Transitions between epithelial and mesenchymal cellular states (EMT/MET) contribute to cancer progression. We hypothesize that EMT followed by MET promotes cell population heterogeneity, favouring tumour growth. We developed an EMT model by on and off exposure of epithelial EpH4 cells (E-cells) to TGFβ1 that mimics phenotypic EMT (M-cells) and MET. We aimed at understanding whether phenotypic MET is accompanied by molecular and functional reversion back to epithelia by using RNA sequencing, immunofluorescence (IF), proliferation, wound healing, focus formation and mamosphere formation assays as well as cell xenografts in nude mice. Phenotypic reverted epithelial cells (RE-cells) obtained after MET induction presented epithelial morphologies and proliferation rates resembling E cells. However, the RE transcriptomic profile and IF staining of epithelial and mesenchymal markers revealed a uniquely heterogeneous mixture of cell subpopulations with a high self-renewal ability. RE cell heterogeneity was stably maintained for long periods after TGFβ1 removal both in vitro and in large tumours derived from the nude mice. Overall, we show that phenotypic reverted epithelial cells (RE cells) do not return to the molecular and functional epithelial state and present mesenchymal features related to aggressiveness and cellular heterogeneity that favour tumour growth in vivo. This work strengthens epithelial cell reprogramming and cellular heterogeneity fostered by inflammatory cues as a tumour growth-promoting factor in vivo. Full article

Dendritic cells (DCs) are antigen-presenting cells (APCs) that regulate the beginning of adaptive immune responses. The mechanisms of tolerance to antigens moving through the digestive tract are known to be regulated by intestinal DCs. Agnatha and Gnathostoma are descendants of a common ancestor. The Ostracoderms gave rise to Cyclostomes, whereas the Placoderms gave rise to Chondrichthyes. Sarcopterygii and Actinopterygii are two evolutionary lines of bony fishes. Brachiopterygii and Neopterygii descend from the Actinopterygii. From Neopterygii, Holostei and Teleostei evolved. Using immunohistochemistry with TLR-2, Langerin/CD207, and MHC II, this study aimed to characterize intestinal DCs, from myxines to teleosts. The findings reveal that DCs are positive for the antibodies tested, highlighting the presence of DCs and DC-like cells phylogenetically from myxines, for the first time, to teleosts. These findings may aid in improving the level of knowledge about the immune system’s evolution and these sentinel cells, which are crucial to the body’s defense. Full article

Levofloxacin is considered an alternative treatment option of Stenotrophomonas maltophilia infections to trimethoprim/sulfamethoxazole. The fluoroquinolone resistance in S. maltophilia is usually caused by an overproduction of efflux pumps. In this study, the contribution of efflux systems to levofloxacin resistance in S. maltophilia clinical isolates was demonstrated using phenotypic (minimal inhibitory concentrations, MICs, of antibiotics determination ± efflux pump inhibitors, EPIs) and molecular (real-time polymerase-chain-reaction and sequencing) methods. Previously, the occurrence of genes encoding ten efflux pumps was shown in 94 studied isolates. Additionally, 44/94 isolates demonstrated reduction in susceptibility to levofloxacin. Only 5 of 13 isolates (with ≥4-fold reduction in levofloxacin MIC) in the presence of EPIs showed an increased susceptibility to levofloxacin and other antibiotics. The overexpression of smeD and smeV genes (in five and one isolate, respectively) of 5 tested efflux pump operons was demonstrated. Sequencing analysis revealed 20–35 nucleotide mutations in local regulatory genes such as smeT and smeRv. However, mutations leading to an amino acid change were shown only in smeT (Arg123Lys, Asp182Glu, Asp204Glu) for one isolate and in smeRv (Gly266Ser) for the other isolate. Our data indicate that the overproduction of the SmeVWX efflux system, unlike SmeDEF, plays a significant role in the levofloxacin resistance. Full article

The side bridge test (SBT) is one of the most popular tests to assess isometric trunk lateral flexor endurance. The aim of this study was to assess the validity and reliability of the SBT in healthy females. Twenty-four (24.58 ± 3.92 years) physically active (1–2 h of moderate physical activity, 2–3 times a week) females voluntarily participated in this study. The surface electromyography (EMG) of eight abdominal, back, shoulder and hip muscles was measured during the SBT. Normalized median frequency slopes (NMF_slope) were calculated to analyze the muscle fatigue. The EMG amplitudes were normalized to maximum EMG values to assess muscle activity intensity. A one-week test-retest design was performed to evaluate the SBT reliability through the ICC_3,1 and typical error. Higher NMF_slopes and normalized EMG amplitudes were found in deltoids, abdominal obliques, rectus abdominis, and erector spinae in comparison to latissimus dorsi, gluteus medius, and rectus femoris. However, no significant differences were found between the trunk lateral flexors and the deltoids. Linear regression analysis showed that SBT performance could be significantly predicted by external oblique and deltoid NMF_slope (adjusted R² = 0.673) and by body mass and trunk height (adjusted R² = 0.223). Consistency analysis showed a high intraclass correlation coefficient (0.81) and a relatively high typical error (10.95 s). Despite the good relative reliability of the SBT, its absolute reliability was low and its validity questionable, as the shoulder muscle activation and fatigue and the individuals’ anthropometric characteristics played an important role in SBT performance. Full article

The primary purpose of the Man and the Biosphere Program is the sustainable development of both the economy and nature conservation activities. Although the effectiveness of eco-tourism to reach this goal has been proposed, due to the lack of long-term monitoring data and a model species, there has been no obvious mechanism to evaluate the effectiveness of this policy. This study explored the effectiveness of the sustainable development policy of HMBR based on 30 years data of monitoring the Tibetan macaque, local human population, visitors, and annual ecotourism income in Huangshan by estimating species habitat suitability and the impact of ecotourism. The results showed increases in the income for the local human population, the number of visitors, and annual eco-tourism. Simultaneously, the reserve’s Tibetan macaque population size and suitable habitat areas increased. The macaques expanded their habitat to the low-altitude buffer zone (400–800 m), an area with lower eco-tourism disturbance. Scenic spots had a significant negative impact on habitat suitability (the substantially increased contributions of scenic spots from 0.71% to 32.88%). Our results and methods provide a suitable evaluation framework for monitoring the sustainable development and effectiveness of eco-tourism and wildlife conservation in Man and the Biosphere reserves. Full article

5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK) is an enzyme that regulates cellular energy homeostasis, glucose, fatty acid uptake, and oxidation at low cellular ATP levels. AMPK plays an important role in several molecular mechanisms and physiological conditions. It has been shown that AMPK can be dysregulated in different chronic diseases, such as inflammation, diabetes, obesity, and cancer. Due to its fundamental role in physiological and pathological cellular processes, AMPK is considered one of the most important targets for treating different diseases. Over decades, different AMPK targeting compounds have been discovered, starting from those that activate AMPK indirectly by altering intracellular AMP:ATP ratio to compounds that activate AMPK directly by binding to its activation sites. However, indirect altering of intracellular AMP:ATP ratio influences different cellular processes and induces side effects. Direct AMPK activators showed more promising results in eliminating side effects as well as the possibility to engineer drugs for specific AMPK isoforms activation. In this review, we discuss AMPK targeting drugs, especially concentrating on those compounds that activate AMPK by mimicking AMP. These compounds are poorly described in the literature and still, a lot of questions remain unanswered about the exact mechanism of AMP regulation. Future investigation of the mechanism of AMP binding will make it possible to develop new compounds that, in combination with others, can activate AMPK in a synergistic manner. Full article

The PIN-FORMED (PIN) proteins represent the most important polar auxin transporters in plants. Here, we characterized the PIN gene family in two olive genotypes, the Olea europaea subsp. europaea var. sylvestris and the var. europaea (cv. ‘Farga’). Twelve and 17 PIN genes were identified for vars. sylvestris and europaea, respectively, being distributed across 6 subfamilies. Genes encoding canonical OePINs consist of six exons, while genes encoding non-canonical OePINs are composed of five exons, with implications at protein specificities and functionality. A copia-LTR retrotransposon located in intron 4 of OePIN2b of var. europaea and the exaptation of partial sequences of that element as exons of the OePIN2b of var. sylvestris reveals such kind of event as a driving force in the olive PIN evolution. RNA-seq data showed that members from the subfamilies 1, 2, and 3 responded to abiotic and biotic stress factors. Co-expression of OePINs with genes involved in stress signaling and oxidative stress homeostasis were identified. This study highlights the importance of PIN genes on stress responses, contributing for a holistic understanding of the role of auxins in plants. Full article

Insects are generally associated with gut bacterial communities that benefit the hosts with respect to diet digestion, limiting resource supplementation, pathogen defense, and ecological niche expansion. Heteroptera (true bugs) represent one of the largest and most diverse insect lineages and comprise species consuming different diets and inhabiting various ecological niches, even including underwater. However, the bacterial symbiotic associations have been characterized for those basically restricted to herbivorous stink bugs of the infraorder Pentatomomorpha. The gut microbiota associated with the megadiverse heteropteran lineages and the implications of ecological and diet variance remain largely unknown. Here, we conducted a bacterial 16S rRNA amplicon sequencing of the gut microbiota across 30 species of true bugs representative of different ecological niches and diets. It was revealed that Proteobacteria and Firmicute were the predominant bacterial phyla. Environmental habitats and diets synergistically contributed to the diversity of the gut bacterial community of true bugs. True bugs living in aquatic environments harbored multiple bacterial taxa that were not present in their terrestrial counterparts. Carnivorous true bugs possessed distinct gut microbiota compared to phytophagous species. Particularly, assassin bugs of the family Reduviidae possessed a characterized gut microbiota predominantly composed of one Enterococcus with different Proteobacteria, implying a specific association between the gut bacteria and host. Overall, our findings highlight the importance of the comprehensive surveillance of gut microbiota association with true bugs for understanding the molecular mechanisms underpinning insect–bacteria symbiosis. Full article

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Background: The origin and early evolution of angiosperms, by far the most important plant group for human beings, are questions demanding answers, mainly due to a lack of related fossils. The Yixian Formation (Lower Cretaceous) is famous for its fossils of early angiosperms, and several Early Cretaceous angiosperms with apocarpous gynoecia have been documented. However, a hypanthium and an inferior ovary are lacking in these fossil angiosperms. Methods: The specimen was collected from the outcrop of the Yixian Formation in Dawangzhangzi in the suburb of Lingyuan, Liaoning, China. The specimen was photographed using a Nikon D200 digital camera, and its details were photographed using a Nikon SMZ1500 stereomicroscope and a MAIA3 TESCAN SEM. Results: A fossil angiosperm, Lingyuananthus inexpectus gen. et sp. nov, is reported from the Lower Cretaceous of China. Differing from those documented previously, Lingyuananthus has a hypanthium, an inferior ovary, and ovules inside its ovary. Such a character assemblage indicates its angiospermous affinity, although not expected by any existing leading angiosperm evolutionary theory. Conclusions: New fossil material with a unique character assemblage falls beyond the expectation of the currently widely accepted theories of angiosperm evolution. Together with independently documented fossils of early angiosperms, Lingyuananthus suggests that at least some early angiosperms’ flowers can be derived in a way that has been ignored previously. Full article

Plyometric training (PT) has been found to be effective for children’s fitness. However, no study has examined the effects of sex on physical fitness adaptations from surface-type PT in children. This study compared the effects of short-term surface-type PT (firm vs. sand) on the physical fitness of schoolchildren of both sexes. Sixty girls (age = 10.00 ± 1.15 years) and sixty boys (age = 10.02 ± 1.12 years) participated in a short-term (4 weeks), randomized and parallel PT design with pre-to-post measurements. Children were divided into two experimental groups (firm group: PT performed on a clay surface, 20 boys and 20 girls; sand group: PT performed on a dry surface of 20 cm deep sand, 20 boys and 20 girls) and a control group (CG, 20 boys and 20 girls). Squat jump, standing long jump, 20 m sprint, 5-10-5 shuttle, dynamic balance, and maximal aerobic velocity were measured at baseline and after intervention. Both experimental groups showed greater pre-post changes in all assessed variables than the CG (p < 0.0001). No significant differences in pre-post changes were observed relative to surface type or sex (p > 0.05). These findings suggest that a twice-weekly PT program induced physical fitness improvements, which may have transfer to health status during childhood. Additionally, surface type and sex did not affect the training-induced changes in physical fitness. Full article

Myocardial wall stress, cytokines, hormones, and ischemia all stimulate B-type (or brain) natriuretic peptide (BNP) gene expression. Within the myocardium, ProBNP-108, a BNP precursor, undergoes glycosylation, after which a portion is cleaved by furin into mature BNP-32 and N-terminal proBNP-76, depending on the glycosylation status. As a result, active BNP, less active proBNP, and inactive N-terminal proBNP all circulate in the blood. There are three major pathways for BNP clearance: (1) cellular internalization via natriuretic peptide receptor (NPR)-A and NPR-C; (2) degradation by proteases in the blood, including neprilysin, dipeptidyl-peptidase-IV, insulin degrading enzyme, etc.; and (3) excretion in the urine. Because neprilysin has lower substrate specificity for BNP than atrial natriuretic peptide (ANP), the increase in plasma BNP after angiotensin receptor neprilysin inhibitor (ARNI) administration is much smaller than the increase in plasma ANP. Currently available BNP immunoassays react with both mature BNP and proBNP. Therefore, BNP measured with an immunoassay is mature BNP + proBNP. ARNI administration increases mature BNP but not proBNP, as the latter is not degraded by neprilysin. Consequently, measured plasma BNP initially increases with ARNI administration by the amount of the increase in mature BNP. Later, ARNI reduces myocardial wall stress, and the resultant reduction in BNP production more than offsets the increase in mature BNP mediated by inhibiting degradation by neprilysin, which lowers plasma BNP levels. These results suggest that even in the ARNI era, BNP can be used for diagnosis and assessment of the pathophysiology and prognosis of heart failure, though the mild increases early during ARNI administration should be taken into consideration. Full article

Background: We aimed to investigate the changes of inflammatory status reflected by serum levels of chitotriosidase (CHT) and neopterin, and how specific tumor markers such as neuron-specific enolase (NSE) and squamous cell carcinoma antigen (SCCA), as well as vitamin D metabolism assessed by vitamin D receptor (VDR) and 25-hydroxy vitamin D₃ (25OHD₃), were modified after the first cycle of chemotherapy in patients with lung cancer. Methods: We performed this first pilot study on twenty patients diagnosed with lung cancer by investigating the serum concentrations of CHT, neopterin, NSE, SCCA, VDR and 25OHD₃ before and after the first cycle of chemotherapy. Results: The post-treatment values of NSE were significantly lower compared to the pre-treatment levels (14.37 vs. 17.10 ng/mL, p = 0.031). We noticed a similar trend in neopterin levels, but the difference was only marginally significant (1.44 vs. 1.17 ng/mL, p = 0.069). On the contrary, the variations of circulating SCCA, CHT, neopterin, VDR and 25OHD₃, before and after treatment, did not reach statistical significance. Conclusion: Only circulating NSE was treatment responsive to the first chemotherapy cycle in patients with lung cancer, while inflammatory markers and vitamin D status were not significantly modified. Full article

As one of the major structural constituents, mobile elements comprise more than half of the human genome, among which Alu, L1, and SVA elements are still active and continue to generate new offspring. One of the major characteristics of L1 and SVA elements is their ability to co-mobilize adjacent downstream sequences to new loci in a process called 3′ DNA transduction. Transductions influence the structure and content of the genome in different ways, such as increasing genome variation, exon shuffling, and gene duplication. Moreover, given their mutagenicity capability, 3′ transductions are often involved in tumorigenesis or in the development of some diseases. In this study, we analyzed 3202 genomes sequenced at high coverage by the New York Genome Center to catalog and characterize putative 3′ transduced segments mediated by L1s and SVAs. Here, we present a genome-wide map of inter/intrachromosomal 3′ transduction variants, including their genomic and functional location, length, progenitor location, and allelic frequency across 26 populations. In total, we identified 7103 polymorphic L1s and 3040 polymorphic SVAs. Of these, 268 and 162 variants were annotated as high-confidence L1 and SVA 3′ transductions, respectively, with lengths that ranged from 7 to 997 nucleotides. We found specific loci within chromosomes X, 6, 7, and 6_GL000253v2_alt as master L1s and SVAs that had yielded more transductions, among others. Together, our results demonstrate the dynamic nature of transduction events within the genome and among individuals and their contribution to the structural variations of the human genome. Full article