Investigation was made of the optical response of metal-dielectric stacks-based cavity structures embedded with graphene microheaters for the purpose of perfect absorption. The absorber configuration exploits the Ge2Sb2Te5 (GST) phase changing medium, and the effects of different parametric and operational conditions on the absorption spectra were explored. The refractive indices of GST layers can be manipulated by the external electrical pulses applied to microheaters. The amplitude and duration of electrical pulses define the crystallinity ratio of the used GST mediums. The results revealed achieving perfect absorption (> 99%) in the visible and infrared (IR) regimes of the electromagnetic spectrum upon incorporating two thin GST layers of different thicknesses (in the stack) in the amorphous state. The proposed configuration showed the capability of introducing independent transition state (amorphous and/or crystalline) for each GST layer-the visible regime could be extended to the IR regime, and the perfect absorption peak in the IR regime could be broadened and red-shifted. It is expected that the structure would find potential applications in active photonic devices, infrared imaging, detectors and tunable absorbers.
Perovskite solar cells based on series of inorganic cesium lead bromide and iodide mixture, CsPbBr3-xI x , where x varies between 0, 0.1, 0.2, and 0.3 molar ratio were synthesized by two step-sequential deposition at ambient condition to design the variations of wide band gap light absorbers. A device with high overall photoconversion efficiency of 3.98 % was obtained when small amount of iodide (CsPbBr2.9I0.1) was used as the perovskite and spiro-OMeTAD as the hole transport material (HTM). We investigated the origin of variation in open circuit voltage, Voc which was shown to be mainly dependent on two factors, which are the band gap of the perovskite and the work function of the HTM. An increment in Voc was observed for the device with larger perovskite band gap, while keeping the electron and hole extraction contacts the same. Besides, the usage of bilayer P3HT/MoO3 with deeper HOMO level as HTM instead of spiro-OMeTAD, thus increased the Voc from 1.16 V to 1.3 V for CsPbBr3 solar cell, although the photocurrent is lowered due to charge extraction issues. The stability studies confirmed that the addition of small amount of iodide into the CsPbBr3 is necessarily to stabilize the cell performance over time.
Tropomyosin receptor kinase C (TrkC) targeted ligand-photosensitizer construct, IYIY-diiodo-boron-dipyrromethene (IYIY-I2-BODIPY) and its scrambled counterpart YIYI-I2-BODIPY have been prepared. IYIY-I2-BODIPY binds TrkC similar to neurotrophin-3 (NT-3), and NT-3 has been reported to modulate immune responses. Moreover, it could be shown that photodynamic therapy (PDT) elevates antitumor immune responses. This prompted us to investigate the immunological impacts mediated by IYIY-I2-BODIPY in pre- and post-PDT conditions. We demonstrated that IYIY-I2-BODIPY (strong response) and YIYI-I2-BODIPY (weak response) at 10 mg/kg, but not I2-BODIPY control, increased the levels of IL-2, IL-4, IL-6 and IL-17, but decreased the levels of systemic immunoregulatory mediators TGF-β, myeloid-derived suppressor cells and regulatory T-cells. Only IYIY-I2-BODIPY enhanced the IFN-γ+ and IL-17+ T-lymphocytes, and delayed tumor growth (~20% smaller size) in mice when administrated daily for 5 days. All those effects were observed without irradiation; when irradiated (520 nm, 100 J/cm2, 160 mW/cm2) to produce PDT effects (drug-light interval 1 h), IYIY-I2-BODIPY induced stronger responses. Moreover, photoirradiated IYIY-I2-BODIPY treated mice had high levels of effector T-cells compared to controls. Adoptive transfer of immune cells from IYIY-I2-BODIPY-treated survivor mice that were photoirradiated gave significantly delayed tumor growth (~40-50% smaller size) in recipient mice. IYIY-I2-BODIPY alone and in combination with PDT modulates the immune response in such a way that tumor growth is suppressed. Unlike immunosuppressive conventional chemotherapy, IYIY-I2-BODIPY can act as an immune-stimulatory chemotherapeutic agent with potential applications in clinical cancer treatment.
Trophic variation in food web structure occurs among and within ecosystems. The magnitude of variation, however, differs from system to system. In ephemeral pond ecosystems, temporal dynamics are relatively more important than in many systems given that hydroperiod is the ultimate factor determining the presence of an aquatic state. Here, using stable isotopes we tested for changes in trophic chain length and shape over time in these dynamic aquatic ecosystems. We found that lower and intermediate trophic level structure increased over time. We discuss these findings within the context of temporal environmental stability. The dynamic nature of these ephemeral systems seems to be conducive to greater levels of intermediate and lower trophic level diversity, with omnivorous traits likely being advantageous.
The method of pre-irradiation grafting was used with the aid of electron beam (EB) accelerator to accomplish the grafting of polyamide 6 fibers (PA6) with glycidyl methacrylate (GMA). The extent to which GMA was grafted on PA6 was found to be markedly influenced by the absorbed dose of radiation and the reaction time of grafting. Trimethylamine (TMA) was afterwards employed for the functionalization of GMA-grafted fibers (PA6-g-GMA). A range of analyses (e.g., FTIR, FESEM, XRD, BET, and pHpzc) were carried out to determine the physiochemical and morphological properties of the fibrous adsorbent. p-Nitrophenol (PNP) adsorption from aqueous solution was conducted with the resulting TMA-(PA6-g-GMA) adsorbent. The adsorption behaviour of PNP on the fibrous adsorbent was clarified by investigating the adsorption kinetics and isotherm. According to the results, the adsorption of PNP on TMA-(PA6-g-GMA) reflected the pseudo-second order model. Meanwhile, the isotherm analysis revealed that the best description of the equilibrium data was provided by Redlich-Peterson model, followed closely by Langmuir isotherm model. The achieved adsorption capacity was highest at 176.036 mg/g. Moreover, the adsorption was indicated by the thermodynamic analysis to be spontaneous and exothermic. Regeneration and recycling of the adsorbent was possible for a minimum of five cycles with no reduction in adsorption capacity. It was concluded that the fibrous adsorbent could have applications for the removal of PNP at industrial pilot scale.
The purpose of this study was to investigate the usefulness of triglyceride to hdl-c ratio (TG:HDL-C) as an insulin resistance (IR) marker for overweight and obese children. A total of 271 blood samples of obese and overweight children aged 9-16 years were analysed for fasting glucose, lipids and insulin. Children were divided into IR and non-insulin resistance, using homeostasis model assessment (HOMA). The children were then stratified by tertiles of TG: HDL-C ratio. The strength between TG:HDL-C ratio and other parameters of IR were quantified using Pearson correlation coefficient (r). Odds ratio was estimated using multiple logistic regression adjusted for age, gender, pubertal stages and IR potential risk factors. Children with IR had significantly higher TG:HDL-C ratio (2.48) (p = 0.01). TG:HDL-C ratio was significantly correlated with HOMA-IR (r = 0.104, p
Up to 25% of breast cancer patients in Asia present with de novo metastatic disease. We examined the survival trends of Asian patients with metastatic breast cancer over fifteen years. The impact of changes in patient's demography, tumor characteristics, tumor burden, and treatment on survival trend were examined. Patients with de novo metastatic breast cancer from three hospitals in Malaysia and Singapore (N = 856) were grouped by year of diagnosis: 1996-2000, 2001-2005 and 2006-2010. Step-wise multivariable Poisson regression was used to estimate the contribution of above-mentioned factors on the survival trend. Proportions of patients presenting with metastatic breast cancer were 10% in 1996-2000, 7% in 2001-2005, and 9% in 2006-2010. Patients in 2006-2010 were significantly older, appeared to have higher disease burden, and received more chemotherapy, endocrine therapy, and surgery of primary tumor. The three-year relative survival in the above periods were 20·6% (95% CI: 13·9%-28·2%), 28·8% (95% CI: 23·4%-34·2%), and 33·6% (95% CI: 28·8%-38·5%), respectively. Adjustment for treatment considerably attenuated the relative excess risk of mortality in recent years, compared to other factors. Substantial improvements in survival were observed in patients with de novo metastatic breast cancer in this study.
Engineered aluminum oxide (Al2O3), titanium dioxide (TiO2), and silicon dioxide (SiO2) nanoparticles (NPs) are utilized in a broad range of applications; causing noticeable quantities of these materials to be released into the environment. Issues of how and where these particles are distributed into the subsurface aquatic environment remain as major challenges for those in environmental engineering. In this study, transport and retention of Al2O3, TiO2, and SiO2 NPs through various saturated porous media were investigated. Vertical columns were packed with quartz-sand, limestone, and dolomite grains. The NPs were introduced as a pulse suspended in aqueous solutions and breakthrough curves in the column outlet were generated using an ultraviolet-visible spectrophotometer. It was found that Al2O3 and TiO2 NPs are easily transported through limestone and dolomite porous media whereas NPs recoveries were achieved two times higher than those found in the quartz-sand. The highest and lowest SiO2-NPs recoveries were also achieved from the quartz-sand and limestone columns, respectively. The experimental results closely replicated the general trends predicted by the filtration and DLVO calculations. Overall, NPs mobility through a porous medium was found to be strongly dependent on NP surface charge, NP suspension stability against deposition, and porous medium surface charge and roughness.
Ruxolitinib is the first janus kinase 1 (JAK1) and JAK2 inhibitor that was approved by the United States Food and Drug Administration (FDA) agency for the treatment of myeloproliferative neoplasms. The drug targets the JAK/STAT signalling pathway, which is critical in regulating the gliogenesis process during nervous system development. In the study, we assessed the effect of non-maternal toxic dosages of ruxolitinib (0-30 mg/kg/day between E7.5-E20.5) on the brain of the developing mouse embryos. While the pregnant mice did not show any apparent adverse effects, the Gfap protein marker for glial cells and S100β mRNA marker for astrocytes were reduced in the postnatal day (P) 1.5 pups' brains. Gfap expression and Gfap+ cells were also suppressed in the differentiating neurospheres culture treated with ruxolitinib. Compared to the control group, adult mice treated with ruxolitinib prenatally showed no changes in motor coordination, locomotor function, and recognition memory. However, increased explorative behaviour within an open field and improved spatial learning and long-term memory retention were observed in the treated group. We demonstrated transplacental effects of ruxolitinib on astrogenesis, suggesting the potential use of ruxolitinib to revert pathological conditions caused by gliogenic-shift in early brain development such as Down and Noonan syndromes.
In the dynamic world of fashion, high-heeled footwear is revered as a symbol of style, luxury and sophistication. Yet, beneath the facade of elegance of classy footwear lies the harsh reality of discomfort and pain. Thus, this study aims to investigate the influence of wearing high-heeled shoes on the sensation of pain across different body regions over a period of 6 h. It involved fifty female participants, all habitual wearers of high-heeled shoes, aged between 20 and 30 years. Each participant kept a record of their perceptions of pain and discomfort every hour for a total of 6 h using a 0-10 pain scale with 0 indicating no pain and 10 indicating severe pain. The findings reveal a progressive rise in pain throughout wear, with the most intense pain reported in the back, calcaneus, and metatarsals. The analysis shows that after approximately 3.5 h, participants experience significant increases in pain levels. However, the relationship between heel height and pain is not linear. It appears that a heel height of 7.5 cm is the threshold where overall body pain becomes significant. The study suggests that a duration of 3.5 h of wear and a heel height of 7.5 cm serve as critical points to decrease overall body pain. Moreover, beyond this heel height, knee pain diminishes compared to other body areas possibly due to the shift towards a more neutral posture. The study findings, coupled with the recommendations, can assist footwear designers in crafting not only stylish but also comfortable shoes.
Low-temperature growth, as well as the transfer free growth on substrates, is the major concern of graphene research for its practical applications. Here we propose a simple method to achieve the transfer free graphene growth on SiO2 covered Si (SiO2/Si) substrate at 250 °C based on a solid-liquid-solid reaction. The key to this approach is the catalyst metal, which is not popular for graphene growth by chemical vapor deposition. A catalyst metal film of 500 nm thick was deposited onto an amorphous C (50 nm thick) coated SiO2/Si substrate. The sample was then annealed at 250 °C under vacuum condition. Raman spectra measured after the removal of the catalyst by chemical etching showed intense G and 2D peaks together with a small D and intense SiO2 related peaks, confirming the transfer free growth of multilayer graphene on SiO2/Si. The domain size of the graphene confirmed by optical microscope and atomic force microscope was about 5 μm in an average. Thus, this approach will open up a new route for transfer free graphene growth at low temperatures.
Diabetic foot ulcers (DFUs) are a common complication of diabetes and can lead to severe disability and even amputation. Despite advances in treatment, there is currently no cure for DFUs and available drugs for treatment are limited. This study aimed to identify new candidate drugs and repurpose existing drugs to treat DFUs based on transcriptomics analysis. A total of 31 differentially expressed genes (DEGs) were identified and used to prioritize the biological risk genes for DFUs. Further investigation using the database DGIdb revealed 12 druggable target genes among 50 biological DFU risk genes, corresponding to 31 drugs. Interestingly, we highlighted that two drugs (urokinase and lidocaine) are under clinical investigation for DFU and 29 drugs are potential candidates to be repurposed for DFU therapy. The top 5 potential biomarkers for DFU from our findings are IL6ST, CXCL9, IL1R1, CXCR2, and IL10. This study highlights IL1R1 as a highly promising biomarker for DFU due to its high systemic score in functional annotations, that can be targeted with an existing drug, Anakinra. Our study proposed that the integration of transcriptomic and bioinformatic-based approaches has the potential to drive drug repurposing for DFUs. Further research will further examine the mechanisms by which targeting IL1R1 can be used to treat DFU.
Circular RNAs (circRNAs) have recently emerged as a large class of novel non-coding RNA species. However, the detailed functional significance of the vast majority of them remains to be elucidated. Most functional characterization studies targeting circRNAs have been limited to resting cells, leaving their role in dynamic cellular responses to stimuli largely unexplored. In this study, we focus on the LPS-induced cytoplasmic circRNA, mcircRasGEF1B, and combine targeted mcircRasGEF1B depletion with high-throughput transcriptomic analysis to gain insight into its function during the cellular response to LPS stimulation. We show that knockdown of mcircRasGEF1B results in altered expression of a wide array of genes. Pathway analysis revealed an overall enrichment of genes involved in cell cycle progression, mitotic division, active metabolism, and of particular interest, NF-κB, LPS signaling pathways, and macrophage activation. These findings expand the set of functionally characterized circRNAs and support the regulatory role of mcircRasGEF1B in immune response during macrophage activation and protection against microbial infections.
Fusarium wilt disease, caused by Fusarium oxysporum f. sp. cubense, especially by tropical race 4 (Foc TR4), is threatening the global banana industry. Musa acuminata Pahang, a wild diploid banana that displays strong resistance to Foc TR4, holds great potential to understand the underlying resistance mechanisms. Microscopic examination reports that, in a wounding inoculation system, the Foc TR4 infection processes in roots of Pahang (resistant) and a triploid cultivar Brazilian (susceptible) were similar by 7 days post inoculation (dpi), but significant differences were observed in corms of both genotypes at 14 dpi. We compare transcriptomic responses in the corms of Pahang and Brazilian, and show that Pahang exhibited constitutive defense responses before Foc TR4 infection and inducible defense responses prior to Brazilian at the initial Foc TR4 infection stage. Most key enzymatic genes in the phenylalanine metabolism pathway were up-regulated in Brazilian, suggesting that lignin and phytotoxin may be triggered during later stages of Foc TR4 infection. This study unravels a few potential resistance candidate genes whose expression patterns were assessed by RT-qPCR assay and improves our understanding the defense mechanisms of Pahang response to Foc TR4.
Carnivorous pitcher plants produce specialised pitcher organs containing secretory glands, which secrete acidic fluids with hydrolytic enzymes for prey digestion and nutrient absorption. The content of pitcher fluids has been the focus of many fluid protein profiling studies. These studies suggest an evolutionary convergence of a conserved group of similar enzymes in diverse families of pitcher plants. A recent study showed that endogenous proteins were replenished in the pitcher fluid, which indicates a feedback mechanism in protein secretion. This poses an interesting question on the physiological effect of plant protein loss. However, there is no study to date that describes the pitcher response to endogenous protein depletion. To address this gap of knowledge, we previously performed a comparative RNA-sequencing experiment of newly opened pitchers (D0) against pitchers after 3 days of opening (D3C) and pitchers with filtered endogenous proteins (>10 kDa) upon pitcher opening (D3L). Nepenthes ampullaria was chosen as a model study species due to their abundance and unique feeding behaviour on leaf litters. The analysis of unigenes with top 1% abundance found protein translation and stress response to be overrepresented in D0, compared to cell wall related, transport, and signalling for D3L. Differentially expressed gene (DEG) analysis identified DEGs with functional enrichment in protein regulation, secondary metabolism, intracellular trafficking, secretion, and vesicular transport. The transcriptomic landscape of the pitcher dramatically shifted towards intracellular transport and defence response at the expense of energy metabolism and photosynthesis upon endogenous protein depletion. This is supported by secretome, transportome, and transcription factor analysis with RT-qPCR validation based on independent samples. This study provides the first glimpse into the molecular responses of pitchers to protein loss with implications to future cost/benefit analysis of carnivorous pitcher plant energetics and resource allocation for adaptation in stochastic environments.
Seaweeds survive in marine waters with high sulfate concentration compared to those living at freshwater habitats. The cell wall polymer of Gracilaria spp. which supplies more than 50% of the world agar is heavily sulfated. Since sulfation reduces the agar quality, it is interesting to investigate the effects of sulfate deprivation on the sulfate contents of seaweed and agar, as well as the metabolic pathways of these seaweeds. In this study, two agarophytes G. changii and G. salicornia were treated under sulfate deprivation for 5 days. The sulfate contents in the seaweed/agar were generally lower in sulfate-deprivated samples compared to those in the controls, but the differences were only statistically significant for seaweed sample of G. changii and agar sample of G. salicornia. RNA sequencing (RNA-Seq) of sulfate-deprivated and untreated seaweed samples revealed 1,292 and 3,439 differentially expressed genes (DEGs; ≥1.5-fold) in sulfate-deprivated G. changii and G. salicornia, respectively, compared to their respective controls. Among the annotated DEGs were genes involved in putative agar biosynthesis, sulfur metabolism, metabolism of sulfur-containing amino acids, carbon metabolism and oxidative stress. These findings shed light on the sulfate deprivation responses in agarophytes and help to identify candidate genes involved in agar biosynthesis.
X-linked agammaglobulinemia (XLA) is a rare genetic disorder, caused by mutations in BTK (Bruton's Tyrosine Kinase) gene. Deep high-throughput RNA sequencing (RNA-Seq) approach was utilized to explore the possible differences in transcriptome profiles of primary monocytes in XLA patients compared with healthy subjects. Our analysis revealed the differences in expression of 1,827 protein-coding genes, 95 annotated long non-coding RNAs (lncRNAs) and 20 novel lincRNAs between XLA patients and healthy subjects. GO and KEGG pathway analysis of differentially expressed (DE) protein-coding genes showed downregulation of several innate immune-related genes and upregulation of oxidative phosphorylation and apoptosis-related genes in XLA patients compared to the healthy subjects. Moreover, the functional prediction analysis of DE lncRNAs revealed their potential role in regulating the monocytes cell cycle and apoptosis in XLA patients. Our results suggested that BTK mutations may contribute to the dysregulation of innate immune system and increase susceptibility to apoptosis in monocytes of XLA patients. This study provides significant finding on the regulation of BTK gene in monocytes and the potential for development of innovative biomarkers and therapeutic monitoring strategies to increase the quality of life in XLA patients.
The infectious bursal disease (IBD) is an acute immunosuppressive viral disease that significantly affects the economics of the poultry industry. The IBD virus (IBDV) was known to infect B lymphocytes and activate macrophage and T lymphocytes, but there are limited studies on the impact of IBDV infection on chicken intraepithelial lymphocyte natural killer (IEL-NK) cells. This study employed an mRNA sequencing approach to investigate the early regulation of gene expression patterns in chicken IEL-NK cells after infection with very virulent IBDV strain UPM0081. A total of 12,141 genes were expressed in uninfected chicken IEL-NK cells, and most of the genes with high expression were involved in the metabolic pathway, whereas most of the low expressed genes were involved in the cytokine-cytokine receptor pathway. A total of 1,266 genes were differentially expressed (DE) at 3 day-post-infection (dpi), and these DE genes were involved in inflammation, antiviral response and interferon stimulation. The innate immune response was activated as several genes involved in inflammation, antiviral response and recruitment of NK cells to the infected area were up-regulated. This is the first study to examine the whole transcriptome profile of chicken NK cells towards IBDV infection and provides better insight into the early immune response of chicken NK cells.
In our previous studies, we generated a short 13 amino acid antimicrobial peptide (AMP), DM3, showing potent antipneumococcal activity in vitro and in vivo. Here we analyse the underlying mechanisms of action using Next-Generation transcriptome sequencing of penicillin (PEN)-resistant and PEN-susceptible pneumococci treated with DM3, PEN, and combination of DM3 and PEN (DM3PEN). DM3 induced differential expression in cell wall and cell membrane structural and transmembrane processes. Notably, DM3 altered the expression of competence-induction pathways by upregulating CelA, CelB, and CglA while downregulating Ccs16, ComF, and Ccs4 proteins. Capsular polysaccharide subunits were downregulated in DM3-treated cells, however, it was upregulated in PEN- and DM3PEN-treated groups. Additionally, DM3 altered the amino acids biosynthesis pathways, particularly targeting ribosomal rRNA subunits. Downregulation of cationic AMPs resistance pathway suggests that DM3 treatment could autoenhance pneumococci susceptibility to DM3. Gene enrichment analysis showed that unlike PEN and DM3PEN, DM3 treatment exerted no effect on DNA-binding RNA polymerase activity but observed downregulation of RpoD and RNA polymerase sigma factor. In contrast to DM3, DM3PEN altered the regulation of multiple purine/pyrimidine biosynthesis and metabolic pathways. Future studies based on in vitro experiments are proposed to investigate the key pathways leading to pneumococcal cell death caused by DM3.
Rafflesia is a unique plant species existing as a single flower and produces the largest flower in the world. While Rafflesia buds take up to 21 months to develop, its flowers bloom and wither within about a week. In this study, transcriptome analysis was carried out to shed light on the molecular mechanism of senescence in Rafflesia. A total of 53.3 million high quality reads were obtained from two Rafflesia cantleyi flower developmental stages and assembled to generate 64,152 unigenes. Analysis of this dataset showed that 5,166 unigenes were differentially expressed, in which 1,073 unigenes were identified as genes involved in flower senescence. Results revealed that as the flowers progress to senescence, more genes related to flower senescence were significantly over-represented compared to those related to plant growth and development. Senescence of the R. cantleyi flower activates senescence-associated genes in the transcription activity (members of the transcription factor families MYB, bHLH, NAC, and WRKY), nutrient remobilization (autophagy-related protein and transporter genes), and redox regulation (CATALASE). Most of the senescence-related genes were found to be differentially regulated, perhaps for the fine-tuning of various responses in the senescing R. cantleyi flower. Additionally, pathway analysis showed the activation of genes such as ETHYLENE RECEPTOR, ETHYLENE-INSENSITIVE 2, ETHYLENE-INSENSITIVE 3, and ETHYLENE-RESPONSIVE TRANSCRIPTION FACTOR, indicating the possible involvement of the ethylene hormone response pathway in the regulation of R. cantleyi senescence. Our results provide a model of the molecular mechanism underlying R. cantleyi flower senescence, and contribute essential information towards further understanding the biology of the Rafflesiaceae family.