There is compelling evidence that the nuclear receptor TRβ, a member of the thyroid hormone receptor (TR) family, is a tumor suppressor in thyroid, breast and other solid tumors. Cell-based and animal studies reveal that the liganded TRβ induces apoptosis, reduces an aggressive phenotype, decreases stem cell populations, and slows tumor growth through modulation of a complex interplay of transcriptional networks. TRβ-driven tumor suppressive transcriptomic signatures include repression of known drivers of proliferation such as PI3K/Akt pathway and activation of novel signaling (JAK1/STAT1) and metabolic reprogramming in both thyroid and breast cancers. The presence of TRβ is also correlated with a positive prognosis and response to therapeutics in BRCA+ and triple-negative breast cancers respectively. Ligand activation of TRβ enhances sensitivity to chemotherapeutics. TRβ co-regulators and bromodomain-containing chromatin remodeling proteins are emergent therapeutic targets. This review considers TRβ as a potential biomolecular diagnostic and therapeutic target.

By virtue of the knowledge of the beneficial effect of the warm and dry storage, for the growth of the chincuya seed embryo, defined as morphological dormancy. The effect of the same type of storage was studied for the seed viability and germination by soaking gibberellic acid. Also, fatty acids and their kinetics were identified during the warm and dry storage. The following treatments were evaluated: storage time (0, 3, 6, 9 and 12 months), seed soaking in gibberellic acid at 350 mg L-1, and for the control, imbibition in distilled water, both for 72 h. The seed viability was evaluated through the stain test with tetrazolium chloride. The embedded seeds were germinated on absorbent paper towels and incubated at different temperatures of 30 ° C during the day and 25 ° C at night and 12 hours of photoperiod. The lipid profile was developed by gas chromatography. Seeds were held at constant temperature of 25 ± 3 ° C, in darkness, during the storage time. Results demon-strated that the high initial viability was maintained until the ninth month, when it decreases and is statisti-cally different from the other treatments. The smaller germination percentage (26.1 %) was observed in the freshly harvested seeds and, the higher one corresponded to the six months (65.6 %), with these differences being statistically significant. Regarding the identified fatty acids and their average content, it was found that 33.41 % corresponded to palmitic acid, 7.72 % to stearic acid; the arachidic acid with 1.30 %, making a total of saturated fatty acids of 42.44 %. The detected unsaturated fatty acids were: palmitoleic acid 1.52 %, oleic acid 43.37 % and linoleic acid 7.24 %, in total, 52.15 %. No significative changes were observed in the fatty acids content that are the largest part of the total seed reserves; although the higher concentrations matched with the longest germination (three months), with an average of 92.84 % total fatty acids. Specified regressions indi-cated with statistical robustness that palmitoleic and palmitic acids increased while the oleic acid decreased during the dry storage. The arachidic acid showed a slightly downward trend. Also, the concentrations of fat-ty acids were significatively different between unstored and unincubated seeds (intact) and unstored and in-cubated, but without germinating seeds (dormant), in the latter, the total fatty acids content was significantly lower. Given that the application of gibberellic acid and warm dry storage favored germination, as well as the change in fatty acid content during warm dry storage, added to the results already reported on morphological changes and embryonic growth as an effect of the same type of storage, it is established that Annona purpurea seeds present morphophysiological dormancy, also this is the first identification report of arachidic and pal-mitoleic acids in chincuya seeds and the higher germination percentage reported (65.6 %).

Only two percent of Glioblastoma multiforme (GBM) patients respond to standard care and survive beyond 36 months (long-term survivors, LTS) while the majority survive less than 12 months (short-term survivors, STS). To understand the mechanism leading to poor survival, we analyzed publicly available datasets of 113 STS and 58 LTS. This analysis revealed 198 differentially expressed genes (DEGs) that characterize aggressive tumor growth and may be responsible for the poor prognosis. These genes belong largely to the GO-categories “epithelial to mesenchymal transition” and “response to hypoxia”. In this paper we applied upstream analysis approach which involves state-of-art promoter analysis and network analysis of the dysregulated genes potentially responsible for short survival in GBM. Binding sites for transcription factors associated with GBM pathology like NANOG, NF-κB, REST, FRA-1, PPARG and seven others were found enriched in the promoters of the dysregulated genes. We reconstructed the gene regulatory network with several positive feedback loops controlled by five master regulators – IGFBP2, VEGFA, VEGF165, PDGFA, AEBP1 and OSMR which can be proposed as biomarkers and as therapeutic targets for enhancing GBM prognosis. Critical analysis of this gene regulatory network gives insights on mechanism of gene regulation by IGFBP2 via several transcription factors including the key molecule of GBM tumor invasiveness and progression, FRA-1. All the observations are validated in independent cohorts and their impact on overall survival is studied.

Objectives: The promising specific growth regulators are employed tissue culture of the bamboo species. The specific natural hardening mixture supports the acclimatization and adaptation of the protected cultivation. The bamboo species contribute to the carbon sequestration and stabilization of the environment. Findings: The growth regulator 2, 4-D encourages callus induction and growth regulators NAA + TDZ, BAP + Kinetin + Gelrite, BAP + Kinetin + Coconut water + myo-inositol, NAA and TDZ impose plant regeneration in the Bambusa species. The growth regulator of 2,4-D, 2,4-D + Kinetin, 2,4-D + BA, 2,4-D + BAP and 2,4-D + NAA + BAP produces callus induction in the Dendrocalamus species. The growth regulator of TDZ, BA and IBA + Coumarin + Putrescine, BAP + GA3, NAA + Kinetin, BA + IBA, BA + Kinetin + NAA, NAA + Kinetin, Kinetin + IAA has facilitated shoot regeneration in the Dendrocalamus species with the specific period. The growth regulator of BA and TDZ; BAP + TDZ, IBA + Coumarin + Putrescine, BAP + GA3, NAA + Kinetin, BA + IBA, BA + Kinetin + NAA, NAA + Kinetin, Kinetin + IAA develops root regeneration with unambiguous time in the Dendrocalamus species. The growth regulator of BAP and Kinetin + BAP imposes shoot regeneration and IBA and IBA + Coumarin + sucrose conducts root regeneration in the edible bamboo. The natural hardening materials of cocopeat, vermicompost, perlite, cow dung, FYM, compost, soil & garden soil and humus soil, perlite, and FYM recommend in the acclimatization and adaptation of the Bambusa species and Dendrocalamus species respectively. Novelty: The standard growth regulators and hardening mixtures impose tissue culture, acclimatization and adaptation in the bamboo species. The bamboo species involves in managing carbon sequestration, biogeochemical cycle and the environment.

Organogenesis and somatic embryogenesis have been widely applied as the two main regeneration pathways in plant tissue culture. However, recalcitrance is still a main restriction in the clonal propagation of many woody species, especially in conifers. They undergo a “phase change” that leads to significant loss of organogenic and embryogenic capacity, thus reducing the responsive tissues or organs to juvenile material, and narrowing the competence window. In this sense, in vitro regeneration of mature conifer trees has been a long-cherished goal in many laboratories worldwide. In this work, apical shoot buds were used as explants for both organogenesis and somatic embryogenesis in order to cloning mature trees of Aleppo pine. Reinvigorated axillary shoots were submitted to somatic embryogenesis induction through the manipulation of culture media, including the use of auxins such as 2,4-D and NAA, cytokinins (BA and kinetin) and phytosulfokine (50, 100 and 200 nM). Although somatic embryos could not be obtained, embryogenic-like tissue was produced followed by the appearance of actively proliferating non-embryogenic calli and differences between treatments were found, especially when phytosulfokine was added to the induction media. Organogenic system produced reinvigorated shoots from both BA treatments tested (22 and 44 µM), from juvenile somatic trees and adult trees, and ex-vitro acclimatized plants were developed.

There is sufficient knowledge of the beneficial effect of warm-dry storage on breaking the morpho-logical dormancy of the chincuya (Annona purpurea Moc. & Sessé ex Dunal) seed embryo. Chincuya is an underutilized, tropical wild species native to Mexico, with potential as a biopesticide. The impact of warm-dry storage and gibberellic acid treatment on seed viability and germination was determined to improve that knowledge further. Also, the content and kinetics of fatty acids in chincuya seeds were profiled during warm-dry storage. Seed treatments included storage time (0, 3, 6, 9, and 12 months), seed imbibition for 72 h in gibberellic acid at 350 mg L-1, and distilled water im-bibition for 72 h for the control treatment. Seed viability was determined using the TTZ classic test. Imbibed seeds were germinated on paper towels and incubated at 30 °C during the day and 25 °C at night in a 12:12 h dark:light photoperiod. The lipid profile was obtained by gas chromatography. During the storage treatment, seeds stayed in darkness at 25 ± 3 °C. Results showed that high viability remained up to month 9 in storage when it significantly decreased. Freshly harvested seeds germi-nated at a statistically significantly lower rate (26.1 %) than six-month-old seeds (65.6 %). The profile of fatty acids breaks down as palmitic acid (33.41 %), stearic acid (7.72 %), and arachidic acid (1.30 %), for a total of 42.44 % of saturated fatty acids. The detected unsaturated fatty acids (52.15 %) were palmitoleic acid (1.52 %), oleic acid (43.37 %), and linoleic acid (7.24 %). No significant changes were detected in fatty acid content; however, the highest fatty acid content (92.84 %) occurred with the highest germination rate. Regression analysis showed significant content changes: palmitoleic and palmitic acid increased while oleic acid decreased during dry storage. Arachidic acid showed a slight downward trend. Also, fatty acid content significantly differed between intact seeds (unstored and unincubated) and latent seeds (unstored, incubated, and ungerminated). The total fatty acids content for latent seeds was significantly lower. These results show that Annona purpurea seeds present morphophysiological dormancy. Also, we document the highest germination rate reported (65.6 %) and report the presence of arachidic and palmitoleic acids in chincuya seeds.

Plant growth regulators (PGRs) and deficit irrigation (DI) play a crucial strategic role in sustaining agricultural yield and reducing water stress in drought prone areas. The study was carried out in 2021-2022 to assess the impact of various PGRs (SA & NAA) & irrigation levels (60% Epan, 80 % Epan, and 100 % Epan) with DI & partial root drying (PRD) irrigation strategies. PGR application boosted fruit yields and demonstrated its significance in reducing water stress by lowering canopy temperature, maintaining higher relative water content in the leaves, modifying stomatal opening, and increasing photosynthetic rate. PGRs were used to assess the increased accumulation of total phenols, flavonoids, and improved antioxidant activity. Results indicated that exogenous use of PGRs like SA+NAA in conjunction with 80% irrigation levels increased fruit yield (31.97 and 40.38%) and water productivity (64.92 and 75.39%) for DI and PRD treatments, respectively. Thus standardizing irrigation and crop management practices including PGR application can be recommended to boost pomegranate productivity particularly in water-scarce environments.

Black Knot (BK) is a deadly disease of European (Prunus domestica) and Japanese (Prunus salicina) plums caused by the hemibiotrophic fungus Apiosporina morbosa. Generally, phytopathogens hamper the balance of primary defense phytohormones such as salicylic acid (SA)-jasmonic acid (JA) balance for disease progression. Thus, we quantified the important phytohormones titers in tissues of susceptible and resistant genotypes belonging to European and Japanese plums at five different time points. The results suggested auxin-cytokinins interplay driven by A. morbosa appeared to be vital in disease progression by hampering the plant defense system via perturbance in SA, JA, and gibberellic acid. The results further point out that SA and JA in plant defense are not necessarily antagonistic always, especially in woody perennials. Results also suggest that the changes in SA and JA content following BK disease infection and progression in plums could be utilized as phytohormonal markers in the identification of BK-resistant cultivars.

Bromodomain (BRD)-containing proteins are involved in many biological processes, most notably epigenetic regulation of transcription, and BRD protein dysfunction has been linked to many diseases, including tumorigenesis. However, the role of BRD proteins in the pathogenesis of uterine fibroids (UFs) is entirely unknown. The present study aimed to determine the expression pattern of BRD9 protein in UFs and matching myometrium and further assess the impact of BRD9 inhibitors on UF phenotype and epigenetic/epitranscriptomic changes. Our studies demonstrated that the levels of BRD9 were significantly upregulated in UFs compared to matched myometrium, suggesting that the aberrant BRD protein expression may contribute to the pathogenesis of UFs. We then evaluated the potential roles of BRD9 using its specific inhibitor I-BRD9. Targeted inhibition of BRD9 suppressed the UF tumorigenesis with increased apoptosis and cell cycle arrest, decreased cell proliferation, and extracellular matrix deposition in UF cells. The latter is the key hallmark of UFs. Unbiased transcriptomic profiling coupled with downstream bioinformatics analysis further and extensively demonstrated that targeted inhibition of BRD9 impacted the cell cycle- and ECM-related biological pathways, reprogrammed the UF cell epigenome and epitranscriptome, and altered miRNA-mediated gene regulation in UFs. Taken together, our data support the critical role of BRD9 in UF cells and the strong interconnection between BRD9 and other pathways controlling the UF progression. Targeted inhibition of BRD proteins might provide a non-hormonal treatment option for this most common benign tumor in women of reproductive age.

Each individual has a unique gut microbiota; therefore the genes in our microbiome outnumber the genes in our genome by about 150 to 1. Perturbation in host nutritional status influences gut microbiome composition and vice versa. The gut microbiome can help in producing vitamins, hormones, and other active metabolites that support the immune system; harvest energy from food; aid in digestion; protect against pathogens; improve gut transit and function; send signals to the brain and other organs, oscillating the circadian rhythm and coordinate with host metabolism through multiple cellular pathways. Gut microbiota can be influenced by host genetics, medications, diet, and lifestyle factors from preterm to aging. So before prescribing a customized treatment, it is crucial to monitor and count the gut flora as a focused biomarker. Many nutritional approaches that have been developed help in maintaining and restoring an optimal microbiome such as specific diet therapy, nutrition interventions and customized eating patterns. One of these approaches is time-restricted feeding/eating (TRF/E), a type of intermittent fasting (IF) in which a subject abstains from food intake for a specific time window. Such a dietary modification might alter and restore the gut microbiome for proper alignment of cellular and molecular pathways throughout the lifespan. In this review, we have highlighted that gut microbiota would be a targeted biomarker and TRF/E would be a targeted approach for restoring the gut microbiome associated molecular pathways like hormonal signaling, the circadian system, metabolic regulators, neural responses, and immune-inflammatory pathways. Consequently, modulation of gut microbiota through TRF/E could contribute in proper utilization and availability of the nutrients and in this way confer protection against diseases for harnessing personalized nutrition approaches to improve human health.

This study evaluated the exogenous application of PGRs substitute chemical fertilization without compromising the growth and yield of tomato in fluctuated day-night temperature and humidity stressed late winter. Two-factor experiment comprising chemical fertilizers at 100, 110, 90 and 80 % of recommended doses besides control and PGRs of GA3; NAA, 4-CPA and SA @ 50 ppm including control was conducted where treatments were assigned in triplicates. Results revealed no significant variation among the fertilizer doses (80% to 110% of recommendation) regarding growth and yield contributing traits while among the PGRs, GA3 @ 50 ppm produced maximum number of flower clusters plant-1 (16.85), flowers (8.80) and fruits (5.79) cluster-1, single fruit weight (67.83 g) and fruit yield (6.61 kg plant-1) of tomato that was statistically identical with the findings of SA. But significant reduction in yield was noted in NAA and 4-CPA (1.20 kg and 1.21 kg plant-1, respectively). Interestingly, GA3 and SA in combination with any doses of the studied fertilizers maximize the tomato morphological and reproductive traits while fertilizer plus NAA and 4-CPA interaction gave the inferior results. Further, correlation matrix and PCA findings revealed that five fertilizer doses have no distinctiveness whereas GA3 and SA has distinct position than other PGRs with the maximum dependent variables those were contributed positively in the total variations. The study findings suggested that 20% fertilizer requirement could be reduced with the substitution of GA3 and SA @ 50 ppm for successful cultivation of tomato in late winter having the extreme environmental issues.

In contrast to some low molar-mass per- and polyfluoroalkyl substances (PFASs), well-established to be toxic, persistent, bioaccumulative and mobile, fluoropolymers (FPs) are water insoluble, safe, bio-inert, durable niche high performance polymers which fulfil the 13 polymer of low concern (PLC) criteria in their recommended conditions of use. In addition, more recent innovations (e.g., the use of non-fluorinated surfactants in aqueous radical (co)polymerization of fluoroalkenes) from industrial manufacturers of FPs are highlighted. This review also aims at showing how these specialty polymers endowed with outstanding properties are essential (even irreplaceable since hydrocarbon polymer alternatives used in similar conditions fail) for our daily life (electronics, Energy, optics, internet of things, transportation, etc) and constitute a special family a part from other “conventional” C1-C10 PFASs found everywhere on the Earth and Oceans. Furthermore, some information reports the recycling (e.g. the unzipping depolymerization of polytetrafluoroethylene, PTFE, into TFE), end of life of FPs, their risk assessment, circular economy and regulations. Various researches are devoted to Environment involving FPs, though they represent a niche volume (with a yearly production of 330,300 tonnes) compared to all plastics (with 460 million tonnes). Complementary to other reviews on PFASs, which lack of such above data, this review presents both fundamental and applied strategies as evidenced by major FP producers.

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

This manuscript explores unmanned aerial vehicle DC motor control performance efficacy of deterministic artificial intelligence in comparison to model-following adaptation, particularly a direct self-tuner with filtering. The deterministic artificial intelligence model made use of self-awareness statements to overcome error in response to permutations of the multi-duty cycle square wave that served as the system input. It can be seen that (despite equivalently powerful estimation techniques) deterministic artificial intelligence provided far superior results: a reduction in peak initial transient error of 55%, and a mean error reduction over 81% with over 65% reduction in error standard deviation compared to a state-of-the-art nonlinear adaptive control method. Deterministic artificial intelligence also was able to very closely track at the switching of the input control, while the benchmark nonlinear adaptive control failed to respond as quickly at these points.

This manuscript compares deterministic artificial intelligence to model following control applied to DC motor control, including evaluation of the threshold computation rate to let unmanned underwater vehicles correctly follow the challenging discontinuous square wave command signal. The approaches presented in the main text are validated in MATLAB®, where the motor process is discretized at multiple step sizes, which is inversely proportional to the computation rate. The performance is evaluated by the error mean and standard deviation. With a large step size, discrete deterministic artificial intelligence shows a larger error mean than the model-following self-turning regulator approach (benchmark selection). However, the performance gets optimized with the step size decreased. The error mean is close to the continuous deterministic artificial intelligence when the step size is reduced to 0.2 seconds, which means that the computation rate and the sampling period restrict discrete deterministic artificial intelligence. In that case, the continuous deterministic artificial intelligence is the most feasible and reliable selection for future applications on unmanned underwater vehicles since it is superior to all the approaches with multiple computation rates.