Sugar transporters are necessary to transfer hexose from cell wall spaces into parenchyma cells to boost hexose accumulation to high concentrations in fruit. Here, we have identified an apple hexose transporter (HTs), MdHT2.2, located in the plasma membrane, which is highly expressed in mature fruit. In a yeast system, the MdHT2.2 protein exhibited high 14 C-fructose and 14 C-glucose transport activity. In transgenic tomato heterologously expressing MdHT2.2, the levels of both fructose and glucose increased significantly in mature fruit, with sugar being unloaded via the apoplastic pathway, but the level of sucrose decreased significantly. Analysis of enzyme activity and the expression of genes related to sugar metabolism and transport revealed greatly up-regulated expression of SlLIN5, a key gene encoding cell wall invertase (CWINV), as well as increased CWINV activity in tomatoes transformed with MdHT2.2. Moreover, the levels of fructose, glucose and sucrose recovered nearly to those of the wild type in the sllin5-edited mutant of the MdHT2.2-expressing lines. However, the overexpression of MdHT2.2 decreased hexose levels and increased sucrose levels in mature leaves and young fruit, suggesting that the response pathway for the apoplastic hexose signal differs among tomato tissues. The present study identifies a new HTs in apple that is able to take up fructose and glucose into cells and confirms that the apoplastic hexose levels regulated by HT controls CWINV activity to alter carbohydrate partitioning and sugar content.

Metal oxide nanoparticles (NPs), such as ZnO, ZnFe2O4, and Fe2O3, are widely used in industry. However, little is known about the cellular pathways involved in their potential toxicity. Here, we particularly investigated the key molecular pathways that are switched on after exposure to sub-toxic doses of ZnO, ZnFe2O4, and Fe2O3 in the in vitro rat alveolar macrophages (NR8383). As in our model, the calculated IC50 were respectively 16, 68, and more than 200 μg/mL for ZnO, ZnFe2O4, and Fe2O3; global gene and protein expression profiles were only analyzed after exposure to ZnO and ZnFe2O4 NPs. Using a rat genome microarray technology, we found that 985 and 1209 genes were significantly differentially expressed in NR8383 upon 4 h exposure to ¼ IC50 of ZnO and ZnFe2O4 NPs, respectively. It is noteworthy that metallothioneins were overexpressed genes following exposure to both NPs. Moreover, Ingenuity Pathway Analysis revealed that the top canonical pathway disturbed in NR8383 exposed to ZnO and ZnFe2O4 NPs was eIF2 signaling involved in protein homeostasis. Quantitative mass spectrometry approach performed from both NR8383 cell extracts and culture supernatant indicated that 348 and 795 proteins were differentially expressed upon 24 h exposure to ¼ IC50 of ZnO and ZnFe2O4 NPs, respectively. Bioinformatics analysis revealed that the top canonical pathways disturbed in NR8383 were involved in protein homeostasis and cholesterol biosynthesis for both exposure conditions. While VEGF signaling was specific to ZnO exposure, iron homeostasis signaling pathway was specific to ZnFe2O4 NPs. Overall, the study provides resource of transcriptional and proteomic markers of response to ZnO and ZnFe2O4 NP-induced toxicity through combined transcriptomics, proteomics, and bioinformatics approaches.

We aimed to identify factors (child diet, physical activity; maternal BMI) associated with body composition of Ghanaian pre-school children.

Pneumothorax (PTX) following cardiac implantable electronic device procedures is traditionally treated with chest tube drainage (CTD). We hypothesized that, in a subset of patients, the less invasive needle aspiration (NA) may also be effective. We compared the strategy of primary NA with that of primary CTD in a single-center observational study.

The studies aimed to evaluate the significance of cereal products as an essential source of Ca, Mg and K in the diets of Poles. The study covered 226 groups of cereal products most popular in Poland: bread, bread rolls, cooked pasta, cooked grains and cooked rice. The content of Ca, Mg and K was determined by means of FAAS. In addition, considering the recommended daily intake of K, Ca and Mg for the Polish population of adults, the percentage share of respective products in daily supply of these minerals was determined. The content of the above-mentioned minerals in all analysed cereal products can be presented as K > Mg > Ca. Intake of cereal products covers the requirement of K, Mg and Ca among adult Poles, respectively, in ca. 9%, ca. 12 (men)-15 (women) % and ca. 3%. The best source of K, Mg and Ca is bread which in the daily diets of Poles supplies more than 90% of minerals consumed with cereal products. It can be claimed that cereal products are a poor source of Ca, but they supply significant amounts of K and Mg in the diets of Poles, especially given that deficiency of such minerals is common in Poland. It would be important to consider obligatory fortification of flour with minerals which are deficient in the diets of Poles.

Conventional myocardial T1 mapping techniques such as modified Look-Locker inversion recovery (MOLLI) generate one T1 map per breathhold. T1 mapping with full left ventricular coverage may be desirable when spatial T1 variations are expected. This would require multiple breathholds, increasing patient discomfort and prolonging scan time.

With over 48,000 species currently described, spiders (Arthropoda: Chelicerata: Araneae) comprise one of the most diverse groups of animals on our planet, and exhibit an equally wide array of fascinating behaviors. Studies of central nervous systems (CNSs) in spiders, however, are relatively sparse, and no reports have yet characterized catecholaminergic (dopamine [DA]- or norepinephrine-synthesizing) neurons in any spider species. Because these neuromodulators are especially important for sensory and motor processing across animal taxa, we embarked on a study to identify catecholaminergic neurons in the CNS of the wolf spider Hogna lenta (Lycosidae) and the jumping spider Phidippus regius (Salticidae). These neurons were most effectively labeled with an antiserum raised against tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. We found extensive catecholamine-rich neuronal fibers in the first- and second-order optic neuropils of the supraesophageal mass (brain), as well as in the arcuate body, a region of the brain thought to receive visual input and which may be involved in higher order sensorimotor integration. This structure likely shares evolutionary origins with the DA-enriched central complex of the Mandibulata. In the subesophageal mass, we detected an extensive filigree of TH-immunoreactive (TH-ir) arborizations in the appendage neuromeres, as well as three prominent plurisegmental fiber tracts. A vast abundance of TH-ir somata were located in the opisthosomal neuromeres, the largest of which appeared to project to the brain and decorate the appendage neuromeres. Our study underscores the important roles that the catecholamines likely play in modulating spider vision, higher order sensorimotor processing, and motor patterning.

Long noncoding RNAs (lncRNAs) play an important role in many biological processes and carcinogenesis. We aimed to explore lncRNA-based pathogenesis, diagnostic biomarkers, and predictive factors of malignant transformation from dysplasia to oral squamous cell carcinoma (OSCC). Microarray data of GSE30784 consisting of 167 OSCC, 17 dysplasia, and 45 normal oral tissues were downloaded from the GEO database. The differentially expressed genes (DEGs) and lncRNAs between the three samples were identified using R, followed by lncRNA-mRNA coexpression and coregulation network analysis for the prediction of lncRNA target genes. Gene Ontology and Kyoto encydopedia of gene and genomes pathway analysis were performed to further characterize potential interactions. A total of 4462 DEGs and 76 differentially expressed lncRNAs were screened between the three groups, and 200 DEGs and only double homeobox A pseudogene 10 (DUXAP10) were screened among the three groups. A total of 1662 interactions of 46 lncRNAs and their coexpressed target genes were predicted, and 38 pairs of lncRNA-lncRNA coregulated 843 target genes. The coregulated target genes significantly enriched in antigen adaptive immune response, activation of phagocytosis receptor signaling, mast granule NF-κB inflammation, etc. Overall, lncRNAs were differentially expressed in OSCC and dysplasia. The target genes might play an important role in the carcinogenesis and development of OSCC. These results improve our understanding regarding the lncRNA-based pathogenesis and identify some potential targets for early diagnosis of malignant transformation from dysplasia to OSCC.

Being physically active postdiagnosis has been associated with lower rates of prostate cancer progression and mortality, but studies investigating postdiagnostic time spent sitting are lacking. We aim to study the association between leisure time sitting after a prostate cancer diagnosis and overall and prostate cancer-specific mortality.

The humanitarian sector is increasingly aware of the role that good quality evidence plays in the underpinning of effective and accountable practice. This review addresses the need for reliable evidence by evaluating current knowledge about the intersection of two key outcome targets of post-disaster shelter response: supporting shelter self-recovery and building back safer. Evidence about post-disaster shelter programmes that aim to improve hazard resistance while supporting shelter self-recovery has been systematically analysed and evaluated. Technical support, especially training in safer construction techniques, was found to be a central programme feature, but the impact of this and other programme attributes on building safety was largely not ascertainable. Programme reports and studies lack sufficient detail, especially on the hazard resistance of repaired houses. Accounts of shelter programmes need to include more reliable reporting of key activities and assessment of outcomes, in order to contribute to the growing evidence base in this field.

Species-rich plant communities have been shown to be more productive and to exhibit increased long-term soil organic carbon (SOC) storage. Soil microorganisms are central to the conversion of plant organic matter into SOC, yet the relationship between plant diversity, soil microbial growth, turnover as well as carbon use efficiency (CUE) and SOC accumulation is unknown. As heterotrophic soil microbes are primarily carbon limited, it is important to understand how they respond to increased plant-derived carbon inputs at higher plant species richness (PSR). We used the long-term grassland biodiversity experiment in Jena, Germany, to examine how microbial physiology responds to changes in plant diversity and how this affects SOC content. The Jena Experiment considers different numbers of species (1-60), functional groups (1-4) as well as functional identity (small herbs, tall herbs, grasses, and legumes). We found that PSR accelerated microbial growth and turnover and increased microbial biomass and necromass. PSR also accelerated microbial respiration, but this effect was less strong than for microbial growth. In contrast, PSR did not affect microbial CUE or biomass-specific respiration. Structural equation models revealed that PSR had direct positive effects on root biomass, and thereby on microbial growth and microbial biomass carbon. Finally, PSR increased SOC content via its positive influence on microbial biomass carbon. We suggest that PSR favors faster rates of microbial growth and turnover, likely due to greater plant productivity, resulting in higher amounts of microbial biomass and necromass that translate into the observed increase in SOC. We thus identify the microbial mechanism linking species-rich plant communities to a carbon cycle process of importance to Earth's climate system.

There is a need to prognosticate the severity of cystic fibrosis (CF) detected by newborn screening (NBS) by early assessment of CF transmembrane conductance regulator (CFTR) protein function. We introduce novel instrumentation and protocol for evaluating CFTR activity as reflected by β-adrenergically stimulated sweat secretion.

ZC4H2 encodes a C4H2 type zinc-finger nuclear factor, the mutation of which has been associated with disorders with various clinical phenotypes in human, including developmental delay, intellectual disability and dystonia. ZC4H2 has been suggested to regulate spinal cord patterning in zebrafish as a co-factor for RNF220, an ubiquitin E3 ligase involved in Gli signaling. Here we showed that ZC4H2 and RNF220 knockout animals phenocopy each other in spinal patterning in both mouse and zebrafish, with mispatterned progenitor and neuronal domains in the ventral spinal cord. We showed evidence that ZC4H2 is required for the stability of RNF220 and also proper Gli ubiquitination and signaling in vivo. Our data provides new insights into the possible etiology of the neurodevelopmental impairments observed in ZC4H2-associated syndromes.

This study aimed to research the understanding and knowledge of cervical cancer, human papilloma virus (HPV), and HPV vaccination, and the acceptance of HPV vaccination, among a population of women in northeastern China. A cross-sectional survey was carried out by questionnaire to investigate knowledge of cervical cancer, HPV, and HPV vaccination. The 230 female participants were native residents of northeastern China, and their ages ranged between 18 and 65 years. Questionnaires were randomly acquired by the respondents from online and paper questionnaire distribution. The questionnaire included questions on three major aspects to record people's perceptions of cervical cancer, HPV, and vaccines. Of the sample of 230 women surveyed, 80.9% had heard of cervical cancer, but understanding was only 15.7%; 38.3% knew about HPV; 20% knew about HPV vaccine; 39.6% agreed to receive HPV vaccination, and the remainder were mainly concerned about its safety and effectiveness. Data analysis showed that age, family income, and whether there was experience of screening all influenced knowledge of cervical cancer, but this was not statistically significant. The level of education had no obvious effect on the degree of knowledge about cervical cancer; however, with an improvement in education, women's awareness of HPV vaccine improved significantly (p < 0.05). Women who have received cervical cancer screening had significantly greater knowledge about cervical cancer and HPV than those with no screening (p < 0.05). Women in northeastern China have little knowledge of cervical cancer, HPV, and HPV vaccine, lack disease knowledge, and hold a skeptical attitude about HPV vaccination. Medical institutions are the main channel providing information to these women.

IgG4-related disease (IgG4-RD) is a unique inflammatory disorder in which Th2 cytokines promote IgG4 production. In addition, recent studies have implicated the Toll-like receptor (TLR) pathway. This study was undertaken to examine the expression of TLRs in salivary glands (SGs) from patients with IgG4-RD.

Ambulatory ECG monitoring is typically achieved using portable devices with limited number of surface leads, autonomy, and length of recording. Smart garments with multiple conductive textile electrodes provide great promise to perform continuous and comfortable ECG monitoring.

Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell neoplasm characterized by an uncontrolled proliferation of moderately and well differentiated cells of the granulocytic lineage. LW-213, a newly synthesized flavonoid compound, was found to exert antitumor effects against breast cancer through inducing G2/M phase arrest. We investigated whether LW-213 exerted anti-CML effects and the underlying mechanisms. We showed that LW-213 inhibited the growth of human CML cell lines K562 and imatinid-resistant K562 (K562r) in dose- and time-dependent manners with IC50 values at the low μmol/L levels. LW-213 (5, 10, 15 μM) caused G2/M phase arrest of K562 and K562r cells via reducing the activity of G2/M phase transition-related proteins Cyclin B1/CDC2 complex. LW-213 treatment induced apoptosis of K562 and K562r cells via inhibiting the expression of CDK9 through lysosome degradation, thus leading to the suppression of RNAPII phosphorylation, down-regulation of a short-lived anti-apoptic protein MCL-1. The lysosome inhibitor, NH4Cl, could reverse the anti-CML effects of LW-213 including CDK9 degradation and apoptosis. LW-213 treatment also degraded the downstream proteins of BCR-ABL1, such as oncoproteins AKT, STAT3/5 in CML cells, which was blocked by NH4Cl. In primary CML cells and CD34+ stem cells, LW-213 maintained its pro-apoptotic activity. In a K562 cells-bearing mice model, administration of LW-213 (2.5, 5.0 mg/kg, ip, every other day for 4 weeks) dose-dependently prolonged the survival duration, and significantly suppressed huCD45+ cell infiltration and expression of MCL-1 in spleens. Taken together, our results demonstrate that LW-213 may be an efficient agent for CML treatment.

Endothelial angiogenesis plays a vital role in recovery from chronic ischemic injuries. ZYZ-803 is a hybrid donor of hydrogen sulfide (H2S) and nitric oxide (NO). Previous studies showed that ZYZ-803 stimulated endothelial cell angiogenesis both in vitro and in vivo. In this study, we investigated whether the signal transducer and activator of transcription 3 (STAT3) and Ca2+/CaM-dependent protein kinase II (CaMKII) signaling was involved in ZYZ-803-induced angiogenesis. Treatment with ZYZ-803 (1 μM) significantly increased the phosphorylation of STAT3 (Tyr705) and CaMKII (Thr286) in human umbilical vein endothelial cells (HUVECs), these two effects had a similar time course. Pretreatment with WP1066 (STAT3 inhibitor) or KN93 (CAMKII inhibitor) blocked ZYZ-803-induced STAT3/CAMKII activation and significantly suppressed the proliferation and migration of HUVECs. In addition, pretreatment with the inhibitors significantly decreased ZYZ-803-induced tube formations along with the outgrowths of branch-like microvessels in aortic rings. In the mice with femoral artery ligation, administration of ZYZ-803 significantly increased the blood perfusion and vascular density in the hind limb, whereas co-administration of WP1066 or KN93 abrogated ZYZ-803-induced angiogenesis. By using STAT3 siRNA, we further explored the cross-talk between STAT3 and CaMKII in ZYZ-803-induced angiogenesis. We found that STAT3 knockdown suppressed ZYZ-803-induced HUVEC angiogenesis and affected CaMKII expression. ZYZ-803 treatment markedly enhanced the interaction between CaMKII and STAT3. ZYZ-803 treatment induced the nuclear translocation of STAT3. We demonstrated that both STAT3 and CaMKII functioned as positive regulators in ZYZ-803-induced endothelial angiogenesis and STAT3 was important in ZYZ-803-induced CaMKII activation, which highlights the beneficial role of ZYZ-803 in STAT3/CaMKII-related cardiovascular diseases.

The aim of this study was to assess the effect of prehospital noninvasive ventilation for acute cardiogenic pulmonary edema on endotracheal intubation rate and on ICU admission rate.

Interpretation of noncoding disease variants, which comprise the vast majority of Genome-wide association studies (GWAS) hits, remains a momentous challenge due to haplotype structure and our limited understanding of the mechanisms and physiological contexts of noncoding elements. GWAS have identified loci underlying human diseases, but assigning the causal nucleotide changes still remain a controversial issue. Here we addressed these issues through the combination of high-density genotyping and epigenomic data using a random forest model to discover the noncoding causal variants. Focusing on autoimmune diseases, we triaged putative causal variants for atopic dermatitis and inflammatory bowel diseases. Making a filtering pipeline, we found three interesting single nucleotide polymorphisms (rs1800630, rs1799964 and rs4796793) in the upstream site of TNF and STAT3 genes, two frequent genes shared in some autoimmune diseases, and show how those variants affect on TNF and STAT3 expression levels. All data and source codes related to this manuscript are available at https://github.com/jieunjung511/Autoimmune-research.