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The literature on East Asian developmental states has mostly focused on economic policies; few studies have investigated how developmentalism affects urbanisation. This study addresses this gap by analysing the formation of a housing system by the developmental state and the role of the housing sector in the transition from an economic miracle in the 1960s to stagnation after the 1990s. Wang, Lee, and Chen (2017) argued that Taiwan’s state bureaucrats played a gradually diminishing role in directing the market. This article takes a different approach by arguing that the government’s interventions on housing intensified after the 1990s; housing finance sectors were formalised, squatters were removed, and interventions based on market mechanisms were employed to stimulate the housing market. However, the lack of an effective state intervention on housing made speculation difficult to control and created an obstacle to economic development. Such housing speculation increased social inequality. [ABSTRACT FROM AUTHOR]

The CD1 and MR1 protein families present lipid antigens and small molecules to T cells, complementing well-studied major histocompatibility complex–peptide mechanisms. The CD1a subtype is highly and continuously expressed within the skin, most notably on Langerhans cells, and has been demonstrated to present self and foreign lipids to T cells, highlighting its cutaneous sentinel role. Alteration of CD1a-dependent T-cell responses has recently been discovered to contribute to the pathogenesis of several inflammatory skin diseases. In this review, we overview the structure and role of CD1a and outline the current evidence implicating CD1a in the development of psoriasis, atopic dermatitis and allergic contact dermatitis. [ABSTRACT FROM AUTHOR]

Background: Acute lung injury (ALI) is a life-threatening respiratory condition characterized by severe inflammation and lung tissue damage, frequently causing rapid respiratory failure and long-term complications. The microRNA let-7a-5p is involved in the progression of lung injury, inflammation, and fibrosis by regulating immune cell activation and cytokine production. This study aims to use an innovative cellular electroporation platform to generate extracellular vesicles (EVs) carring let-7a-5p (EV-let-7a-5p) derived from transfected Wharton's jelly-mesenchymal stem cells (WJ-MSCs) as a potential gene therapy for ALI. Methods: A cellular nanoporation (CNP) method was used to induce the production and release of EV-let-7a-5p from WJ-MSCs transfected with the relevant plasmid DNA. EV-let-7a-5p in the conditioned medium were isolated using a tangential flow filtration (TFF) system. EV characterization followed the minimal consensus guidelines outlined by the International Society for Extracellular Vesicles. We conducted a thorough set of therapeutic assessments, including the antifibrotic effects using a transforming growth factor beta (TGF-β)-induced cell model, the modulation effects on macrophage polarization, and the influence of EV-let-7a-5p in a rat model of hyperoxia-induced ALI. Results: The CNP platform significantly increased EV secretion from transfected WJ-MSCs, and the encapsulated let-7a-5p in engineered EVs was markedly higher than that in untreated WJ-MSCs. These EV-let-7a-5p did not influence cell proliferation and effectively mitigated the TGF-β-induced fibrotic phenotype by downregulating SMAD2/3 phosphorylation in LL29 cells. Furthermore, EV-let-7a-5p regulated M2-like macrophage activation in an inflammatory microenvironment and significantly induced interleukin (IL)-10 secretion, demonstrating their modulatory effect on inflammation. Administering EVs from untreated WJ-MSCs slightly improved lung function and increased let-7a-5p expression in plasma in the hyperoxia-induced ALI rat model. In comparison, EV-let-7a-5p significantly reduced macrophage infiltration and collagen deposition while increasing IL-10 expression, causing a substantial improvement in lung function. Conclusion: This study reveals that the use of the CNP platform to stimulate and transfect WJ-MSCs could generate an abundance of let-7a-5p-enriched EVs, which underscores the therapeutic potential in countering inflammatory responses, fibrotic activation, and hyperoxia-induced lung injury. These results provide potential avenues for developing innovative therapeutic approaches for more effective interventions in ALI. [ABSTRACT FROM AUTHOR]

Multiple forms of interference and noise that impact the receiver's capacity to receive and interpret satellite signals, and consequently the preciseness of positioning and navigation, may be present during the processing of Global Positioning System (GPS) navigation. The non-Gaussian noise predominates in the signal owing to the fluctuating character of both natural and artificial electromagnetic interference, and the algorithm based on the minimum mean-square error (MMSE) criterion performs well when assuming Gaussian noise, but drops when assuming non-Gaussian noise. The maximum correntropy criteria (MCC) adaptive filtering technique efficiently reduces pulse noise and has adequate performance in heavy-tailed noise, which addresses the issue of filter performance caused by the presence of non-Gaussian or heavy-tailed unusual noise values in the localizing measurement noise. The adaptive kernel bandwidth (AKB) technique employed in this paper applies the calculated adaptive variables to generate the kernel function matrix, in which the adaptive factor can modify the size of the kernel width across a reasonably appropriate spectrum, substituting the fixed kernel width for the conventional MCC to enhance the performance. The conventional maximum correntropy criterion-based extended Kalman filter (MCCEKF) algorithm's performance is significantly impacted by the value of the kernel width, and there are certain predetermined conditions in the selection based on experience. The MCCEKF with a fixed adaptive kernel bandwidth (MCCEKF-AKB) has several advantages due to its novel concept and computational simplicity, and gives a qualitative solution for the study of random structures for generalized noise. Additionally, it can effectively achieve the robust state estimation of outliers with anomalous values while guaranteeing the accuracy of the filtering. [ABSTRACT FROM AUTHOR]

Background: Metastasis is a multistep process involving the migration and invasion of cancer cells and is a hallmark of cancer malignancy. Long non-coding RNAs (lncRNAs) play critical roles in the regulation of metastasis. This study aims to elucidate the role of the lncRNA solute carrier organic anion transporter family member 4A1-antisense 1 (SLCO4A1-AS1) in metastasis and its underlying regulatory mechanisms. Methods: A comprehensive analysis of the Gene Expression Omnibus (GEO) database were used to identify metastasis-associated lncRNAs. Transwell migration and invasion assays, and a tail vein-injection mouse model were used to assess the migration and invasion of cancer cells in vitro and in vivo, respectively. High-throughput screening methods, including MASS Spectrometry and RNA sequencing (RNA-seq), were used to identify the downstream targets of SLCO4A1-AS1. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting, RNA pull-down, RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH), and chromatin immunoprecipitation (ChIp) assays were conducted to identify and validate the underlying regulatory mechanisms of SLCO4A1-AS1. Results: SLCO4A1-AS1 reduced cancer cell migration and invasion by disrupting cytoskeleton filaments, and was associated with longer overall survival in patients with lung adenocarcinoma. SLCO4A1-AS1 directly interacted with the DNA-binding protein, TOX High Mobility Group Box Family Member 4 (TOX4), to inhibit TOX4-induced migration and invasion. Furthermore, RNA-seq revealed that neurotensin receptor 1 (NTSR1) is a novel and convergent downstream target of SLCO4A1-AS1 and TOX4. Mechanistically, SLCO4A1-AS1 functions as a decoy of TOX4 by interrupting its interaction with the NTSR1 promoter and preventing NTSR1 transcription. Functionally, NTSR1 promotes cancer cell migration and invasion through cytoskeletal remodeling, and knockdown of NTSR1 significantly inhibits TOX4-induced migration and invasion. Conclusion: These findings demonstrated that SLCO4A1-AS1 antagonizes TOX4/NTSR1 signaling, underscoring its pivotal role in lung cancer cell migration and invasion. These findings hold promise for the development of novel therapeutic strategies targeting the SLCO4A1-AS1/TOX4/NTSR1 axis as a potential avenue for effective therapeutic intervention in lung cancer. [ABSTRACT FROM AUTHOR]

Background Empyema thoracis is a serious infectious disease and is associated with high morbidity and mortality. The perioperative outcomes between culture-positive and culture-negative empyema after thoracoscopic decortication remained controversial, especially since there were no studies that reported the survival outcomes between culture-positive and culture-negative empyema. Methods This single-institute study involved a retrospective analysis. Patients with empyema thoracis who underwent thoracoscopic decortication between January 2012 and December 2021 were included in the study. Patients were grouped into a culture-positive group and a culture-negative group according to culture results obtained no later than 2 weeks after surgery. Results A total of 1087 patients with empyema received surgery, and 824 were enrolled after exclusion. Among these, 366 patients showed positive culture results and 458 patients showed negative results. Longer intensive care unit stays (11.69 vs 5.64 days, P <.001), longer ventilator usage (24.70 vs 14.01 days, P =.002), and longer postoperative hospital stays (40.83 vs 28.37 days, P <.001) were observed in the culture-positive group. However, there was no significant difference in 30-day mortality between the 2 groups (5.2% in culture negative vs 5.0% in culture positive, P =.913). The 2-year survival was not significantly different between the 2 groups (P =.236). Conclusions Patients with culture-positive or culture-negative empyema who underwent thoracoscopic decortication showed similar short-term and long-term survival outcomes. A higher risk of death was associated with advanced age, a higher Charlson Comorbidity Index score, phase III empyema, and a cause other than pneumonia. [ABSTRACT FROM AUTHOR]

To explore the relationship of systemic lupus erythematosus (SLE) and subsequent glaucoma incidence. Patients with SLE were defined as those newly diagnosed by International Classification of Diseases, 9th Revision, Clinical Modification (ICD‐9‐CM) code 710.0 in at least 3 outpatient visits or 1 hospitalization during 2000–2012 by using the National Health Insurance Research Database. We selected a non‐SLE comparison cohort at a 1:1 ratio by propensity score matching on age, gender, index date, comorbidities and medications. We identified outcome as the incident glaucoma in patients with SLE. Multivariate Cox regression analysis was used to calculate the adjusted hazard ratio (aHR) in 2 groups. Kaplan‐ Meier analysis was performed to estimate the cumulative incidence rate between both groups. There were 1743 patients who were included in the SLE group and non‐SLE group. The aHR of glaucoma was 1.56 (95% CI = 1.03–2.36) in the SLE group, compared to non‐SLE controls. Subgroup analysis showed that SLE patients present greater risk of glaucoma, especially in males (aHR = 3.76; 95% CI, 1.5–9.42), and the P for interaction between gender and risk of glaucoma was 0.026. This cohort study showed that patients with SLE have 1.56‐fold risk of glaucoma development. Gender acted as an effect modifier between SLE and the risk of new‐onset glaucoma. [ABSTRACT FROM AUTHOR]

Background: Asymmetric dimethylarginine (ADMA), which is significantly elevated in the plasma of cancer patients, is formed via intracellular recycling of methylated proteins and serves as a precursor for resynthesis of arginine. However, the cause of ADMA elevation in cancers and its impact on the regulation of tumor immunity is not known. Methods: Three mouse breast cell lines (normal breast epithelial HC11, breast cancer EMT6 and triple negative breast cancer 4T1) and their equivalent 3D stem cell culture were used to analyze the secretion of ADMA using ELISA and their responses to ADMA. Bone marrow-derived macrophages and/or RAW264.7 cells were used to determine the impact of increased extracellular ADMA on macrophage-tumor interactions. Gene/protein expression was analyzed through RNAseq, qPCR and flow cytometry. Protein functional analyses were conducted via fluorescent imaging (arginine uptake, tumor phagocytosis) and enzymatic assay (arginase activity). Cell viability was measured via MTS assay and/or direct cell counting using Countess III FL system. Results: For macrophages, ADMA impaired proliferation and phagocytosis of tumor cells, and even caused death in cultures incubated without arginine. ADMA also led to an unusual macrophage phenotype, with increased expression of arginase, cd163 and cd206 but decreased expression of il10 and dectin-1. In contrast to the severely negative impacts on macrophages, ADMA had relatively minor effects on proliferation and survival of mouse normal epithelial HC11 cells, mouse breast cancer EMT6 and 4T1 cells, but there was increased expression of the mesenchymal markers, vimentin and snail2, and decreased expression of the epithelial marker, mucin-1 in EMT6 cells. When tumor cells were co-cultured ex vivo with tumor antigen in vivo-primed splenocytes, the tumor cells secreted more ADMA and there were alterations in the tumor cell arginine metabolic landscape, including increased expression of genes involved in arginine uptake, metabolism and methylation, and decreased expression of a gene that is responsible for arginine demethylation. Additionally, interferon-gamma, a cytokine involved in immune challenge, increased secretion of ADMA in tumor cells, a process attenuated by an autophagy inhibitor. Conclusion: Our results suggest initial immune attack promotes autophagy in tumor cells, which then secrete ADMA to manipulate macrophage polarization favoring tumor tolerance. [ABSTRACT FROM AUTHOR]

To report the 5-year results of chorioretinal atrophy (CRA) progression in patients with punctate inner choroidopathy (PIC) or multifocal choroiditis (MFC). A retrospective study included PIC/MFC patients with secondary CRA formation. The area of CRA was measured and the progression rate was calculated. Multiple regression analysis was performed to investigate risk factors associated with CRA progression. Forty-five eyes of 36 patients were included. The mean CRA size significantly increased after an average of 4.83 years of follow-up with progression rate of 0.69 mm2/year. Moreover, we had identified the axial length and initial PIC lesion number as significant risk factors for CRA progression. Significant CRA enlargement is noted in PIC/MFC patients after 5 years of follow-up. The progression rate is associated with axial length and initial PIC numbers. Aggressive treatment is suggested for eyes with more initial lesion numbers and longer axial length to control the faster CRA progression. [ABSTRACT FROM AUTHOR]

Purpose: To report the long-term prognosis of punctate inner choroidopathy (PIC) or multifocal choroiditis (MFC) and associated zonal outer retinopathy (ZOR).Method: Retrospective study in patients with PIC/MFC and ZOR with a clinical follow-up of 4 years or longer.Results: There were 14 patients in this study (M: F = 11:3). All patients received systemic steroid therapy. The initial and final median logarithm of minimal angle of resolution of BCVA were 1.00 and 0.22 (p = .002). Ellipsoid zone recovery was noted in all patients. The median visual field loss improved from -6.38 dB to -3.41 dB (p = .035). The median of total area of PIC/MFC lesions enlarged from 6.82 mm2 to 8.77 mm2 (p = .005). Recurrent disease was noted in 4 eyes and maintenance steroid was needed in 3 eyes.Conclusion: With steroid therapy, most patients with PIC/MFC and ZOR had good visual prognosis. [ABSTRACT FROM AUTHOR]

Background: A significant portion of COVID-19 sufferers have asthma. The impacts of asthma on COVID-19 progression are still unclear but a modifying effect is plausible as respiratory viruses are acknowledged to be an important trigger for asthma exacerbations and a different, potentially type-2 biased, immune response might occur. In this study, we compared the blood circulating cytokine response to COVID-19 infection in patients with and without asthma. Methods: Plasma samples and clinical information were collected from 80 patients with mild (25), severe (36) or critical (19) COVID-19 and 29 healthy subjects at the John Radcliffe Hospital, Oxford, UK. The concentrations of 51 circulating proteins in the plasma samples were measured with Luminex and compared between groups. Results: Total 16 pre-existing asthma patients were found (3 in mild, 10 in severe, and 3 in critical COVID-19). The prevalence of asthma in COVID-19 severity groups did not suggest a clear correlation between asthma and COVID-19 severity. Within the same COVID-19 severity group, no differences were observed between patients with or without asthma on oxygen saturation, CRP, neutrophil counts, and length of hospital stay. The mortality in the COVID-19 patients with asthma (12.5%) was not higher than that in patients without asthma (17.2%). No significant difference was found between asthmatic and non-asthmatic in circulating cytokine response in different COVID-19 severity groups, including the cytokines strongly implicated in COVID-19 such as CXCL10, IL-6, CCL2, and IL-8. Conclusions: Pre-existing asthma was not associated with an enhanced cytokine response after COVID-19 infection, disease severity or mortality. [ABSTRACT FROM AUTHOR]

To assess the 3-year outcome of half-dose verteporfin photodynamic therapy (PDT) in central serous chorioretinopathy (CSC) with optical coherence tomography angiography (OCT-A) detected choroidal neovascularization (CNV), we performed a retrospective, interventional study. Patients were divided into 2 groups according to the fluorescein angiography: point source leakage in group 1 and diffuse oozing in group 2. Data were collected from patients including changes of best-corrected visual acuity (BCVA), size of CNV, central macular thickness (CMT), choroidal thickness (CT), reabsorption of subretinal fluid (SRF), sessions of half-dose PDT, and the number of intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF). There was a total of 34 eyes in 32 patients included. The mean sessions of half-dose PDT was 1.50 ± 0.75. The mean number of IVI of anti-VEGF was 1.38 ± 3.34. BCVA improved from 0.38 ± 0.33 to 0.20 ± 0.22 (p < 0.001). Mean CMT was significantly reduced along with reduced CT and increased size of CNV. SRF was totally reabsorbed in 31 eyes. Patients in group 1 had significant less sessions of PDT and better final BCVA. In conclusion, half-dose PDT treatment was effective for CSC with CNV. Patients with diffuse oozing in FA may fare less well with half-dose PDT. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs control gene expression by post-transcriptional inhibition. Dysregulation of the expressions of miR-199a/214 cluster has been linked to cardiovascular diseases. This study aimed at identifying potential microRNAs related to vascular senescence. Methods: Seven candidate microRNAs (miR-19a, −20a, −26b, −106b, − 126, − 214, and − 374) related to cell proliferation were tested for their expressions under CoCl2-induced hypoxia in vascular smooth muscle cells (VSMCs). After identification of miR-214 as the candidate microRNA, telomere integrity impairment and cell cycle arrest were examined in VSMCs by using miR-214 mimic, AntagomiR, and negative controls. To investigate the clinical significance of miR-214 in vascular diseases, its plasma level from patients with carotid artery stenosis (CAS) was assessed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Results: CoCl2 treatment for 48 h suppressed cell proliferation and angiogenesis as well as enhanced cell senescence in VSMCs. Besides, miR-214 level was elevated in both intracellular and exosome samples of VSMCs after CoCl2 treatment. Manipulating miR-214 in VSMCs demonstrated that miR-214 not only inhibited angiogenic and proliferative capacities but also promoted senescence through the suppression of quaking. Additionally, circulating miR-214 level was upregulated in CAS patients with high low-density lipoprotein cholesterol (LDL-C) value. Conclusion: Our findings suggested that miR-214 plays a role in the modulation of VSMC angiogenesis, proliferation, and senescence with its plasma level being increased in CAS patients with elevated LDL-C value, implying that it may be a vascular senescence marker and a potential therapeutic target for vascular diseases. [ABSTRACT FROM AUTHOR]

Innate lymphocyte populations are emerging as key effectors in tissue homeostasis, microbial defense, and inflammatory skin disease. The cells are evolutionarily ancient and carry conserved principles of function, which can be achieved through shared or unique specific mechanisms. Recent technological and treatment advances have provided insight into heterogeneity within and between individuals and species. Similar pathways can extend through to adaptive lymphocytes, which softens the margins with innate lymphocyte populations and allows investigation of nonredundant pathways of immunity and inflammation that might be amenable to therapeutic intervention. Here, we review advances in understanding of innate lymphocyte biology with a focus on skin disease and the roles of commensal and pathogen responses and tissue homeostasis. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the long-term outcome of active choroidal neovascularization (CNV) in punctate inner choroidopathy (PIC) or multifocal choroiditis (MFC) after intravitreal bevacizumab treatment.Methods: Retrospective study of consecutive patients of PIC/MFC complicated with active CNV. Outcome measures included best-corrected visual acuity (BCVA), total number of intravitreal injections of bevacizumab and recurrence of CNV. Correlation analysis was performed to find the correlation of various clinical factors and final BCVA.Results: There were 23 eyes in 22 patients with a mean age of 33.22 years included in this study. The mean duration of follow-up was 6.48 years. Improvement of BCVA was noted through the first 3 years and at the final follow-up. BCVA at 1, 6, 12 months and recurrence of CNV were correlated with final BCVA.Conclusion: Most patients of PIC/MFC complicated with CNV managed with intravitreal bevacizumab had improved BCVA over 4 years. [ABSTRACT FROM AUTHOR]

Three essential criteria are important for social activity planning: (1) finding attendees familiar with the initiator, (2) ensuring most attendees have tight social relations with each other, and (3) selecting an activity period available to all. In this paper, we propose the Social-Temporal Group Query (STGQ) to find suitable time and attendees with minimum total social distance. We first prove that the problem is NP-hard and inapproximable within any ratio. Next, we design two algorithms, SGSelect and STGSelect, which include effective pruning techniques to substantially reduce running time. Moreover, as users may iteratively adjust query parameters to fine tune the results, we study the problem of Subsequent Social Group Query (SSGQ). We propose the Accumulative Search Tree and Social Boundary, to cache and index intermediate results of previous queries in order to accelerate subsequent query processing. Experimental results indicate that SGSelect and STGSelect are significantly more efficient than baseline approaches. With the caching mechanisms, processing time of subsequent queries can be further reduced by 50-75 percent. We conduct a user study to compare the proposed approach with manual activity coordination. The results show that our approach obtains higher quality solutions with lower coordination effort, thereby increasing the users’ willingness to organize activities. [ABSTRACT FROM AUTHOR]

This article presents LightPainter, an interactive tool that promotes creative long-exposure photography through an intuitive drawing metaphor and flexible spatiotemporal mapping from videos to composite images. We discuss the power of software-defined exposure and the tools capability to facilitate creating sophisticated long-exposure effects in challenging scenarios. [ABSTRACT FROM AUTHOR]

Strain TTM-94T, isolated from a water sample taken from the Caohu River in Taiwan, was characterized using a polyphasic taxonomic approach. Cells of strain TTM-94T were Gram-staining-negative, aerobic, poly-β-hydroxybutyrate-accumulating, motile by a single polar flagellum, short rod-shaped and surrounded by a thick capsule and it formed cream colored colonies. Growth occurred at 20-30 °C (optimum, 30 °C), at pH 6.0-8.0 (optimum, pH 6.0), and in the presence of 0-2% NaCl (optimum 0.5%). Phylogenetic analyses based on 16S rRNA gene sequences showed that strain TTM-94T belonged to the genus Aquincola in the Rubrivivax-Roseateles-Leptothrix-Ideonella-Aquabacterium branch of the class Betaproteobacteria and its most closely related neighbour was Aquincola tertiaricarbonis L10T with sequence similarity of 97.0%. Strain TTM-94T contained summed feature 3 (comprising C16:1ω7c and/or C16:1ω6c), C16:0 and C18:1ω7c as the predominant fatty acids. The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and several uncharacterized lipids. The major respiratory quinone was Q-8. Genomic DNA G + C content of strain TTM-94T was 70.7 mol%. Strain TTM-94T exhibited less than 30% DNA-DNA relatedness with A. tertiaricarbonis L10T. Differential phenotypic properties, together with the phylogenetic inference, demonstrate that strain TTM-94T should be classified as a novel species of the genus Aquincola, for which the name Aquincola amnicola sp. nov. is presented. The type strain is TTM-94T (= BCRC 80890T = LMG 28709T). [ABSTRACT FROM AUTHOR]

Rubisco-based engineered Escherichia coli MZLFB ( E. coli BL21(DE3) Δ zwf , Δ ldh , Δ frd ) containing heterologous phosphoribulokinase (Prk) and Ribulose-1,5- bisphosphate carboxylase/oxygenase (Rubisco) was constructed for the mixotrophic growth. However, in situ CO 2 recycling was hindered by clogs of pyruvate during glucose metabolism, which consequently resulted in an insufficient regeneration of NAD + through the pflB -mediated ethanol production. Recombinant plasmid pLOI295 (encodes pyruvate decarboxylase and alcohol dehydrogenase II, referred to as the Pdc-based carbon tap valve (CTV) for convenience) was introduced into E. coli MZLFB + CTV to bypass the pflB -mediated ethanol production. Results show that while the C-2/C-1 ratio ( i.e., the molar ratio of ethanol and acetate to formate and total CO 2 ) for parental strain MZLFB was 1.0 ± 0.1, the C-2/C-1 for MZLFB + CTV increased to 1.6 ± 0.1. This indicates that the Pdc-based CTV enhanced the performance of in situ CO 2 recycling. By simultaneously utilizing glucose and CO 2 , the fermentation product yield of MZLFB + CTV exceeded the normal theoretical yield and reached 2.2 ± 0.0 (mol/mol). In silico analysis shows that 61% of the glucose consumption went through the Rubisco-based engineered pathway when the CTV was equipped. Also shown are the average CO 2 consumption rate of 55.3 mg L −1 ·h −1 and an average ethanol production rate of 144.8 mg L −1 ·h −1 . The conversion of CO 2 to ethanol through the Rubisco-based engineered pathway and the Pdc-based carbon tap valve is important for mixotrophic growth, since these two modules serve as the energy sink to achieve intracellular energy balance. Also, during mixotrophic growth, ATP production from a certain percentage (39% in this study) of the EMP pathway activity is needed for mixotrophic growth. [ABSTRACT FROM AUTHOR]

Advances in experimental and computational techniques allow us to study the structure and dynamics of large biomolecular assemblies at increasingly higher resolution. However, with increasing structural detail it can be challenging to unravel the mechanism underlying the function of molecular machines. One reason is that atomistic simulations become computationally prohibitive. Moreover it is difficult to rationalize the functional mechanism of systems composed of tens of thousands to millions of atoms by following each atom’s movements. Coarse graining (CG) allows us to understand biological structures from a hierarchical perspective and to gradually zoom into the adequate level of structural detail. This article introduces a Bayesian approach for coarse graining biomolecular structures. We develop a probabilistic model that aims to represent the shape of an experimental structure as a cloud of bead particles. The particles interact via a pairwise potential whose parameters are estimated along with the bead positions and the CG mapping between atoms and beads. Our model can also be applied to density maps obtained by cryo-electron microscopy. We illustrate our approach on various test systems. [ABSTRACT FROM AUTHOR]

We report a general copper-catalyzed cross-coupling of thiols with aryl halides by using N-aryl- N′-alkyl oxalic diamide ( L3) or N, N′-dialkyl oxalic diamide ( L5) as the ligand. Both aryl and alkyl thiols can be coupled with unactivated aryl bromides and chlorides to give the desired products in good yields. Furthermore, this system features a broad substrate scope and good tolerance of functional groups. Importantly, the oxalic diamides are stable and can be prepared easily from commercially available and cheap starting materials. [ABSTRACT FROM AUTHOR]

Both copper (Cu) and silver (Ag) have been studied extensively for electrical conductor applications. To expand the applications, two bonding designs were implemented in this paper. For the first design, a 50- \mu \textm Ag layer was annealed at 400 °C to increase Ag grain size, thereby making it more ductile. For the second design, a 5- \mu \textm Ag layer with cavities was created to release the thermal induced stress and allow easier plastic deformation for the bonding medium. For both designs, the resulting Cu substrates were bonded to Cu chips by the solid-state bonding process. The cross sections of bonded samples show no visible voids or gaps on Cu/Ag and Ag/Cu interfaces. The breaking forces of ten samples tested far exceed the requirement specified in the military standards MIL-STD-883J Method 2019.9. The successful demonstrations of solid-state bonding between Ag and Cu should open the possibility of bringing alternatives for bonding methods in the field of electronic packaging. [ABSTRACT FROM PUBLISHER]

The total bilirubin value of a male infant was 385 μmol/l on day 5. Liver function test results were normal and there was no evidence of sepsis and no hemolysis reaction. Phototherapy was administered and on day 8 the patient's total bilirubin level was 255 μmol/l. Intermittent episodes of hyperbilirubinemia occurred without phototherapy, with the total bilirubin level reaching 335 μmol/l on day 19. A 3-day regimen of phenobarbital was administered and on day 24 his total bilirubin level was 180 μmol/l. The patient was discharged. At the age of 2 months, the total bilirubin value was 27 μmol/l. His direct bilirubin value was <15% of total bilirubin in every determination. A family study of the UDP-glu-curonosyltransferase ( UGT ) 1A1 gene showed that the infant carries a homozygous mutation at nucleotide -3279 plus compound heterozygous mutations at nucleotides 782 and 1091. The mutation at nucleotide 782 is a novel finding. Gilbert's syndrome was diagnosed. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs), including conventional DCs (cDCs) and plasmacytoid DCs (pDCs) are critical for initiating and controlling the immune response. However, study of DC, particularly pDC, function is hampered by their low frequency in lymphoid organs, and existing methods for in vitro DC generation preferentially favor the production of cDCs over pDCs. Here, we demonstrated that pDCs could be efficiently generated in vitro from common lymphoid progenitors (CLPs) using Flt3 ligand (FL) in three different culture systems, namely feeder-free, BM-feeder and AC-6-feeder. This was in stark contrast to common DC progenitors (CDPs), in which cDCs were prominently generated under the same conditions. Moreover, the efficiency and function of pDCs generated from these three systems varied. While AC-6 system showed the greatest ability to support pDC development from CLPs, BM-feeder system was able to develop pDCs with better functionality. pDCs could also be expanded in vivo using hydrodynamic gene transfer of FL, which was further enhanced by the combined treatment of FL and IFN-α. Interestingly, IFN-α selectively promoted the proliferation of CLPs and not CDPs, which might contribute to enhanced pDC development. Together, we have defined conditions for in vitro and in vivo generation of pDCs, which may be useful for investigating the biology of pDCs. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the association of cigarette smoking with semen quality and reproductive hormone levels in 192 healthy men 20–65 years old, Kaohsiung, Taiwan. Exposure to cigarette smoking was classified three ways based on: 1) smoking status (yes vs. no); 2) the number of cigarettes per day (0, 1–10, > 10); and 3) pack-years (0, 1–10, 11–20, > 20). Serum levels of total testosterone (TT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and total estradiol (TE) were measured. Semen quality, including concentration, motility, vitality, and morphology, were assessed. Mean levels of smoking, semen quality, and hormones were compared using the multiple linear regression, while controlling for possible confounding factors, including age, body mass index (BMI), cadmium levels in seminal plasma, and alcohol consumption. Current smokers, who smoked 10 cigarettes per day, had a lower mean percentage of normal morphology (3.2% and 5.5% in nonsmokers,P= 0.040), and a higher mean level of TT (454.7 pmol/L and 439.8 pmol/L in nonsmokers,P= 0.048), as compared with nonsmokers. Also, current smokers at > 20 pack-year had a lower percentage of normal morphology and a lower mean level of TT as compared with nonsmokers; no significant difference was observed in LH, FSH, sperm concentration, vitality, and motility between smokers and nonsmokers based on the number of cigarette per day and the pack-year. Sperm vitality statistically correlated with FSH (β = −0.36P= 0.015) and TE (β = 0.35,P= 0.018), while motility statistically correlated with TT (β = 0.228,P= 0.045). Normal morphology did not statistically correlated with all reproductive hormones. [ABSTRACT FROM AUTHOR]

The objective of this article was to assess whether benzo(a)pyrene (B[a]P) alters reproductive hormones, which in turn leads to decreased spermatozoa quality and spermatogenic cell levels. Hsd: ICR (CD1) 10-week old males were orally exposed to B[a]P at 1, 10, 50, and 100 mg/kg/day of body weight for 30 and 60 days. At the end of the experiment, mice were anesthetized and reproductive tissues, i.e., testes, seminal vesicles, and epididymis, were collected. Spermatogenic cells and mature spermatozoa were recovered from the testes and cauda epididymis, respectively. Spermatozoa quality, including concentration, morphology, motility, and viability, was examined. Testosterone, estradiol, follicle stimulating hormone (FSH), and luteinizing hormone (LH) levels in serum were determined using the Enzyme Immunoassay/Enzyme Linked Immunosorbent Assay (EIA/ELISA). Mice exposed to B[a]P at 50 mg/kg/day and 100 mg/kg/day for 30 days and 60 days exhibited a significantly decrease in serum testosterone and estradiol levels as compared with the control, while FSH and LH remained stable. The levels of testosterone and estradiol were positively correlated with decreased spermatozoa motility (p = 0.025 and 0.014, respectively), viability (p = 0.002 and 0.018, respectively), and morphology (p = 0.007 and 0.018, respectively), but the hormone levels did not correlate with spermatozoa levels. The testosterone and estradiol levels did not correlate with the levels of spermatogonia, pachytene spermatocytes, round spermatids, and elongated spermatids. Subchronic exposure to B[a]P could modulate the production of testosterone and estradiol, which subsequently influence spermatozoa quality. [ABSTRACT FROM PUBLISHER]

Background: Fungal empyema is an uncommon disease and is associated with a high mortality rate. Surgical intervention is suggested in stage II and III empyema. However, there were no studies that reported the outcomes of surgery for fungal empyema. Methods: This study is a retrospective analysis in a single institute. Patients with empyema thoracis who underwent thoracoscopic decortication between January 2012 and December 2021 were included in the study. We separated the patients into a fungal empyema group and a bacterial empyema group according to culture results. We used 1:3 propensity score matching to reduce selection bias. Results: There were 1197 empyema patients who received surgery. Of these, 575 patients showed positive culture results and were enrolled. Twenty-eight patients were allocated to the fungal empyema group, and the other 547 patients were placed in the bacterial empyema group. Fungal empyema showed significantly longer intensive care unit stay (16 days vs. 3 days, p = 0.002), longer median ventilator usage duration (20.5 days vs. 3 days, p = 0.002), longer hospital stay duration (40 days vs. 17.5 days, p < 0.001) and a higher 30-day mortality rate (21.4% vs. 5.9%, p < 0.001). Fungal empyema revealed significantly poorer 1-year survival rate than bacterial empyema before matching (p < 0.001) but without significant difference after matching. Conclusions: The fungal empyema patients had much worse surgical outcomes than the bacterial empyema patients. Advanced age and high Charlson Comorbidity Index score are independent predictors for poor prognosis. Prompt surgical intervention combined with the use of antifungal agents was the treatment choice for fungal empyema. [ABSTRACT FROM AUTHOR]

While tendons typically undergo primary tensile loading, the human supraspinatus tendon (SST) experiences substantial amounts of tension, compression, and shear in vivo. As a result, the functional roles of the extracellular matrix components, in particular the proteoglycans (PGs), are likely complex and important. The goal of this study was to determine the PG content in specific regions of the SST that exhibit differing mechanical function. The concentration of aggrecan, biglycan, and decorin was determined in six regions of the human SST using immunochemical techniques. We hypothesized that aggrecan concentrations would be highest in areas where the tendon likely experiences compression; biglycan levels would be highest in regions likely subjected to injury and/or active remodeling such as the anterior regions; decorin concentrations would be highest in regions of greatest tensile stiffness. Our results generally supported these hypotheses and demonstrated that aggrecan and biglycan share regional variability, with increased concentration in the anterior and posterior regions and smaller concentration in the medial regions. Decorin, however, was in high concentration throughout all regions. The data presented in this study represent the first regional measurements of PG in the SST. Together with our previous regional measurements of mechanical properties, these data can be used to evaluate SST structure-function relationships. With knowledge of the differences in specific PG content, their spatial variations in the SST, and their relationships to tendon mechanics, we can begin to associate defects in PG content with specific pathology, which may provide guidance for new therapeutic interventions. [ABSTRACT FROM AUTHOR]

Abstract: Hybrid films of pentacene and aluminum nanoparticles were prepared by depositing pentacene on a SiO2 surface decorated with aluminum nanoparticles and used as the active channel materials in a thin film transistor. Surface pre-treatment of the aluminum nanoparticles with oxygen plasma and/or organophosphonic acids render the particles surface with different coatings and work functions, which affect the charge trapping/storing ability of the nanoparticles. This in turn results in an electric bistability of the pentacene film-based transistor/memory devices. Correlations of memory window, switching response, and memory retention characteristics with the aluminum nanoparticle surface treatment are provided. [Copyright &y& Elsevier]

Abstract: The objective was to investigate the upstream apoptotic mechanisms that were triggered by a styrylpyrone derivative, goniothalamin (GTN), in tumor protein p53 (TP53)-positive and -negative hepatocellular carcinoma (HCC)-derived cells. Effects of GTN were evaluated by the flow cytometry, alkaline comet assay, immunocytochemistry, small-hairpin RNA interference, mitochondria/cytosol fractionation, quantitative reverse transcription-polymerase chain reaction, immunoblotting analysis and caspase 3 activity assays in two HCC-derived cell lines. Results indicated that GTN triggered phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1, also known as NOXA)-mediated apoptosis via TP53-dependent and -independent pathways. In TP53-positive SK-Hep1 cells, GTN furthermore induced TP53 transcription-dependent and -independent apoptosis. After GTN treatment, accumulation of reactive oxygen species, formation of DNA double-strand breaks, transactivation of TP53 and/or PMAIP1 gene, translocation of TP53 and/or PMAIP1 proteins to mitochondria, release of cytochrome c from mitochondria, cleavage of caspases and induction of apoptosis in both cell lines were sustained. GTN might represent a novel class of anticancer drug that induces apoptosis in HCC-derived cells through PMAIP1 transactivation regardless of the status of TP53 gene. [Copyright &y& Elsevier]

Housing speculation has been a major housing problem and hence a major concern of social movements in Taiwan since the mid-1980s. Although the government has implemented various schemes to slow down housing prices, past policies have not sought to change the fundamental structure of the housing system or its speculative tendencies. Since the late-1980s, a civil movement has been building up behind the issue of affordable rented housing, resisting the tendency towards intensified housing commodification that has served the interests of developers at the expense of the socially vulnerable. In late 2010, the Taiwanese social rented housing movement successfully pressed the passage of a policy supporting five social housing projects, as well as a luxury tax policy on housing. It has not, however, managed to change the more significant land tax system and the strong coalition between the state and private developers. There remain many struggles ahead in terms of reversing the trend toward privatisation and in advancing the cause of socialising housing. This paper assesses the struggle and recent successes of the Taiwanese housing movements in context of the speculative market booms that have characterised the housing sector for nearly three decades. [ABSTRACT FROM PUBLISHER]

In this paper, we present an orientation inference framework for reconstructing implicit surfaces from unoriented point clouds. The proposed method starts from building a surface approximation hierarchy comprising of a set of unoriented local surfaces, which are represented as a weighted combination of radial basis functions. We formulate the determination of the globally consistent orientation as a graph optimization problem by treating the local implicit patches as nodes. An energy function is defined to penalize inconsistent orientation changes by checking the sign consistency between neighboring local surfaces. An optimal labeling of the graph nodes indicating the orientation of each local surface can, thus, be obtained by minimizing the total energy defined on the graph. The local inference results are propagated over the model in a front-propagation fashion to obtain the global solution. The reconstructed surfaces are consolidated by a simple and effective inspection procedure to locate the erroneously fitted local surfaces. A progressive reconstruction algorithm that iteratively includes more oriented points to improve the fitting accuracy and efficiently updates the RBF coefficients is proposed. We demonstrate the performance of the proposed method by showing the surface reconstruction results on some real-world 3-D data sets with comparison to those by using the previous methods. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that plasma visfatin concentrations will be higher in women with polycystic ovary syndrome (PCOS) than in women without PCOS. Design: Clinical study. Setting: University hospital. Patient(s): A total of 52 women were evaluated. Twenty-six had PCOS, and the remaining 26 were healthy women with regular menstrual cycles who served as control subjects. Intervention(s): Plasma visfatin concentrations were analyzed with the use of RIA. Main Outcome Measure(s): Serum concentrations of FSH, LH, TSH, PRL, T, insulin, E2, and visfatin. Result(s): Plasma visfatin concentrations were significantly higher in the PCOS group (336.8 ± 50.2 ng/mL) than in the healthy control group (282.4 ± 43.3 ng/mL). Logistic regression analysis indicated a significant association between odds ratio (OR) values of PCOS and visfatin levels (OR = 2.81; 95% confidence interval [CI], 2.74–2.90), T (OR = 3.39; 95% CI, 2.85–4.16), and LH levels (OR = 3.49; 95% CI, 2.79–4.56). There was no correlation between plasma visfatin concentrations and T, insulin, and LH levels or age in either the PCOS group or the control group. We observed that plasma visfatin levels were positively correlated with body mass index in the PCOS group (r = 0.396, r 2 = 0.157) but not in the control group (r = −0.328, r 2 = 0.108). Conclusion(s): Our data show that women with PCOS exhibit higher plasma visfatin levels than control subjects of similar body mass index. Further studies are required to clarify the etiology and effects of hypervisfatinemia in women with PCOS. [Copyright &y& Elsevier]

Abstract: Objective: To determine whether there is a correlation between adiponectin levels and glucose levels in women screened for gestational diabetes mellitus by means of a 50-g oral glucose challenge test, and to examine the difference in adiponectin levels between women who tested negative, and those who tested false positive. We further calculated the correlations between adiponectin levels and glucose levels, body mass index, gestational age and maternal age. Methods: A case control study included 171 mothers with negative or false positive results in the 1-h 50-g glucose challenge test at 24–28 gestational weeks. Serum adiponectin levels were determined by radioimmunoassay at the time of the glucose challenge test. Results: There was a significant difference between women who tested negative at screening, and those who tested false positive with respect to age, prepregnancy body weight and body mass index, and adiponectin levels. Correlation analysis showed adiponectin levels to be negatively correlated to glucose levels (r =−0.193, P =0.011). To examine the association between glucose levels, adiponectin levels and demographic variables, multiple linear regression analysis was carried out. Prepregnancy body mass index and age accounted for 14.6% of the variance in the glucose challenge test. Adiponectin levels did not contribute independently to the variation in glucose levels. A further multiple linear regression analysis was undertaken to investigate the association between adiponectin levels and age, prepregnancy body mass index and glucose levels in the glucose challenge test. In this regression model, prepregnancy body mass index and age explained 12.1% of the variance in adiponectin levels. Conclusions: In conclusion, our study indicated a negative correlation between adiponectin and glucose levels in women screened for gestational diabetes mellitus by a glucose challenge test. We further found that maternal age and body mass index were independent risk factors for a false positive glucose challenge test. Reduced adiponectin levels in women who tested false positive on the glucose challenge test were dependent on advanced age and higher body mass index. [Copyright &y& Elsevier]

Objective: To test the hypothesis that plasma visfatin concentrations will be lower in women with gestational diabetes mellitus, we evaluated women with gestational diabetes mellitus and healthy pregnant women, and then correlated their plasma visfatin concentrations with body mass index (BMI) and various other parameters. Methods: A total of 40 women were evaluated: 20 women with gestational diabetes mellitus and 20 healthy pregnant women to serve as control subjects. Plasma visfatin concentrations were analyzed using an enzyme-linked immunosorbent assay. Results: Plasma visfatin concentrations were significantly lower in the gestational diabetes mellitus group (9.4 ± 3.8 ng/mL) than in the healthy control group (12.6 ± 4.5 ng/mL) (P = .023). A negative correlation was found between plasma visfatin concentrations and maternal age (r = −0.399, P = .011), first trimester body weight (r = −0.350, P = .027), and first trimester BMI (r = −0.336, P = .034). Multiple linear regression analysis revealed that maternal age (P = .017) and gestational diabetes mellitus/no gestational diabetes mellitus (P = .044) were independently related to plasma visfatin concentrations. However, no relationship was found with either gestational age at the time of sampling or first trimester BMI. Conclusions: Our results show that there are decreased concentrations of plasma visfatin in gestational diabetes mellitus subjects and this may indicate that visfatin plays a role in the pathogenesis of gestational diabetes mellitus. However, further experiments are needed to clarify this role. [Copyright &y& Elsevier]

The CD3+/TCRαβ+ T-cell-mediated hepatic inflammation induced by Propionibacterium acnes could be divided into an acute and a chronic phase. The acute phase occurred within 72 h after injection and displayed hepatic apoptosis. Anti-TNFα antibody inhibited both the P. acnes-induced hepatic apoptosis and lymphocyte infiltration seen in this phase, indicating the involvement of this cytokine. Thereafter, a chronic phase was manifested from days 7 to 14 after injection. It was characterized as granulomatous inflammation admixed with apoptosis of infiltrating lymphocytes and some hepatocytes. Immunohistochemical staining showed that the infiltrating lymphocytes displayed TNFα, TNF type I receptor and a variety of cytokines including IL-1β, IL-4, IL-6, IL-10, IFNγ or IL-12. Interestingly, in naive mice, the arteries in the liver constitutively expressed IFNγ. Its expression appeared to be substantially increased at 48 h, decreased at 72 h, and increased again on day 14 after P. acnes injection. Furthermore, Fas or FasL was only detected on the lymphocytes within the granuloma. We conclude that P. acnes can induce a TNFα-mediated acute hepatic apoptosis which subsequently progress to a T-cell-mediated granulomatous hepatitis with increased expression of multiple cytokines and Fas/FasL. [ABSTRACT FROM AUTHOR]

Background: This study tested the hypothesis that inflammatory and interleukin (IL)-17 signalings were essential for acute liver ischemia (1 h)-reperfusion (72 h) injury (IRI) that was effectively ameliorated by adipose-derived mesenchymal stem cells (ADMSCs) and tacrolimus. Methods: Adult-male SD rats (n = 50) were equally categorized into groups 1 (sham-operated-control), 2 (IRI), 3 [IRI + IL-17-monoclonic antibody (Ab)], 4 (IRI + tacrolimus), 5 (IRI + ADMSCs) and 6 (IRI + tacrolimus-ADMSCs) and liver was harvested at 72 h. Results: The main findings included: (1) circulatory levels: inflammatory cells, immune cells, and proinflammatory cytokines as well as liver-damage enzyme at the time point of 72 h were highest in group 2, lowest in group 1 and significantly lower in group 6 than in groups 3 to 5 (all p < 0.0001), but they did not differ among these three latter groups; (2) histopathology: the liver injury score, fibrosis, inflammatory and immune cell infiltration in liver immunity displayed an identical pattern of inflammatory cells among the groups (all p < 0.0001); and (3) protein levels: upstream and downstream inflammatory signalings, oxidative-stress, apoptotic and mitochondrial-damaged biomarkers exhibited an identical pattern of inflammatory cells among the groups (all p < 0.0001). Conclusion: Our results obtained from circulatory, pathology and molecular-cellular levels delineated that acute IRI was an intricate syndrome that elicited complex upstream and downstream inflammatory and immune signalings to damage liver parenchyma that greatly suppressed by combined tacrolimus and ADMSCs therapy. [ABSTRACT FROM AUTHOR]

Background: We tested the hypothesis that extracorporeal shockwave treatment (ESWT) can abolish inflammation and restore urothelial barrier integrity in acute interstitial cystitis by upregulating the fatty acid receptor GPR120. Methods: A total of 30 female Sprague-Dawley rats were categorized into five groups: (1) sham-operated rats (SC); (2) rats treated with ESWT (SC + ESWT); (3) rats with bladder irritation using 150 mg/kg cyclophosphamide through intraperitoneal injection; (4) cyclophosphamide rats treated with ESWT (cyclophosphamide+ESWT); (5) cyclophosphamide rats treated with GPR120 agonist (cyclophosphamide+GW9508). Results: On Day 3, urine and bladder specimens were collected for biochemical, histopathological, immunological, and immunoblotting analysis. Following stimulation with cyclophosphamide, the inhibition of the elevated levels of TAK1/NF-κB and phospho-TAK1/NF-κB by ESWT and GPR120 agonists in RT4 cells was associated with a suppression of NF-κB translocation from the cytosol to the nucleus. Accordingly, this anti-inflammatory effect was abolished by GPR120 antagonist and knockdown of GPR120. Histologically, bladder inflammation in cyclophosphamide-treated rats was suppressed by GW9508 or ESWT. Masson's trichrome and Sirius red staining revealed that cyclophosphamide treatment enhanced synthesis of extracellular matrix in rats that was reversed by GW9508 or ESWT. Upregulated pro-inflammatory mediators and cytokines in the cyclophosphamide-treated rats were also suppressed in the GW9508- or ESWT-treated rats. The significantly increased inflammatory cell infiltration as well as the impaired urothelial integrity of the bladder after cyclophosphamide treatment were reversed by treatment with GW9508 or ESWT. Conclusions: These findings suggest that GPR120, the sensing receptor for ESWT, may be useful in the treatment of interstitial cystitis by inhibiting inflammatory response in bladder cells. [ABSTRACT FROM AUTHOR]

Simple Summary: We aimed to investigate if VDT could be applied as a predictor of clinical outcome in segmentectomy and wedge resection. We retrospectively studied 96 NSCLC patients post sublobar resection from 2012 to 2018, collecting two chest CT scans preoperatively of each case and calculating VDT. The receiver operating characteristic curve was constructed to identify the optimal cut-off point of VDTs as 133 days. We divided patients into two groups: VDT < 133 days (n = 22) and VDT ≥ 133 days (n = 74). Univariable and multivariable analyses were performed for comparative purposes. Our study demonstrated that the five year OS rates of patients with VDTs ≧ 133 days and VDTs < 133 days, respectively, were 89.9% and 71.9% (p = 0.003), and the five year DFS rates were 95.9% and 61.5% (p = 0.002). Thus, we concluded that VDT can be a powerful prognostic predictor and provides an essential role in planning surgical procedures. Background: Volume doubling time (VDT) has been proven to be a powerful predictor of lung cancer progression. In non-small cell lung cancer patients receiving sublobar resection, the discussion of correlation between VDT and surgery was absent. We proposed to investigate the surgical outcomes according to VDT. Methods: We retrospectively studied 96 cases post sublobar resection from 2012 to 2018, collecting two chest CT scans preoperatively of each case and calculating the VDT. The receiver operating characteristic curve was constructed to identify the optimal cut-off point of VDTs as 133 days. We divided patients into two groups: VDT < 133 days and VDT ≥ 133 days. Univariable and multivariable analyses were performed for comparative purposes. Results: Univariable and multivariable analyses revealed that the consolidation and tumor diameter ratio was the factor of overall survival (OS), and VDT was the only factor of disease-free survival (DFS). The five year OS rates of patients with VDTs ≥ 133 days and VDTs < 133 days, respectively, were 89.9% and 71.9%, and the five year DFS rates were 95.9% and 61.5%. Conclusion: As VDT serves as a powerful prognostic predictor and provides an essential role in planning surgical procedures, the evaluation of VDT preoperatively is highly suggested. [ABSTRACT FROM AUTHOR]

A practical synthetic method for the synthesis of diversified thioethers using oxalic diamides as highly air ‐ stable ligands through copper catalysis is demonstrated. A variety of aryl and alkyl thiols were successfully coupled with aryl bromides and aryl chlorides to afford the corresponding thioethers in good yields. This work is the first copper ‐ catalyzed thioetherification of unactivated aryl chlorides. More information can be found in the Full Paper by C. ‐ F. Lee et al. on page 10087. [ABSTRACT FROM AUTHOR]

Aims: Matching a crop's nitrogen (N) preference with the specific form of N is critical to enhance N recovery efficiency (NRE). Many studies show that maize (Zea mays L.) has a preference for NH4+ uptake over NO3−, but the contribution of this preference to NRE is unclear. This study evaluated the utilization of ammonium (NH4+) and nitrate (NO3−) by maize and its relationship with NRE. Methods: Maize (cv. 'Zhengdan 958') seedlings were grown in a soil culture experiment with 15NH4+ or 15NO3− applied to sterilized or non-sterilized soils, and in a hydroponic experiment supplied with NH4+ or NO3−. We recorded maize root and shoot growth and N uptake, and the distribution of 15N-labeled N in the soil–plant system. Results: Ammonium application enhanced maize root and shoot growth and N uptake compared with those of NO3−-treated plants in both culture systems. This enhancement by NH4+ was further promoted in sterilized soil. More applied N remained in soil supplied with NO3− than with NH4+ after seedling harvest. The NRE of NH4+ in maize was significantly higher than that of NO3−, while a similar proportion of applied N was lost with NH4+ or NO3−supply. Conclusions: Ammonium supply enhances maize growth and NRE compared with NO3− under the present experimental condition, which may be attributable to the superior capability of maize to utilize NH4+. [ABSTRACT FROM AUTHOR]

Background. This study was aimed at testing the association between the therapeutic efficacy of CD34+ cell treatment in patients with end-stage diffuse coronary artery disease as reflected in angiographic grading and results of directed in vivo angiogenesis assay (DIVAA) on their isolated peripheral blood mononuclear cell- (PBMC-) derived endothelial progenitor cells (EPCs). Methods. Angiographic grades (0: <5%; 1: 5–35%; 2: 35–75%; 3: >75%) which presented the improvement of vessel density pre- and post-CD34+ treatment were given to 30 patients with end-stage diffuse coronary artery disease having received CD34+ cell treatment. The patients were categorized into low-score group (angiographic grade 0 or 1, n=12) and high-score group (angiographic grade 2 or 3, n=18). The percentages of circulating EPCs with KDR+/CD34+/CD45−, CD133+/CD34+/CD45−, and CD34+ were determined in each patient using flow cytometry. PBMC-derived EPCs from all patients were subjected to DIVAA through a 14-day implantation in nude mice. The DIVAA ratio (i.e., mean fluorescent units in angioreactors with EPCs/mean fluorescent units in angioreactors without EPCs) was obtained for each animal with implanted EPCs from each patient. Results and Conclusions. The number of EPCs showed no significant difference among the two groups. The DIVAA ratio in the high-score group was significantly higher than that in the low-score group (p=0.0178). Logistic regression revealed a significant association between the DIVAA ratio and angiographic grading (OR 3.12, 95% CI: 1.14–8.55, p=0.027). The area under the ROC curve (AUC) was 0.8519 (p=0.0013). We proposed that DIVAA may be a reliable tool for assessing coronary vascularization after CD34+ cell treatment. [ABSTRACT FROM AUTHOR]

Elevations in C-reactive protein (CRP) levels are positively correlated with the progress of type 2 diabetes mellitus. However, the effect of CRP on pancreatic insulin secretion is unknown. Here, we showed that purified human CRP impaired insulin secretion in isolated mouse islets and NIT-1 insulin-secreting cells in dose- and time-dependent manners. CRP increased NADPH oxidase-mediated ROS (reactive oxygen species) production, which simultaneously promoted the production of nitrotyrosine (an indicator of RNS, reactive nitrogen species) and TNFα, to diminish cell viability, insulin secretion in islets and insulin-secreting cells. These CRP-mediated detrimental effects on cell viability and insulin secretion were significantly reversed by adding NAC (a potent antioxidant), apocynin (a selective NADPH oxidase inhibitor), L-NAME (a non-selective nitric oxide synthase (NOS) inhibitor), aminoguanidine (a selective iNOS inhibitor), PDTC (a selective NFκB inhibitor) or Enbrel (an anti-TNFα fusion protein). However, CRP-induced ROS production failed to change after adding L-NAME, aminoguanidine or PDTC. In isolated islets and NIT-1 cells, the elevated nitrotyrosine contents by CRP pretreatment were significantly suppressed by adding L-NAME but not PDTC. Conversely, CRP-induced increases in TNF-α production were significantly reversed by administration of PDTC but not L-NAME. In addition, wild-type mice treated with purified human CRP showed significant decreases in the insulin secretion index (HOMA-β cells) and the insulin stimulation index in isolated islets that were reversed by the addition of L-NAME, aminoguanidine or NAC. It is suggested that CRP-activated NADPH-oxidase redox signaling triggers iNOS-mediated RNS and NFκB-mediated proinflammatory cytokine production to cause β cell damage in state of inflammation. [ABSTRACT FROM AUTHOR]

Background: Assessing the prognosis preoperatively in patients with upper tract urothelial carcinoma (UTUC) remains a challenge for urologists. Gross hematuria (GH) and flank pain (FP) are the 2 most common and easily perceived symptoms of UTUC. Therefore, we aimed to investigate the prognostic values of GH and FP in patients with UTUC after undergoing radical nephroureterectomy (RNU). Methods: This article retrospectively analyzed 179 patients with UTUC who underwent RNU and examined the associations between the FP, GH, and long-term survival. After dividing patients into 4 subgroups (presenting as GH without FP, FP without GH, no FP and GH, FP with GH), we focused on the prognostic values of the 4 subgroups using univariate and multivariate analyses. We then proposed a risk stratification model for UTUC based on the independent prognostic factors for cancer-specific survival (CSS) with external validation (146 additional UTUC patients formed the validation cohort). Results: Patients with FP had worse oncological outcomes than those without FP (P <.05). After dividing the 179 patients into 4 subgroups, the "FP without GH" subgroup suffered the worst oncological outcomes (P <.001). The Cox multivariate regression analysis showed that "FP without GH" (P <.001), tumor multifocality (P =.005), and pathological stage (P =.004) were independent prognostic factors for CSS. Good performance of the risk stratification model was achieved in both the training and external validation cohorts. Conclusion: The presence of "flank pain without gross hematuria" was one of the independent risk factors of CSS and OS besides the pathological stage and tumor multifocality. To our knowledge, this is the first study that adding complaint to risk stratification model in UTUC. [ABSTRACT FROM AUTHOR]

Plasmacytoid dendritic cells (pDCs) are the most potent type I interferon (IFN-I) producing cells during infections and inflammation. While cDCs can be generated from either myeloid or lymphoid lineages, the developmental origin and signals controlling pDC development remain elusive. Here, we report a synergistic role for IFN-I and Flt3 ligand (FL) in pDC development from common lymphoid progenitors (CLPs). Both conventional DCs (cDCs) and pDCs were generated from CLPs in response to FL, while pDC generation required higher concentrations of FL and concurrent IFN-I signaling. An absence of IFN-I receptor or impairment of IFN-I signaling significantly impeded pDC development from CLPs. Competitive adoptive transfer showed that the defective pDC development was intrinsic to the loss of IFN-I signaling in CLPs. Interestingly, Flt3 expression was reduced in Ifnar1 −/− CLPs as opposed to WT CLPs. Concomitantly, FL-activated signaling, proliferation and survival of CLPs were attenuated in the absence of IFNAR1. Restoration of Flt3 expression in Ifnar1 −/− CLPs rescued pDC development. FL also enhanced Flt3 expression on CLPs in an IFN-I-dependent manner. Furthermore, FL induced IFN-I production in CLPs. While exogenous IFN-I augmented pDC generation, neutralization of IFNAR1 blocked pDC formation from WT CLPs. The dose-dependent effect of FL on DC homeostasis supports the instructive model, at least, for CLPs. Collectively; these results define a critical role for the FL/IFN-I/Flt3 axis in pDC differentiation from CLPs and identify a potential target for therapeutic intervention in inflammatory and autoimmune diseases associated with pDCs. [ABSTRACT FROM AUTHOR]

This study investigated the hypothesis that probiotics enhanced the therapeutic effect of adipose-derived mesenchymal stem cells (ADMSCs) on alleviating neuropathic pain (NP) due to chronic constriction injury (CCI) mainly through regulating the microbiota in rats. SD rats (n = 50) were categorized into group 1 (sham-control), group 2 (NP), group 3 (NP + probiotics (i.e., 1.5 billion C.F.U./day/rat, orally 3 h after NP procedure, followed by QOD 30 times)), group 4 (NP + ADMSCs (3.0 × 105 cells) 3 h after CCI procedure, followed by QOD six times (i.e., seven times in total, i.e., mimic a clinical setting of drug use) and group 5 (NP + probiotics + ADMSCs (3.0 × 105 cells)) and euthanized by day 60 after NP induction. By day 28 after NP induction, flow-cytometric analysis showed circulating levels of early (AN-V+/PI−) and late (AN-V+/PI+) apoptotic, and three inflammatory (CD11b-c+, Ly6G+ and MPO+) cells were lowest in group 1 and significantly progressively reduced in groups 2 to 5 (all p < 0.0001). By days 7, 14, 21, 28, and 60 after CCI, the thresholds of thermal paw withdrawal latency (PWL) and mechanical paw withdrawal threshold (PWT) were highest in group 1 and significantly progressively increased in groups 2 to 5 (all p < 0.0001). Numbers of pain-connived cells (Nav1.8+/peripherin+, p-ERK+/peripherin+, p-p38+/peripherin+ and p-p38+/NF200+) and protein expressions of inflammatory (p-NF-κB, IL-1ß, TNF-α and MMP-9), apoptotic (cleaved-caspase-3, cleaved-PARP), oxidative-stress (NOX-1, NOX-2), DNA-damaged (γ-H2AX) and MAPK-family (p-P38, p-JNK, p-ERK1/2) biomarkers as well as the protein levels of Nav.1.3, Nav.1.8, and Nav.1.9 in L4-L5 in dorsal root ganglia displayed an opposite pattern of mechanical PWT among the groups (all p < 0.0001). In conclusion, combined probiotic and ADMSC therapy was superior to merely one for alleviating CCI-induced NP mainly through suppressing inflammation and oxidative stress. [ABSTRACT FROM AUTHOR]

Background: This study tested the hypothesis that overexpression of cellular prion protein in endothelial progenitor cells (PrPcOE-EPCs), defined as "rejuvenated EPCs," was superior to EPCs for salvaging the critical limb ischemia (CLI) induced after 28-day chronic kidney disease (CKD) induction in rat. Methods and Results: Cell viability and flow cytometric analyses of early/late apoptosis/total-intracellular ROS/cell cycle (sub-G1, G2/M phase) were significantly higher in EPCs + H2O2 than in EPCs that were significantly reversed in PrPcOE-EPCs + H2O2 (all p < 0.001). The protein expressions of inflammation (IL-1ß/IL-6/MMP-9/p-NF-κB) were significantly increased in EPC + TNF-α than in EPCs that were significantly reversed in PrPcOE-EPCs + TNF-α (all p < 0.001). Adult-male SD rats (n = 8/each group) were categorized into group 1 (sham-operated control), group 2 (CKD + CLI), group 3 [CKD + CLI + EPCs by intravenous (0.6 × 105)/intra-muscular (0.6 × 105) injections at 3 h after CLI induction], group 4 (CKD + CLI + PrPcOE-EPCs/dose-administration as group 3) and group 5 (CKD + CLI + siPrnp-EPCs/dose-administration as group 3). By day 14 after CLI induction, the ratio of ischemia to normal blood flow (INBF) in CLI area was highest in group 1/lowest in group 2/significantly higher in group 4 than in groups 3/5 and significantly higher in group 3 than in group 5 (all p < 0.0001). Histopathology demonstrated that the angiogenesis (number of small vessels/CD31 + cells) exhibited a similar trend, whereas the fibrosis/kidney injury score exhibited an opposite pattern of INBF among the groups (all p < 0.0001). The protein expressions of angiogenesis (SDF-1α/VEGF/CXCR4)/cell-stress signaling (p-PI3K/p-Akt/p-m-TOR) were significantly and progressively increased from groups 1–4 that were reversed in group 5 (all p < 0.0001). The protein expressions of fibrotic (p-Smad3/TGF-ß)/oxidative-stress (NOX-1/NOX-2/oxidized-protein)/apoptotic (mitochondrial-Bax/cleaved caspase3/cleaved PARP)/mitochondrial-damaged (cytosolic-cytochrome-C) biomarkers displayed an opposite pattern of INBF among the groups (all p < 0.0001). Conclusion: PrPcOE-EPCs were superior to EPCs only therapy for salvaging the CLI. [ABSTRACT FROM AUTHOR]

Mast cell products and high levels of type 2 cytokines are associated with severe dengue disease. Group 2 innate lymphoid cells (ILC2) are type-2 cytokine-producing cells that are activated by epithelial cytokines and mast cell-derived lipid mediators. Through ex vivo RNAseq analysis, we observed that ILC2 are activated during acute dengue viral infection, and show an impaired type I-IFN signature in severe disease. We observed that circulating ILC2 are permissive for dengue virus infection in vivo and in vitro, particularly when activated through prostaglandin D2 (PGD2). ILC2 underwent productive dengue virus infection, which was inhibited through CRTH2 antagonism. Furthermore, exogenous IFN-β induced expression of type I-IFN responsive anti-viral genes by ILC2. PGD2 downregulated type I-IFN responsive gene and protein expression; and urinary prostaglandin D2 metabolite levels were elevated in severe dengue. Moreover, supernatants from activated ILC2 enhanced monocyte infection in a GM-CSF and mannan-dependent manner. Our results indicate that dengue virus co-opts an innate type 2 environment to escape early type I-IFN control and facilitate viral dissemination. PGD2 downregulates type I-IFN induced anti-viral responses in ILC2. CRTH2 antagonism may be a therapeutic strategy for dengue-associated disease. Group 2 innate lymphoid cells are activated during acute dengue viral infection in human, downregulate type I-IFN responsive gene and protein expression through Prostaglandin D2, and are permissive for productive dengue viral infection. [ABSTRACT FROM AUTHOR]

Background: This experimental study was designed as a preclinical study for testing the hypothesis that intrarenal arterial (IRA) transfusion of human umbilical cord-derived mesenchymal stem cells (HUCDMSCs) therapy preserved the residual renal function of diabetic kidney disease (DKD) in rat [induction by 5/6 nephrectomy of left kidney and right nephrectomy, followed by intraperitoneal administration of aminoguanidine (180 mg/kg) and streptozotocin (30 mg/kg)]. Methods: Animals (n = 24) were categorized into group 1 (sham-operated control), group 2 (DKD), group 3 [DKD + HUCDMSCs (2.1 × 105/IRA injection at day 28 after CKD induction)] and group 4 [(DKD + HUCDMSCs (6.3 × 105/IRA injection)]. Results: By day 60 after DKD induction, the kidneys were harvested and the result showed that the creatinine level, ratio of urine protein/urine creatinine and kidney injury score were lowest in group 1, highest in group 2 and significantly lower in group 4 than in group 3 (all p < 0.0001). The protein expressions of apoptotic (cleaved caspase-3/cleaved PARP/mitochondrial Bax), fibrotic (TGF-ß/p-Smad3), autophagic (ratio of LC3B-II/LC3B-I, Atg5/Beclin-1), oxidative stress (NOX-1/NOX-2/oxidized protein/p22phox), mitochondrial/DNA-damaged (cytosolic-cytochrome-C/DRP1/γ-H2AX) and inflammatory (MMP-9/TNF-α/p-NF-κB) biomarkers exhibited an identical pattern, whereas the protein expressions of angiogenesis factors (CD31/vWF/vascularity) exhibited an opposite pattern of creatinine level among the groups (all p < 0.0001). Histopathological findings demonstrated the renal tubular-damaged (KIM-1)/kidney fibrosis area/oxidative stress (8-OHdG + cells) expressed an identical pattern, whereas the podocyte components (ZO-1/synaptopodin/podocin) exhibited an opposite pattern of creatinine level among the groups (all p < 0.0001). No tumorigenesis or immune rejection event was identified. Conclusion: IRA injection of xenogeneic MSCs was safe and effectively protected the residual renal function and architectural integrity in DKD rat. [ABSTRACT FROM AUTHOR]

Overproduction of N-terminal pyroglutamate (pGlu)-modified proteins utilizing Escherichia coli or eukaryotic cells is a challenging work owing to the fact that the recombinant proteins need to be recovered by proteolytic removal of fusion tags to expose the N-terminal glutaminyl or glutamyl residue, which is then converted into pGlu catalyzed by the enzyme glutaminyl cyclase. Herein we describe a new method for production of N-terminal pGlu-containing proteins in vivo via intracellular self-cleavage of fusion tags by tobacco etch virus (TEV) protease and then immediate N-terminal cyclization of passenger target proteins by a bacterial glutaminyl cyclase. To combine with the sticky-end PCR cloning strategy, this design allows the gene of target proteins to be efficiently inserted into the expression vector using two unique cloning sites (i.e., SnaB I and Xho I), and the soluble and N-terminal pGlu-containing proteins are then produced in vivo. Our method has been successfully applied to the production of pGlu-modified enhanced green fluorescence protein and monocyte chemoattractant proteins. This design will facilitate the production of protein drugs and drug target proteins that possess an N-terminal pGlu residue required for their physiological activities. [ABSTRACT FROM AUTHOR]