiation, tumor growth and some cardiovascular and cerebrovascular diseases. Although evidences are emerging for the antiviral immunity of a few BMPs, more BMPs are needed to determine whether this function is universal. Here we identified the zebrafish bmp4 ortholog, whose expression is up-regulated by challenge with virus or its mimic poly(I:C). Overexpression of bmp4 in EPC cells significantly decreased the viral titer of GCRV-infected cells. Moreover, compared to wild type zebrafish, viral load and mortality were significantly increased in both larvae and adults of bmp4-/- mutant zebrafish infected with GCRV virus. We further demonstrated that Bmp4 promotes the phosphorylation of Tbk1 and Irf3 through p38 MAPK pathway, thereby inducing the production of type I IFNs in response to virus infection. These data suggest that Bmp4 runs an important role in the host defense against virus infection. Our study expands the understanding of BMP protein functions and opens up new targets for the control of viral infection.

Knee Osteoarthritis (KOA) is a chronic disease characterized by progressive disability and joint pain. Meniscus chondrocytes apoptosis is the main cause of reduced chondrocyte number and self-repair function. The purpose of this study was to investigate the role of miR-27b-3p in KOA.In this study, we found that the expression of miR-27b-3p was downregulated in cultured IL-1β treated chondrocyte and cartilage tissues in KOA. KOA overexpression evidently reduced IL-1β induced chondrocyte apoptosis and caspase-3 and caspase-9 expression.The upregulated iNOS and COX-2 mRNA and proteins expression was also inhibited by miR-27b-3p mimics. The expression of nitric oxide, PGE2, TNF-α and IL-6 was also inhibited by miR-27b-3p mimics. The target gene of miR-27b-3p was confirmed to be BDNF. TrkB/CREB pathway was proved to be the downstream pathway of miR-27b-3p/BDNF axis.The apoptotic cell percentage and nitric oxide, PGE2, TNF-α and IL-6 expression was induced by BDNF+IL-1β. This induction was inhibited by miR-27b-3p mimics. The cartilage tissues stained with safranin O results showed miR-27b-3p greatly decreased KOA induced cartilage degradation. The expression of BDNF、TrkB and p-CREB was inhibited by len-miR-27b-3p. MiR-27b-3p also reduced the expression of TNF-α、IL-6 and Bax, and increased Bcl-2 expression. These results indicated miR-27b-3p could applied to inhibit the development of KOA and miR-27b-3p/BDNF/TrkB/CREB pathway could serve as novel treatment target to handle KOA.

The nuclear factor-ĸB (NF-ĸB) transcriptional system is a major effector pathway involved in inflammatory responses. Previous studies found that a Gardenia decoction (GD) inhibited the expression of NF-κB in a lipopolysaccharide (LPS)-stimulated mouse intestinal injury model. Herein, we hypothesized that geniposide (GE), a component of Gardenia jasminoides Ellis, also exerts anti-inflammatory effects and inhibits NF-ĸB activity in LPS-induced intestinal epithelial cells (IEC-6). IEC-6 cells were stimulated with LPS, following which the effects of GE on NF-ĸB signaling in the IEC-6 cells were examined by western blotting to detect IĸB phosphorylation/degradation. The expression of NF-κB was determined by immunofluorescence assay (IFA). Enzyme-linked immunosorbent assay (ELISA) was used to detect the inhibitory effect of GE on the release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) activated by LPS in IEC-6 cells. In addition, the migration ability of IEC-6 cells was observed by the scratch method. These results showed that GE dose-dependently downregulated levels of the proinflammatory cytokines TNF-α, IL-6 and IL-1β that had been upregulated by LPS and suppressed the phosphorylation of IĸB and NF-ĸB induced by LPS. Our findings indicated that GE could reduce LPS-induced NF-ĸB signaling and proinflammatory expression in IEC-6 cells and significantly enhance the migration of IEC-6 cells. Moreover, GE inhibited the expression of NF-κB, nuclear transfer, and transcriptional activity in IEC-6 cells. GE could block the synthesis of inflammatory factors of IEC-6 cells by inhibiting activation of the IĸB/NF-κB signaling pathway induced by LPS.

The imipramine ONC201 exerts a novel anti-proliferative activity over a wide spectrum of cancer cell types. ONC201 activates integrated stress response pathway that is associated with induction of Damage Inducible Transcript 3 (DDIT3, also known as C/EBP homologous protein or CHOP). We questioned whether the ONC201/CHOP crosstalk is regulated by diverse signaling pathways in non-metastatic versus metastatic cancer cell lines. Therefore, the Dukes' type B colorectal adenocarcinoma non-metastatic (SW480) and metastatic (LS-174T) cell lines were treated with ONC201. Cell proliferation and apoptosis were evaluated by MTT assay, flow cytometry analysis, gene expression was assessed by Affymetrix microarray, and key regulatory proteins were validated by Western blot assays. Unlike LS-174T cells, SW480 cells were resistant to ONC201 treatment. Gene ontology pathway enrichment analysis of differentially expressed genes revealed substantial differences between LS-174T and SW480 responsiveness to ONC201 treatment. In both cell lines, CHOP expression was upregulated in response to ONC201 treatment, however, its upstream regulatory mechanisms were not identical. Although, PERK, ATF6 and IRE1 ER-stress pathways were found to upregulated CHOP in both cell types, the BAK/BAX pathway was a notable regulator of CHOP in the metastatic LS-174T cells alone. In addition, CHOP RNA splicing profiles were varied between the two cell lines, which was further modified in response to ONC201 treatments. In conclusion, we delineated the signaling mechanisms regulating the expression of CHOP in non-metastatic versus metastatic colorectal cells in response to ONC201 treatment. The observed differences were related to cellular plasticity and metabolic reprogramming.

Cervical cancer is known as one of the most important cancers in women worldwide. Chemotherapy is a standard treatment for advanced/recurrent cervical cancer in which the prognosis of the disease is really poor and the 1-year survival chance in these patients is maximally 20%. However, resistance to anticancer drugs is a major problem in treating cancer. Cervical cancer stem cells are considered as a fundamental cause of chemo and radio-resistance and also relapse after primary successful treatment. Signaling pathways include a wide range of molecular mechanisms contribute to drug resistance. Recently, microRNAs (miRNAs) are announced as a group of molecular biomarkers involving in response to chemotherapy in cancer patients. As the miRNAs, there are some long non-coding RNAs (LncRNAs) which their aberrant expression is considered as a biomarker for monitoring chemoresistance. In this review, we summarized current reports about the involvement of signaling pathways during chemoresistance in cervical cancer. Then, genes that have been demonstrated their involvement during drug resistance in cervical cancer were tabulated. Further, miRNAs that have been reported as biomarkers during treatment are listed. By bioinformatic analysis, we predictedmiR-335-5p and miR-16-5p as the most potential biomarkers for monitoring resistance to chemotherapy. Finally, long non-coding RNAs that have been introduced in recent studies as novel biomarkers during the response to chemotherapy were mentioned.

Rice (Oryza sativa L.) processing yields ~60 million metric tons of bran annually. Rice genes producing bran metabolites of nutritional and human health importance were assessed across 17 diverse cultivars from seven countries using non-targeted metabolomics and resulted in 378-430 metabolites. Gambiaka cultivar had the highest number and Njavara had the lowest number of metabolites. The 71 rice bran compounds of significant variation by cultivar included 21 amino acids, seven carbohydrates, two metabolites from cofactors and vitamins, 33 lipids, six nucleotides, and two secondary metabolites. Tryptophan, -ketoglutarate, γ-tocopherol/β-tocopherol and γ-tocotrienol are example bran metabolites with extensive cultivar variation and genetic information. 34 rice bran components that varied between cultivars linked to 535 putative biosynthetic genes using to the OryzaCyc 4.0, Plant Metabolic Network database. Rice genes responsible for bran composition with animal and human health importance is available for rice breeding programs to utilize in crop improvement.

Here we first report, how cholera toxin (CT) A subunit (CTA), the bacterial enzyme moiety responsible of cell signaling alteration, can take over the exosomal pathway, spread extracellularly and be transmitted in a cell population. A first evidence for long-term transmission of CT toxic effect via extracellular vesicles was obtained in CHO cells. To follow CT intracellular route towards exosome secretion we adopted a strategy apt to convert multivesicular body (MVB) derived exosomes in traceable fluorescent vectors. CT treated Me665 cells, a human melanoma cell line highly expressing caveolin-1 (Cav-1) and GM1, were used to purify and characterize fluorescent exosomes. Our results clearly show association of CT with exosomes together with typical exosomal markers and the HSP90 and PDI molecules, the required membrane translocation elements of CTA to the cytoplasm. Confocal microscopy proved direct CT containing fluorescent exo transfer into CHO cells coupled with the morphological cell change characteristic of CT action. Moreover, direct assessment of cAMP levels in Me665 cells treated with CT containing exo showed an efficient induction of cAMP increase comparable with CT alone. From our results, we can infer that CT can exploit exosome-mediated cell communication to target and extend its pathophysiological action throughout cell tissues.

Human immunodeficiency virus (HIV) and malaria, caused by infection with Plasmodium spp., are endemic in similar geographical locations. As a result, there is high potential for HIV/Plasmodium co-infection, which increases the pathology of both diseases. However, the immunological mechanisms underlying the exacerbated disease pathology observed in co-infected individuals are poorly understood. Here, we used the rhesus macaque (RM) model to characterize the immunopathogenic impact of Plasmodium fragile co-infection during antiretroviral therapy (ART)-treated simian immunodeficiency virus (SIV)-infection. We observed that P. fragile co-infection resulted in parasitemia and anemia, as well as persistently detectable viral loads (VL) and decreased absolute CD4+ T-cell counts despite daily ART treatment. Notably, P. fragile co-infection was associated with increased levels of inflammatory cytokines linked with neutrophil function, including monocyte chemoattractant protein 1 (MCP-1). P. fragile co-infection was associated with increased levels of neutrophil elastase, a plasma marker of neutrophil extracellular trap (NET) formation, but significant decreases in markers of neutrophil degranulation, potentially indicating a shift in neutrophil functionality during co-infection. Finally, we characterized levels of plasma markers of gastrointestinal (GI) barrier permeability and microbial translocation and observed significant correlations between indicators of GI dysfunction, clinical markers of SIV and Plasmodium infection, and neutrophil frequency and function. Taken together, these data indicate that neutrophil-driven inflammation and GI dysfunction may underlie heightened SIV/P. fragile co-infection pathogenesis.

Opuntia ficus-indica has always interacted with many phytophagous insects at its center of origin; two of them are Dactylopius coccus and D. opuntiae. D. coccus, or true cochineal, is produced to extract carminic acid, and D. opuntiae or wild cochineal is a key invasive pest of O. ficus-indica in more than 20 countries around the world. Despite the economic and environmental relevance of this cactus and, D. opuntiae and D. coccus, there are few studies that have explored volatile organic compounds (VOCs) derived from the plant-insect interaction. The aim of this work was to determine VOCs of D. coccus and D. opuntiae feeding on cultivars suitable for their development and to identify different VOCs in cladodes infested by each Dactylopius species. Volatiles were identified through their essential oils, which were obtained by hydrodistillation. A total of 66 VOCs from both Dactylopius species were identified, and 125 from the Esmeralda and Rojo Pelón cultivars infested by D. coccus and D. opuntiae, respectively, were determined. Differential VOCs production due to infestation by each Dactylopius species was also found. Some changes in methyl salicylate, terpenes such as linalool or the alcohol p-vinylguaiacol were related to Dactylopius feeding on cladodes of their respective cultivars. Changes in these VOCs and their probable role in plant defense mechanisms should receive more attention because this knowledge could improve D. coccus rearing, or to its inclusion in breeding programs for D. opuntiae control in regions where it is a key pest of O. ficus-indica.

In the recent past, the number of invasive species around the world has increased significantly due to increased globalization and climate change. Understanding biological invasions under climate change is crucial for sustainable conservation of biodiversity. The insect pest Pseudococcus viburni (Signoret) can cause damages to plants, resulting in leaf yellowing, leaf defoliation, and reduced plant growth. A serious attack by this insect post can even lead to the entire plant withering and dying, bringing huge economic and ecological losses. Despite these damages, the potential distribution range and management strategies for this insect pest are poorly understood. Based on historical distribution data and environmental factors, the present study predicted the potentially suitable areas for P. viburni spread under different climate change scenarios using MaxEnt (maximum entropy). The results showed that precipitation of the coldest quarter (Bio19), precipitation seasonality (Bio15), and mean temperature of the wettest quarter (Bio8) were the most important environmental factors determining the distribution of P. viburni. Under the current climate conditions, its potential suitable areas are southern China, the whole of Japan, North America (especially the eastern part of the United States), the southwestern part of South America, the Mediterranean coast and most of Europe, the central part of Africa i.e., the south of the Sahara Desert and most of the southern coast of Australia. The total area of habitats suitable for this insect pest is predicted to be increased in the future. In order to prevent P. viburni transmission and spread, there is a need to strengthen the monitoring and quarantine measures against this pest at the Southern ports.

Lignin, and its by-products in the effluent of most agrochemical-based industries like pulp and paper, increase environmental pollution. There is, therefore, an increasing demand to degrade lignin and its derivatives using bacteria-produced ligninolytic enzymes. This study focused on optimizing growth and lignin peroxidase production of ligninolytic potential bacterial strains (E. coli accession no: LR0250096.1 and P. aeruginosa accession no: CP031449.2) for the first time. A submerged fermentation process was used to simultaneously optimize growth and crude lignin peroxidase production using kraft lignin as the substrate. The E. coli and P. aeruginosa were separately cultured under different pH, temperature, lignin (substrate) concentration and incubation periods. It was observed that the enzyme production was growth dependent. The optimum conditions for E. coli were pH 7.5, temperature 30 °C and lignin concentration 1 g/L. For P. aeruginosa the best conditions were pH 6.5, temperature 40 °C and lignin concentration 1 g/L. The enzyme production peaked after 7 days of incubation for both organisms were 21.53 ± 3.11 mg/ml and 18.13 ± 2.1 mg/ml respectively. It is apparent that both E. coli (LR0250096.1) and P. aeruginosa (CP031449.2) are mesophiles bacteria. E. coli function best in alkaline pH while P. aeruginosa prefers a slightly acidic environment. Hence, they are promising candidates in the reduction of lignocellulosic wastes.

The development of good conductivity p-type β-Ga2O3 is critical to realize its devices and applications. The nitrogen-doped p-type β-Ga2O3 films with enhanced conductivity characteristics were prepared through the thermal oxidation of GaN in the N2O atmosphere. Further measurements were performed on the oxidized films at 1000, 1050, and 1100 °C to have insight into the underlying mechanism of the thermally activated transformation process. The room temperature photoluminescence (PL) spectra demonstrated a moderate ultraviolet emission peak at 246 nm, confirming the generation of gallium oxide with a band gap of ~5.0 eV. The normalized X-ray diffraction (XRD), the high-resolution transmission electron microscopy (HRTEM), and the selected area electron diffraction (SAED) patterns were used to confirm the characteristic of polycrystalline and anisotropic growth. Then, the effects of the oxidation temperature on the amount of incorporated nitrogen were analyzed using secondary ion mass spectrometry (SIMS). Moreover, the ionization energy of the acceptor of films oxidized at 1000, 1050, and 1100 °C was calculated and analyzed using the temperature-dependent Hall test results. The results showed that nitrogen doping was the main contributor to p-type electrical properties. The activation energy of the polycrystalline β-Ga2O3 prepared through thermal oxidation of GaN in the N2O atmosphere was estimated to be 147.175 kJ·mol-1 using the Arrhenius plot, which was considerably lower than that of both dry and wet oxidations of GaN in O2 ambient, thus confirming the efficiency of thermal oxidation of GaN in N2O.

The Mediterranean region offers good weather conditions for outdoor pig production (OPP), which is considered more environmentally friendly than intensive indoor production. However, the continuous input of food and pigs' excreta increases the soil organic matter (SOM) and phosphorus (P), increasing the risk of waterbodies eutrophication. This work aimed at evaluating in OPP areas soil P dynamics and the role of SOM on P sorption and P release. The experiment was done for two years, at an area of 2.8 ha with an animal charge of 9 adults ha-1. Georeferenced soil samples were taken at 0.20 m depth, and a soil P sorption experiment was carried out. At the end of the experiment, for the background value, the levels of SOM increased between 85–376%, and Olsen P values ranged between -82–884%. SOM levels above 2% caused a decrease in the binding energy of P sorption according to the linear model b=-15.541SOM+115.20 (p <0.01) as well as a decrease of the soil P sorption capacity Qmax=-41.272SOM+298.37 (p <0.01). To avoid the accumulation of SOM and P preventing hotspots for waterbodies eutrophication, an adequate animal charge together with soil cultivation for pig grazing can be a cost-effective practice.

Antisense technologies consist of the utilization of oligonucleotides or oligonucleotide analogs to interfere with undesirable biological processes, commonly through inhibition of expression of selected genes. This field holds a lot of promise for the treatment of a very diverse group of diseases including viral and bacterial infections, genetic disorders, and cancer. To date, drugs approved for utilization in clinics or in clinical trials target diseases other than bacterial infections. Although several groups and companies are working on different strategies, the application of antisense technologies to prokaryotes still lags with respect to those that target other human diseases. In those cases where the focus is on bacterial pathogens, a subset of the research is dedicated to produce antisense compounds that silence or reduce expression of antibiotic resistance genes. Therefore, these compounds will be adjuvants administered with the antibiotic to which they reduce resistance levels. A varied group of oligonucleotide analogs like phosphorothioate or phosphorodiamidate morpholino residues, as well as peptide nucleic acids, locked nucleic acids and bridge nucleic acids, the latter two in gapmer configuration, have been utilized to reduce resistance levels. The major mechanisms of inhibition include eliciting cleavage of the target mRNA by the host’s RNase H or RNase P, and steric hindrance. The different approaches targeted resistance to β-lactams including carbapenems, aminoglycosides, chloramphenicol, macrolides, and fluoroquinolones.

Adsorption is an effective strategy for the removal of pollutants from the wastewater. Herein, a 2-hydroxyterephthalic acid (HTC) modified hypercrosslinked polymer (HTC-HCP) is successfully synthesized via Friedel-Crafts reactions, and used as an adsorbent for the different types of pollutants including organic contaminants and heavy metal ions from wastewater. Excellent adsorption capacities are observed for amines (aniline, p-methylaniline (p-MA), p-chloroaniline (p-CA), and p-aminobenzoic acid (p-ABA)), phenols (phenol, p-chlorophenol (4-CP) Bisphenol A (BPA), 1-Naphthol (1-NP)), dyes (rhodamine B (RhB) and methyl orange (MO)), and metal ions (Pb2+, Hg2+, and Cd2+). The resulting polymers exhibited excellent adsorption performance towards these pollutants. Especially, the removal rate of aniline is above 95% in the concentration of 2.5 mg/L in 40 min at 25 °C. The interaction mechanism has been investigated, and confirmed by FTIR and the theoretical calculation results. It is due to surface complexation and chemisorption between adsorbent and adsorbate. The polymer exhibits good performance such as high adsorption capacity, high separation efficiency, biodegradable properties, and easy regeneration, suggesting that its potential technological applications for the removal of organic compounds and heavy metal ions from actual industrial effluent.

In these times electricity is big trouble of problem facing by the world. Therefore, there is necessitating for the property basis of energy that is employed for as bio-electricity. Many of the scientists and researchers are trying to find out the sustainable energy generates with the help of plant microbial fuel cell. Plant microbial fuel cell (P-MFCs) could be feasibility technology approach of bio-electricity generation which is mutualism interaction of the plants along with their rhizospheric bacteria. In the present study, Plant-microbial fuel cell was observed in grass e-table evaluated in term of bioelectricity generation from Cynodon dactylon (Dooba Ghas). This e-table was connected with electrode and different condition (physical and chemical) to detect the change in bioelectric potential. It was found that maximum voltage generated among all the conditions was 4.24 ±2V at 15 days by using Cynodon dactylon through P-MFCs. The potential difference generated through P-MFCs was measured using a multimeter. The generation of bioelectricity was observed under different conditions like exposure to light and shade condition measured for voltage was found to be significantly different parameters. The maximum recorded under light and shade conditions were 3.82 ±2 V and 4.25 ±2 V respectively at 15 days of incubation.

Alterations in root morphology and physiology are important strategies in plants to adapt to low-phosphorus (P) environments. Maize genotypes differed in nitrogen (N) efficiency may also respond differently to low P stress. This study aimed to investigate the responses of root morphological and physiological traits of these two maize cultivars to P deficit and how these traits were linked with the acquisition of soil P. Two maize cultivars, XY335 (N efficient) and ZD958 (N inefficient), were cultivated for 40 days in a calcareous loamy soil amended with (high P) or without (low P) P. Functional root traits were used to evaluate the morphological and physiological responses to low P supply. Two separate short-term experiments determined the correlation between P uptake rate and P supply intensity (hydroponic) or root hair length under two P treatments (rhizobox). Low P status significantly simulated biomass allocation to roots, specific root length and exudations of carboxylates, while decreased root diameter and rhizosphere pH in both maize cultivars. Two cultivars had different total root length and root surface area under low P stress: increased in ZD958 and decreased in XY335. Both genotypes developed longer root hair under P deficit. ZD958 (greater biomass and shoot P content) has a greater capability at accessing soil P than XY335. Rhizosphere exudation of citric acid was significantly higher in ZD958 than in XY335, while there was not significant genotypic difference in rhizosphere pH and exudation of malic acid and acid phosphatase activity. ZD958 had higher P uptake rate than XY335 when solution P was between 12.5 and 250 µM. This study identified ZD958 as a P-efficient genotype, which better adapted to low P stress by altering root physiological traits (exudation of citric acid and P uptake rate), rather than root morphological traits (total root length, root surface area, root hair length). Our results highlight the importance of analyzing root morphological and physiological traits to enhance our understanding of the physiological mechanisms of P acquisition.

Background/Objectives: Post traumatic growth (PTG) has the potential to draw positive consequences from trauma. Hence, the interest of finding ways to promote PTG. Research has identified an attentional bias towards positive resilience-related words (e.g., “persistence”, “purpose”) in university students who report high PTG after experiencing adversities. Although people can respond to these experiences by showing low PTG, this bias seems to help with their struggle by making purposeful contents more accessible. Therefore, boosting attentional bias towards positive resilience-related words could help people with low PTG. Methods: In this study, the participants were thirty-six university students who had experienced bullying before entering university. Using a Stroop emotional task, they identified the color of resilience and neutral words, either positive or negative, before and after being submitted to transcranial direct current stimulation. Stimulation was targeted at the right temporal area involved in intentionality processing. Results: In the anodal condition, the results support a stimulation effect on the resilience attentional bias that could benefit participants with low PTG. A significant moderation of approach motivation for this effect was also found. Specifically, only when participants had medium or high approach motivation, did stimulation boost the attentional bias in students with low PTG. Conclusions: These results support that tDCS stimulation in this brain area is effective in enhancing resilience attentional bias in low PTG students. However, for this effect to occur it is necessary to have approach motivation, which is motivation related to goals.

Forest quality has a significant impact on carbon emissions of the economic system. This paper, based on an analysis of the Environmental Kuznets Curve (EKC) of Forest quality and carbon emission of economic systems, explores effective carbon emission reduction paths from the perspective of symbiosis between Forest quality and economic growth system. This paper carries out empirical analysis based on the provincial-level regional data of China and EKC panel data analysis for several major geographic regions in China. The correlation statistical test shows that the model considering Forest quality is more consistent with the test requirements. It is found that the overall EKC curve of China as a whole shows an inverted U-shape. In light of geographic differences, the EKC curve in the northwest also shows an inverted U-shape; it shows a U-shaped curve in North, Northeast, and East China. Meanwhile, in South Central and Southwest China, there is an approximately linear increasing curve. The data simulation of the symbiotic system of Forest quality and economic growth suggests that simultaneously increasing the proportion of forestry output value and the systematic carbon inhibition coefficient is the most effective pathway for carbon emission reduction. Choosing an appropriate carbon reduction pathway can contribute to the sustainable development of Forest quality and economic growth. The main research highlight of this paper is the application of the symbiotic system model to the EKC analysis of carbon emissions from the economic system with Forest quality.

Sepsis, characterized by a dysregulated systemic inflammatory response to infection, remains a significant global health burden, despite substantial advancements in its treatment. An understanding of the underlying mechanisms driving sepsis is crucial for the development of targeted therapeutic strategies. Silent information regulator 1 (SIRT1), a member of the class III histone deacetylases, plays a pivotal role in regulating gene expression by catalyzing the deacetylation of lysine residues on non-histone and histone proteins. With the advancement of sepsis research, SIRT1 has been shown to exert significant anti-inflammatory, anti-oxidative, anti-apoptotic, and metabolic regulatory effects, positioning it as a potential therapeutic target for sepsis. This article reviews the latest progress on research into the signaling pathways modulated by SIRT1 in sepsis and its associated regulatory mechanisms to further elucidate the pathogenesis of sepsis and assist in guiding clinical treatment.

Green leaf volatiles (GLVs) are important in giving grape a fresh and green aroma. But the changes in GLVs during the phenological development of grapevines are not well known. This study analysed the GLVs and transcription levels of associated biosynthetic genes in six grape species from the Loess Plateau region at five stages of maturation. Thirteen GLVs were detected, showing unique patterns for each grape type at various growth phases. The primary components in six grapes were (E)-2-Hexenal, (E)-2-Hexen-1-ol, and Hexanal. With the exception of Cabernet Franc in 2019, the overall GLV contents of the six types generally increased during growth and development, peaking or stabilizing at harvest. And Sauvignon Blanc, Cabernet Gernischt, and Cabernet Sauvignon exhibited higher total contents among the varieties. Correlation analysis revealed a strong positive correlation between the levels of Hexanal, 1-Hexanol, (E)-2-Hexen-1-ol, (Z)-3-Hexenyl acetate, Nonanal, and (E, E)-2,6-Nonadienal and the expression of VvHPL and VvAAT genes in the LOX-HPL pathway. Specifically, VvHPL emerges as a potential candidate gene responsible for species-specific differences in GLV compounds. Comprehending the changing patterns in the biosynthesis and accumulation of GLVs offers viticulturists and enologists the opportunity to devise targeted strategies for improving the aromatic profile of grapes and wines.

Glioblastoma multiforme (GBM), the most prevalent primary malignant brain tumor in adults, exhibits a dismal 6.9% five-year survival rate post-diagnosis. Thymoquinone (TQ), the most abundant bioactive compound in Nigella Sativa, has been extensively researched for its anti-cancer properties across various human cancers. Yet, its specific anticancer mechanisms and pathways in glioblastoma remain to be elucidated. In this study, we assessed the impact of different TQ concentrations on the viability of A172 cells using WST-8 and Toluidine blue assays, followed by RNA sequencing (RNA-seq) to identify differentially expressed genes (DEGs). We confirmed their expression levels through quantitative RT-PCR and performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for these DEGs. RNA-seq revealed no significant gene expression changes at 2.5 µM and 5 µM TQ concentrations. However, at 25 µM and 50 µM, TQ significantly reduced cell viability in a dose-dependent manner. We identified 1548 DEGs at 25 µM TQ (684 upregulated, 864 downregulated) and 2797 DEGs at 50 µM TQ (1528 upregulated, 1269 downregulated), with 1202 DEGs common to both concentrations. TQ inhibited key pathways such as PI3K-Akt signaling, calcium signaling, focal adhesion, and ECM-receptor interaction in A172 cells. It downregulated several potential oncogenes (e.g., AEBP1, MIAT) and genes linked to GBM proliferation and migration (e.g., SOCS2, HCP5), while modulating Wnt signaling and upregulating tumor suppressor genes (e.g., SPRY4, BEX2). TQ also affected p53 downstream targets, maintaining p53 levels. This study elucidates the anticancer mechanisms of TQ in A172 GBM cells, underscoring its effects on multiple signaling pathways and positioning TQ as a promising candidate for innovative glioblastoma treatment strategies.

Chondrocytes maintain the normal morphological structure and physiological function of articular cartilage. However, the increased expression of inflammatory mediators and matrix-degrading enzymes in chondrocytes can promote ECM degradation, consequently disrupting the physiological function of articular cartilage and ultimately leading to the onset of osteoarthritis (OA). Usnic acid (UA), an extract derived from plants, possesses multiple bioactive properties including anti-inflammatory and antioxidant effects. Hence, this study aims to explore the molecular mechanisms underlying its protective effects in an in vitro simulated model of OA in rat chondrocytes. In vivo experiments encompassed three groups: Control, Model, and Usnic acid (50 mg/kg), with sample extraction following 12 weeks of administration. Pathological alterations in articular cartilage were evaluated using Safranin O-fast green staining. Immunohistochemistry (ICH) analysis was employed to assess the expression of matrix degradation-related markers. The levels of serum cytokines were quantified via ELISA assays. In this study, primary rat chondrocytes were employed as the experimental subject. After a 24-hour treatment period, culture supernatants, total RNA, total protein, and nuclear protein were extracted from the different chondrocyte groups. ELISA and qPCR methods were used to measure levels of IL-6, TNF-α, and PGE2. WB and qPCR were employed to assess levels of p65, p-p65, IκBα, p-IκBα, Nrf2, HO-1, NQO1 ADAMTS-4, MMP-1, MMP-3, MMP-13, INOS, COX-2, and COL2A1. IF analysis was performed to examine Nrf2, p-p65 and COL2A1. Results: (1) In vivo, intraperitoneal injection of usnic acid (50mg/kg) can alleviate pathological changes in articular cartilage and the levels of inflammatory and oxidative-related matrix in the serum. (2) UA reduced the level of inflammatory cytokines in IL-1β-induced chondrocytes supernatant. (3) UA can produce anti-inflammatory and antioxidant effects and inhibit chondrocytes matrix degradation through the Nrf2 and NF-κB pathways. (3) The mechanism by which UA exerts a protective role in chondrocytes is mediated by Nrf2 Conclusion: UA inhibits the expression of chondrocyte matrix degradation-related components through Nrf2 mediated Nrf2 pathway and NF-κB pathway, promotes the production of protective substances, and ultimately exerts a protective effect on chondrocytes.

Background: The molecular domestication of the gag gene of retrotransposons and retroviruses gave rise to the Gagr gene in the genome of Drosophila. The Gagr protein has a conservative structure in all Drosophila species, suggesting an essential function. As we previously shown, the Gagr gene may play a part in immune response and processes linked to stress reactions. Methods: Tub-GAL4&gt;UAS-Gagr flies, which had the Gagr gene knockdown in all tissues, were compared with the control hybrid Tub-GAL4&gt;w1118. Gagr gene function was verified by RNA-sequencing followed by RT-PCR and physiological tests. Results: In contrast to the control strain, we observed that flies with the Gagr gene knockdown had a shorter lifespan, but the mutant strain was more resistant to heat stress. Also, the Gagr knockdown strain had higher level of transcription of the immune response genes, according to a transcriptome analysis. It has been shown that the ammonium persulfate used to induce stress causes the Toll, Jal-STAT, and Jnk/MAPK signaling pathways to become activated, which results in a systemic response in numerus tissues in the control strain. Conversely, the Gagr gene mutant strain exhibits low expression of the stress response. Enrichment of the molecular function of genes overexpressed under ammonium persulfate stress in the control strain, but not in the Gagr knockdown mutant, revealed a category with 19 transcription factors involved in the control of organism development, morphogenesis and the functioning of the central nervous system. Their expression pattern and the Gagr gene's expression pattern match. The data obtained demonstrates the importance Gagr is to maintaining both the body's immune system and homeostasis.

Over the years, network analysis became a promising strategy to analyze complex system, i.e. systems composed by a large number of interacting elements. In particular, multilayer networks have emerged as a powerful framework for modelling and analysing complex systems with multiple types of interactions. Network analysis can be applied to pharmacogenomics to gain insights into the interactions between genes, drugs, and diseases. By integrating network analysis techniques with pharmacogenomic data, the goal consists to uncover complex relationships and identify key genes to use in pathway enrichment analysis to figure out biological pathways involved in drug response and adverse reactions. In this study, we model omics, diseases and drugs data together through the multilayer network representation. Then, we mined the multilayer network with a community detection algorithm by obtaining top communities. After that, we used the identified list of genes from the communities to perform pathway enrichment analysis (PEA) to figure out the biological function affected form the selected genes. The results show that the genes forming the top community have the multiple roles through different pathways.

Context. During the COVID-19 pandemic, patient care was mainly organised around the hospital. Pre-hospital care has, to our knowledge, never been evaluated. Objective: To evaluate the impact of pre-hospital pathways on hospitalisation during the last part of the pandemic. Design. This was a monocentric retrospective analysis of prospectively collected medical records. Data from patients admitted to our institute between 1 February and 7 March 2022 were analysed. Main Outcome Measure(s): The primary outcomes were defined as the number of hospitalisations, resuscitations, and deaths at the time of interview and in the subsequent 30 days. The main explanatory variables were times from onset of symptoms to care, age, gender, News2 score, comorbidities, and pre-hospital pathways and their duration. Results: Three pre-hospital pathways have been identified: a pathway in which the patient consults a general practitioner for a test (PHP1); a pathway in which the patient consulted for care (PHP2); and no pre-hospital pathway and direct admission to hospital (PHP3). Factors independently associated with outcome (hospitalisation) were being male (OR 95% CI; 2.21 [1.01–4.84], p=0,04), News2 score (OR 95% CI; 2.04 [1.65–2.51], p<0.001), obesity (OR 95% CI; 3.45 [1.48–8.09], p=0.005), D-dimers > 0.5 µg/ml (OR 95% CI; 3.45 [1.47–8.12], p=0.005), prolonged time from symptoms to hospital care (PHP duration) (OR 95% CI; 1.07 [1.01–1.14], p=0.03). All things being equal, patients with a “PHP2” pre-hospital pathway had a higher probability of hospitalisation compared to those with a “PHP3” pre-hospital pathway (OR 95% CI; 4.31 [1.48–12.55], p=0.007). Conclusions. Along with recognised risk factors such as gender, News 2 score, and obesity, the patient’s pre-hospital pathway is an important risk factor associated with hospitalisation.

To reveal the relationship between metallodrugs and cancer malignancy, molecular networks of anti-cancer drugs were analyzed. Molecular networks in several types of cancers were analyzed in Ingenuity Pathway Analysis (IPA). Analysis of carboplatin revealed the causal network in diffuse large B-cell lymphoma. Analysis of 12 analyses of cisplatin treatment identified causal networks including camptothecin and NUPR1. The causal network of camptothecin, which includes PTEN, FAS, and IRF1, was inactivated in diffuse-type GC and activated in intestinal-type GC. Upstream regulator analysis of cisplatin revealed an increase in FAS, BTG2, SESN1 and CDKN1A, and the involvement of the tumor microenvironment pathway. Upstream regulators of cisplatin-treated lung adenocarcinoma included a histone deacetylase inhibitor, trichostatin A (TSA). Causal network of arsenic was inactivated in diffuse-type GC and activated in intestinal-type GC, and included ERK, EGFR, SRC, IKK and TP53. Prediction of RNA-RNA interactions with the causal network of arsenic identified 10 microRNAs including mir-101, mir-103, and mir-22. The results revealed the involvement of EMT in arsenic treatment. Analysis of oxaliplatin, a platinum drug, revealed that the SPINK1 pancreatic cancer pathway is inactivated in ischemic cardiomyopathy. The study showed the importance of the relationship between platinum drugs or arsenic trioxide and the tumor microenvironment in the treatment of resistant cancer in humans.

The innate immune system is the first line of host defense sensing viral infection. Manganese (Mn) has recently been found to be involved in the activation of innate immune DNA sensing cGAS-STING pathway and subsequent anti-DNA virus function. However, whether Mn2+ mediates host defense against RNA viruses is still unclear. In the current study, we demonstrated that Mn2+ exhibited antiviral effects against various animal and human viruses including RNA viruses such as PRRSVs and the VSV as well as a DNA virus such as the HSV1 in a dose-dependent manner. Moreover, cGAS and STING were both investigated in the Mn2+ mediated antiviral roles using the knockout cells made by CRISPR-Cas9 approach. Unexpectedly, the results revealed that neither cGAS knockout nor STING knockout had any effect on Mn2+ mediated antiviral functions. Nevertheless, we verified that Mn2+ promoted the activation of cGAS-STING signaling pathway. These findings suggest that Mn2+ has broad spectrum antiviral activities in a cGAS-STING pathway independent manner. This study also provides significant insights into redundant mechanisms participating in the Mn2+ antiviral functions and also indicates new target for Mn2+ antiviral therapeutics.

ExuR and UxuR are paralogous proteins belonging to the GntR family of transcriptional regulators. Both are known to control hexuronic acid metabolism in a variety of Gammaproteobacteria but the relative impact of each of them is still unclear. Here, we apply 2D difference electrophoresis followed by mass-spectrometry to characterise the changes in the Escherichia coli proteome in response to the uxuR or exuR deletion. Our data clearly show that the effects are different: deletion of uxuR resulted in significantly enhanced expression of D-mannonate dehydratase UxuA and flagellar protein FliC, and inhibition of outer membrane porin OmpF, while the absence of ExuR did not significantly alter the spectrum of detected proteins.This suggests that the roles of proteins predicted as homologs are far from identical. Effects of uxuR deletion were largely dependent on the cultivation conditions: during growth with glucose, UxuA and FliC were dramatically altered, while during growth with glucuronate activation of both was not so prominent. During growth on glucose, the maximal activation was detected for FliC. This was further confirmed by expression analysis and physiological tests thus suggesting involvement of UxuR in the regulation of bacterial motility and biofilm formation.

Hyperactivation of Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling is an attractive therapeutic target for tumor therapy. Herein, forty-eight novel meridianin derivatives were designed and synthesized, and their anti-tumor activity were evaluated in vitro both for activity optimization and structure-activity relationship (SAR) study. The results indicated that most derivatives exhibited significantly improved anti-tumor activity, especially for compound 6e. The compound 6e contains an isothiouronium linked by an alkyl chain consisting of 6 carbon atoms with IC50 ranging from 1.11 to 2.80 μM on various cancer cell lines. Consistently, 6e dose dependently induced the apoptosis of A549 and DU145 cells, in which STAT3 are constitutively active. Western blotting assays indicated that the phosphorylation levels of JAK1, JAK2 and STAT3 were inhibited by 6e at 5 μM without significant change in total STAT3 level. Moreover, 6e also suppressed the expressions of STAT3 downstream genes, including c-Myc, Cyclin D1 and Bcl-XL at 10 μM. An additional in vivo study revealed that 6e at the dose of 10 mg/kg could potently inhibit the DU145 xenograft tumor without obvious body-weight loss. These results clearly indicate that 6e could be a potential anti-tumor agent by targeting JAK/STAT3 signaling pathway.

Wnt/β-catenin signaling pathway plays an established role in various diseases and is considered a hallmark of endometrial cancer (EC). Special AT-rich sequence-binding protein 1 and 2 (SATB1 and SATB2) are nuclear matrix-associated proteins involved in chromatin remodeling and regulation of gene expression. SATB1 promotes the progression of numerous types of cancers, whereas SATB2 acts as a tumor suppressor. Despite a recent progress in our knowledge about EC, the exact mechanisms that control their proliferation and metastatic potential still remain unknown. The aim of our study was to investigate the association between Wnt3A, β-catenin, SATB1 and SATB2 protein level and the clinicopathological features of EC patients. 92 EC patients, aged 37-84, were enrolled to our study. The immunoexpression of WNT3A was found in specimens from all EC patients, β-catenin was expressed in 97% of the cases, SATB1 in 87%. The significant association between Wnt3a expression and tumor grade was found; moreover mean IRS for Wnt3a turned out to be significantly lower in high-grade tumors than in low-grade malignancies (p=0.038). In turn, immunoexpression of β-catenin varied significantly across FIGO stages and was associated with the presence of lymph node metastases. Mean IRS for β-catenin in patients with lymph node metastases was significantly lower than in those without (p = 0.028). The Kaplan-Meier analyses demonstrated a stepwise impairment of cancer overall survival with increasing SATB1 expression. In conclusion, both Wnt/β-catenin signaling pathway and SATB1 contribute to progression of EC. Downregulation of β-catenin may predispose to lymphatic spread of EC. In turn, downregulation of Wnt3a seems to be characteristic for high-grade tumors, but probably does not play a role in formation of lymph node metastases. The important role of SATB1 as a predictor of poor survival and could be helpful in establishing a more accurate prognosis in endometrial cancer patients.

Student-centered teaching practices such as active learning continue to gain momentum in college science education. Many instructors committed to these innovative practices transform their classroom beyond the standard lecture. Nevertheless, widespread implementation of these practices is limited because the learning benefits for students are often attained through increased instructional complexity to which many instructors cannot commit. When co-instructors are teaching the course, the level of commitment to building a student-centered classroom may be even more profound. For these reasons, new tools are needed to help instructors and co-instructors plan, organize, evaluate, and communicate their classroom innovations. Pathway modeling is a tool with potential to fill this gap. Unlike curriculum mapping -- which identifies academic content gaps, redundancies, and misalignments by examining a series of courses within a plan of study – course pathway modeling creates a visual map of a single course and reveals how teaching practices influence short-, mid-, and long-term student learning outcomes. This essay demonstrates how course pathway modeling can help co-instructors better represent the complexity of student-centered teaching practices. We include guides for creating course pathway models and discuss how this approach offers the potential to improve curricular design, course evaluation, student assessment, and communication between co-instructors.

Cisplatin-based chemotherapy has long been viewed as the first-line chemotherapy for advanced and metastatic urothelial carcinoma (UC). However, many patients with UC have been classified as “cisplatin-ineligible patient”, which requires alternative chemotherapy due to their poor responses. In fact, vast majority of those who initially responded to cisplatin-based chemotherapy eventually progressed. Understanding of UC tumor immunology provided an immunopathogenic bases for immune checkpoint inhibitors, targeting PD-1 and CTLA-4, to treat cisplatin ineligible metastatic UC and patients with platinum-refractory metastatic UC. In 2020, data from the trail further showed that PD-L1 inhibitors benefit prolonged survival and progression-free survival as maintenance therapy. Besides immune-targeting therapies, manipulation of tumor microenvironment via metabolic pathways alternation, such as inhibiting tumor glycolysis, lactate accumulation and exogenous glutamine uptake, has been investigated in the past few years. In this comprehensive review, we started by introducing traditional chemotherapy of UC, and summarized current evidences supporting the use of immune checkpoint inhibitors and highlighted ongoing clinical trials. Lastly, we reviewed the tumor metabolic characteristic and the anti-tumor treatments targeting metabolic pathways.

Emerging viruses description have grown at an unprecedented rate since the beginning of the 21^st century. The emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its related illness, Coronavirus Disease 2019 (COVID-19) has been reported as the third highly pathogenic coronavirus introducing itself into human population in the current era after the SARS-CoV and Middle East Respiratory Syndrome (MERS-CoV). Molecular and cellular studies considering the pathogenesis of this novel coronavirus are still in the early stages of research, however, regarding the similarity of SARS-CoV-2 and other coronaviruses, it could be hypothesized that the NF-κB, Cytokine regulation, ERK, and TNF-α signaling pathways are the more likely causes of inflammation upon onset of COVID-19. There are several drugs prescribed and used to alleviate the activity of these inflammatory cellular signaling pathways which might be beneficial for developing novel therapeutic modalities against COVID-19. In this review, we briefly summarized the alteration of cellular signaling pathways affected by coronavirus infection, particularly SARS-CoV and MERS-CoV and tabulated the current therapeutic agents approved for previous human diseases.

Secondary phenolic metabolites are defined as valuable natural products synthesized by different organisms that are not essential for growth and development. These compounds play an essential role in plant defense mechanisms, and an important role in the pharmaceutical, cosmetics, food, and agricultural industries. Despite the vast chemical diversity of natural compounds, their content in plants is very low, in consequence, it eliminates the possibility of the production of these interesting secondary metabolites from plants. Therefore, microorganisms are widely used as cell factories by industrial biotechnology to the production of different non-native compounds. Among microorganisms commonly used in biotechnological applications, yeasts are prominent host for the diverse secondary metabolite biosynthetic pathways. Saccharomyces cerevisiae is often regarded as the better host organism for the heterologous production of phenolics compounds, especially if the expression of different plant genes is necessary.

Causal molecular interactions represent key building blocks used in computational modeling, where they facilitate the assembly of regulatory networks. These regulatory networks can then be used to predict biological and cellular behavior by system perturbations and in silico simulations. Today, broad sets of these interactions are being made available in a variety of biological knowledge resources. Moreover, different visions, based on distinct biological interests, have led to the development of multiple ways to describe and annotate causal molecular interactions. Therefore, data users can find it challenging to efficiently explore resources of causal interaction and to be aware of recorded contextual information that ensures valid use of the data. This manuscript presents a review of public resources collecting causal interactions and the different views they convey, together with a thorough description of the export formats established to store and retrieve these interactions. Our goal is to raise awareness amongst the targeted audience, i.e., logical modelers, but also any scientist interested in molecular causal interactions, about existing data resources and how to get familiar with them.

Computational simulation using mathematical models is a useful method for understanding the complex behavior of a living system. The majority of studies using mathematical models to reveal biological mechanisms uses one of the two main approaches: the bottom-up or the top-down approach. When we aim to analyze a large-scale network, such as a comprehensive knowledge-integrated model of a target phenomenon, for example a whole-cell model, the variation of analyses is limited to particular kind of analysis because of the size and complexity of the model. To analyze a large-scale regulatory network of neural differentiation, we developed a hybrid method that combines both approaches. To construct a mathematical model, we extracted network motifs, subgraph structures that recur more often in a metabolic network or gene regulatory network than in a random network, from a large-scale regulatory network, detected regulatory motifs among them, and combined these motifs. We confirmed that the model reproduced the known dynamics of HES1 and ASCL1 before and after differentiation, including oscillation and equilibrium of their concentrations. The model also reproduced the effects of overexpression and knockdown of the Id2 gene. Our model suggests that the characteristic change in HES1 and ASCL1 expression in the large-scale regulatory network is controlled by a combination of four feedback loops, including a large loop which has not been focused on. The model extracted by our hybrid method has the potential to reveal the critical mechanisms of neural differentiation. The hybrid method is applicable to other biological events.

Lily–belong to the genus Lilium is one of the top cut flowers worldwide. Production and propagation of bulblets in vitro is an important approach for high-volume production, but not proved satisfactory. Hence, the aim of this study was to describe and compare the performances of morphological characteristics of the lily bulb in vivo produced by in vitro and conventional culture method and compare the production timelines in vitro vs conventional culture method. In results, it seems clear that in vitro re-culture of lily bulblet was able to be sustained and maintained its growth and so, ontogenic development after their performance in soil. Our results demonstrate that in the conventional pathway, the course of bulblet growth to bulb and ontogenic development took 3–4 growing seasons to reach the adult flowering phase. On the other hand, along with the re-culture in vitro, the course of bulb growth and ontogenic development took 1–2 growing seasons to reach the adult flowering phase because of the increasing initial bulb size and advancement of ontogenic development. Other than bulblet production through bulb scale explant, this study represents the first report on the method of in vitro bulb production of lily through re-culture by in vitro pathway with a comparison of the timelines and ontogenic development obtained from in vitro versus conventional pathway.

Aim: To evaluate the impact of applying alternative diagnostic criteria for gestational diabetes mellitus (GDM) during the COVID-19 pandemic on GDM prevalence, obstetrical and perinatal outcomes, and costs, as compared to the standard diagnostic method. Methods: A cohort of pregnant individuals undergoing GMD screening with the alternative GDM method, which uses plasma glucose (fasting or non-fasting) and HbA1c, was compared with a cohort of pregnant individuals undergoing the standard GDM screening method. Both cohorts were obtained from 6 hospitals across Catalonia, Spain, from April 2020 to April 2022. The primary outcome was large for gestational age rate at birth. Secondary outcomes were composite adverse outcomes including pregnancy complications, delivery complications, and neonatal complications. Cost differences between screening methods were also evaluated. A similar analysis was performed in the subgroup diagnosed with GDM. Results: Data were collected from 1,543 pregnant individuals in the standard screening group and 2,197 in the alternative screening group. The standard screening group had a higher GDM diagnostic rate than the alternative screening group (10.8% vs 6.9%, respectively; p<0.0001). The primary outcome (large for gestational age rate) was similar between groups: 200/1543 (13.0%) vs 303/2197 (13.8%). The adjusted OR for this outcome was 1.74 (95% CI: 0.74-4.10). An adjusted analysis showed no differences between groups in composite adverse outcomes for pregnancy complications (OR: 1.11; 95% CI: 0.91-1.36), delivery complications (OR: 0.95; 95% CI: 0.75-1.19), and neonatal complications (OR: 1.28; 95% CI: 0.94-1.75). Among individuals diagnosed with GDM, the large for gestational age rate was similar between groups: 13/166 (7.8 %) vs 15/151 (9.9 %). The OR adjusted for this outcome was 1.24 (95% CI: 0.51-3.09). An adjusted analysis showed no differences in composite adverse outcomes for pregnancy complications (OR: 1.57; 95% CI: 0.84-2.98), delivery complications (OR: 1.21; 95% CI: 0.63-2.35), and neonatal complications (OR: 1.35; 95% CI: 0.61-3.04). The mean cost (which included expenses for consumables, equipment and personnel) of the alternative screening method was 46.0 euros (22.3 SD), as compared to 85.6 euros (67.5 SD) for the standard screening method. Conclusions: In this Spanish population during the COVID-19 pandemic, GDM prevalence was lower in the alternative screening group than in the standard screening group. After adjusting for GDM risk factors, outcomes related to obstetrics, delivery, and neonatal complications were comparable between both groups. Finally, the alternative screening method was cheaper than the standard screening method.

Antecedents. EFs (EFs) are the basis for establishing a goal and working towards that goal by coordinating thoughts and actions. EFs are fundamental to several aspects of daily life, specifically for academic performance. Aim. To analyze and compare the development of EFs in the transition period between the first and second cycles of Early Childhood Education. Methodology. Non-experimental methodology, ex post facto design, descriptive, cross-sectional evolution study. Participants. Preschoolers of different educational levels (first and second cycle of Infant Education). In this study the participants have been evaluated by different informants: 54.42% by parents and 45.58% by teachers. In relation to gender, 52.65% were male and 47.35% were female. In relation to age, 37.54% had a range of 2-3 years and 62.46% had a range of 4-5 years. Measurement. Instrument development of EFs were evaluated using BRIEF-P by key informants. Results. Preschoolers in the first cycle show significantly higher scores than preschoolers in the second cycle in BRIEP-P. Conclusions. The development of EF is key in these first key moments, having a special impact on later development and academic performance. It is necessary to work on EFs from the first cycle of Early Childhood Education, considering the evolutionary development of EFs.

Growth hormone therapy (GHT) can improve growth velocity and final height but can also accelerated the process of bone growth, which is related to structural bone modelling, both in formation and resorption. The study evaluated the capacity of bone turnover markers to predict early growth response to one year GHT in short stature children born as small for gestational age (SGA). 25 prepubertal SGA children were included. We have estimated P1NP (N-terminal procollagen type 1), CTX (C-terminal telopeptide of collagen type I), P3NP (N-terminal procollagen type III), NT-pro-CNP (amino-terminal C-type natriuretic peptide) and Ca-P metabolism using standard ECLIA, IRA and ELISA methods. A statistically significant increase in bone resorption markers (Ctx ) was found both at 6 and 12 months. P1NP bone markers increased at 6 months and after 12 months of therapy. The P3NP marker of collagen synthesis also increased after 12 months of therapy. We obtained significant increases in phosphorus levels at 6 and 12 months and similarly ALP. We have found a significant correlation between height (cm) and Ctx after 6 -12 months as well as P1NP / height (SD) after 12 months. Calcium levels significantly correlated with height (SD) after 12 months. We find a strong reaction of bone resorption and bone formation markers during growth hormone therapy that may determine their selection as prediction of GH treatment outcome in SGA children. However, the issue requires further research.

Polysulfides are endogenously produced in mammals and generally associated with protective functions. Our aim was to investigate the effect of dimethyl trisulfide (DMTS) in a mouse model of acute stress. DMTS activates transient receptor potential ankyrin 1 (TRPA1) channels and leads to neuropeptide release, potentially that of substance P (SP). We hypothesize that DMTS might inhibit the degrading enzymes of endocannabinoids, so this system was also investigated as another possible pathway for mediating the effects of DMTS. Trpa1 gene wild type (WT) and knock out (KO) mice were used to confirm the role of the TRPA1 ion channel in mediating the effects of DMTS. C57BL/6J, NK1 gene KO, and Tac1 gene KO mice were used to evaluate the effect of DMTS on the release and expression of SP. Some C57BL/6J animals were treated with AM251, an inhibitor of the cannabinoid CB1 receptor, to elucidate the role of the endocannabinoid system in these processes. Open field test (OFT) and forced swim test (FST) were performed in each mouse strain. Tail suspension test (TST) was performed in TRPA1 WT and KO animals. C-FOS immunohistochemistry was carried out on TRPA1 WT animals. DMTS treatment increased the number of highly active periods and decreased immobility time in the FST in WT animals, but had no effect on Trpa1 KO mice. DMTS administration induced neuronal activation in stress-related brain areas such as the locus coeruleus, dorsal raphe nucleus, lateral septum, paraventricular nucleus of the thalamus, and paraventricular nucleus of the hypothalamus. DMTS may have a potential role in the regulation of stress-related processes, and the TRPA1 ion channel may also be involved in mediating the effects of DMTS. DMTS can be an ideal candidate for further study as a potential remedy in stress-related disorders.

p-Toluenesulfonic acid is commercially available, non-toxic, cheap organic compound with robust stability. p-Toluenesulfonic acid is solid, non-corrosive and a strong organic acid that can be handled easily. Due to this p-toluenesulfonic acid could be the better replacement of other conventional acids like nitric acid, sulfuric acid, perchloric acid and AlCl3 in organic transformations. Moreover, p-toluenesulfonic acid could be used synergistically with other mode of catalysis like transition metal catalysis and photocatalysis. In recent years, the use of this solid organic acid in organic and polymer synthesis has grown tremendously. In this review, we present an overview of p-toluenesulfonic acid promoted various organic reactions with particular emphasis to the more recently reported methods. In some cases, we also detailed the understanding of the reactions by providing the reaction mechanism. Despite these advances, there are still many opportunities for the development of new reactions using PTSA. Industry and academia have become more conscious to adopt sustainable chemical processes using safer reagents and solvents and the use of PTSA in this context is highly significant. This review will inspire researchers for further reaction development employing p-toluenesulfonic acid.

Sechium compositum (Cucurbitaceae) is a wild species that is distributed in the Soconusco region, Chiapas, Mexico, and the border with Guatemala. This species has an intangible biochemical value resulting from the pharmacological relevance of its secondary metabolites. However, as a consequence of the lack of knowledge about its importance, it is being displaced from its habitat at an accelerated rate, incurring the risk of genetic loss. Therefore, an in vitro culture protocol with two experimental phases was evaluated to propagate, conserve, and regenerate this species. The first phases considered the multiplication of seedlings, adding seven concentrations (0.1, 0.2, 0.4, 0.6, 0.8, 1.0, 1.2 mg mL-1) of 6-benzylaminopurine (BA) and thidiazuron (TDZ) and evaluating the number of buds, shoots, and seedling height. The best multiplication response was recorded with 0.1, 0.2, 0.4, and 1.0 mg L-1 of BA and 0.1 mg L-1 of TDZ, as well as the MS base culture medium. With 0.1 mg L-1 of BA, 52-mm height, 1.36 shoots, and 9.22 buds were obtained, surpassing the MS control (MS culture medium alone); likewise, twice more roots (80%) and a 14% reduction in the bud structure were packed in 50 repetitions. The second phase consisted of inducing callus formation from stem and leaf explants through the addition of 0.5, 1.0, and 2.0 mg L-1 of TDZ and 2,4-Dichlorophenoxyacetic acid (2,4-D) to the medium. The results demonstrated that the induction of callogenesis in S. compositum has a better start from the stem in a medium with 2.0 mg L-1 of 2,4-D, whose value was 4.89 —equivalent to 97.8% callus formation around the explant. The addition of 500 mg L-1 of polyvinylpyrrolidone (PVP) is also suggested to reduce oxidation. This protocol represents a significant advance in the conservation, multiplication, and callogenesis of S. compositum and contributes to its rescue and revaluation in the face of the danger of extinction.

In this study, we investigate the existence of positive solutions within a system of Riemann-Liouville fractional differential equations that incorporate the (r1,r2,r3)-Laplacian operator while being subject to three-point boundary conditions. These equations incorporate various fractional derivatives and are influenced by parameters represented as (ψ1,ψ2,ψ3). Our approach involves employing techniques such as cone expansion and compression of the functional type, in conjunction with the Leggett-Williams fixed point theorem, to establish the existence of positive solutions. To emphasize the practical significance of our findings in the realm of fractional differential equations, we provide two illustrative examples.

In recent years, numerous approaches have been developed to comprehend the molecular altera-tions underlying thyroid cancer (TC) oncogenesis and explore novel therapeutic strategies for TC. It is now well established that the neurokinin-1 receptor (NK-1R) is overexpressed in cancer cells and that NK-1R is essential for viability of cancer cells. The binding of substance P (SP) to NK-1R in neoplastic cells plays a pivotal role in cancer progression by promoting neoplastic cell growth, protecting tumour cells from apoptosis, triggering invasion and metastasis through enhanced migration of cancer cells, and stimulating endothelial cell proliferation for tumour angiogenesis. Remarkably, all types of human TC (papillary, follicular, medullary, anaplastic), as well as met-astatic lesions, exhibit overexpression of SP and NK-1R compared to the normal thyroid gland. TC cells synthesize and release SP, which exerts its multiple functions through autocrine, para-crine, intracrine, and neuroendocrine processes, including the regulation of tumour burden. Con-sequently, the secretion of SP from TC results in increased SP levels in plasma, which are signifi-cantly higher in TC patients compared to controls. Additionally, NK-1R antagonists have demonstrated a dose-dependent antitumour action. They impair cancer cell proliferation on one side and induce apoptosis of tumour cells on the other side. Furthermore, it has been demonstrat-ed that NK-1R antagonists inhibit neoplastic cell migration, thereby impairing both invasiveness and metastatic abilities, as well as angiogenesis. Given the consistent overexpression of NK-1R in all types of TC, targeting this receptor represents a promising therapeutic approach for TC. Therefore, NK-1R antagonists, such as the drug aprepitant, may represent novel drugs for TC treatment.

The aim of this systematic review is to describe and to identify prospect of β-Tricalcium Phosphate (β-TCP) as Alveolar Bone Grafting (ABG) in Cleft Lip/Palate (CL/P) or alveolar bone cleft defect. A systematic review protocol based on Preferred Reporting Items for Systematic Reviews and Meta Analyses 2020 (PRISMA 2020) was drafted. The literature search was conducted with MEDLINE/PubMed, Web of Science/ ISI-Web of Knowledge, Scopus and Cochrane Library with English language and no publication year limits. The keywords yielded a total of 5824 publications. There are 3196 suitable articles to evaluate after removing duplicates and languages. Afterward, 1315 studies left after doing title and abstract reading. In addition, 85 full-articles were assessed for eligibility. The read the complete texts of those papers and eventually chose 20 that matched the inclusion requirements. Thirteen of the twenty studies included in this systematic review had a low risk of bias, one had a high risk of bias, and six had moderate bias which not report the randomization. β-TCP as ABG is biocompatible, visible and practical, offers a less invasive procedure, and does not interfere with orthodontic treatment. β-TCP as synthetic ABG can be the alternative to autologous bone grafts with several terms and conditions. Improvement of β-TCP efficacy for ABG in CL/P or alveolar bone cleft defects can be done by a tissue engineering approach combining β-TCP with growth factor, mesenchymal stem cells, or other graft materials and modification of β-TCP physical properties.

Respiratory syncytial virus (RSV) RNA synthesis takes place in cytoplasmic viral factories also called inclusion bodies (IBs), which are membrane-less organelles concentrating the viral RNA polymerase complex. IBs assembly is driven by liquid-liquid phase separation promoted by interactions between the viral nucleoprotein N and the phosphoprotein P. We recently demonstrated that cyclopamine (CPM) inhibits RSV multiplication by disorganizing and hardening IBs. Although a single mutation in the viral transcription factor M2-1 induced resistance to CPM, the mechanism of action of CPM still remains to be characterized. Here, using FRAP experiments on reconstituted pseudo-IBs both in cellula and in vitro, we first demonstrated that CPM activity depends on the presence of M2-1 together with N and P. We show that CPM impairs the competition between P and RNA binding to M2-1. As mutations on both P and M2-1 induced resistance against CPM activity, we suggest that CPM may affect the dynamics of the M2-1−P interaction, thereby affecting the relative mobility of proteins contained in RSV IBs. Overall, our results reveal that stabilizing viral protein-protein interactions is an attractive new antiviral approach. They pave the way for the rational chemical optimization of new specific anti-RSV molecules.

The paper considers coherent states for the representation of Weyl commutation relations over a field of $p$-adic numbers. A geometric object, a lattice in vector space over a field of p-adic numbers, corresponds to the family of coherent states. It is proved that the bases of coherent states corresponding to different lattices are mutually unbiased, and the operators defining the quantization of symplectic dynamics are Hadamard operators.

A paradigm shift away from null hypothesis significance testing seems in progress. Based on simulations, we illustrate some of the underlying motivations. First, P-values vary strongly from study to study, hence dichotomous inference using significance thresholds is usually unjustified. Second, statistically significant results have overestimated effect sizes, a bias declining with increasing statistical power. Third, statistically non-significant results have underestimated effect sizes, and this bias gets stronger with higher statistical power. Fourth, the tested statistical hypotheses usually lack biological justification and are often uninformative. Despite these problems, a screen of 48 papers from the 2020 volume of the Journal of Evolutionary Biology exemplifies that significance testing is still used almost universally in evolutionary biology. All screened studies tested default null hypotheses of zero effect with the default significance threshold of p = 0.05, none presented a pre-specified alternative hypothesis, pre-study power calculation, and the probability of ‘false negatives’(beta error). The results sections of the papers presented 49 significance tests on average (median 23, range 0–390). Of 41 studies that contained verbal descriptions of a ‘statistically non-significant’ result, 26 (63%) falsely claimed the absence of an effect. We conclude that studies in ecology and evolutionary biology are mostly exploratory and descriptive. We should thus shift from claiming to ‘test’ specific hypotheses statistically to describing and discussing many hypotheses (possible true effect sizes) that are most compatible with our data, given our statistical model. We already have the means for doing so, because we routinely present compatibility (‘confidence’) intervals covering these hypotheses.

A vivid debate is ongoing in the scientific community about statistical malpractice and the related publication bias. No general consensus exists on the consequences and this is reflected in heterogeneous rules defined by scientific journals on the use and reporting of statistical inference. This paper aims at discussing how the debate is perceived by the agricultural economics community and implications for our roles as researchers, contributors to the scientific publication process, and teachers. We start by summarizing the current state of the p-value debate and the replication crisis, and commonly applied statistical practices in our community. This is followed by motivation, design, results and discussion of a survey on statistical knowledge and practice among the researchers in the agricultural economics community in Austria, Germany and Switzerland. We conclude that beyond short-term measures like changing rules of reporting in publications, a cultural change regarding empirical scientific practices is needed that stretches across all our roles in the scientific process. Acceptance of scientific work should largely be based on the theoretical and methodological rigor and where the perceived relevance arises from the questions asked, the methodology employed, and the data used but not from the results generated. Revised and clear journal guidelines, the creation of resources for teaching and research, and public recognition of good practice are suggested measures to move forward.

We utilized laser irradiation as a potential technique in tuning the electrical performance of NiOx/SiO2 thin film transistors (TFTs). By optimizing the laser fluence and the number of laser pulses, the TFT performance is evaluated in terms of mobility, threshold voltage, on/off current ratio and subthreshold swing, all of which were derived from the transfer and output characteristics. The 500 laser pulses irradiated NiOx/SiO2 TFT exhibited an enhanced mobility of 3 cm2/V-s from a value of 1.25 cm2/V-s for as-deposited NiOx/SiO2 TFT. The laser-irradiated NiOx material likely has a significant concentration of defect gap states, which could also be involved in light absorption processes. Second, and more importantly, the excess energy that the photogenerated charge carriers possess (due to the significant difference between the photon energy and the bandgap of NiOx), combined with the very high light intensity, would result in complex thermal and photo thermal changes thus resulting in an enhanced electrical performance of p-type NiOx/SiO2 TFT structure.

Increasing evidence suggests that prenatal exposure to opioids can adversely influence brain development, yet, limited data exists on the effects of opioid-exposure on preschool language development. Our study aimed to characterize the nature and prevalence of language problems in children prenatally exposed to opioids, and the factors that support or hinder language acquisition. A sample of 100 children born to pregnant women in methadone maintenance treatment and 110 randomly identified non-exposed children were studied from birth to age 4.5 years. At 4.5 years, 89 opioid-exposed and 103 non-exposed children completed the preschool version of the Clinical Evaluation of Language Fundamentals (CELF-P) as part of a comprehensive neurodevelopmental assessment. Children prenatally exposed to opioid had poorer receptive and expressive language outcomes at age 4.5 years compared to non-exposed children. After adjustment for child sex, maternal education, other pregnancy substance use, maternal pregnancy nutrition and prenatal depression, opioid exposure remained a significant independent predictor of children’s total CELF-P language score. Examination of a range of potential intervening factors showed that a composite measure of the quality of parenting and home environment at 18 months and early childhood education participation at 4.5 years were important positive mediators.

A renewable cyclic monoterpene obtained from citrus peel, limonene is widely used as a fra-grance, nutraceutical ingredient, antibacterial, biopesticide, and green extraction solvent. Indus-trial demand largely exceeds supply. After reviewing recent advances in the recovery of limonene from citrus peel and residues with a particular attention to benign-by-design extractive processes, we focus on the latest results in its dehydrogenation to p-cymene via heterogeneous catalysis.

Distinguishable annual growth rings produce in Pinus roxburghii are an asset to find out the age of individual tree. This paper aimed to determine the age of P. roxburghii through coring samples and test the relationship with forest production. The biomass estimated, girths measured at two different sections and heights measured which allowed to determine the rate of tapering of the stand. The regression analysis was performed to test the relationship between various variables. The mean age of the P. roxburghii stand was found to be 23.97 (~24 years). The result showed the significant (p<0.05) positive correlation coefficient has been seen between age with girth at breast height, biomass, volume and carbon stock. However, no significant (p>0.05) correlation (r = 0.08) was found between age and height of the stand. In contrast, a correlation between diameter at breast height (DBH) was significant (p<0.05) and positive with volume, biomass, but no significant (p>0.05) correlation (r = 0.14) found between DBH and height of the stand. However, height has a significant (p<0.05) positive correlation with biomass. The mean biomass was 375 kg and mean annual increment (MAI) was 15 kg per tree. Rate of tapering of the studied stand predicted to be 3 cm diameter decreased with trunk height running at 100 cm from base to upward of P. roxburghii stand and vice versa. Result suggests that height-age relation is very weak whereas age, DBH, biomass and carbon has a significant correlation signifies that time-based forests' production and potential production estimation can be obtained in a relatively accurate way by utilizing the age of stand. The time-based forest production analysis is pioneer work in Nepal. The study affirms the tree ring count in P. roxburghii would be a credible and accurate method to determine the age of standing trees.

In this work, magnetic CuFe₂O₄/Ag nanoparticles activated by porous covalent organic frameworks (COF) was fabricated to evaluate the heterogenous reduction of 4-nitrophenol (4-NP). The core-shell CuFe₂O₄/Ag@COF was successfully prepared by polydopamine reduction of silver ions on CuFe₂O₄ nanoparticles, followed by COF layer condensation. With integrating the intrinsic characteristics of the magnetic CuFe₂O₄/Ag core and COF layer, the obtained nanocomposite exhibited features of high specific surface area (464.21 m² g^-1), ordered mesoporous structure, strong environment stability, as well as fast magnetic response. Accordingly, the CuFe₂O₄/Ag@COF catalyst showed good affinity towards 4-NP via π-π stacking interactions and possessed enhanced catalytic activity compared with CuFe₂O₄/Ag and CuFe₂O₄@COF. The pseudo-first-order rate constant of CuFe₂O₄/Ag@COF (0.77 min^-1) is 3 and 5 times higher than CuFe₂O₄/Ag and CuFe₂O₄@COF, respectively. The characteristics of bi-catalytic CuFe₂O₄/Ag and the porous COF shell of CuFe₂O₄/Ag@COF made a contribution to improve the activity of 4-NP reduction. The present work demonstrated a facile strategy to fabricate COF activated nano-catalysts with enhanced performance in the fields of nitrophenolic wastewater treatment.

In this paper, we have used magnetron sputtering to grow the high-quality GeSn layer on Ge (100) with Sn compositin up to 7%. The crystallinity of the GeSn layer is pretty good, and the strain relaxation degree of the GeSn layer is evaluated to be approximately 50%. The root mean square (RMS) value is 0.8 nm, and the averaged TDDs in the GeSn layer is 8.7×109 cm-2, which is obtained from the rocking curve of GeSn layer along (004) plane. PL measurement result shows the significant optical emission from the deposited high-quality GeSn layer, which also means that magnetron sputtering is an optional way to achieve the higher Sn composition GeSn luminescent material. To verify whether our deposited GeSn can used for optoelectronic devices, we fabricate the simple vertical p-i-n diode, and the room temperature current-voltage (I-V) characteristic was obtained. This result paves the way for future sputtered-GeSn optimization, which is critical for the optoelectronic application.

In this work, nylon 6/ P(N-phenylmaleimide-alt-styrene) blends were prepared by melt blending, and the mechanical, heat-resistant, crystallographic and dynamical mechanical properties of nylon 6/ P(N-phenylmaleimide-alt-styrene) blends with different contents were investigated and analyzed. The results showed that the mechanical properties decreased with increasing PNS, while the heat deflection temperature (HDT), relative crystallinity (Xn), and storage modulus (G’) increased with increasing PNS. The results of differential Scanning Calorimetry (DSC) proved the PNS played the positive role of nucleating PA6. And the results of dynamic mechanical analysis (DMA) proved the PNS could improve the rigidity of PA6/PNS blends. From the SEM, these PNS domains were between 0.2 and 4 μm in diameter. The experimental results indicated that the addition of PNS improved the rigidity of PA6/PNS blends, and then improved the heat-resistant property.

Incidental P losses from non-point sources may contribute to eutrophication and to decreased soil fertility. These incidents have been related to heavy rainfall on freshly fertilized agricultural soils and little is known about such incidents on more natural soils or in forests. The aim of this work is to determine if incidents of high P leaching also occur in spruce forests, and if such incidents are of significance in P cycling. We found a peak in the mineral soil solution showing that single events of high P leaching occur. The orthophosphate concentration in the Bf-horizon of the 80-year old spruce forest peaked in the autumn of the second year of a continuous monitoring. The concentration increased by more than 85 times compared to the highest concentration obtained earlier during the sampling. The amount leached during this 6 months peak is 10 times higher than the average annual leaching. This P leaching might be due to a combination of high P deposition/through-fall and a high anion exchange with dissolved-organic-carbon and Cl-. We suggest that single events of high sub-surface P leaching may contribute to the overall P leaching, and might increase with the global warming as more DOC is expected to be released to the soil solution.