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Rapid sintering technology has become one of the most direct methods for shortening the manufacturing time of zirconia restorations. This study aimed to explore the aging resistance of rapid-sintered 5 mol% yttria-partially-stabilized zirconia (5Y-PSZ).Specimens were made from two types of 5Y-PSZ material and subjected to rapid sintering (RS) and conventional sintering (CS). After in vitro aging for 5 h, morphology observation, grain size measurement, and phase composition analysis were performed. The mechanical properties were evaluated by biaxial, three-point flexural tests, and the Vickers microhardness test. Results were analyzed by 3-way ANOVA.Both the RS group and the CS group had a dense microstructure. The tested zirconia ceramics had different grain sizes, which were affected by the interaction between the sintering method and aging. Both groups revealed the same characteristic peaks of the cubic phase after aging. Regardless of the sintering method used, there was no significant difference in the mechanical properties of the tested zirconia before and after aging.The rapid-sintered 5Y-PSZ materials had a microstructure, phase composition and mechanical properties similar to those of conventional sintered materials. The characteristics of the materials prepared using the two sintering methods did not change significantly after aging.

Iron-sulfur (Fe-S) cluster (ISC) cofactors are required for the function of many critical cellular processes. In the ISC Fe-S cluster biosynthetic pathway, IscU assembles Fe-S cluster intermediates from iron, electrons, and inorganic sulfur, which is provided by the cysteine desulfurase enzyme IscS. IscU also binds to Zn, which mimics and competes for binding with the Fe-S cluster. Crystallographic and nuclear magnetic resonance spectroscopic studies reveal that IscU is a metamorphic protein that exists in multiple conformational states, which include at least a structured form and a disordered form. The structured form of IscU is favored by metal binding and is stable in a narrow temperature range, undergoing both cold and hot denaturation. Interestingly, the form of IscU that binds IscS and functions in Fe-S cluster assembly remains controversial. Here, results from variable temperature electrospray ionization (vT-ESI) native ion mobility mass spectrometry (nIM-MS) establish that IscU exists in structured, intermediate, and disordered forms that rearrange to more extended conformations at higher temperatures. A comparison of Zn-IscU and apo-IscU reveals that Zn(II) binding attenuates the cold/heat denaturation of IscU, promotes refolding of IscU, favors the structured and intermediate conformations, and inhibits the disordered high charge states. Overall, these findings provide a structural rationalization for the role of Zn(II) in stabilizing IscU conformations and IscS in altering the IscU active site to prepare for Zn(II) release and cluster synthesis. This work highlights how vT-ESI-nIM-MS can be applied as a powerful tool in mechanistic enzymology by providing details of relationships among temperature, protein conformations, and ligand/protein binding.

A nanofibrous polyaniline interlayer controls the reaction dynamics of the interfacial polymerization through its reversible acid doping chemistry.

BackgroundThe interactions between tumor cells and the host immune system play a crucial role in lung cancer progression and resistance to treatment. The alterations of EGFR signaling have the potential to produce an ineffective tumor-associated immune microenvironment by upregulating a series of immune suppressors, including inhibitory immune checkpoints, immunosuppressive cells, and cytokines. Elevated Heparin-binding EGF-like growth factor (HB-EGF) expression, one EGFR ligand correlated with higher histology grading, worse patient prognosis, and lower overall survival rate, acts as a chemotactic factor. However, the role of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in the accumulation of immune cells in the tumor microenvironment remains unclear.MethodsThe clinical association of HB-EGF expression in lung cancer was examined using the Gene Expression Omnibus (GEO) repository. HB-EGF expression in different cell types was determined using single-cell RNA sequencing (scRNA-seq) dataset. The correlation between HB-EGF expression and cancer-immune infiltrated cells was investigated by performing TIMER and ClueGo pathways analysis from TCGA database. The chemotaxis of HB-EGF and macrophage infiltration was investigated using migration and immunohistochemical staining.ResultsThe high HB-EGF expression was significantly correlated with poor overall survival in patients with lung adenocarcinoma (LUAD) but not lung squamous cell carcinoma (LUSC). Moreover, HB-EGF expression was correlated with the infiltration of monocytes, macrophages, neutrophils, and dendritic cells in LUAD but not in LUSC. Analysis of scRNA-seq data revealed high HB-EGF expression in lung cancer cells and myeloid cells. Results from the pathway analysis and cell-based experiment indicated that elevated HB-EGF expression was associated with the presence of macrophage and lung cancer cell migration. HB-EGF was highly expressed in tumors and correlated with M2 macrophage infiltration in LUAD.ConclusionsHB-EGF is a potential prognostic marker and therapeutic target for lung cancer progression, particularly in LUAD.

Yu-Min Lin,1 Chia-Lin Chou,2,3 Yu-Hsuan Kuo,4,5 Hung-Chang Wu,4,6 Chia-Jen Tsai,7 Chung-Han Ho,8,9 Yi-Chen Chen,8 Ching-Chieh Yang,6,7,&ast; Cheng‐Wei Lin10– 12,&ast; 1Division of Hepatogastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan; 2Division of Colorectal Surgery, Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan; 3Department of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan; 4Division of Hematology and Oncology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan; 5Department of Cosmetic Science, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan; 6Department of Pharmacy, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan; 7Department of Radiation Oncology, Chi Mei Medical Center, Tainan, Taiwan; 8Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan; 9Department of Information Management, Southern Taiwan University of Science and Technology, Tainan, Taiwan; 10Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 11Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan; 12Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan&ast;These authors contributed equally to this workCorrespondence: Ching-Chieh YangDepartment of Radiation Oncology Chi-Mei Medical Center, No. 901, Zhonghua Road, Yung Kang District, Tainan City, 701, Taiwan, Republic of ChinaTel +88662812811Email cleanclear0905@gmail.comCheng‐Wei LinDepartment of Biochemistry and Molecular Biology, School of Medicine, College of Medicine, Taipei Medical University, 250 Wu ‐ Xing Street, Taipei, 11031, Taiwan, Republic of ChinaEmail cwlin@tmu.edu.twPurpose: A lymph node (LN) yield ≥ 12 is required to for accurate determination of nodal status for colorectal cancer but cannot always be achieved after neoadjuvant therapy. This study aims to determine the difference in LN yield from rectal cancer patients treated with and without neoadjuvant therapy and the effects of specific LN yields on survival.Patients and Methods: The study cohort included a total of 4344 rectal cancer patients treated between January 2007 and December 2015, 2260 (52.03%) of whom received neoadjuvant therapy. Data were retrieved from the Taiwan nationwide cancer registry database. The minimum acceptable LN yield below 12 was investigated using the maximum area under the ROC curve.Results: The median LN yield was 12 (8– 17) for patients who received neoadjuvant therapy and 17 (13– 24) for those who did not. The recommended LN yield ≥ 12 was achieved in 82.73% of patients without and 57.96% of those with neoadjuvant therapy (p < 0.0001). Patients with LN yield ≥ 12 had a higher OS probability than did those with LN < 12 (OR, 1.33; 95% CI, 1.06– 1.66; p = 0.0124). However, the predictive accuracy for survival was greater for LN yield ≥ 10 (AUC, 0.7767) than cut-offs of 12, 8, or 6, especially in patients with pathologically-negative nodes (AUC, 0.7660).Conclusion: Neoadjuvant therapy significantly reduces the LN yield in subsequent surgery. A lower yield (LN ≥ 10) may be adequate for nodal evaluation in rectal cancer patients after neoadjuvant therapy.Keywords: rectal cancer, neoadjuvant therapy, lymph node yield, quality, survival

Aims/Introduction: To investigate the association between specific bacterial pathogens and treatment outcome in patients with limb‐threatening diabetic foot infection (LT‐DFI). Materials and Methods: Consecutive patients treated for LT‐DFI in a major diabetic foot center in Taiwan were analyzed between the years 2014 and 2017. Patients with positive wound culture results at first aid were enrolled. Clinical factors, laboratory data, and wound culture results were compared. Lower‐extremity amputations and in‐hospital mortality were defined as a poor outcome. Results: Among the 558 patients, 272 (48.7%) patients had lower extremity amputation and 22 (3.9%) patients had in‐hospital mortality. Gram‐negative bacterial (GNB) infection was the independent factor following factors adjustment. When all the 31 microorganisms were analyzed, only E. coli (adjusted odds ratio [aOR], 3.01; 95% CI, 1.60–5.65), Proteus spp. (aOR, 2.99; 95% CI, 1.69–5.29), and Pseudomonas aeruginosa (aOR, 2.00; 95% CI 1.20–3.32) were associated with poor outcome. The analysis of specific GNB species in association with major‐ or minor‐ amputation have been reported. No specific pathogen was associated with cause of death in patients with mortality within 30 days. The antimicrobial‐resistant strains were not associated with a poor treatment outcome. Conclusions: The presence of GNB was associated with limb amputations. This study provides insight into more timely and appropriate management of the diabetic foot infection.

Obesity is a well-known risk factor for breast cancer formation and is associated with elevated mortality and a poor prognosis. An obesity-mediated inflammatory microenvironment is conducive to the malignant progression of tumors. However, the detailed molecular mechanism is still needed to be clarified. Herein, we identified that breast cancer cells from mice with diet-induced obesity exhibited increased growth, invasiveness, and stemness capacities. A transcriptome analysis revealed that expressions of interleukin 33 (IL33) signaling pathway-related genes were elevated in obesity-associated breast cancer cells. Importantly, IL33 expression was significantly associated with the yes-associated protein (YAP) signature, and IL33 was transcriptionally regulated by YAP. Suppression of IL33 reduced tumor migration and invasion, while the addition of IL33 activated nuclear factor (NF)-κB signaling and revived tumor mobility in YAP-silenced cells. Furthermore, suppression of YAP attenuated IL33 expression which was accompanied by relief of obesity-mediated immunosuppression. Clinical analyses showed that IL33 expression was markedly associated with macrophage and regulatory T cell infiltration. These findings reveal a crucial role of the YAP/IL33 axis in promoting aggressiveness and immunosuppression of obesity-associated breast cancer progression.

Stabilities and structure(s) of proteins are directly coupled to their local environment or Gibbs free energy landscape as defined by solvent, temperature, pressure, and concentration. Solution pH, ionic strength, cofactors, chemical chaperones, and osmolytes perturb the chemical potential and induce further changes in structure, stability, and function. At present, no single analytical technique can monitor these effects in a single measurement. Mass spectrometry and ion mobility-mass spectrometry play increasingly essential roles in studies of proteins, protein complexes, and even membrane protein complexes; however, with few exceptions, the effects of the solution temperature on the stability and structure(s) of analytes have not been thoroughly investigated. Here, we describe a new variable-temperature electrospray ionization (vT-ESI) source that utilizes a thermoelectric chip to cool and heat the solution contained within the static ESI emitter. This design allows for solution temperatures to be varied from ~5 to 98 °C with short equilibration times (

The induction of green globular bodies (GGBs) represents an unique phenomenon in the tissue culture of pteridophytes. In this first attempt study GGBs were induced with the embryos of Adiantum reniforme var. sinense. The influences of basal salts, plant growth regulators, sugar concentrations, and gelling agents on the proliferation and differentiation of GGBs were examined. The highest induction rate of GGBs resulted from Murashige & Skoog (MS) medium supplemented with benzyl aminopurine (BA) (0.1 mg L−1) and 1-naphthaleneacetic acid (NAA) (0.15 mg L−1). The subsequent proliferation of GGBs required a higher concentration of NAA (10 mg L−1) to have the highest fresh weight of 0.29 g. However, cytokinins, such as BA, kinetin (KT), and thidiazuron (TDZ), exhibited inhibitory effects on GGB proliferation. Hyponex was superior to MS medium in terms of GGBs proliferation and differentiation, which led to the highest fresh weight (1.72±0.63 g) and shoot number (7.25±1.89) after 60 days of cultivation. Among different sucrose concentration in media, GGBs cultured with 15 g L−1 sucrose had the highest fresh weight (1.01 g). Gelling agents also showed evident effects on the proliferation of GGBs, and the fresh weight of GGBs cultured in gelrite medium was approximately three times greater than that of GGBs cultured in agar medium. Distinct histological characteristics of embryos and GGBs were revealed by paraffin sections. All regenerates from GGBs survived in the greenhouse, with normal appearances, after acclimation in the medium of peat soil and pearlite (1:1).

The shipper selects a suitable shipping route and plans for a voyage in order to import and export cargo on the basis of published sailing schedules. The reliability of the sailing schedule will influence the shipper’s logistics expense, which means that the logistics costs will depend on the reliability of schedules published by container shipping companies. Therefore, it is important to consider factors which can cause delays would for container ships sailing on sea routes. The reliability of published sailing schedules can be affected by a number of different factors. This study adopts the multi-criteria decision making (MCDM) method to estimate the importance of the delaying factors in a sailing schedule. In addition, the consistent fuzzy preference relations (CFPR) method is applied to identify the subjective importance (weights) of the delaying factors. The entropy weight method combined with the actual performance of the container shipping company are both used when estimating the objective importance (weights) of the delaying factors. According to the analysis results, the criteria can be divided into four quadrants with different management implications, which indicate that instructions for chase strategy, sailing schedule control, fleet allocation, transship operation arrangement and planning for ports in routes are often ignored by container shipping companies. Container shipping companies should consider adjusting their operational strategies, which would greatly improve their operational performance.

Rotationally averaged collision cross section (CCS) values for a series of proteins and protein complexes ranging in size from 8.6 to 810 kDa are reported. The CCSs were obtained using a native electrospray ionization drift tube ion mobility-Orbitrap mass spectrometer specifically designed to enhance sensitivity while having high-resolution ion mobility and mass capabilities. Periodic focusing (PF)-drift tube (DT)-ion mobility (IM) provides first-principles determination of the CCS of large biomolecules that can then be used as CCS calibrants. The experimental, first-principles CCS values are compared to previously reported experimentally determined and computationally calculated CCS using projected superposition approximation (PSA), the Ion Mobility Projection Approximation Calculation Tool (IMPACT), and Collidoscope. Experimental CCS values are generally in agreement with previously reported CCSs, with values falling within ~5.5%. In addition, an ion mobility resolution (CCS centroid divided by CCS fwhm) of ~60 is obtained for pyruvate kinase (MW ~ 233 kDa); however, ion mobility resolution for bovine serum albumin (MW ~ 68 kDa) is less than ~20, which arises from sample impurities and underscores the importance of sample quality. The high resolution afforded by the ion mobility-Orbitrap mass analyzer provides new opportunities to understand the intricate details of protein complexes such as the impact of post-translational modifications (PTMs), stoichiometry, and conformational changes induced by ligand binding.

Ultrafine CoO particles immobilized into the mesopores of three-dimensional cubic bimodal ordered mesoporous carbon CMK-9 is successfully prepared by using a combination of nanocasting and wet-impregnation methods. It is found that the cubic bimodal interconnected mesoporous framework of CMK-9 plays a crucial role in achieving the excellent electrochemical performances by assisting the rapid mass and charge transfer. Among the prepared nanocomposites, CoO(10)@CMK-9 delivers a discharge capacity of 830 mAh g-1 after 200 cycles at a current density of 100 mA g-1 in lithium-ion batteries. At a higher current density of 1000 mA g-1 , the anode presents an outstanding discharge capacity of 636 mAh g-1 after 200 cycles. In sodium-ion batteries, the anode provides a discharge capacity of 296 mAh g-1 after 250 cycles at a current density of 100 mA g-1 . The remarkable performances of CoO(10)@CMK-9 demonstrate the promising potentials of the nanocomposite as the anode for rechargeable batteries.

Fucoidan is a fucose-rich polysaccharide that has gained attention for its various anticancer properties. However, the effect and underlying mechanism of fucoidan on triple-negative breast cancer (TNBC) are still unknown. Herein, we investigated the anticancer potential of fucoidan from Laminaria japonica. We found that fucoidan showed modest antiproliferative activity against TNBC cells, while it effectively reduced migratory and invasive capacities. Mechanistically, fucoidan suppressed activation of MAPK and PI3K followed by inhibition of AP-1 and NF-κB signaling in TNBC. Additionally, fucoidan downregulated expressions of proangiogenic factors in TNBC cells, and fucoidan blocked tumor-elicited tube formation by human umbilical vascular endothelial cells (HUVECs). We also observed that fucoidan blocked tumor adhesion and invasion towards HUVECs. Surprisingly, fucoidan robustly suppressed tube formation on HUVECs. Moreover, fucoidan inhibited in vivo angiogenesis and micrometastasis in a transgenic zebrafish model. Together, L. japonica fucoidan exhibits potent antitumor effects by its attenuation of invasiveness and proangiogenesis in TNBC.

Lung cancer is the most commonly diagnosed cancer worldwide, and metastasis in lung cancer is the leading cause of cancer‐related deaths. Thus, understanding the mechanism of lung cancer metastasis will improve the diagnosis and treatment of lung cancer patients. Herein, we found that expression of cluster of differentiation 109 (CD109) was correlated with the invasive and metastatic capacities of lung adenocarcinoma cells. CD109 is upregulated in tumorous tissues, and CD109 overexpression was associated with tumor progression, distant metastasis, and a poor prognosis in patient with lung adenocarcinoma. Mechanistically, expression of CD109 regulates protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling via its association with the epidermal growth factor receptor (EGFR). Inhibition of CD109 decreases EGFR phosphorylation, diminishes EGF‐elicited activation of AKT/mTOR, and sensitizes tumor cells to an EGFR inhibitor. Taken together, our results show that CD109 is a potential diagnostic and therapeutic target in lung cancer patients., CD109 promotes lung cancer metastasis through promoting EGFR‐AKT‐mTOR signaling and CD109 is an independent prognostic marker for lung adenocarcinoma.

Graphene oxide (GO) membranes have great potential for separation applications due to their low-friction water permeation combined with unique molecular sieving ability. However, the practical use of deposited GO membranes is limited by the inferior mechanical robustness of the membrane composite structure derived from conventional deposition methods. Here, we report a nanostructured GO membrane that possesses great permeability and mechanical robustness. This composite membrane consists of an ultrathin selective GO nanofilm (as low as 32 nm thick) and a postsynthesized macroporous support layer that exhibits excellent stability in water and under practical permeability testing. By utilizing thin-film lift off (T-FLO) to fabricate membranes with precise optimizations in both selective and support layers, unprecedented water permeability (47 L·m-2·hr-1·bar-1) and high retention (>98% of solutes with hydrated radii larger than 4.9 A) were obtained.

Objective The use of sodium-glucose co-transporter 2 inhibitors (SGLT2is) may be associated with ketoacidosis. Therefore, the associated risk factors should be identified. In particular, information regarding the effects of the co-administration of anti-diabetic drugs is lacking. Methods We performed a retrospective study of 68 consecutive patients with diabetes who were taking an SGLT2i and attending a single medical center. After a period of treatment (median 78 days), their circulating ketone concentrations were measured. The concomitant use of other anti-diabetic drugs was analyzed to identify independent risk factors associated with ketosis. Results Twenty-five participants were taking empagliflozin, 23 were taking dapagliflozin, and 20 were taking canagliflozin. During the treatment period, no ketoacidotic events were recorded and their mean circulating ketone concentrations at the end of the study period were similar (0.3 mmol/L in the empagliflozin group, 0.26 mmol/L in the dapagliflozin group, and 0.25 mmol/L in the canagliflozin group). After adjustment for the use of anti-diabetic drugs, pioglitazone was found to be independently associated with a risk of high circulating ketone concentration (B value: 0.361, 95% confidence interval: 0.181–0.541). Conclusion SGLT2i-associated ketoacidosis was found to be infrequent, but the concomitant use of pioglitazone was associated with a higher risk of ketosis.

Iron-sulfur (Fe-S) cluster cofactors are required for the function of many critical cellular processes. These cofactors are assembled and inserted into apo target proteins by conserved Fe-S cluster biosynthetic pathways. In the ISC system of E. coli, the scaffold protein IscU assembles Fe-S cluster intermediates from iron, electrons, and inorganic sulfur, which is provided by the cysteine desulfurase enzyme IscS. IscU also binds to Zn, which mimics and competes for binding with the Fe-S cluster. Crystallographic and nuclear magnetic resonance (NMR) spectroscopic studies reveal that IscU is a metamorphic protein that exists in multiple conformational states, which include at least a structured form and a disordered form. The structured form of IscU is favored by metal binding and is stable in a narrow temperature range, undergoing both cold and hot denaturation. However, there is controversy over whether the structured or disordered form of IscU binds to IscS and functions in Fe-S cluster assembly. The recent development of variable-temperature electrospray ionization (vT-ESI) native ion mobility mass spectrometry (nIM-MS) enables probing the temperature dependence of macromolecular conformation and binding events in a single experiment. Here, vT-ESI nIM-MS results established that IscU exists in structured, intermediate, and disordered conformations. IscU samples shift towards high-charge states that have more extended conformations under extreme temperatures, consistent with cold/heat denaturation. A comparison of Zn-IscU and apo-IscU reveals that Zn(II) binding (i) attenuates the cold/heat-denaturation of IscU and promotes the refolding of IscU; (ii) favors the structured aand intermediate conformations and inhibits the disordered high charge states; and (iii) attenuates collisional induced unfolding (CIU) of intermediate conformations. Moreover, IscS was shown to alter the local conformation around the IscU active site, resulting in weakened Zn(II) affinity. Overall, these findings provide structural rationalization of the role of Zn(II) on stabilizing IscU conformation and the role of IscS on altering the IscU active site to prepare for Zn(II) release and cluster synthesis. This work highlights how vT-ESI-nMS can be applied as a powerful tool in mechanistic enzymology by providing details of relationships among temperature, protein conformations, and ligand/protein binding.

The interfacial properties within a composite structure of membranes play a vital role in the separation properties and application performances. Building an interlayer can facilitate the formation of a highly selective layer as well as improve the interfacial properties of the composite membrane. However, it is difficult for a nanomaterial-based interlayer to increase the flux and retention of nanofiltration membranes simultaneously. Here, we report a nanofiltration membrane with a hybrid dimensional titania interlayer that exhibits excellent separation performance. The interlayer, composed of Fe-doped titania nanosheets and titania nanoparticles, helps the formation of an ultrathin (∼30 nm thick) and defect-free polyamide selective layer with an ideal nanostructure. The hybrid dimensional interlayer endows the membrane with a superior permeability and alleviates flux decline. In addition, the rigid interlayer framework on a PVDF support drastically improves the pressure resistance of nanofiltration membranes and shows negligible flux loss up to 1.5 MPa of pressure.

Background and AimsThe long-term survival in people with type 2 diabetes following first diagnosis of diabetic foot complications (FDDFC) is unclear. The object is to evaluate the mortality rate in subjects with type 2 diabetes following FDDFC and the impacts of the major cardiovascular comorbidities.MethodsNationwide data were analyzed for subjects with T2D and DFC between 2003 and 2017 according to ICD-9 coding. DFC was defined with the codes of ulcers, infections, or severe peripheral artery disease that required intervention (PAD) to mimic the real world diagnosis. Criteria of FDDFC were preceded by a period without any DFC for at least 5 years. Major cardiovascular comorbidities: established PAD and cardiovascular diseases (CVD: including coronary heart disease (CHD), stroke, or heart failure) before the index date as well as lower-extremity amputations (LEA) at the index episode were analyzed.ResultsAmong 300,115 subjects with DFC, a total of 103,396 patients had FDDFC. The mean 5-year survival rate of these subjects was 81.05%. Using subjects without associated major cardiovascular comorbidity as baseline, the adjusted hazard ratios (aHR) were1.43 (95% confidence interval 1.38–1.49) in group PAD-/CVD+, followed by 1.70 (1.59–1.80) in PAD+/CVD- and 1.98 (1.89–2.08) in PAD+/CVD+. The aHR was further increased in patients with PAD who additionally had heart failure (3.77, 3.50–4.05), stroke (2.06, 1.95–2.18), or CHD (1.89, 1.79–2.00). Subjects with PAD rather than other CVD were associated with LEA at FDDFC. Patients with major LEA (above the ankle) at FDDFC episode had lower 5-year survival rate (65.01%) followed by those with minor LEA (72.24%) and without LEA (81.61%).ConclusionsCardiovascular comorbidity as well as LEA status at the event of FDDFCs were both associated with patient survival outcomes. Earlier identification of this large population could lead to higher survival rates.

To disclose prevalence, demographic, foot characteristics as well as management and lower-extremity amputations (LEAs) of subjects with end-stage renal disease (ESRD) on diabetic foot diseases (DFDs).Data were derived from the Taiwan National Health Insurance Research Database between 2004 and 2017. DFDs were defined as ulcers, infections, or severe peripheral arterial diseases (PADs) in patients with type 2 diabetes. Clinical characteristics were analyzed between subjects with and without ESRD.Subjects with ESRD have increased impacts on the DFD population either from annual prevalence (2.7 % to 10.42 %, P for trend 0.001), or proportional representation in LEAs (7.91 % to 26.37 %, P 0.001) over 14 years. The annual trends for major-LEAs rates have decreased in both subjects with and without ESRD (13.67 % to 5.82 % and 3.48 % to 1.47 %, both P 0.001). Notably, the concomitant increase of endovascular treatments (EVTs) (7.09 % to 29.41 %, P 0.001) was associated with the decrease of major-LEAs (P for interaction 0.001) in subjects with ESRD.As the annual prevalence of subjects with ESRD has increased 3.9-fold over years, they now account for more than 30% of annual major-LEA of the total DFD population. Interdisciplinary team approach and aggressive EVTs might reduce major-LEAs in these patients.

Long-term exposure to PMAssociations of serum lnc-IL7R levels with lung function, emphysema, and previous PMLnc-IL7R levels decreased in COPD patients and were negatively correlated with emphysema or PMLnc-IL7R attenuates PM

Recent advances in wearable and implantable electronics have increased the demand for biocompatible integrated energy storage systems. Conducting polymers, such as polyaniline (PANi), have been suggested as promising electrode materials for flexible biocompatible energy storage systems, based on their intrinsic structural flexibility and potential polymer chain compatibility with biological interfaces. However, due to structural disorder triggering insufficient electronic conductivity and moderate electrochemical stability, PANi still cannot fully satisfy the requirements for flexible and biocompatible energy storage systems. Herein, we report a biocompatible physiological electrolyte activated flexible supercapacitor encompassing crystalline tetra-aniline (c-TANi) as the active electrode material, which significantly enhances the specific capacitance and electrochemical cycling stability with chloride electrochemical interactions. The crystallization of TANi endows it with sufficient electronic conductivity (8.37 S cm-1) and a unique Cl- dominated redox charge storage mechanism. Notably, a fully self-healable and biocompatible supercapacitor has been assembled by incorporating polyethylene glycol (PEG) with c-TANi as a self-healable electrode and a ferric-ion cross-linked sodium polyacrylate (Fe3+-PANa)/0.9 wt% NaCl as a gel electrolyte. The as-prepared device exhibits a remarkable capacitance retention even after multiple cut/healing cycles. With these attractive features, the c-TANi electrode presents a promising approach to meeting the power requirements for wearable or implantable electronics.

Carbon dioxide (CO2) capture from fossil-fuel-based power plants requires scalable membranes with high CO2 permeability and reasonable CO2/N2 selectivity. Conventional membranes based on polyanilin...

For the past 30 years, thin-film membrane composites have been the state-of-the-art technology for reverse osmosis, nanofiltration, ultrafiltration, and gas separation. However, traditional membrane casting techniques, such as phase inversion and interfacial polymerization, limit the types of material that are used for the membrane separation layer. Here, we describe a novel thin-film liftoff (T-FLO) technique that enables the fabrication of thin-film composite membranes with new materials for desalination, organic solvent nanofiltration, and gas separation. The active layer is cast separately from the porous support layer, allowing for the tuning of the thickness and chemistry of the active layer. A fiber-reinforced, epoxy-based resin is then cured on top of the active layer to form a covalently bound support layer. Upon submersion in water, the cured membrane lifts off from the substrate to produce a robust, freestanding, asymmetric membrane composite. We demonstrate the fabrication of three novel T-FLO membranes for chlorine-tolerant reverse osmosis, organic solvent nanofiltration, and gas separation. The isolable nature of support and active-layer formation paves the way for the discovery of the transport and selectivity properties of new polymeric materials. This work introduces the foundation for T-FLO membranes and enables exciting new materials to be implemented as the active layers of thin-film membranes, including high-performance polymers, two-dimensional materials, and metal-organic frameworks.

Polyaniline was first confirmed as a dark green precipitate on an electrode during the electrochemical polymerization of aniline in 1862. Since then, scientists have been studying the kinetics and growth mechanisms of polyaniline through the electrochemical approach. Studies have shown that p-phenylenediamine, p-aminodiphenylamine, and other aromatic small molecules may serve as initiators for accelerating the polymerization reaction due to the autocatalytic effect of polyaniline. However, little research has been focused on the catalytic effects of introducing oligoanilines. In this paper, quantitative rate constants for the electrochemical polymerization of aniline in both HCl and acetonitrile/HCl solutions with 0.5 mol % of added oligoanilines including diphenylamine, N-phenyl-p-phenylenediamine, 1,4-phenylenediamine, N,N′-diphenyl-1,4-phenylenediamine, 4,4′-diaminodiphenylamine, and tetraaniline in both emeraldine and leucoemeraldine states are reported. Among all the rate constants, N-phenyl-p-phenyl...

We here present an object-based image analysis (OBIA) approach to identify temporal changes in radar intensity images and to locate land-cover changes caused by mass-wasting processes at small to large scales, such as landslides. OBIA was introduced to systematically and semi-automatically detect landslides in image pairs with an overall accuracy of at least 60% when compared to in-situ landslide inventory data. Our approach is based upon change detection in intensity images that remain in their original imaging coordinate system rather than being map projected, in order to reduce image artefacts. Intensity images in their native coordinate frame allow for a consistent level of detection of land-cover changes. If wrapped within a continuous monitoring framework, our approach might help to assist to not only assess large-scale landslides as they occur, but to identify subtle movements prior to slope failure in order to launch mitigation measures and response.

This study evaluates the performance of the Taiwan Earth System Model version 1 (TaiESM1) in simulating the observed climate variability in the historical simulation of the Coupled Model Intercomparison Phase 6 (CMIP6). TaiESM1 is developed on the basis of the Community Earth System Model version 1.2.2, with the inclusion of several new physical schemes and improvements in the atmosphere model. The new additions include an improved triggering function in the cumulus convection scheme, a revised distribution‐based formula in the cloud fraction scheme, a new aerosol scheme, and a unique scheme for three‐dimensional surface absorption of shortwave radiation that accounts for the influence of complex terrains. In contrast to the majority of model evaluation processes, which focus mainly on the climatological mean, this evaluation focuses on climate variability parameters, including the diurnal rainfall cycle, precipitation extremes, synoptic eddy activity, intraseasonal fluctuation, monsoon evolution, and interannual and multidecadal atmospheric and oceanic teleconnection patterns. A series of intercomparisons between the simulations of TaiESM1 and CMIP6 models and observations indicate that TaiESM1, a participating model in CMIP6, can realistically simulate the observed climate variability at various time scales and are among the leading CMIP6 models in terms of many key climate features.

Conjugated polyaniline can impact the field of water filtration membranes due to its hydrophilic and antibacterial nature, facile and inexpensive synthesis procedure, heat and acid tolerance, and unique doping/dedoping chemistry. However, the gelation effect, its rigid backbone, and the limited hydrophilicity of polyaniline severely restrict the adaptability to membranes and their antifouling performance. This Mini Review summarizes important works of polyaniline-related ultrafiltration membranes, highlighting solutions to conquer engineering obstacles in processing and challenges in enhancing surface hydrophilicity with an emphasis on chemistry. As a pH-responsive polymer convertible to a conductive salt, this classic material should continue to bring unconventional advances into the realm of water filtration membranes.

The enhancement of charged-particle pairs with large pseudorapidity difference and small azimuthal angle difference, often referred to as the "ridge signal", is a phenomenon widely observed in high multiplicity proton-proton, proton-ion and deutron-ion collisions, which is not yet fully understood. In heavy-ion collisions, the hydrodynamic expansion of the Quark-Gluon Plasma is the most popular explanation of the ridge signal. Measurements in the $e^+e^-$ collision system, without the complexities introduced by hadron structure in the initial state, can be a new opportunity to examine the formation of a ridge signal. The first measurement of two-particle angular correlation functions in high multiplicity $e^+e^-$ collisions at $\sqrt{s}=10.52$ GeV is reported. About $31.5~{\rm fb}^{-1}$ hadronic $e^+e^-$ annihilation data collected by the Belle detector at KEKB are used in this study. Two-particle angular correlation functions are measured over the full azimuth and large pseudorapidity intervals which are defined by either the electron beam axis or the event thrust as a function of charged particle multiplicity. The measurement in the event thrust analysis, with mostly quark and anti-quark pairs determining the reference axis, is sensitive to soft gluon emissions associated with the outgoing (anti-)quarks. No significant ridge signal is observed with analyses performed in either coordinate system. Near-side jet correlations appear to be absent in the thrust axis analysis. The measurements are compared to predictions from various $e^+e^-$ event generators and expected to provide new constraints to the phenomenological models in the low collision energy regime.

Exposure to environmental and occupational contaminants leads to lung cancer. 3-Nitrobenzanthrone (3-nitro-7H-benz[de]anthracen-7-one, 3-NBA) is a potential carcinogen in ambient air or diesel particulate matter. Studies have revealed that short-term exposure to 3-NBA induces cell death, reactive oxygen species activation, and DNA adduct formation and damage. However, details of the mechanism by which chronic exposure to 3-NBA influences lung carcinogenesis remain largely unknown. In this study, human lung epithelial BEAS-2B cells were continuously exposed to 0-10-μM 3-NBA for 6 months. NanoString analysis was conducted to evaluate gene expression in the cells, revealing that 3-NBA-mediated transformation results in a distinct gene expression signature including carbon cancer metabolism, metastasis, and angiogenesis. Alterations in tumor-promoting genes such as EREG (epiregulin), SOX9, E-cadherin, TWIST, and IL-6 were involved in epithelial cell aggressiveness. Kaplan-Meier plotter analyses indicated that increased EREG and IL-6 expressions in early-stage lung cancer cells are correlated with poor survival. In vivo xenografts on 3-NBA-transformed cells exhibited prominent tumor formation and metastasis. EREG knockout cells exposed to 3-NBA for a short period exhibited high apoptosis and low colony formation. By contrast, overexpression of EREG in 3-NBA-transformed cells markedly activated the PI3K/AKT and MEK/ERK signaling pathways, resulting in tumorigenicity. Furthermore, elevated IL-6 and EREG expressions synergistically led to STAT3 signaling activation, resulting in clonogenic cell survival and migration. Taken together, chronic exposure of human lung epithelial cells to 3-NBA leads to malignant transformation, in which the EREG signaling pathway plays a pivotal mediating role. • Short-term exposure of lung epithelial cells to 3-NBA can lead to ROS production and cell apoptosis. • Long-term chronic exposure to 3-NBA upregulates the levels of tumor-promoting genes such as EREG and IL-6. • Increased EREG expression in 3-NBA-transformed cells markedly contributes to tumorigenesis through PI3K/AKT and MEK/ERK activation and synergistically enhances the IL-6/STAT3 signaling pathway, which promotes tumorigenicity.

BackgroundDiabetic foot infection (DFI) is a limb- and life-threatening complication for diabetic patients needing immediate and comprehensive treatment. Early referral of DFI patients to a diabetic foot center is recommended but there appears limited validated evidence, with the association between referral time and clinical outcomes of limb- preservation or in-hospital mortality still lacking.MethodsThis retrospective research studied consecutive type 2 diabetic patients with DFI treated at the major diabetic foot center in Taiwan from 2014 to 2017. Six hundred and sixty-eight patients presented with limb-threatening DFI. After stratifying their referral days into quartiles, the demographic information and clinical outcomes were analyzed.ResultsOne hundred and seventy-two patients were placed in the first quartile (Q1) with less than 9 days of referral time; 164 in the second quartile (Q2) with 9-21 days; 167 in the third quartile (Q3) with 21-59 days; and 165 in the fourth quartile (Q4) with >59 days. End-stage renal disease (ESRD), major adverse cardiac events (MACE) and peripheral arterial disease (PAD) were noted as being higher in the Q4 group compared with the Q1 group (25.45% vs 20.35% in ESRD, 47.27% vs 26.16% in MACE and 78.79% vs 52.33% in PAD respectively). The Q1 group had more patients presenting with systemic inflammatory responsive syndrome (SIRS) (29.07% in Q1 vs 25.45% in Q4 respectively,P=0.019). Regarding poor outcome (major lower-extremity amputation (LEA) or in-hospital mortality), the Q4 group had 21.21% of patients in this category and the Q1 group had 10.47%. The odds ratio of each increased referral day on poor prognosis was 1.006 with 95% confidence interval 1.003–1.010 (P=P=0.003) and those with PAD (OR 1.004, 95% CI 1.001–1.008,P=0.028).ConclusionsThe deferred referral of DFI patients to the diabetic foot center might be associated with poor treatment outcome either in major LEA or mortality, particularly in patients with SIRS or PAD. Both physician and patient awareness of disease severity and overcoming the referral barrier is suggested.Trial registrationNot applicable.

We propose a novel way to search for axion(-like) particles in heavy-ion collisions using prompt photons as the probe and the property of conversion between photon and axion(-like) particles under a strong magnetic field generated in the non-central collisions. The expected result reveals that a new phase space region of the coupling constant for photon and axion(-like) particles can be covered in the future high energy nuclear colliders.

Triple-negative breast cancer (TNBC) exhibits a higher level of glycolytic capacity and are commonly associated with an inflammatory microenvironment, but the regulatory mechanism and metabolic crosstalk between the tumor and tumor microenvironment (TME) are largely unresolved. Here, we show that glucose transporter 3 (GLUT3) is particularly elevated in TNBC and associated with metastatic progression and poor prognosis in breast cancer patients. Expression of GLUT3 is crucial for promoting the epithelial-to-mesenchymal transition and enhancing invasiveness and distant metastasis of TNBC cells. Notably, GLUT3 is correlated with inflammatory gene expressions and is associated with M1 tumor-associated macrophages (TAMs), at least in part by C-X-C Motif Chemokine Ligand 8 (CXCL8). We found that expression of GLUT3 regulates CXCL8 production in TNBC cells. Secretion of CXCL8 participates in GLUT3-overexpressing TNBC cells-elicited activation of inflammatory TAMs, which further enhances GLUT3 expression and mobility of TNBC cells. Our findings demonstrate that aerobic glycolysis in TNBC not only promotes aggressiveness of tumor cells but also initiates a positive regulatory loop for enhancing tumor progression by modulating the inflammatory TME.

Iron-sulfur (Fe-S) clusters have a key role in many biochemical processes and are essential for most life forms. Despite recent mechanistic advances in understanding the Fe-S cluster biosynthetic pathway, critical questions remain unresolved. Although human NFS1 and E. coli IscS share ∼60% sequence identity, NFS1 exhibits low activity and requires activation by the Friedreich’s ataxia protein frataxin (FXN) for in vivo function. Surprisingly, structures of the human complex reveal three distinct quaternary structures with one form exhibiting the same subunit interactions as IscS. An architectural switch model has been proposed in which evolutionarily lost interactions between NFS1 subunits results in the formation of low-activity architectures; FXN binding compensates for these lost interactions and facilitates a subunit rearrangement to activate the complex. Here, we used a structure and evolution-guided approach to identify three conserved residues proposed to weaken interactions between NFS1 subunits and transplanted these amino acids into IscS. Compared to native IscS, the engineered variant had a 4000-fold weaker dimer interface and diminished activity that correlated with the absence of the second catalytic subunit. Remarkably, the addition of the FXN homolog to the engineered variant stimulated the decay of the Cys-quinonoid pyridoxal 5’-phosphate intermediate, shifted IscS from the monomeric to dimeric form, and increased the cysteine desulfurase activity, reproducing results from the human system and supporting the architectural switch model. Overall, these studies indicate a weakening of the homodimeric interface was a key development during the evolution of the eukaryotic system and provide new insights into the role of FXN.

Thin-film composite (TFC) membranes are favored for precise molecular sieving in liquid-phase separations; they possess high permeability due to the minimal thickness of the active layer and the high porosity of the support layer. However, current TFC membrane fabrication techniques are limited by the available materials for the selective layer and do not demonstrate the level of structural control needed to substantially advance organic solvent nanofiltration (OSN) membrane technology. In this work, we employ the newly developed thin-film lift-off (T-FLO) technique to fabricate polybenzimidazole (PBI) TFC membranes with porous support layers uniquely tailored to OSN. The drop-cast dense PBI selective layers endow the membranes with an almost complete rejection of common small dye molecules. The polymeric support layer is optimized by a combinatorial approach using four different monomers that alter the cross-linking density and polymer chain flexibility of the final composite. These two properties substantially affect the porogen holding capacity of the reticular polymer network, leading to the formation of different macropore structures. With a 150 nm thick PBI selective layer and fine-tuning of the support layer, the resulting membrane achieves stable and superior permeance of 14.0, 11.7, 16.4, 11.4, 17.1, and 19.7 L m-2 h-1 bar-1 for water, ethanol, methanol, isopropanol, tetrahydrofuran (THF), and acetonitrile, respectively.

Conjugated polyaniline has shown anticorrosive, hydrophilic, antibacterial, pH-responsive, and pseudocapacitive properties making it of interest in many fields. However, in situ grafting of polyaniline without harsh chemical treatments is challenging. In this study, we report a simple, fast, and non-destructive surface modification method for grafting tetraaniline (TANI), the smallest conjugated repeat unit of polyaniline, onto several materials via perfluorophenylazide photochemistry. The new materials are characterized by nuclear magnetic resonance (NMR) and electrospray ionization (ESI) mass spectroscopy. TANI is shown to be covalently bonded to important carbon materials including graphite, carbon nanotubes (CNTs), and reduced graphene oxide (rGO), as confirmed by transmission electron microscopy (TEM). Furthermore, large area modifications on polyethylene terephthalate (PET) films through dip-coating or spray-coating demonstrate the potential applicability in biomedical applications where high transparency, patternability, and low bio-adhesion are needed. Another important application is preventing biofouling in membranes for water purification. Here we report the first oligoaniline grafted water filtration membranes by modifying commercially available polyethersulfone (PES) ultrafiltration (UF) membranes. The modified membranes are hydrophilic as demonstrated by captive bubble experiments and exhibit extraordinarily low bovine serum albumin (BSA) and Escherichia coli adhesions. Superior membrane performance in terms of flux, BSA rejection and flux recovery after biofouling are demonstrated using a cross-flow system and dead-end cells, showing excellent fouling resistance produced by the in situ modification.

Stiff-person syndrome (SPS) is highly associated with anti-glutamic acid decarboxylase (GAD) antibody. However, GAD antibodies alone appear to be insufficient to cause SPS, and they possibly are involved in only part of its pathophysiology. It is suspected that the symptoms of SPS get precipitated by external stimuli. Here, we briefly introduce the case of a patient with latent autoimmune diabetes who developed SPS through the action of subcutaneously injected insulin. A 43-year-old man was diagnosed with diabetes and initially well-controlled with oral hypoglycemic agents but progressed to requiring insulin within 1 year of diagnosis. Two months after the initiation of basal insulin therapy, he presented with abdominal stiffness and painful muscle spasms, involving the lower limbs, which resulted in walking difficulty, and thus, he refused insulin injections thereafter. He had been treated with oral anti-diabetic agents instead of insulin for 10 years until premixed insulin twice daily was started again due to poor diabetes control. Immediately after insulin injection, abdominal muscle rigidity and spasms were noted. When insulin was not administered, frequent episodes of diabetic ketoacidosis occurred. Serum GAD antibody test was positive and there was no positivity for islet antigen-2 antibody. A glucagon stimulation test demonstrated relative insulin deficiency, indicative of latent autoimmune diabetes in adults (LADA). Tolerable muscle rigidity was achieved when the dosage of basal insulin was split into two separate daily injections with lower amounts of units per injection. This case highlights a different form of autoimmune diabetes in SPS. To our knowledge, this is the first report of SPS described shortly after the initiation of insulin therapy that required basal insulin to achieve tolerable muscle symptoms and better glucose control, without the development of diabetic ketoacidosis.

Despite rapidly evolving pathobiological mechanistic demystification, coupled with advances in diagnostic and therapeutic modalities, chronic obstructive pulmonary disease (COPD) remains a major healthcare and clinical challenge, globally. Further compounded by the dearth of available curative anti-COPD therapy, it is posited that this challenge may not be dissociated from the current lack of actionable COPD pathognomonic molecular biomarkers. There is accruing evidence of the involvement of protracted ‘smoldering’ inflammation, repeated lung injury, and accelerated lung aging in enhanced predisposition to or progression of COPD. The relatively novel uncharacterized human long noncoding RNA lnc-IL7R (otherwise called LOC100506406) is increasingly designated a negative modulator of inflammation and regulator of cellular stress responses; however, its role in pulmonary physiology and COPD pathogenesis remains largely unclear and underexplored. Our previous work suggested that upregulated lnc-IL7R expression attenuates inflammation following the activation of the toll-like receptor (TLR)-dependent innate immune system, and that the upregulated lnc-IL7R is anti-correlated with concomitant high PM2.5, PM10, and SO2 levels, which is pathognomonic for exacerbated/aggravated COPD in Taiwan. In the present study, our quantitative analysis of lnc-IL7R expression in our COPD cohort (n = 125) showed that the lnc-IL7R level was significantly correlated with physiological pulmonary function and exhibited COPD-based stratification implications (area under the curve, AUC = 0.86, p < 0.001). We found that the lnc-IL7R level correctly identified patients with COPD (sensitivity = 0.83, specificity = 0.83), precisely discriminated those without emphysematous phenotype (sensitivity = 0.48, specificity = 0.89), and its differential expression reflected disease course based on its correlation with the COPD GOLD stage (r = −0.59, p < 0.001), %LAA-950insp (r = −0.30, p = 0.002), total LAA (r = −0.35, p < 0.001), FEV1(%) (r = 0.52, p < 0.001), FVC (%) (r = 0.45, p < 0.001), and post-bronchodilator FEV1/FVC (r = 0.41, p < 0.001). Consistent with other data, our bioinformatics-aided dose–response plot showed that the probability of COPD decreased as lnc-IL7R expression increased, thus, corroborating our posited anti-COPD therapeutic potential of lnc-IL7R. In conclusion, reduced lnc-IL7R expression not only is associated with inflammation in the airway epithelial cells but is indicative of impaired pulmonary function, pathognomonic of COPD, and predictive of an exacerbated/ aggravated COPD phenotype. These data provide new mechanistic insights into the ailing lung and COPD progression, as well as suggest a novel actionable molecular factor that may be exploited as an efficacious therapeutic strategy in patients with COPD.