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With ageing populations, new elderly end-stage kidney disease (ESKD) cases rise. Unlike younger patients, elderly ESKD patients are less likely to undergo kidney transplant, and therefore the decision of receiving peritoneal dialysis (PD) and hemodialysis (HD) is more crucial. A total of 36,852 patients, aged more than 65, who were newly diagnosed with ESKD and initiated renal replacement therapy between 2013 and 2019 were identified. These patients were categorized into two groups: the PD group and the HD group according to their long-term renal replacement treatment. After propensity score matching, the PD group (n = 1628) displayed a lower incidence of major adverse cardiac and cerebrovascular events (MACCE) (10.09% vs. 13.03%, hazard ratio (HR): 0.74, 95% confidence interval (CI): 0.66-0.83), malignancy (1.23% vs. 2.14%, HR: 0.55, 95% CI: 0.40-0.76), and MACCE-associated mortality (1.35% vs. 2.25%, HR: 0.62, 95% CI: 0.46-0.84) compared to the HD group (n = 6512). However, the PD group demonstrated a higher rate of infection (34.09% vs. 24.14%, HR: 1.28, 95% CI: 1.20-1.37). The risks of all-cause mortality and infection-associated mortality were not different. This study may provide valuable clinical information to assist elderly ESKD patients to choose HD or PD as their renal replacement therapy., (© 2023. The Author(s).)

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous tumor that is highly aggressive and ranks fifth among the most common cancers worldwide. Although, the researches that attempted to construct a diagnostic model were deficient in HNSCC. Currently, the gold standard for diagnosing head and neck tumors is pathology, but this requires a traumatic biopsy. There is still a lack of a noninvasive test for such a high-incidence tumor. In order to screen genetic markers and construct diagnostic model, the methods of random forest (RF) and artificial neural network (ANN) were utilized. The data of HNSCC gene expression was accessed from Gene Expression Omnibus (GEO) database; we selected three datasets totally, and we combined 2 datasets (GSE6631 and GSE55547) for screening differentially expressed genes (DEGs) and chose another dataset (GSE13399) for validation. Firstly, the 6 DEGs (CRISP3, SPINK5, KRT4, MMP1, MAL, SPP1) were screened by RF. Subsequently, ANN was applied to calculate the weights of 6 genes. Besides, we created a diagnostic model and nominated it as neuralHNSCC, and the performance of neuralHNSCC by area under curve (AUC) was verified using another dataset. Our model achieved an AUC of 0.998 in the training cohort, and 0.734 in the validation cohort. Furthermore, we used the Cell-type Identification using Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm to investigate the difference in immune cell infiltration between HNSCC and normal tissues initially. The selected 6 DEGs and the constructed novel diagnostic model of HNSCC would make contributions to the diagnosis., (© 2023. The Author(s).)

Optic neuritis (ON) is a frequent presentation at onset of multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). The pathophysiology underlying these diseases, especially MOGAD, is still being elucidated. While obesity has been reported to potentially be a risk factor for MS, this has not been explored in NMOSD or MOGAD. We aimed to investigate a possible association between obesity (body mass index [BMI] > 30 kg/m 2 ) in patients with MOGAD, aquaporin 4-IgG positive NMOSD (AQP4-IgG+ NMOSD) or MS. In this multicenter non-interventional retrospective study, data was collected from patients with a first ever demyelinating attack of ON subsequently diagnosed with MOGAD (n = 44), AQP4-IgG+ NMOSD (n = 49) or MS (n = 90) between 2005 and 2020. The following data was collected: age, sex, ethnicity, BMI (documented before corticosteroid treatment), and the ON etiology after diagnostic work-up. A mixed model analysis was performed to assess the potential of obesity or BMI to predict MOGAD-ON, and to distinguish MOGAD-ON from AQP4-IgG+ NMOSD-ON and MS-ON. Main outcome measures included BMI in patients with acute ON and subsequent diagnosis of MOGAD, AQP4-IgG+ NMOSD or MS. A higher BMI was significantly associated with a diagnosis of MOGAD-ON (p < 0.001); in MOGAD patients the mean BMI was 31.6 kg/m 2 (standard deviation (SD) 7.2), while the mean BMI was 24.7 kg/m 2 (SD 5.3) in AQP4-IgG+ NMOSD patients, and 26.9 kg/m 2 (SD 6.2) in MS patients. Mixed-effects multinomial logistic regression, adjusted for age and sex, with obesity as a binary variable, revealed that obesity was associated with a higher odds ratio (OR) of a subsequent MOGAD diagnosis (OR 5.466, 95% CI [2.039, 14.650], p = 0.001) in contradistinction with AQP4-IgG+ NMOSD. This study suggests an association between obesity and MOGAD. Our findings require further exploration, but could have significant pathophysiologic implications if confirmed in larger prospective studies., (© 2022. The Author(s).)

The outcomes of patients with incident kidney failure who start hemodialysis are influenced by several factors. Whether hemodialysis facility characteristics are associated with patient outcomes is unclear. We included adults diagnosed as having kidney failure requiring hemodialysis during January 1, 2001 to December 31, 2013 from the Taiwan National Health Insurance Research Database to perform this retrospective cohort study. The exposures included different sizes and levels of hemodialysis facilities. The outcomes were all-cause mortality, cardiovascular death, infection-related death, hospitalization, and kidney transplantation. During 2001-2013, we identified 74,406 patients and divided them in to three groups according to the facilities where they receive hemodialysis: medical center (n = 8263), non-center hospital (n = 40,008), and clinic (n = 26,135). The multivariable Cox model demonstrated that a larger facility size was associated with a low mortality risk (hazard ratio [HR] 0.991, 95% confidence interval [95% CI] 0.984-0.998; every 20 beds per facility). Compared with medical centers, patients in non-center hospitals and clinics had higher mortality risks (HR 1.13, 95% CI 1.09-1.17 and HR 1.11, 95% CI 1.06-1.15, respectively). Patients in medical centers and non-center hospitals had higher risk of hospitalization (subdistribution HR [SHR] 1.11, 95% CI 1.10-1.12 and SHR 1.22, 95% CI 1.21-1.23, respectively). Patients in medical centers had the highest rate of kidney transplantation among the three groups. In patients with incident kidney failure, a larger hemodialysis facility size was associated with lower mortality. Overall, medical center patients had a lower mortality rate and higher transplantation rate, whereas clinic patients had a lower hospitalization risk., (© 2021. The Author(s).)

There has been no long-term clinical follow-up data of survivors or victims of sudden cardiac death (SCD). The Taiwan multi-center sudden arrhythmia death syndrome follow-up and clinical study (TFS-SADS) is a collaborative multi-center study with median follow-up time 43 months. In this cohort, the clinical characteristics of these SADS patients were compared with those with ischemic heart disease (IHD). In this SCD cohort, around half (42%) were patients with IHD, which was different from Caucasian SCD cohorts. Among those with normal heart, most had Brugada syndrome (BrS). Compared to those with SADS, patients with IHD were older, more males and more comorbidities, more arrhythmic death, and lower left ventricular ejection fraction. In the long-term follow-up, patients with SADS had a better survival than those with IHD (p < 0.001). In the Cox regression analysis to identify the independent predictors of mortality, older age, lower LVEF, prior myocardial infarction and history of out-of-hospital cardiac arrest were associated with higher mortality and beta blocker use and idiopathic ventricular fibrillation or tachycardia (IVF/IVT) with a better survival during follow-up. History of prior MI was associated with more arrhythmic death. Several distinct features of SCD were found in the Asia-Pacific region, such as higher proportion of SADS, poorer prognosis of LQTS and better prognosis of IVF/IVT. Patients with SADS had a better survival than those with IHD. For those with SADS, patients with channelopathy had a better survival than those with cardiomyopathy., (© 2021. The Author(s).)

Acute kidney injury (AKI) is a common complication in acute heart failure (AHF) and is associated with prolonged hospitalization and increased mortality. The aim of this study was to externally validate existing prediction models of AKI in patients with AHF. Data for 10,364 patients hospitalized for acute heart failure between 2008 and 2018 were extracted from the Chang Gung Research Database and analysed. The primary outcome of interest was AKI, defined according to the KDIGO definition. The area under the receiver operating characteristic (AUC) curve was used to assess the discrimination performance of each prediction model. Five existing prediction models were externally validated, and the Forman risk score and the prediction model reported by Wang et al. showed the most favourable discrimination and calibration performance. The Forman risk score had AUCs for discriminating AKI, AKI stage 3, and dialysis within 7 days of 0.696, 0.829, and 0.817, respectively. The Wang et al. model had AUCs for discriminating AKI, AKI stage 3, and dialysis within 7 days of 0.73, 0.858, and 0.845, respectively. The Forman risk score and the Wang et al. prediction model are simple and accurate tools for predicting AKI in patients with AHF.

Numerous techniques have been demonstrated for effective generation of orbital angular momentum-carrying radiation, but intracavity generation of continuously tunable pulses in the femtosecond regime remains challenging. Even if such a creation was realized, the generated pulses-like all pulses in reality-are complex and transitory objects that can only be comprehensively characterized via multidimensional spaces. An integrated lasing system that generates pulses while simultaneously quantifies them can achieve adaptive pulse tailoring. Here, we report a femtosecond pulse scope that unifies vector vortex mode-locked lasing and vectorial quantification. With intracavity-controlled Pancharatnam-Berry phase modulation, continuous and ergodic generation of spirally polarized states along a broadband higher-order Poincaré sphere was realized. By intrinsically coupling a two-dimensional polarization-sensitive time-scanning interferometer to the laser, multidimensional spatiotemporal features of the pulse were further visualized. The proposed methodology paves the way for design optimization of ultrafast optics by integrating complex femtosecond pulse generation and structural customization, facilitating its applications in optical physics research and laser-based manufacturing.

To investigate the particle size distribution of particulate matter and the concentration of specific perfluorinated compounds in indoor dust samples from several locations. Then, we used cell-based assays to investigate the effect of perfluorinated compounds on human corneal epithelial (HCEpiC), endothelial cells (HCEC) and retinal pigment epithelial cells (RPE). Indoor dust samples were collected at five different locations and PM 50-10 , PM 10-2.5 , and PM 2.5-1 were fractionized. The presence and levels of 8:2 fluorotelomer alcohol, 10:2 fluorotelomer alcohol, and perfluorooctanoic acid were detected by gas chromatography-mass spectrometry. The effect of perfluorooctanoic acid on the activation of reactive oxygen species, transepithelial resistance as well as the expression of interleukin (IL)-6 and IL-8 were determined. The basolateral media of human corneal epithelial or human corneal endothelial cells were used to treat human corneal endothelial or retinal pigment epithelial cells, respectively to indicate the potential of ocular surface inflammation may result in retinal inflammation. Among perfluorinated compounds, only perfluorooctanoic acid was detected in all indoor dust samples. Perfluorooctanoic acid had the highest concentration among all perfluorinated compounds in the samples. Exposure to perfluorooctanoic acid impaired tight junction sealing and increased the levels of reactive oxygen species in human corneal epithelial cells. In human corneal epithelial cells, secretion of IL-6 and IL-8 in both apical and basolateral media was promoted significantly by perfluorooctanoic acid treatment. Stimulation with the basolateral media from perfluorooctanoic acid-treated human corneal epithelial cells induced inflammation in human corneal endothelial cells. The treatment of retinal pigment epithelial cells with the basolateral media from stimulated human corneal endothelial cells also elicited the secretion of proinflammatory cytokines. The results indicate that perfluorooctanoic acid exposure impaired the tight junction of corneal cells and caused inflammatory reactions in the retina. Exposure of the cornea to perfluorooctanoic acid contained in particulate matter might induce oxidative stress and inflammation in the retina and represent a risk factor for age-related macular degeneration.

In patients with chronic hepatitis C (CHC), the effects of baseline characteristics, virological profiles, and therapeutic outcome to pegylated interferon plus ribavirin (PR) therapy on autoimmune diseases are unknown. Taiwanese Chronic Hepatitis C Cohort is a nationwide hepatitis C virus registry cohort comprising 23 hospitals of Taiwan. A total of 12,770 CHC patients receiving PR therapy for at least 4 weeks between January 2003 and December 2015 were enrolled and their data were linked to the Taiwan National Health Insurance Research Database for studying the development of 10 autoimmune diseases. The mean follow-up duration was 5.3 ± 2.9 years with a total of 67,930 person-years, and the annual incidence of systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) was 0.03%. Other autoimmune diseases were not assessable due to few events. Body mass index ≥24 kg/m 2 was an independent predictor of the low incidence of SLE or RA (hazard ratio 0.40, 95% confidence interval 0.17-0.93, p = 0.034). A sustained virological response (SVR) to PR therapy was not associated with the low incidence of SLE or RA in any subgroup analysis. CHC patients achieving SVR to PR therapy did not exhibit an impact on the incidence of SLE or RA compared with non-SVR patients.

Combination use of digoxin and other medications might lead to worse outcomes in patients with atrial fibrillation (AF). We sought to investigate whether digoxin-amiodarone combination would lead to worse outcome than digoxin alone in patients with AF. Adult patients with AF and received digoxin treatment from random samples of 1,000,000 individuals covered by the National Health Insurance in Taiwan were included. Baseline characteristics including risk factors and medications were matched by propensity score (PS) in those with and without addition of amiodarone treatment. A total of 5,040 AF patients taking digoxin therapy was included. PS matching identified 1,473 patients receiving digoxin-amiodarone combination and 2,660 patients receiving digoxin with a median follow-up of 1,331 days. Digoxin-amiodarone combination was associated with increased all-cause mortality (adjusted hazard ratio (HR): 1.640, 95% confidence interval (CI): 1.470-1.829, P < 0.001). The risk of mortality increased regardless of duration of combination. Risk of sudden cardiac death was not increased in the combination group (HR: 1.304, 95% CI: 1.049-1.622, P = 0.017). Death due to non-arrhythmic cardiac disease, cerebrovascular disease, and other vascular disease were higher in the combination group than the digoxin group. In conclusion, in patients with AF, digoxin-amiodarone combination therapy is associated with excess mortality than digoxin alone.

Hepatitis C virus (HCV) eradication by antivirals promote fibrosis modification. Whether host genetics determined fibrosis regression in chronic hepatitis C (CHC) patients with sustained virological response (SVR) is to be determined. One hundred and fifty-six SVR patients with paired liver biopsy before and after antivirals were enrolled. Host genetic factors including single nucleotide polymorphism rs17047200 of tolloid-like 1(TLL-1) were analyzed for their association with fibrosis modification. The proportions of improved, unchanged and worsening fibrotic stags were 39.1% (n = 61), 39.1% (n = 61), and 21.8% (n = 34), respectively. The rate of annual fibrotic improvement was 0.16 ± 0.79. There was a significant trend of increased fibrotic improvement rate in patients from F01 to F4 (P < 0.001). However, the rate of improvement seemed more limited in cirrhotic patients among those with advanced liver disease. Patients with fibrotic improvement had a significantly higher proportion of TLL-1 rs17047200 AA genotype compared to those without (92.5% vs. 79.3%, p = 0.039). Logistic regression analysis revealed that the TLL-1 rs17047200 AA genotype was the only independent factor associated with fibrosis improvement (odds ratio/95% confidence intervals: 3.2/1.01-10.12, p = 0.047). Compared with TLL-1 rs17047200 non-AA carriers, a significantly higher proportion of fibrosis improvement in AA genotype carriers was observed among patients with F0-2 (33.3% vs. 0%, p = 0.005) but not with F34 (70% vs. 80%, p = 1). We concluded that TLL-1 genetic variants determined fibrotic improvement in CHC with curative antivirals, particularly in patients with mild liver disease.

Biomarkers that represent the structural and functional integrity of the motor system enable us to better assess motor outcome post-stroke. The degree of overlap between the stroke lesion and corticospinal tract (CST Injury) is a measure of the structural integrity of the motor system, whereas the left-to-right motor cortex resting state connectivity (LM1-RM1 rs-connectivity) is a measure of its functional integrity. CST Injury and LM1-RM1 rs-connectivity each individually correlate with motor outcome post-stroke, but less is understood about the relationship between these biomarkers. Thus, this study investigates the relationship between CST Injury and LM1-RM1 rs-connectivity, individually and together, with motor outcome. Twenty-seven participants with upper limb motor deficits post-stroke completed motor assessments and underwent MRI at one time point. CST Injury and LM1-RM1 rs-connectivity were derived from T1-weighted and resting state functional MRI scans, respectively. We performed hierarchical multiple regression analyses to determine the contribution of each biomarker in explaining motor outcome. The interaction between CST Injury and LM1-RM1 rs-connectivity does not significantly contribute to the variability in motor outcome. However, inclusion of both CST Injury and LM1-RM1 rs-connectivity explains more variability in motor outcome, than either alone. We suggest both biomarkers provide distinct information about an individual's motor outcome.

The misfolding and accumulation of tau protein into intracellular aggregates known as neurofibrillary tangles is a pathological hallmark of neurodegenerative diseases such as Alzheimer's disease. However, while tau propagation is a known marker for disease progression, exactly how tau propagates from one cell to another and what mechanisms govern this spread are still unclear. Here, we report that cellular internalization of tau is regulated by quaternary structure and have developed a cellular assay to screen for genetic modulators of tau uptake. Using CRISPRi technology we have tested 3200 genes for their ability to regulate tau entry and identified enzymes in the heparan sulfate proteoglycan biosynthetic pathway as key regulators. We show that 6-O-sulfation is critical for tau-heparan sulfate interactions and that this modification regulates uptake in human central nervous system cell lines, iPS-derived neurons, and mouse brain slice culture. Together, these results suggest novel strategies to halt tau transmission.

Osteoporosis results from the imbalance between bone resorption and bone formation, and restoring the normal balance of bone remodeling is highly desirable for identification of better treatment. In this study, using a cell-based high-throughput screening model representing Runt-related transcription factor 2 (RUNX2) transcriptional activity, we identified a novel small-molecular-weight compound, T63, as an efficient up-regulator of osteogenesis. T63 increased the alkaline phosphatase (ALPL) activity and mineralization as well as gene expression of Alpl and other osteogenic marker genes in mouse osteoblasts and mesenchymal stem cell-like cells. Upon induction of osteoblast differentiation, T63 inhibited adipogenic differentiation in the pluripotent mesenchymal cells. Consistently, T63 up-regulated RUNX2 mRNA and protein levels, and knockdown of RUNX2 reduced the osteogenic role of T63. Mechanistically, T63 activated both BMPs and WNT/β-catenin signaling pathways. Inhibition of either signaling pathway with specific inhibitor suppressed T63-induced RUNX2 expression and the osteogenic phenotypes. Moreover, T63 markedly protected against bone mass loss in the ovariectomized and dexamethasone treated rat osteoporosis model. Collectively, our data demonstrate that T63 could be a promising drug candidate and deserves further development for potential therapeutics in osteoporosis.

The introduction of the concept of valley pseudospin to phononic crystals has made a remarkable topologically protected interface transport of sound, which opens a novel research area referred to as valley Hall topological insulators. Here, we demonstrate the simultaneous multi-band edge states of shear vertical waves in two-dimensional phononic crystals with veins. The multi-band edge states are topologically valley-protected and are obtained by simultaneously gapping multiple Dirac points at K (or K') under the inversion symmetry breaking. As the relative radius of the two adjacent steel columns varies, the band diagram undergoes a topological transition which can be characterized by topological charge distributions and opposite valley Chern numbers. Subsequently, the vortex chirality of the bulk valley modes is unveiled. With numerical simulations, simultaneous multi-band valley dependent edge states and the associated valley-protected backscattering suppression around the curved waveguide are further demonstrated. Our work could become a promising platform for applications of multi-functional topological acoustic devices.

Ciliary motion plays a critical role in the overall respiratory health of the upper airway. These cilia beat at a native frequency and in a synchronized pattern to continuously transport foreign particulate trapped in a layer of mucous out of the upper airway. Disruption of ciliary motion can lead to severe respiratory diseases and compromised respiratory function. Currently, the study of cilia requires expensive high speed cameras and high powered microscopes which is unsuitable for in vivo imaging and diagnosis. Doppler based optical coherence tomography has the potential to visualize the microscopic motion of cilia during their beating cycle. We demonstrate the development of a high-speed Doppler optical coherence tomography system that not only can rapidly determine the cilia beat frequency, but also simultaneously visualize the temporal cilia beating pattern which plays critical roles in cilia function.

Cystic fibrosis transmembrane conductance regulator (CFTR), known as a cAMP-activated Cl - channel, is widely expressed at the apical membrane of epithelial cells in a wide variety of tissues. Of note, despite the abundant expression of CFTR in mammalian kidney, the role of CFTR in kidney disease development is unclear. Here, we report that CFTR expression is downregulated in the UUO (unilateral ureteral obstruction)-induced kidney fibrosis mouse model and human fibrotic kidneys. Dysfunction or downregulation of CFTR in renal epithelial cells leads to alteration of genes involved in Epithelial-Mesenchymal Transition (EMT) and kidney fibrosis. In addition, dysregulation of CFTR activates canonical Wnt/β-catenin signaling pathways, whereas the β-catenin inhibitor reverses the effects of CFTR downregulation on EMT marker. More interestingly, CFTR interacts with Dishevelled 2 (Dvl2), a key component of Wnt signaling, thereby suppressing the activation of β-catenin. Compared to wild type, deltaF508 mice with UUO treatment exhibit significantly higher β-catenin activity with aggregated kidney fibrogenesis, which is reduced by forced overexpression of CFTR. Taken together, our study reveals a novel mechanism by which CFTR regulates Wnt/β-catenin signaling pertinent to progression of kidney fibrosis and indicates a potential treatment target.

The human papillomavirus (HPV) plays a central role in cervical carcinogenesis and its oncogene E7 is essential in this process. We showed here that E7 abrogated the G1 cell cycle checkpoint under hypoxia and analyzed key cell cycle related proteins for their potential role in this process. To further explore the mechanism by which E7 bypasses hypoxia-induced G1 arrest, we applied a proteomic approach and used mass spectrometry to search for proteins that are differentially expressed in E7 expressing cells under hypoxia. Among differentially expressed proteins identified, Cdc6 is a DNA replication initiation factor and exhibits oncogenic activities when overexpressed. We have recently demonstrated that Cdc6 was required for E7-induced re-replication. Significantly, here we showed that Cdc6 played a role in E7-mediated G1 checkpoint abrogation under hypoxic condition, and the function could possibly be independent from its role in DNA replication initiation. This study uncovered a new function of Cdc6 in regulating cell cycle progression and has important implications in HPV-associated cancers.

The emergence of resistance to imatinib mediated by mutations in the BCR-ABL has become a major challenge in the treatment of chronic myeloid leukemia (CML). Alternative therapeutic strategies to override imatinib-resistant CML are urgently needed. In this study, we investigated the effect of AKI603, a novel small molecule inhibitor of Aurora kinase A (AurA) to overcome resistance mediated by BCR-ABL-T315I mutation. Our results showed that AKI603 exhibited strong anti-proliferative activity in leukemic cells. AKI603 inhibited cell proliferation and colony formation capacities in imatinib-resistant CML cells by inducing cell cycle arrest with polyploidy accumulation. Surprisingly, inhibition of AurA by AKI603 induced leukemia cell senescence in both BCR-ABL wild type and T315I mutation cells. Furthermore, the induction of senescence was associated with enhancing reactive oxygen species (ROS) level. Moreover, the anti-tumor effect of AKI603 was proved in the BALB/c nude mice KBM5-T315I xenograft model. Taken together, our data demonstrate that the small molecule AurA inhibitor AKI603 may be used to overcome drug resistance induced by BCR-ABL-T315I mutation in CML.

Bondarzewia is a conspicuous and widely distributed mushroom genus, but little is known about its origin and biogeography. Here, we investigated the systematics and biogeography of Bondarzewia species using multi-locus phylogenetic analysis. Four genetic markers, including the internal transcribed spacer (ITS), large nuclear ribosomal RNA subunit (nLSU), elongation factor 1-α (tef1) and mitochondrial small subunit rDNA (mtSSU), were used to infer the phylogenetic relationships of Bondarzewia. We performed Bayesian evolutionary analysis on the gene datasets of the largest and second largest subunits of RNA polymerase II (RPB1 and RPB2). From the results, we inferred that the maximum crown age of Bondarzewia is approximately 25.5 million-years-ago (Mya) and that tropical East Asia is likely to be its ancestral area, with three possible expansions leading to its distribution in North America, Europe and Oceania.

We investigate the relationship between two kinds of ground-state local convertibility and quantum phase transitions in XY model. The local operations and classical communications (LOCC) convertibility is examined by the majorization relations and the entanglement-assisted local operations and classical communications (ELOCC) via Rényi entropy interception. In the phase diagram of XY model, LOCC convertibility and ELOCC convertibility of ground-states are presented and compared. It is shown that different phases in the phase diagram of XY model can have different LOCC or ELOCC convertibility, which can be used to detect the quantum phase transition. This study will enlighten extensive studies of quantum phase transitions from the perspective of local convertibility, e.g., finite-temperature phase transitions and other quantum many-body models.

Physical and chemical insult-induced bone marrow (BM) damage often leads to lethality resulting from the depletion of hematopoietic stem and progenitor cells (HSPCs) and/or a deteriorated BM stroma. Notch signaling plays an important role in hematopoiesis, but whether it is involved in BM damage remains unclear. In this study, we found that conditional disruption of RBP-J, the transcription factor of canonical Notch signaling, increased irradiation sensitivity in mice. Activation of Notch signaling with the endothelial cell (EC)-targeted soluble Dll1 Notch ligand mD1R promoted BM recovery after irradiation. mD1R treatment resulted in a significant increase in myeloid progenitors and monocytes in the BM, spleen and peripheral blood after irradiation. mD1R also enhanced hematopoiesis in mice treated with cyclophosphamide, a chemotherapeutic drug that induces BM suppression. Mechanistically, mD1R increased the proliferation and reduced the apoptosis of myeloid cells in the BM after irradiation. The β chain cytokine receptor Csf2rb2 was identified as a downstream molecule of Notch signaling in hematopoietic cells. mD1R improved hematopoietic recovery through up-regulation of the hematopoietic expression of Csf2rb2. Our findings reveal the role of Notch signaling in irradiation- and drug-induced BM suppression and establish a new potential therapy of BM- and myelo-suppression induced by radiotherapy and chemotherapy.

Diagnosis and treatment of vocal fold lesions has been a long-evolving science for the otolaryngologist. Contemporary practice requires biopsy of a glottal lesion in the operating room under general anesthesia for diagnosis. Current in-office technology is limited to visualizing the surface of the vocal folds with fiber-optic or rigid endoscopy and using stroboscopic or high-speed video to infer information about submucosal processes. Previous efforts using optical coherence tomography (OCT) have been limited by small working distances and imaging ranges. Here we report the first full field, high-speed, and long-range OCT images of awake patients' vocal folds as well as cross-sectional video and Doppler analysis of their vocal fold motions during phonation. These vertical-cavity surface-emitting laser source (VCSEL) OCT images offer depth resolved, high-resolution, high-speed, and panoramic images of both the true and false vocal folds. This technology has the potential to revolutionize in-office imaging of the larynx.

The surface phase junction of nanocrystalline TiO2 plays an essential role in governing its photocatalytic activity. Thus, facile and simple methods for preparing phase-junction TiO2 photocatalysts are highly desired. In this work, we show that phase-junction TiO2 is directly synthesized from Ti foil by using a simple calcination method with hydrothermal solution as the precursor below the phase transition temperature. Moreover, the ratio of rutile to anatase in the TiO2 samples could be readily tuned by changing the ratio of weight of Ti foil to HCl, which is used as the hydrothermal precursor, as confirmed by the X-ray diffraction analysis. In the photocatalytic reaction by the TiO2 nanocomposite, a synergistic effect between the two phases within a certain range of the ratio is clearly observed. The results suggest that an appropriate ratio of anatase to rutile in the TiO2 nanocomposite can create more efficient solid-solid interfaces upon calcination, thereby facilitating interparticle charge transfer in the photocatalysis.

Scaling-up of high-cell-density fermentation (HCDF) of Pichia pastoris from the lab or pilot scale to the demonstration scale possesses great significance because the latter is the final technological hurdle in the decision to go commercial. However, related investigations have rarely been reported. In this paper, we study the scaling-up processes of a recombinant P. pastoris from the pilot (10 to 100-L) to the demonstration (1,000-L) scales, which can be used to convert 7-β-xylosyl-10-deacetyltaxol into 10-deacetyltaxol by the β-xylosidase for semi-synthesis of Taxol. We demonstrated that a pure oxygen supplement can be omitted from the HCDF if the super atmospheric pressure was increased from 0.05 to 0.10 ± 0.05 MPa, and we developed a new methanol feeding biomass-stat strategy (0.035 mL/g/h) with 1% dissolved oxygen and 100 g/L initial induction biomass (dry cell weight). The scaling-up was reproducible, and the best results were obtained from the 1,000-L scale, featuring a shorter induction time and the highest enzyme activities and productions, respectively. The specific growth and specific production rates were also determined. This study lays a solid foundation for the commercial preparation of 10-deacetyltaxol through the recombinant yeast. It also provides a successful paradigm for scaling-up HCDF of P. pastoris to the demonstration scale.

Heart failure with preserved ejection fraction (HFPEF) is characterized by myocardial interstitial fibrosis. A total of 146 patients with HFPEF, were recruited. HFPEF severity was determined using Doppler imaging (E/Em) and also cardiac magnetic resonance imaging (CMRI). Canine modeling of HFPEF was induced by aortic banding. Hemodynamic and echocardiographic data were obtained before and after pressure loading and myocardial Galectin-3 was determined. Mechanical stretch of cultured cardiomyocytes served as the cellular model of HFPEF. Patients with severe HFPEF had significantly higher plasma Galectin-3 levels. Significant correlation between plasma Galectin-3 and E/Em in advanced HFPEF patients was noted. After 2 weeks of pressure overload in canine models, the protein expression of Galectin-3 from LV myocardial tissue was significantly increased (p < 0.01) compared with controls. Galectin-3 expression paralleled the severity of LV diastolic dysfunction by evaluation of CMRI (r = -0.58, p = 0.003) and tissue fibrosis (r = 0.59, p = 0.002). After adjusting for confounders for diastolic dysfunction, Galectin-3 levels were still associated with diastolic parameters both in humans (p < 0.001) and canine model (p = 0.041). Mechanical stretch increased Galectin-3 secretion in cultured cardiomyocytes. Both plasma and myocardial Galectin-3 levels correlated with severity of cardiac diastolic dysfunction.

Of the two cultivated species of allopolyploid cotton, Gossypium barbadense produces extra-long fibers for the production of superior textiles. We sequenced its genome (AD)2 and performed a comparative analysis. We identified three bursts of retrotransposons from 20 million years ago (Mya) and a genome-wide uneven pseudogenization peak at 11-20 Mya, which likely contributed to genomic divergences. Among the 2,483 genes preferentially expressed in fiber, a cell elongation regulator, PRE1, is strikingly At biased and fiber specific, echoing the A-genome origin of spinnable fiber. The expansion of the PRE members implies a genetic factor that underlies fiber elongation. Mature cotton fiber consists of nearly pure cellulose. G. barbadense and G. hirsutum contain 29 and 30 cellulose synthase (CesA) genes, respectively; whereas most of these genes (>25) are expressed in fiber, genes for secondary cell wall biosynthesis exhibited a delayed and higher degree of up-regulation in G. barbadense compared with G. hirsutum, conferring an extended elongation stage and highly active secondary wall deposition during extra-long fiber development. The rapid diversification of sesquiterpene synthase genes in the gossypol pathway exemplifies the chemical diversity of lineage-specific secondary metabolites. The G. barbadense genome advances our understanding of allopolyploidy, which will help improve cotton fiber quality.

Macrophages in a tumor microenvironment have been characterized as M1- and M2-polarized subtypes. Here, we discovered the different macrophages' impacts on lung cancer cell A549. The M2a/M2c subtypes promoted A549 invasion and xenograft tumor growth. The M1 subtype suppressed angiogenesis. M1 enhanced the sensitivity of A549 to cisplatin and decreased the tube formation activity and cell viability of A549 cells by inducing apoptosis and senescence. Different macrophage subtypes regulated genes involved in the immune response, cytoskeletal remodeling, coagulation, cell adhesion, and apoptosis pathways in A549 cells, which was a pattern that correlated with the altered behaviors of the A549 cells. Furthermore, we found that the identified M1/M2 gene signatures were significantly correlated with the extended overall survival of lung cancer patients. These results suggest that M1/M2 gene expression signature may be used as a prognostic indicator for lung cancer patients, and M1/M2 polarization may be a target of investigation of immune-modulating therapies for lung cancer in the future.

The influence of patatin-like phospholipase domain-containing 3 (PNPLA3) genetic variants in the development of liver steatosis in Asian chronic hepatitis C patients remains elusive. A total of 1018 biopsy-proven chronic hepatitis C patients were enrolled for evaluation. The proportions of PNPLA3 rs738409 GG genotype carriage were 7.8% (44/563), 15.8% (58/367) and 19.3% (17/88) in patients with no (liver fat content < 5%), mild (5-33%) and moderate/severe (> 66%) hepatic steatosis, respectively (trend P < 0.001). Stepwise logistic regression analysis revealed that the strongest factor independently associated with steatosis was the carriage of the PNPLA3 rs738409 GG genotype (odds ratio [OR]/95% confidence intervals [CI]:2.34/1.557-3.515, P < 0.001). Among the patients with BMI < 24 kg/m(2), carriage of the rs738409 GG genotype was the only factor associated with hepatic steatosis (OR/CI:3.44/1.824-6.500, P < 0.001). PNPLA3 genetic variants had minimal effects on hepatic steatosis among overweight or obese patients. Compared to patients with BMI < 24 kg/m(2)/non-GG genotype, those with BMI >24 kg/m(2)/GG genotype were more likely to have hepatic steatosis (OR/CI:3.87/2.292-6.524, P < 0.001). In conclusions, both PNPLA3 genetic variants and BMI played important roles in hepatic steatosis among Asian chronic hepatitis C patients. However, the genetic effect was mainly restricted to non-obese patients.

Intraventricular hemorrhage is associated with poor functional outcomes in patients with intracerebral hemorrhage (ICH). We aimed to investigate the association between intraventricular hemorrhage and early hematoma expansion in patients with ICH. Patients with ICH who underwent a baseline CT scan within six hours after onset of symptoms were included. The follow-up CT scan was performed within 24 hours after the baseline CT scan. Univariate and multivariable logistic regression were used to assess the relationship between presence of intraventricular hemorrhage and early hematoma expansion. A total of 160 patients were included in the study. Significant hematoma growth was observed in 52 (32.5%) patients presenting within six hours after onset of symptoms. Intraventricular hemorrhage was observed in 66 (41.25%) patients with ICH. Multivariate analyses demonstrated that a short time from onset to baseline CT scan, the initial hematoma volume, and the presence of intraventricular hemorrhage on follow-up CT scan were independently associated with hematoma enlargement. The presence of intraventricular hemorrhage on follow-up CT scan can be associated with hematoma expansion in patients with ICH.

Curcumin is a major component of turmeric and reportedly has anti-inflammatory and anti-oxidant effects. Neuroinflammation has been recognized to play an important role in the pathogenesis of various diseases in the central nervous system. Here we investigated the anti-nociceptive and anti-neuroinflammatory effect of curcumin on arthritic pain in rats. We found that repeated oral treatment with curcumin, either before or after complete Freund's adjuvant (CFA) injection, dose-dependently attenuated CFA-induced mechanical allodynia and thermal hyperalgesia, but had no effect on joint edema. Repeated intrathecal injection of curcumin reversed CFA-induced pain hypersensitivity. Furthermore, such a curcumin treatment reduced CFA-induced activation of glial cells and production of inflammatory mediators [interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and monocyte inflammatory protein-1 (MIP-1α)] in the spinal cord. Curcumin also decreased lipopolysaccharide-induced production of IL-1β, tumor necrosis factor-α, MCP-1, and MIP-1α in cultured astrocytes and microglia. Our results suggest that intrathecal curcumin attenuates arthritic pain by inhibiting glial activation and the production of inflammatory mediators in the spinal cord, suggesting a new application of curcumin for the treatment of arthritic pain.

The NAD(P)H dehydrogenase complex is encoded by 11 ndh genes in plant chloroplast (cp) genomes. However, ndh genes are truncated or deleted in some autotrophic Epidendroideae orchid cp genomes. To determine the evolutionary timing of the gene deletions and the genomic locations of the various ndh genes in orchids, the cp genomes of Vanilla planifolia, Paphiopedilum armeniacum, Paphiopedilum niveum, Cypripedium formosanum, Habenaria longidenticulata, Goodyera fumata and Masdevallia picturata were sequenced; these genomes represent Vanilloideae, Cypripedioideae, Orchidoideae and Epidendroideae subfamilies. Four orchid cp genome sequences were found to contain a complete set of ndh genes. In other genomes, ndh deletions did not correlate to known taxonomic or evolutionary relationships and deletions occurred independently after the orchid family split into different subfamilies. In orchids lacking cp encoded ndh genes, non cp localized ndh sequences were identified. In Erycina pusilla, at least 10 truncated ndh gene fragments were found transferred to the mitochondrial (mt) genome. The phenomenon of orchid ndh transfer to the mt genome existed in ndh-deleted orchids and also in ndh containing species.

In complex financial systems, the sector structure and volatility clustering are respectively important features of the spatial and temporal correlations. However, the microscopic generation mechanism of the sector structure is not yet understood. Especially, how to produce these two features in one model remains challenging. We introduce a novel interaction mechanism, i.e., the multi-level herding, in constructing an agent-based model to investigate the sector structure combined with volatility clustering. According to the previous market performance, agents trade in groups, and their herding behavior comprises the herding at stock, sector and market levels. Further, we propose methods to determine the key model parameters from historical market data, rather than from statistical fitting of the results. From the simulation, we obtain the sector structure and volatility clustering, as well as the eigenvalue distribution of the cross-correlation matrix, for the New York and Hong Kong stock exchanges. These properties are in agreement with the empirical ones. Our results quantitatively reveal that the multi-level herding is the microscopic generation mechanism of the sector structure, and provide new insight into the spatio-temporal interactions in financial systems at the microscopic level.

Decomposition of perfluorooctanoic acid (C7F15COOH, PFOA) has been gaining increasing interests because it is a ubiquitous environmental contaminant and resistant to the most conventional treatment processes. In this work, the rapid and complete mineralization of PFOA and simultaneous defluorination were achieved by γ-ray irradiation with a (60)Co source. The degradation rate of PFOA by γ-ray irradiation would be high, and a pseudo-first-order kinetic rate constant of 0.67 h(-1) could be achieved in the N2 satured condition at pH 13.0. The experimental results and quantum chemical calculation confirmed that two radicals, i.e., hydroxyl radical (·OH) and aqueous electrons (eaq(-)), were responsible for the degradation of PFOA, while only either eaq(-) or ·OH might not be able to accomplish complete mineralization of PFOA. The synergistic effects of ·OH and eaq(-) involved in the cleavage of C-C and C-F bonds, and therefore complete mineralization of PFOA were achieved. The intermediate products were identified and the degradation pathway was also proposed. The results of this study may offer a useful, high-efficient approach for complete mineralizing fluorochemicals and other persistent pollutants.

Interactions between metals and activated sludge microorganisms substantially affect the speciation, immobilization, transport, and bioavailability of trace heavy metals in biological wastewater treatment plants. In this study, the interaction of Cu(II), a typical heavy metal, onto activated sludge microorganisms was studied in-depth using a multi-technique approach. The complexing structure of Cu(II) on microbial surface was revealed by X-ray absorption fine structure (XAFS) and electron paramagnetic resonance (EPR) analysis. EPR spectra indicated that Cu(II) was held in inner-sphere surface complexes of octahedral coordination with tetragonal distortion of axial elongation. XAFS analysis further suggested that the surface complexation between Cu(II) and microbial cells was the distorted inner-sphere coordinated octahedra containing four short equatorial bonds and two elongated axial bonds. To further validate the results obtained from the XAFS and EPR analysis, density functional theory calculations were carried out to explore the structural geometry of the Cu complexes. These results are useful to better understand the speciation, immobilization, transport, and bioavailability of metals in biological wastewater treatment plants.

Bipolar disorder (BD) is a debilitating mental disorder that cannot be diagnosed by objective laboratory-based modalities. Our previous studies have independently used nuclear magnetic resonance (NMR)-based and gas chromatography-mass spectrometry (GC-MS)-based metabonomic methods to characterize the urinary metabolic profiles of BD subjects and healthy controls (HC). However, the combined application of NMR spectroscopy and GC-MS may identify a more comprehensive metabolite panel than any single metabonomic platform alone. Therefore, here we applied a dual platform (NMR spectroscopy and GC-MS) that generated a panel of five metabolite biomarkers for BD-four GC-MS-derived metabolites and one NMR-derived metabolite. This composite biomarker panel could effectively discriminate BD subjects from HC, achieving an area under receiver operating characteristic curve (AUC) values of 0.974 in a training set and 0.964 in a test set. Moreover, the diagnostic performance of this panel was significantly superior to the previous single platform-derived metabolite panels. Thus, the urinary biomarker panel identified here shows promise as an effective diagnostic tool for BD. These findings also demonstrate the complementary nature of NMR spectroscopy and GC-MS for metabonomic analysis, suggesting that the combination of NMR spectroscopy and GC-MS can identify a more comprehensive metabolite panel than applying each platform in isolation.

We develop a simple method to fabricate the two-stacked graphene monolayers and investigate the electronic transport in such a system. The independence of the two graphene monolayers gives rise to the asymmetric resistance-gate voltage curves and an eight-fold degeneracy of Landau level. The position of the maximum resistance of the transfer curves shifts towards higher gate voltage with increasing magnetic field, which is attributed to the magnetic field induced interlayer decoupling of the stacked graphene monolayers.

Bioelectrochemical systems (BESs) share the principle of the microbially catalyzed anodic substrate oxidation. Creating an electrode interface to promote extracellular electron transfer from microbes to electrode and understanding such mechanisms are crucial for engineering BESs. In this study, significantly promoted electron transfer and a 10-times increase in current generation in a BES were achieved by the utilization of carbon nanotube (CNT) network, compared with carbon paper. The mechanisms for the enhanced current generation with the CNT network were elucidated with both experimental approach and molecular dynamic simulations. The fabricated CNT network was found to be able to substantially enhance the interaction between the c-type cytochromes and solid electron acceptor, indicating that the direct electron transfer from outer-membrane decaheme c-type cytochromes to electrode might occur. The results obtained in this study will benefit for the optimized design of new materials to target the outer membrane proteins for enhanced electron exchanges.

Electrochemically active bacteria (EAB) are ubiquitous in environment and have important application in the fields of biogeochemistry, environment, microbiology and bioenergy. However, rapid and sensitive methods for EAB identification and evaluation of their extracellular electron transfer ability are still lacking. Herein we report a novel photometric method for visual detection of EAB by using an electrochromic material, WO(3) nanoclusters, as the probe. This method allowed a rapid identification of EAB within 5 min and a quantitative evaluation of their extracellular electron transfer abilities. In addition, it was also successfully applied for isolation of EAB from environmental samples. Attributed to its rapidness, high reliability, easy operation and low cost, this method has high potential for practical implementation of EAB detection and investigations.

Bi₂Se₃ nanocrystals with various morphologies, including nanotower, nanoplate, nanoflake, nanobeam and nanowire, have been synthesized. Well-distinguished Shubnikov-de Haas (SdH) oscillations were observed in Bi₂Se₃ nanoplates and nanobeams. Careful analysis of the SdH oscillations suggests the existence of Berry's phase π, which confirms the quantum transport of the surface Dirac fermions in both Bi₂Se₃ nanoplates and nanobeams without intended doping. The observation of the singular quantum transport of the topological surface states implies that the high-quality Bi₂Se₃ nanostructures have superiorities for investigating the novel physical properties and developing the potential applications.

In bioelectrochemical system (BES) the extracellular electron transfer (EET) from bacteria to anode electrode is recognized as a crucial step that governs the anodic reaction efficiency. Here, we report a novel approach to substantially enhance the microbial EET by immobilization of a small active phenothiazine derivative, methylene blue, on electrode surface. A comparison of the currents generated by Shewanella oneidensis MR-1 and its mutants as well as the electrochemical analytical results reveal that the accelerated EET was attributed to enhanced interactions between the bacterial outer-membrane cytochromes and the immobilized methylene blue. A further investigation into the process using in situ Raman spectro-electrochemical method coupled with density functional theory calculations demonstrates that the electron shuttling was achieved through the change of the molecule conformation of phenothiazine in the redox process. These results offer useful information for engineering BES.