A series of porphyrins bearing alkoxyl and/or alkyl chains were prepared to investigate the roles of alkoxyl/alkyl chains in the enhanced photovoltaic performance of the dyes. Based on the ...experimental results and the molecular simulations, we demonstrated that suitable long alkoxyl chains are capable of wrapping the porphyrin core, thus resulting in decreased dye aggregation, elevated excited states and LUMOs, and improved photovoltaic performance.
Pancreatic ductal adenocarcinoma (PDA) is a pernicious disease characterized by an immunosuppressive milieu that is unresponsive to current immunotherapies. Interleukin-1 receptor antagonist (IL-1Ra) ...is a natural anti-inflammatory cytokine; however, its contribution to cancer pathogenesis and immunosuppression remains elusive. In this research, we investigated the role and mechanism of IL-1Ra in malignant progression of PDA.
Through analyzing clinical dataset and examining the pathological tumor tissues and serum samples, we have demonstrated that IL-1Ra expression is elevated in human PDA and positively associated with malignant progression of PDA. To study the biological function of IL-1Ra in tumors, we generated a set of mouse pancreatic cancer cell lines with a knockout (KO) of the Il1rn gene, encoding IL-1Ra, and compared the tumor growth rates in immune-competent and immune-deficient mice. We found that the Il1rn KO cells exhibited greater tumor inhibition in immune-competent mice, highlighting the crucial role of a functional immune system in Il1rn KO-mediated anti-tumor response. Consistently, we found an increase in CD8
T cells and a decrease in CD11b
Ly6G
immunosuppressive mononuclear population in the tumor microenvironment of Il1rn KO-derived tumors. To monitor the inhibitory effects of IL-1Ra on immune cells, we utilized a luciferase-based reporter CD4
T cell line and splenocytes, which were derived from transgenic mice expressing ovalbumin-specific T cell receptors in CD8
T cells, and mice immunized with ovalbumin. We showed that IL-1Ra suppressed T cell receptor signaling and inhibited antigen-specific interferon-γ (IFN-γ) secretion and cytolytic activity in splenocytes.
Our findings illustrate the immunosuppressive properties of the natural anti-inflammatory cytokine IL-1Ra, and provide a rationale for considering IL-1Ra-targeted therapies in the treatment of PDA.
The aim of this study is to determine the roles of global histone acetylation (Ac)/methylation (me), their modifying enzymes, and gene-specific histone enrichment in obstructive sleep apnea (OSA). ...Global histone modifications, and their modifying enzyme expressions were assessed in peripheral blood mononuclear cells from 56 patients with OSA and 16 matched subjects with primary snoring (PS). HIF-1α gene promoter-specific H3K36Ac enrichment was assessed in another cohort (28 OSA, 8 PS). Both global histone H3K23Ac and H3K36Ac expressions were decreased in OSA patients versus PS subjects. H3K23Ac expressions were further decreased in OSA patients with prevalent hypertension. HDAC1 expressions were higher in OSA patients, especially in those with excessive daytime sleepiness, and reduced after more than 6 months of continuous positive airway pressure treatment. H3K79me3 expression was increased in those with high C-reactive protein levels. Decreased KDM6B protein expressions were noted in those with a high hypoxic load, and associated with a higher risk for incident cardiovascular events or hypertension. HIF-1α gene promoter-specific H3K36Ac enrichment was decreased in OSA patients versus PS subjects. In vitro intermittent hypoxia with re-oxygenation stimuli resulted in HDAC1 over-expression and HIF-1α gene promoter-specific H3K36Ac under-expression, while HDAC1 inhibitor, SAHA, reversed oxidative stress through inhibiting NOX1. In conclusions, H3K23/H3K36 hypoacetylation is associated with the development of hypertension and disease severity in sleep-disordered breathing patients, probably through up-regulation of HDAC1, while H3K79 hypermethylation is associated with higher risk of cardiovascular diseases, probably through down-regulation of KDM6B.
Grid-based approach is typically adopted to estimate the Newmark-type displacement for regional seismic landslide hazard assessment. However, the approach is limited to the assumption of infinite ...slope and rigid block movement, which may be different from the actual behavior of slope under seismic loading. In this study, a slope unit-based approach is proposed to quickly estimate earthquake-induced displacements for finite slopes in regional scale. Hence, regional seismic landslide hazard can be assessed by the estimated displacements. The approach is advantageous as it considers slope geometry, determines the failure mode automatically, and considers the interaction of incident wave and slope. The implementation of the approach is demonstrated by considering two areas that experience severe landslides during the Chi-Chi and Northridge earthquakes. Results show that the prediction rate of the proposed method is up to 73% compared with the landslide inventory given the estimated displacements.
•A slope unit-based approach is proposed to assess regional seismic landslide hazard.•Slope geometry, failure mode, and interaction of incident wave and slope are considered.•The approach is demonstrated by two areas that experience severe landslides during the Chi-Chi and Northridge earthquakes.•The prediction rate of the proposed method is up to 73% compared with the landslide inventory.
We designed a stepwise approach for co-sensitization of a zinc porphyrin sensitizer (LD12) with a spirally configured organic dye (CD5) for dye-sensitized solar cells. The co-sensitized LD12 + CD5 ...device showed significantly enhanced
V
OC
and
J
SC
relative to its individual single-dye sensitized devices. Upon optimization, the device made of the LD12 + CD5 system yielded
J
SC
/mA cm
2
= 16.7,
V
OC
/V = 0.74, FF = 0.73 and
= 9.0%; this performance is superior to that of either individual device made from LD12 (
= 7.5%) and CD5 (
= 5.7%) under the same conditions of fabrication. To understand the effects of the potential shift and charge recombination on the cell performance, we measured charge-extraction (CE) and intensity-modulated photovoltage spectra (IMVS). Upon sensitization with each dye, the TiO
2
potentials are similar, but co-sensitization causes the potential to shift down (cathodic shift). Charge recombination was significantly retarded for the co-sensitized system relative to each individual dye-sensitized system, to account for the enhanced
V
OC
for the former relative to the latter. A test of stability indicates a systematic trend between the LD12 + CD5 and LD12 devices; the performance of the co-sensitized device degraded only 15% and remained stable during the period of 5001000 h near 295 K.
A stepwise co-sensitization of a zinc porphyrin (LD12) with an organic dye (CD5) on TiO
2
film significantly improved the photovoltaic performance of the device.
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•A new series of sustainable polyamide elastomers was synthesized using a bio-based dimer diamine monomer.•The branched-structured dimer diamine efficiently suppressed the ...crystallinity of the polyamide elastomer system and induced chainentanglement networks for enhancing melt strength.•The new system was successfully applied to the fabrication of microcellular foams with a high expansion ratio and robust dimensional stability, effectively overcoming the foaming difficulties of high crystallinity and insufficient melt strength in traditional polyamide 6.•The foamed products could be facilely recycled and reprocessed due to the advantages of non-crosslinking and additive-free.
In this study, we developed a sustainable polyamide foam system. A new series of polyamide elastomers was synthesized using a bio-based dimer diamine monomer as a building block to copolymerize with aminocaproic acid and adipic acid through step-growth polymerization, followed by supercritical CO2 foaming for the fabrication of microcellular foams. The introduction of the branched-structured dimer diamine monomer effectively restricted the molecular packing and hydrogen bonding density of the polyamide system, leading to numerous small crystals acting as nucleation sites for heterogeneous cell nucleation. Simultaneously, the branched long chains of the dimer diamine formed chainentanglement networks, which increased the material melt strength against the elongational stresses of cell growth. The synergistic effect provided by dimer diamine led to the successful manufacture of foamed samples with a high expansion ratio and robust dimensional stability, effectively overcoming the foaming difficulties of high crystallinity and insufficient melt strength in traditional polyamide 6 (PA6). In addition, this polyamide elastomer foam system could be recycled and reprocessed due to the advantages of non-crosslinking and additive-free. Therefore, the study’s findings constitute a promising direction for the usage of renewable sources in the development of foamable polyamide materials for sustainable applications in the plastics industry.
To investigate the impact of an electronic medical record management system (EMRMS) on disease activity and the frequency of outpatient visits among patients with ankylosing spondylitis (AS). We ...identified 652 patients with AS who were followed up for at least 1 year before and after the first Ankylosing Spondylitis Disease Activity Score (ASDAS) assessment and compared the number of outpatient visits and average visit time within 1 year before and after the initial ASDAS assessment. Finally, we analyzed 201 patients with AS who had complete data and received ≥ 3 continuous ASDAS assessments at an interval of 3 months, and we compared the results of the second and third ASDAS assessments with those of the first. The number of annual outpatient visits increased after ASDAS assessment (4.0 (4.0, 7.0) vs. 4.0 (4.0, 8.0), p < 0.001), particularly among those with a high initial disease activity. The average visit time was reduced within 1 year after ASDAS assessment (6.4 (8.5, 11.2) vs. 6.3 (8.3, 10.8) min, p = 0.073), especially among patients whose with an inactive disease activity was < 1.3 (ASDAS C-reactive protein (CRP) 6.7 (8.8, 11.1) vs. 6.1 (8.0, 10.3) min, p = 0.033; ASDAS erythrocyte sedimentation rate (ESR) 6.4 (8.7, 11.1) vs. 6.1 (8.1, 10.0) min, p = 0.027). Among patients who received at least three ASDAS assessments, the third ASDAS-CRP tended to be lower than the first (1.5 (0.9, 2.1) vs. 1.4 (0.8, 1.9), p = 0.058). The use of an EMRMS increased the frequency of ambulatory visits among AS patients with high and very high disease activity and reduced the visit time among those with an inactive disease. Continual ASDAS assessments may help control the disease activity of patients with AS.
Lower urinary tract symptoms (LUTS), such as urgency, urinary incontinence, and/or difficulty voiding, hamper the quality of life (QoL) of patients with spinal cord injury (SCI). If not managed ...adequately, urological complications, such as urinary tract infection or renal function deterioration, may further deteriorate the patient's QoL. Botulinum toxin A (BoNT-A) injection within the detrusor muscle or urethral sphincter yields satisfactory therapeutic effects for treating urinary incontinence or facilitating efficient voiding; however, adverse effects inevitably follow its therapeutic efficacy. It is important to weigh the merits and demerits of BoNT-A injection for LUTS and provide an optimal management strategy for SCI patients. This paper summarizes different aspects of the application of BoNT-A injection for lower urinary tract dysfunctions in SCI patients and provides an overview of the benefits and drawbacks of this treatment.
We have previously demonstrated that the ECMWF ensemble (ECEPS) provides early forecasts not only of the Time-to-Tropical Storm (T2TS) and of the Time-to-Hurricane (T2HU), but also of the ...Time-Ending-Hurricane (TEHU) and Time-Ending-Tropical Storm (TETS) times and positions along those 15-day ECEPS track forecasts, which then provides an opportunity for high-wind warnings along the path during the entire lifecycle of these Hurricanes. The focus in this study is the Decision Flowchart that has been developed to assist the forecasters to select the pre-formation disturbance that is most likely to become the next Tropical Storm with the potential to become a Hurricane. The most crucial decision is to detect and eliminate any disturbance that likely originated from a precursor Caribbean false alarm circulation. Summaries of other steps in the Decision Flowchart “To Watch”, or to reject, other storm options in the twice-daily ECEPS forecasts are provided for Hurricanes Enrique and Felicia, and for strong Tropical Storm Guillermo and weak Tropical Storm Jimena. The first detections in the ECEPS forecasts for the Tropical Storms during the 2021 season averaged 6 days, 18 h in advance with a range of only 2 days, 6 h in advance for TS Terry to 9 days, 18 h in advance for TS Sandra.
•Motor incoordination in SCA17 mice was initiated at 6 weeks old.•The TBP nuclear aggregation and microglia activation occurred in the SCA17 mice at 4 weeks old.•Gliosis of astrocytes and Bergmann ...glia, pERK, Bax/Bcl2 ratio, and caspase-3 were increased at 6 weeks old.•The activation of pERK occurs in the cerebellar astrocytes and Bergmann glia might contribute to the elevated gliosis and the neuronal apoptosis in the SCA17 mice.
Spinocerebellar ataxia type 17 (SCA17) is an autosomal dominant neurodegenerative disease caused by CAG expansion in the gene encoding the TATA-binding protein (TBP). The neurological features of SCA17 are Purkinje cell loss and gliosis. We have generated SCA17 transgenic mice which recapitulate the patients’ phenotypes and are suitable for the study of the SCA17 pathomechanism. Our previous study identified the activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) occurred in the SCA17 cerebella, this study aims to study the role of ERK activation in SCA17. The levels of pERK, calbindin, and gliosis markers on the mouse cerebellum at 4-8 weeks old were analyzed to elucidate the correlation among behavioral performance, ERK activation and Purkinje cell degeneration. The motor incoordination was initiated in SCA17 mice at 6 weeks old. We found that the presence of TBP nuclear aggregation and microglia activation were observed at 4 weeks old. Gliosis of astrocytes and Bergmann glia, pERK, Bax/Bcl2 ratio, and caspase-3 were significantly increased in the 6-week-old SCA17 mouse cerebellum. In addition to the polyglutamine-protein aggregation in Purkinje cells caused apoptosis cell-autonomously, a significant body of evidence have shown that ERK pathways involves in neuronal apoptosis. Our study showed that the activation of ERK in the astrocytes and Bergmann glia was identified as preceding motor deficits, which suggest the elevated gliosis by ERK activation may contribute to neuronal apoptosis in SCA17 mice.
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