Adopting a Civil Sphere Theory framework, we argue that Taiwan’s efforts at containing COVID-19 resulted from its “societalization” of pandemic unpreparedness, which was triggered by the 2003 SARS ...outbreak and resumed during the COVID-19 pandemic. Societalization refers to the process through which institutional failures are transformed into societal crises, with the civil sphere mobilized to discuss institutional dysfunctions, push for reforms, and attempt to democratize or otherwise transform institutional cultures. The societalization of pandemic unpreparedness in Taiwan led to reforms of the public health administration and the medical profession, thereby establishing state mechanisms for encouraging early responses and coordinating centralized command during outbreaks, and healthcare infrastructures for coordinating patient transfer and ensuring supplies of personal protective equipment. Reflections upon past uncivil acts among citizens motivated the civil sphere to foster a discourse of interdependence, redefining the boundaries between individual choices and civic virtues. Meanwhile, unaddressed challenges remained, including threats related to Taiwan’s political polarization. Our paper challenges the thesis of “authoritarian advantage,” highlighting how democratic societies can foster social preparedness to respond to crises. By illustrating how societalization can reach temporary closures but become reactivated subsequently, our study extends the theory of societalization by explicating its historical dimension.
The downregulation of melatonin receptor 1A (MTNR1A) is associated with a range of pathological conditions, including membranous nephropathy. Knowledge of the mechanism underlying MTNR1A expression ...has been limited to the transcriptional regulation level. Here, RNA interference screening in human kidney cells revealed that heterogeneous nuclear ribonucleoprotein L (hnRNPL) upregulated MTNR1A RNA post‐transcriptionally. hnRNPL knockdown or overexpression led to increased or decreased levels of cyclic adenosine monophosphate‐responsive element‐binding protein phosphorylation, respectively. Molecular studies showed that cytoplasmic hnRNPL exerts a stabilizing effect on the MTNR1A transcript through CA‐repeat elements in its coding region. Further studies revealed that the interaction between hnRNPL and MTNR1A serves to protect MNTR1A RNA degradation by the exosome component 10 protein. MTNR1A, but not hnRNPL, displays a diurnal rhythm in mouse kidneys. Enhanced levels of MTNR1A recorded at midnight correlated with robust binding activity between cytoplasmic hnRNPL and the MTNR1A transcript. Both hnRNPL and MTNR1A were decreased in the cytoplasm of tubular epithelial cells from experimental membranous nephropathy kidneys, supporting their clinical relevance. Collectively, our data identified cytoplasmic hnRNPL as a novel player in the upregulation of MTNR1A expression in renal tubular epithelial cells, and as a potential therapeutic target.
Our results suggest that the diurnal rhythmic variation in melatonin receptor 1A (MTNR1A) levels may depend on binding to heterogeneous nuclear ribonucleoprotein L (hnRNPL) in the cytoplasm. Both hnRNPL and MTNR1A were downregulated in the cytoplasm of renal tubular epithelial cells from experimental membranous nephropathy kidneys. Our results provide a positive oscillatory mechanism between the cytoplasmic hnRNPL protein and the MTNR1A messenger RNA for the modulation of this pathological condition.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
With the improvement in children's acute lymphoblastic leukemia (ALL) care, the survival rate in children ALL has improved much. Methotrexate (MTX) plays an essential role in the success of ...children's ALL treatment. Since hepatotoxicity is commonly reported in individuals treated with intravenous or oral MTX, our study further examined the hepatic effect following intrathecal MTX treatment, which is an essential treatment for leukemia patients. Specifically, we examined the pathogenesis of MTX hepatotoxicity in young rats and explored the impact of melatonin treatment in protection against MTX hepatotoxicity. Successfully, we found that melatonin was able to protect against MTX hepatotoxicity.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Patients with hemoglobinopathies have been reported to have higher rates of pulmonary complications. Few studies have investigated the association between thalassemia and asthma in children.
We used ...the data of one million individuals randomly selected from the Registry for Beneficiaries of the National Health Insurance Research Database. One thalassemic child was matched with four control children without thalassemia according to sex, birth year, birth season, prematurity, and previous enteroviral infection.
A total of 800 hundred thalassemic children and 3200 controls were included. Children with thalassemia had higher rates of developing asthma (41.81 vs 25.70 per 1000 person-years, P < 0.001) than the non-thalassemia controls with an adjusted hazard ratio of 1.37 (95% confidence interval CI = 1.19-1.58). Boys in the thalassemia cohort had a significantly higher adjusted incidence hazard ratio (IRR) of asthma than those in the non-thalassemia cohort (adjusted IRR = 1.45, 95% CI = 1.02-1.73). The risk of atopic and nonatopic asthma was higher in the thalassemia cohort than in the non-thalassemia cohort (IRR = 1.3, 1.61, respectively).
Children with thalassemia were more likely to develop asthma. More attention should be paid to the early diagnosis of asthma and prevention of asthma attacks.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cell alignment is a critical factor to govern cellular behavior and function for various tissue engineering applications ranging from cardiac to neural regeneration. In addition to physical geometry, ...strain is a crucial parameter to manipulate cellular alignment for functional tissue formation. In this paper, we introduce a simple approach to generate a range of gradient static strains without external mechanical control for the stimulation of cellular behavior within 3D biomimetic hydrogel microenvironments. A glass-supported microfluidic chip with a convex flexible polydimethylsiloxane (PDMS) membrane on the top was employed for loading the cells suspended in a prepolymer solution. Following UV crosslinking through a photomask with a concentric circular pattern, the cell-laden hydrogels were formed in a height gradient from the center (maximum) to the boundary (minimum). When the convex PDMS membrane retracted back to a flat surface, it applied compressive gradient forces on the cell-laden hydrogels. The concentric circular hydrogel patterns confined the direction of hydrogel elongation, and the compressive strain on the hydrogel therefore resulted in elongation stretch in the radial direction to guide cell alignment. NIH3T3 cells were cultured in the chip for 3 days with compressive strains that varied from ~65% (center) to ~15% (boundary) on hydrogels. We found that the hydrogel geometry dominated the cell alignment near the outside boundary, where cells aligned along the circular direction, and the compressive strain dominated the cell alignment near the center, where cells aligned radially. This study developed a new and simple approach to facilitate cellular alignment based on hydrogel geometry and strain stimulation for tissue engineering applications. This platform offers unique advantages and is significantly different from the existing approaches owing to the fact that gradient generation was accomplished in a miniature device without using an external mechanical source.
Membranous nephropathy (MN), a type of glomerular nephritis, is one of the most common causes of nephrotic syndrome in adults. Although it is known that melatonin plays a protective role in MN, the ...role of melatonin receptors in the pathophysiology of MN is unclear. Using an experimental MN model and clinical MN specimens, we studied melatonin receptor expression and found that melatonin receptor 1A (MTNR1A) expression was significantly downregulated in renal tubular epithelial cells. Molecular studies showed that the transcription factor pituitary homeobox‐1 (PITX1) promoted MTNR1A expression via direct binding to its promoter. Treatment of a human tubular cell line with albumin to induce injury resulted in the stable reduction in MTNR1A and PITX1 expression. PITX1 levels were significantly downregulated in tubular epithelial cells from mice MN kidneys and MN renal specimens. Knockdown of MTNR1A, PITX1, or cyclic adenosine monophosphate‐responsive element‐binding protein (CREB) decreased E‐cadherin (CDH1) expression, but upregulated Per2 and α‐smooth muscle actin (αSMA) expression. Blockade of the MTNR1A receptor with luzindole in MN mice further impaired renal function; this was accompanied by CDH1 downregulation and Per2 and αSMA upregulation. Together, our results suggest that in injured tissue, decreased PITX1 expression at the MTNR1A promoter regions leads to decreased levels of MTNR1A in renal tubular epithelial cells, which increases the future risk of MN.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Formation of multifunctional, heterogeneous, and encoded hydrogel building blocks, or microgels, by crosslinking and assembly of microgels are two essential steps in establishing hierarchical, ...complicated, and three-dimensional (3D) hydrogel architectures that recapitulate natural and biological structures or originate new materials by design. However, for the variety of the hydrogel materials crosslinked differently and for the varied scales of microgels and architectures, the formation and assembly processes are usually performed separately, which increases the manufacturing complexity of designed hydrogel materials. We show the construction of hydrogel architectures through programmable formation and assembly on an electromicrofluidic platform, adopting two reciprocal electric manipulations (electrowetting and dielectrophoresis) to manipulate varied objects (i) in multiple phases, including prepolymer liquid droplets and crosslinked microgels, (ii) on a wide range of scales from micrometer functional particles or cells to millimeter-assembled hydrogel architectures, and (iii) with diverse properties, such as conductive and dielectric droplets that are photocrosslinkable, chemically crosslinkable, or thermally crosslinkable. Prepolymer droplets, particles, and dissolved molecules are electrically addressable to adjust the properties of the microgel building blocks in liquid phase that subsequently undergo crosslinking and assembly in a flexible sequence to accomplish heterogeneous and seamless hydrogel architectures. We expect the electromicrofluidic platform to become a general technique to obtain 3D complex architectures.
Purpose This study compares 1 ) progressive dental and skeletal changes, 2 ) postsurgical stability, and 3 ) treatment efficacy of patients with skeletal Class III correction with and without ...presurgical orthodontic treatment. Patients and Methods The study includes 53 patients who underwent orthognathic surgery (OGS) to correct skeletal Class III malocclusion. The patient grouping is based on presurgical orthodontics: surgical-first (SF) approach (n = 18) and modified-conventional (MC) approach (n = 35). This study divides the MC group into 2 groups based on whether patients underwent tooth extraction in the presurgical phase (Ext group) (n = 10) or not (Nxt group) (n = 25). Serial lateral cephalometric film measurements identify skeletal and dental changes before treatment (T1), before OGS (T2), 1 month after OGS (T3), and at completion of treatment (T4). This investigation reviews the medical charts for treatment progress and duration. Results In the presurgical phase, the Ext group showed mild retraction of the upper incisors and more proclination of the lower incisors than the Nxt group. The skeletal sagittal parameters were similar from T1 to T4 in both the SF and MC groups. In the SF group, SN/U1 decreased 6.2° after surgery and was mildly proclined at T4; in the MC group, upper incisor inclination (SN/U1) increased 1.8° from T1 to T4, being 9.4° greater than that in the SF group at T4. The lower incisor inclination (MP/L1) was similar at T4 in both groups. In the MC group, the MP/L1 was shown to be proclined 4.5° before surgery, retroclined 1.9° after surgery, and further retroclined 4.5° until T4. The relapse rate of the mandibular setback was 14.3% in the SF group and 15.7% in the MC group without significant differences. The percentage of sagittal relapse less than 2 mm was 50% in the SF group and 54% in the MC group. The ratio was greater in the MC group with a relapse between 2 and 4 mm but lesser with a relapse greater than 4 mm. The Ext group showed a 3-month longer treatment duration than the Nxt group. Conclusion The amount of skeletal correction and postsurgical relapse, as well as treatment duration, were no different in Class III OGS patients with or without presurgical orthodontic treatment. The presurgical work of lower incisor proclination returned to an inclination similar to the initial status after completing treatment. The final outcome of patients evidenced no difference in lower incisor inclination, with or without presurgical orthodontics.
Efficiency in reutilization of Ca-based waste for carbon capture has gained high interest. Besides, the CO2 capture mechanism will be influenced by several operating parameters. Observation of ...carbonation by Ca-based slags (desulfurization slag/De-S, electric arc furnace/EAF slag, and bottom ash/BA) in this study indicated that De-S had the highest Ca(OH)2 content (73%) and largest surface area which led to the best slag utilization. This slag was further applied in the test under various operating conditions including temperature, space velocity, and the content of gas impurity (H2O and SO2). Higher temperature and lower space velocity promoted efficient carbonation. De-S endured the presence of ≤5% water vapor content in the simulated gas. Higher SO2 content in the simulated gas initiated the formation of CaSO4 and declined the CO2 capture capacity. Discussion in this study was complemented by the characterization of slags before and after carbonation process along with reaction kinetics analysis.
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•Desulfurization slag had high Ca(OH)2 and surface area for efficient CO2 capture.•Water vapor below 5% supported carbonation but exceeding content led to a decline.•SO2 reduced the carbonation reaction due to blocking from CaSO4.•Deactivation Type I was well fitted the result with Ea of 352.2 kJ/mol.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
: Idiopathic membranous nephropathy (MN), an autoimmune‐mediated glomerulonephritis, is one of the most common causes of nephrotic syndrome in adults. Therapeutic agents for MN remain ill defined. ...We assessed the efficacy of melatonin therapy for MN. Experimental murine MN was induced with cationic bovine serum albumin, and the mice were immediately administered 20 mg/kg melatonin or phosphate‐buffered saline subcutaneously once a day. Disease severity was verified by examining serum and urine metabolic profiles and renal histopathology. The expression of cytokines and oxidative stress markers, cell apoptosis, and the associated mechanisms were also determined. Mice treated with melatonin displayed a significant reduction in proteinuria and a marked amelioration of glomerular lesions, with attenuated immunocomplex deposition. The subpopulations of T cells were not altered, but the CD19+ B‐cell subpopulation was significantly reduced in the MN mice treated with melatonin. The expression of cytokine mRNAs in splenocytes indicated that melatonin reduced the expression of proinflammatory cytokines and increased the expression of anti‐inflammatory cytokines (interleukin 10). The production of reactive oxygen species and TUNEL‐positive apoptotic cells in the kidney were also significantly reduced in the melatonin‐treated MN mice. Melatonin also upregulated heme oxygenase 1 (HO1) and ameliorated MN. The blockade of HO1 expression with SnPP, a HO1 inhibitor, attenuated HO1 induction by melatonin and thus mitigated its renoprotective effects during MN. Our results suggest that melatonin treatment ameliorates experimental MN via multiple pathways, including by its antioxidative, antiapoptotic, and immunomodulatory effects. Melatonin should be considered a potential therapeutic intervention for MN in the future.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK