PTEN is a tumour suppressor gene, and its loss of function is frequently observed in both heritable and sporadic cancers. It is involved in a great variety of biological processes, including maintenance of genomic stability, cell survival, migration, proliferation and metabolism. A better understanding of PTEN activity and regulation has therefore emerged as a subject of primary interest in cancer research. Gynaecological cancers are variously interested by PTEN deregulation and many perspective in terms of additional prognostic information and new therapeutic approaches can be explored. Here, we present the most significant findings on PTEN in gynaecological cancers (ovarian, endometrial, cervical, vulvar and uterine cancer) focusing on PTEN alterations incidence, biological role and clinical implications.

: Background and objectives: Prompt identification of patients with acute traumatic coagulopathy (ATC) is necessary to expedite appropriate treatment. An early clinical prediction tool that does not require laboratory testing is a convenient way to estimate risk. Prediction models have been developed, but none are in widespread use. This systematic review aimed to identify and assess accuracy of prediction tools for ATC. Materials and Methods: A search of OVID Medline and Embase was performed for articles published between January 1998 and February 2018. We searched for prognostic and predictive studies of coagulopathy in adult trauma patients. Studies that described stand-alone predictive or associated factors were excluded. Studies describing prediction of laboratory-diagnosed ATC were extracted. Performance of these tools was described. Results: Six studies were identified describing four different ATC prediction tools. The COAST score uses five prehospital variables (blood pressure, temperature, chest decompression, vehicular entrapment and abdominal injury) and performed with 60% sensitivity and 96% specificity to identify an International Normalised Ratio (INR) of >1.5 on an Australian single centre cohort. TICCS predicted an INR of >1.3 in a small Belgian cohort with 100% sensitivity and 96% specificity based on admissions to resuscitation rooms, blood pressure and injury distribution but performed with an Area under the Receiver Operating Characteristic (AUROC) curve of 0.700 on a German trauma registry validation. Prediction of Acute Coagulopathy of Trauma (PACT) was developed in USA using six weighted variables (shock index, age, mechanism of injury, Glasgow Coma Scale, cardiopulmonary resuscitation, intubation) and predicted an INR of >1.5 with 73.1% sensitivity and 73.8% specificity. The Bayesian network model is an artificial intelligence system that predicted a prothrombin time ratio of >1.2 based on 14 clinical variables with 90% sensitivity and 92% specificity. Conclusions: The search for ATC prediction models yielded four scoring systems. While there is some potential to be implemented effectively in clinical practice, none have been sufficiently externally validated to demonstrate associations with patient outcomes. These tools remain useful for research purposes to identify populations at risk of ATC.

The charging efficiency of a lithium-ion capacitor (LIC) is an important problem. Until now, due to the stepwise charging method, the charging efficiency of 95.5% has been realized. However, the problem is that the issue of what level the charging efficiency can be increased to, is yet to be well investigated. In this article, the problem is investigated under the galvanostatic charging condition. The charging efficiency is measured as a function of the charging current. As a result, it can be more than 99.5% when the charging is quasi-static, in other words, an adiabatic process is realized. Next, the problem of how much energy can be taken out from the energy-stored capacitor is investigated with a load resistor circuit. It is clarified that the discharging energy from the capacitor is equal to the stored energy in the case when a load resistor is used and the discharging is quasi-static. It is confirmed that LICs are suitable for use as energy storage devices.

Transforming growth factor beta (TGF-β) is a determinant for inflammation and fibrosis in cardiac and skeletal muscle in Chagas disease. To determine its regulatory mechanisms, we investigated the response of Trypanosoma cruzi-infected cardiomyocytes (CM), cardiac fibroblasts (CF), and L6E9 skeletal myoblasts to TGF-β. Cultures of CM, CF, and L6E9 were infected with T. cruzi (Y strain) and treated with TGF-β (1-10 ng/mL, 1 h or 48 h). Fibronectin (FN) distribution was analyzed by immunofluorescence and Western blot (WB). Phosphorylated SMAD2 (PS2), phospho-p38 (p-p38), and phospho-c-Jun (p-c-Jun) signaling were evaluated by WB. CF and L6E9 showed an increase in FN from 1 ng/mL of TGF-β, while CM displayed FN modulation only after 10 ng/mL treatment. CF and L6E9 showed higher PS2 levels than CM, while p38 was less stimulated in CF than CM and L6E9. T. cruzi infection resulted in localized FN disorganization in CF and L6E9. T. cruzi induced an increase in FN in CF cultures, mainly in uninfected cells. Infected CF cultures treated with TGF-β showed a reduction in PS2 and an increase in p-p38 and p-c-Jun levels. Our data suggest that p38 and c-Jun pathways may be participating in the fibrosis regulatory process mediated by TGF-β after T. cruzi infection.

The aim of our study was to compare the degree of brain atrophy in centenarians and in seniors 70-99 years old. The study group consisted of 23 patients aged 100-106 years. The control group consisted of 90 patients, 30 in each age subgroup 90-99, 80-89, 70-79. In all the patients, the brain atrophy linear parameters were measured on computed tomography scans, in relation to both "subcortical atrophy", evaluated as progressive widening of the ventricular system, and "cortical atrophy", defined as widening of subarachnoid space. Secondary indices based on the parameters were calculated. Correlations between the above parameters/indices and age were tested. Significantly different values between the centenarians and the control group were found in the brain atrophy parameters: A, B, C, E, FI, ICR, ICL, SW, CFW, F/A 'frontal horn index', A/G 'Evans index', D/A 'ventricular index', H/E 'cella media Schiersmann index', A+B 'Huckman number'. Correlations between parameter/index and age were found for: A, B, C, FI, ICR, ICL, SW, F/A 'frontal horn index', A/G 'Evans index', D/A 'ventricular index', H/E 'cella media Schiersmann index', A+B 'Huckman number'. Brain atrophy associated with aging is a continuously advancing process, affecting centenarians even more than people before the "magic" threshold of 100 years.

Green-colored fiber (GCF) is the unique raw material for naturally colored cotton textile but we know little about the pigmentation process in GCF. Here we compared transcriptomes and metabolomes of 12, 18 and 24 days post-anthesis (DPA) fibers from a green fiber cotton accession and its white-colored fiber (WCF) near-isogenic line. We found a total of 2047 non-redundant metabolites in GCF and WCF that were enriched in 80 pathways, including those of biosynthesis of phenylpropanoid, cutin, suberin, and wax. Most metabolites, particularly sinapaldehyde, of the phenylpropanoid pathway had a higher level in GCF than in WCF, consistent with the significant up-regulation of the genes responsible for biosynthesis of those metabolites. Weighted gene co-expression network analysis (WGCNA) of genes differentially expressed between GCF and WCF was used to uncover gene-modules co-expressed or associated with the accumulation of green pigments. Of the 16 gene-modules co-expressed with fiber color or time points, the blue module associated with G24 (i.e., GCF at 24 DPA) was of particular importance because a large proportion of its genes were significantly up-regulated at 24 DPA when fiber color was visually distinguishable between GCF and WCF. A total of 56 hub genes, including the two homoeologous Gh4CL4 that could act in green pigment biosynthesis, were identified among the genes of the blue module that are mainly involved in lipid metabolism, phenylpropanoid biosynthesis, RNA transcription, signaling, and transport. Our results provide novel insights into the mechanisms underlying pigmentation of green fibers and clues for developing cottons with stable green colored fibers.

Sterols, especially cholesterol (Chl), are fundamental for animal survival. Insects lacking the ability to synthesize Chl are sterol auxotrophic animals and utilize dietary Chl and phytosterols to survive. The sterols obtained from a diet are distributed to the tissues; however, sterol homeostasis in insect tissues remains to be elucidated. This study sought to understand the sterol characteristics of insect tissues through detailed sterol quantification and statistics. The combination of sterol quantification using liquid chromatography tandem mass spectrometry (LC-MS/MS) and principal component analysis (PCA) revealed tissue-specific sterol characteristics in the silkworm, Bombyx mori, a phytophagous insect. We found that insect tissues have tissue-intrinsic sterol profiles. The brain has a unique sterol composition as compared to other tissues-high concentration of Chl and less accumulation of phytosterols. Other tissues also have intrinsic sterol characteristics, which when defined by dietary sterols or Chl metabolites, indicate preference for a sterol and consistently manage their own sterol homeostasis. Though most tissues never change sterol profiles during development, the brain drastically changes its sterol profile at the wandering stage, indicating that it could alter sterol composition in preparation for metamorphosis. These results suggest the existence of tissue- and sterol-specific systems for sterol homeostasis in insects.

In this study, SiO2@Au@4-MBA@Ag (4-mercaptobenzoic acid labeled gold-silver-alloy-embedded silica nanoparticles) nanomaterials were investigated for the detection of thiram, a pesticide. First, the presence of Au@4-MBA@Ag alloys on the surface of SiO2 was confirmed by the broad bands of ultraviolet-visible spectra in the range of 320-800 nm. The effect of the 4-MBA (4-mercaptobenzoic acid) concentration on the Ag shell deposition and its intrinsic SERS (surface-enhanced Raman scattering) signal was also studied. Ag shells were well coated on SiO2@Au@4-MBA in the range of 1-1000 µM. The SERS intensity of thiram-incubated SiO2@Au@4-MBA@Ag achieved the highest value by incubation with 500 µL thiram for 30 min, and SERS was measured at 200 µg/mL SiO2@Au@4-MBA@Ag. Finally, the SERS intensity of thiram at 560 cm-1 increased proportionally with the increase in thiram concentration in the range of 240-2400 ppb, with a limit of detection (LOD) of 72 ppb.

A novel lipid inhibition peptide Leu-Leu-Val-Val-Try-Pro-Trp-Thr-Gln-Arg (PP1) (MW 1274.53 Da) was obtained from Chlorella pyenoidose using enzymatic hydrolysis, gel filtration chromatography, and LC-MS/MS. Its lipid inhibition effects indicated that the synthetic peptide PP1 exhibits a good inhibitory effect against porcine pancreatic lipase (PL) (47.95%) at 200 μg/mL, which could be attributed to its hydrogen binding into catalytic sites of PL (Ser153, Asp177, and His 264) by docking analysis. Furthermore, in 3T3-L1 cells, the synthetic PP1 remarkedly decreased the accumulation of intracellular triacylglycerol (27.9%, 600 μg/mL), which carried a similar consequence as the positive drug simvastatin (24.1%, 10 μM). Western blot revealed that PP1 inhibited the lipid accumulation and fatty acid synthesis in 3T3-L1 adipocytes in two pathways, primarily: nonalcoholic fatty liver disease (NAFLD) pathway (C/EBPα, SREBP-1c, AMPKα) and AMPK signaling pathway (SREBP-1c, PPARγ, AMPKα). In short, these results support that PP1 can be used as a potential agent against obesity.

The cytotrophoblast of human placenta transitions into an outer multinucleated syncytiotrophoblast (STB) layer that covers chorionic villi which are in contact with maternal blood in the intervillous space. During pregnancy, the Zika virus (ZIKV) poses a serious prenatal threat. STB cells are resistant to ZIKV infections, yet placental cells within the mesenchyme of chorionic villi are targets of ZIKV infection. We seek to determine whether ZIKV can open the paracellular pathway of STB cells. This route is regulated by tight junctions (TJs) which are present in the uppermost portion of the lateral membranes of STB cells. We analyzed the paracellular permeability and expression of E-cadherin, occludin, JAMs -B and -C, claudins -1, -3, -4, -5 and -7, and ZO-1, and ZO-2 in the STB of placentae from ZIKV-infected and non-infected women. In ZIKV-infected placentae, the pattern of expression of TJ proteins was preserved, but the amount of claudin-4 diminished. Placentae from ZIKV-infected women were permeable to ruthenium red, and had chorionic villi with a higher mean diameter and Hofbauer hyperplasia. Finally, ZIKV added to the basolateral surface of a trophoblast cell line reduced the transepithelial electrical resistance. These results suggest that ZIKV can open the paracellular pathway of STB cells.

The genus Sedum, with about 470 recognized species, is classified in the family Crassulaceae of the order Saxifragales. Phylogenetic relationships within the Saxifragales are still unresolved and controversial. In this study, the plastome of S. plumbizincicola was firstly presented, with a focus on the structural analysis of rrn operon and phylogenetic implications within the order Saxifragaceae. The assembled complete plastome of S. plumbizincicola is 149,397 bp in size, with a typical circular, double-stranded, and quadripartite structure of angiosperms. It contains 133 genes, including 85 protein-coding genes (PCGs), 36 tRNA genes, 8 rRNA genes, and four pseudogenes (one ycf1, one rps19, and two ycf15). The predicted secondary structure of S. plumbizincicola 16S rRNA includes three main domains organized in 74 helices. Further, our results confirm that 4.5S rRNA of higher plants is associated with fragmentation of 23S rRNA progenitor. Notably, we also found the sequence of putative rrn5 promoter has some evolutionary implications within the order Saxifragales. Moreover, our phylogenetic analyses suggested that S. plumbizincicola had a closer relationship with S. sarmentosum than S. oryzifolium, and supported the taxonomic revision of Phedimus. Our findings of the present study will be useful for further investigation of the evolution of plastid rRNA operon and phylogenetic relationships within Saxifragales.

Background and Objectives: The complex concept of rational suicide, defined as a well-thought-out decision to die by an individual who is mentally competent, is even more controversial in the case of older adults. Materials and Methods: With the aim of better understanding the concept of rational suicide in older adults, we performed a systematic review of the literature, searching PubMed and Scopus databases and eventually including 23 published studies. Results: The main related topics emerging from the papers were: depression, self-determination, mental competence; physicians' and population's perspectives; approach to rational suicide; ageism; slippery slope. Conclusions: Despite contrasting positions and inconsistencies of the studies, the need to carefully investigate and address the expression of suicidal thoughts in older adults, as well as behaviours suggesting "silent" suicidal attitudes, clearly emerges, even in those situations where there is no diagnosable mental disorder. While premature conclusions about the "rationality" of patients' decision to die should be avoided, the possibility of rational suicide cannot be precluded.

Elephants have complex social systems that are predominantly driven by ecological factors in situ. Within zoos, elephants are held in relatively static social groups and the factors observed driving social relationships in the wild are largely absent. Little research has investigated the effect of social group factors in zoos on elephant social interactions. The aim of this research was to establish whether there is a relationship between social group factors and social behaviour, in order to identify factors that make elephant herds more or less likely to be compatible. Results will facilitate recommendations for optimum social groupings for zoo elephants. Behavioural data quantifying social interactions were collected between January 2016 and February 2017 at seven UK and Irish zoos and safari parks from 10 African and 22 Asian elephants. Social interactions were split into four categories: positive physical, positive non-physical, negative physical and negative non-physical. Social interactions were related to age (positive physical higher and negative non-physical lower in calves than adults), personality (elephants with higher sociability scores engaged in more positive interactions and less negative interactions), presence of calves in the herd (herds with calves had more positive non-physical), relatedness to other elephants in the herd (positive non-physical were higher when relatives were in the group and negative non-physical were higher between unrelated elephants) and species (Asian elephants engaged in more positive non-physical than African elephants). A greater understanding of factors that may contribute to the success of zoo-elephant social groups is important for individual and herd welfare as it will enable evidence-based decisions which have minimal impact on social structures to be executed. This knowledge will enable proactive management approaches to be undertaken and will thus be paramount in ensuring optimal welfare for elephant herds moving forwards.

Diabetes causes various macrovascular and microvascular alterations, often culminating in major clinical complications (first of all, stroke) that lack an effective therapeutic intervention. N-palmitoylethanolamide-oxazoline (PEA-OXA) possesses anti-inflammatory and potent neuroprotective effects. Although recent studies have explained the neuroprotective properties of PEA-OXA, nothing is known about its effects in treating cerebral ischemia.

In this study, we designed, synthesized, and characterized ultrahigh purity single-walled carbon nanotube (SWCNT)-alginate hydrogel composites. Among the parameters of importance in the formation of an alginate-based hydrogel composite with single-walled carbon nanotubes, are their varying degrees of purity, their particulate agglomeration and their dose-dependent correlation to cell viability, all of which have an impact on the resultant composite's efficiency and effectiveness towards cell-therapy. To promote their homogenous dispersion by preventing agglomeration of the SWCNT, three different surfactants-sodium dodecyl sulfate (SDS-anionic), cetyltrimethylammonium bromide (CTAB-cationic), and Pluronic F108 (nonionic)-were utilized. After mixing of the SWCNT-surfactant with alginate, the mixtures were cross-linked using divalent calcium ions and characterized using Raman spectroscopy. Rheometric analysis showed an increase in complex viscosity, loss, and storage moduli of the SWCNT composite gels in comparison with pure alginate gels. Scanning electron microscopy revealed the presence of a well-distributed porous structure, and all SWCNT-gel composites depicted enhanced electrical conductivity with respect to alginate gels. To characterize their biocompatibility, cardiomyocytes were cultured atop these SWCNT-gels. Results comprehensively implied that Pluronic F108 was most efficient in preventing agglomeration of the SWCNTs in the alginate matrix, leading to a stable scaffold formation without posing any toxicity to the cells.

Background: Very few experimental studies exist describing the effect of changes to the built environment and opportunities for physical activity (PA). We examined the impact of an urban trail created on a frozen waterway on visitor counts and PA levels. Methods: We studied a natural experiment in Winnipeg, Manitoba, Canada that included 374,204 and 237,362 trail users during the 2017/2018 and 2018/2019 winter seasons. The intervention was a 10 km frozen waterway trail lasting 8-10 weeks. The comparator conditions were the time periods immediately before and after the intervention when ~10 kms of land-based trails were accessible to the public. A convenience sample of 466 participants provided directly measured PA while on the frozen waterway. Results: Most trail users were 35 years or older (73%), Caucasian (77%), and had an annual household income >$50,000 (61%). Mean daily trail network visits increased ~four-fold when the frozen waterway was open (median and interquartile range (IQR) = 710 (239-1839) vs. 2897 (1360-5583) visits/day, p < 0.001), compared with when it was closed. Users achieved medians of 3852 steps (IQR: 2574-5496 steps) and 23 min (IQR: 13-37 min) of moderate to vigorous intensity PA (MVPA) per visit, while 37% of users achieved ≥30 min of MVPA. Conclusion: A winter-specific urban trail network on a frozen waterway substantially increased visits to an existing urban trail network and was associated with a meaningful dose of MVPA. Walking on water could nudge populations living in cold climates towards more activity during winter months.

Polyimides (PIs) represent a benchmark for high-performance polymers on the basis of a remarkable collection of valuable traits and accessible production pathways and therefore have incited serious attention from the ever-demanding medical field. Their characteristics make them suitable for service in hostile environments and purification or sterilization by robust methods, as requested by most biomedical applications. Even if PIs are generally regarded as "biocompatible", proper analysis and understanding of their biocompatibility and safe use in biological systems deeply needed. This mini-review is designed to encompass some of the most robust available research on the biocompatibility of various commercial or noncommercial PIs and to comprehend their potential in the biomedical area. Therefore, it considers (i) the newest concepts in the field, (ii) the chemical, (iii) physical, or (iv) manufacturing elements of PIs that could affect the subsequent biocompatibility, and, last but not least, (v) in vitro and in vivo biocompatibility assessment and (vi) reachable clinical trials involving defined polyimide structures. The main conclusion is that various PIs have the capacity to accommodate in vivo conditions in which they are able to function for a long time and can be judiciously certified as biocompatible.

Cholangiocarcinoma (CCA) caused by chronic liver fluke infection is a major public health problem in Northeast Thailand. Identification of CCA risk groups is urgently needed for the control of CCA in this region. Periductal fibrosis (PDF) induced by chronic inflammation of bile ducts is known as a pre-neoplastic lesion of CCA. We aimed to identify the serum CCA and PDF biomarkers using mass spectrometry (UPLC-ESI-QqQ) with multiple reaction mode (MRM) analysis. Here, serum levels of serotransferrin glycoforms at the glycopeptide level were measured in the sera of CCA (n = 100), PDF (n = 50), and healthy control (n = 100) subjects. The results indicated that serotransferrin peptide levels were generally the same between the control and PDF groups, whereas CCA patients had reduced levels. Moreover, 56 serotransferrin glycoforms were detected, with nine increased in CCA compared to control subjects. Among them, the serum levels of four glycoforms were increased in PDF and CCA patients compared to control subjects. In particular, highly sialylated multi-branched glycans of serotransferrin serum were significantly correlated with poor prognosis and tumor stage in CCA patients. Taken together, these glycoforms could be used as risk biomarkers and prognosis and diagnosis markers of CCA.

Xanthones are important chemical constituents of Garcinia xanthochymus and varied bioactivities including cytotoxicity. However, their anti-tumor mechanism has remained unknown. Here, we isolated and identified a new xanthone named garciniaxanthone I (1) and five known compounds from the bark of G. xanthochymus. Their structures were elucidated by NMR analysis and HRESIMS. The anti-proliferation activities of all isolated compounds were evaluated on four human tumor cell lines (HepG2, A549, SGC7901, MCF-7). The results demonstrated that the anti-proliferation activity of xanthone was related to the number and location of prenyl groups. We further found that garciniaxanthone I (GXI) could induce HepG2 apoptosis and enhance the expression of cleaved caspase-8, caspase-9, and caspase-3. GXI could also increase Bax level and concurrently reduce the overexpression of Bcl-2, Bcl-XL, Mcl-1, and surviving in HepG2 cells. Moreover, GXI could inhibit cell migration of HepG2 cells by inhibiting the expressions of MMP-7 and MMP-9. In summary, our study suggests that GXI could induce HepG2 apoptosis via the mitochondrial pathway and might become a lead compound for liver cancer treatment.

Toll-like receptor 5 (TLR5) plays an important role in immune system. In this study, we performed transcriptome analysis of the duodenum in E. coli F18-resistant and -sensitive Sutai weaned piglets and analyzed the differential expression of TLR5. The cellular localization of TLR5 was investigated, and the effect of TLR5 expression on E. coli invasion was evaluated after pig small intestinal epithelial cell lines (IPEC-J2) were stimulated by E. coli. The results showed that TLR5 expression level in duodenum and jejunum were significantly higher in E. coli F18-sensitive than in E. coli F18-resistant piglets. TLR5 protein was mainly expressed in the cytoplasm and cell membrane. The expression of genes associated with the TLR5 signaling pathway were significantly higher in TLR5-overexpressed cells than in control cells. Bacterial adhesion was higher in TLR5-overexpressed cells than in blank cells and lower in TLR5 interference than in blank cells. The core promoter region of TLR5 included two CpG islands and 16 acting elements. The methylation of the mC-6 site in the second CpG island of the promoter region had a regulatory effect on TLR5 expression. Therefore, TLR5 plays an important regulatory role on E. coli invasion. Low expression of TLR5 inhibited the immune response and decreased cell damage, which was conducive to the resistance to E. coli stimulation. In conclusion, this study preliminarily revealed the molecular mechanism of TLR5 gene regulating the resistance of piglets to Escherichia coli, and provided a new candidate gene for screening Escherichia coli resistance markers in pigs.