Pirin Promotes the Progression of Non-Small-Cell Lung Cancer by Increasing ODC1 to Suppress Autophagy.

Non-small-cell lung cancer (NSCLC), a common malignant tumor, requires deeper pathogenesis investigation. Autophagy is an evolutionarily conserved lysosomal degradation process that is frequently blocked during cancer progression. It is an urgent need to determine the novel autophagy-associated regulators in NSCLC. Here, we found that pirin was upregulated in NSCLC, and its expression was positively correlated with poor prognosis. Overexpression of pirin inhibited autophagy and promoted NSCLC proliferation. We then performed data-independent acquisition-based quantitative proteomics to identify the differentially expressed proteins (DEPs) in pirin-overexpression (OE) or pirin-knockdown (KD) cells. Among the pirin-regulated DEPs, ornithine decarboxylase 1 (ODC1) was downregulated in pirin-KD cells while upregulated along with pirin overexpression. ODC1 depletion reversed the pirin-induced autophagy inhibition and pro-proliferation effect in A549 and H460 cells. Immunohistochemistry showed that ODC1 was highly expressed in NSCLC cancer tissues and positively related with pirin. Notably, NSCLC patients with pirinhigh/ODC1high had a higher risk in terms of overall survival. In summary, we identified pirin and ODC1 as a novel cluster of prognostic biomarkers for NSCLC and highlighted the potential oncogenic role of the pirin/ODC1/autophagy axis in this cancer type. Targeting this pathway represents a possible therapeutic approach to treat NSCLC.

Gray and white matter abnormalities in children with type 2 and 3 SMA: A morphological assessment.

This study investigated the changes in brain gray and white matter structure in SMA patients and their correlation with the severity of the disease. A total of 43 SMA patients (including 22 type II and 21 type III SMA patients) and 37 healthy controls were evaluated by MRI. The gray matter volume, gray matter thickness, gray matter surface area, and white matter volume of designated brain regions automatically segmented by FreeSurfer, were compared. We evaluate clinical characteristics of SMA and study the correlation between clinical characteristics and structural changes. SMA showed significant bilateral cortical superficial area loss in the frontal, parietal, and temporal lobes and global white matter volume decreases. Moreover, these patients were also found with an increased mean thickness of entire brain and right gray matter. An increased right postcentral gyrus superficial area, right central sulcus volume, and white matter volume of the right postcentral were associated with higher HFMSE scores. CONCLUSION: Type 2 and 3 children SMA had extensive, multifocal, symmetrical gray and white matter alterations. Postcentral gyrus degeneration of SMA was associated with the severity of muscular atrophy. The lack of SMN protein possibly interacted with cerebellar structural changes in somatosensory areas. WHAT IS KNOWN: • MRI has found brain changes in SMA patients, however, there is no unified conclusion and lack of correlation with clinical degree in children SMA with type 2-3. WHAT IS NEW: • Type II and II children SMA had extensive, multifocal, symmetrical gray and white matter alterations. Postcentral gyrus degeneration of SMA was associated with the severity of muscular atrophy. Cerebellar structural changes in somatosensory areas may attribute to the lack of SMN protein.

Incorporation of Selenium Derived from Nanoparticles into Plant Proteins in Vivo.

Diets comprising selenium-deficient crops have been linked to immune disorders and cardiomyopathy. Selenium nanoparticles (SeNPs) have emerged as a promising nanoplatform for selenium-biofortified agriculture. However, SeNPs fail to reach field-scale applications due to a poor understanding of the fundamental principles of its behavior. Here, we describe the transport, transformation, and bioavailability of SeNPs through a combination of in vivo and in vitro experiments. We show synthesized amorphous SeNPs, when sprayed onto the leaves of Arabidopsis thaliana, are rapidly biotransformed into selenium(IV), nonspecifically incorporated as selenomethionine (SeMet), and specifically incorporated into two selenium-binding proteins (SBPs). The SBPs identified were linked to stress and reactive oxygen species (mainly H2O2 and O2-) reduction, processes that enhance plant growth and primary root elongation. Selenium is transported both upwards and downwards in the plant when SeNPs are sprayed onto the leaves. With the application of Silwet L-77 (a common agrochemical surfactant), selenium distributed throughout the whole plant including the roots, where pristine SeNPs cannot reach. Our results demonstrate that foliar application of SeNPs promotes plant growth without causing nanomaterial accumulation, offering an efficient way to obtain selenium-fortified agriculture.

Construction and Validation of a Novel Web-Based Nomogram for Solitary Plasmacytoma of Bone of the Spine: A Real-World Analysis Based on the Surveillance, Epidemiology, and End Results Database.

OBJECTIVE: Solitary plasmacytoma of bone of the spine (SPBS) was rarely detected in the past. However, its incidence has gradually increased with improvements in the diagnosis and understanding of the disease. We aimed to conduct a population-based cohort study to characterize the prevalence and factors associated with SPBS and develop a prognostic nomogram for predicting the overall survival of SPBS patients with a real-world analysis based on the surveillance, epidemiology, and end results database. METHODS: Patients with SPBS at diagnosis were identified using the SEER database from 2000-2018. Multivariable and univariate logistic regression analyses were used to identify factors for developing a novel nomogram. Nomogram performance was evaluated using the calibration curve, area under the curve (AUC), and decision curve analyses. Kaplan-Meier analysis was used to estimate survival durations. RESULTS: A total of 1,147 patients were selected for survival analysis. Multivariate analysis demonstrated that independent predictors for SPBS were as follows: ages: 61-74 and 75-94, marital status: unmarried, treatment: radiation alone and radiation with surgery. The 1-, 3-, and 5-year AUCs for OS were 0.733, 0.735, and 0.735 in the training cohort and 0.754, 0.777, and 0.791 in the validation cohort, respectively. The C-index values in the 2 cohorts were 0.704 and 0.729. The results indicated that nomograms could satisfactorily identify patients with SPBS. CONCLUSIONS: Our model effectively demonstrated the clinicopathological features of SPBS patients. The results indicated that the nomogram had a favorable discriminatory ability, good consistency, and yielded clinical benefits for SPBS patients.

The functional change of the P2X7R containing the Ala348 to Thr polymorphism is associated with the pathogenesis of gout.

Our previous study has shown that ATP action on P2X7R could be the second signal to induce the onset of gouty arthritis. However, the functional changes of P2X7R single nucleotide polymorphisms (SNPs) on the effects of ATP-P2X7R-IL-1ß signaling pathway and uric acid remained unknown. We aimed to investigate the association between the functional change of P2X7R containing the Ala348 to Thr polymorphisms (rs1718119) and the pathogenesis of gout. First, 270 gout patients and 70 hyperuricemic patients (without gout attack history in recent 5 years) were recruited for genotyping. In addition, the changes of ATP-induced pore formation were assessed in HEK-293T cells overexpressing different mutants in P2RX7, and the effects on P2X7R-NLRP3-IL-1ß pathway activation were explored in P2RX7 overexpression THP-1 cells. The risk allele for gout was A at rs1718119, and the AA and AG genotypes exhibited a higher risk of gout. Furthermore, Ala348 to Thr mutants increased P2X7-dependent ethidium+ bromide uptake, upregulated IL-1ß and NLRP3 levels as compared to the wild-type. We suggest that genetic polymorphisms of P2X7R containing the Ala348 to Thr are associated with the increased risk of gout, showing an enhanced gain-of-function effect on the development of this disease.

MR microneurography of human peripheral fascicles using a clinical 3T MR scanner.

BACKGROUND AND PURPOSE: Knowledge of nerve fascicular structures is essential for managing peripheral nerve disorders. This study aimed to investigate the feasibility of z-axis high-resolution magnetic resonance (MR) microneurography (zH-MRMN) in displaying the three-dimensional structures of tibial nerve fascicles in vivo using a 3T MR scanner. MATERIALS AND METHODS: Twelve volunteers underwent z-axis conventional-resolution MR microneurography (zC-MRMN) and zH-MRMN of tibial nerves. The visibility scores of the nerve fascicles (VSNFs) on axial zC-MRMN images and axial zH-MRMN multiplanar reformation (MPR) images were compared. The nerve fascicle appearances on the longitudinal zH-MRMN MPR images were described. RESULTS: In the nerve segments whose long axes were perpendicular to the imaging planes of both zC-MRMN and zH-MRMN, the VSNFs were not significantly different between the axial images of the two modalities (P = 0.083). In the nerve segments whose long axes were not perpendicular to the imaging planes of zC-MRMN, the VSNFs on the axial zC-MRMN images were significantly lower than those on the axial zH-MRMN MPR images that were angled perpendicular to the long axis of the tibial nerve (P < 0.001). CONCLUSIONS: The longitudinal zH-MRMN MPR images clearly displayed the changing features of the intraneural fascicles as well as the gross morphology of the tibial nerves. zH-MRMN can clearly delineate the topography of the tibial nerve fascicles in vivo through use of a 3T MR scanner.

ART1 and putrescine contribute to rice aluminum resistance via OsMYB30 in cell wall modification.

Cell wall is the first physical barrier to aluminum (Al) toxicity. Modification of cell wall properties to change its binding capacity to Al is one of the major strategies for plant Al resistance; nevertheless, how it is regulated in rice remains largely unknown. In this study, we show that exogenous application of putrescines (Put) could significantly restore the Al resistance of art1, a rice mutant lacking the central regulator Al RESISTANCE TRANSCRIPTION FACTOR 1 (ART1), and reduce its Al accumulation particularly in the cell wall of root tips. Based on RNA-sequencing, yeast-one-hybrid and electrophoresis mobility shift assays, we identified an R2R3 MYB transcription factor OsMYB30 as the novel target in both ART1-dependent and Put-promoted Al resistance. Furthermore, transient dual-luciferase assay showed that ART1 directly inhibited the expression of OsMYB30, and in turn repressed Os4CL5-dependent 4-coumaric acid accumulation, hence reducing the Al-binding capacity of cell wall and enhancing Al resistance. Additionally, Put repressed OsMYB30 expression by eliminating Al-induced H2 O2 accumulation, while exogenous H2 O2 promoted OsMYB30 expression. We concluded that ART1 confers Put-promoted Al resistance via repression of OsMYB30-regulated modification of cell wall properties in rice.

Observation of the density dependence of the closed-channel fraction of a 6Li superfluid.

Atomic Fermi gases provide an ideal platform for studying pairing and superfluid physics, using a Feshbach resonance between closed-channel molecular states and open-channel scattering states. Of particular interest is the strongly interacting regime. We show that the closed-channel fraction [Formula: see text] provides an effective probe for important many-body interacting effects, especially through its density dependence, which is absent from two-body theoretical predictions. Here we measure [Formula: see text] as a function of interaction strength and the Fermi temperature [Formula: see text] in a trapped 6Li superfluid throughout the entire Bardeen-Cooper-Schrieffer-Bose-Einstein-condensate crossover, in quantitative agreement with theory when important thermal contributions outside the superfluid core are taken into account. Away from the deep-BEC regime, the fraction [Formula: see text] is sensitive to [Formula: see text]. In particular, our data show [Formula: see text] with [Formula: see text] at unitarity, in quantitative agreement with calculations of a two-channel pairing fluctuation theory, and [Formula: see text] increases rapidly into the BCS regime, reflecting many-body interaction effects as predicted.

Temperature-Dependent Decay of Quasi-Two-Dimensional Vortices across the BCS-BEC Crossover.

We systematically study the decay of quasi-two-dimensional vortices in an oblate strongly interacting Fermi gas over a wide interaction range and observe that, as the system temperature is lowered, the vortex lifetime increases in the Bose-Einstein condensate (BEC) regime but decreases at unitarity and in the Bardeen-Cooper-Schrieffer (BCS) regime. The observations can be qualitatively captured by a phenomenological model simply involving diffusion and two-body collisional loss, in which the vortex lifetime is mostly determined by the slower process of the two. In particular, the counterintuitive vortex decay in the BCS regime can be interpreted by considering the competition between the temperature dependence of the vortex annihilation rate and that of unpaired fermions. Our results suggest a competing mechanism for the complex vortex decay dynamics in the BCS-BEC crossover for the fermionic superfluids.

Second sound attenuation near quantum criticality.

Second sound attenuation, a distinctive dissipative hydrodynamic phenomenon in a superfluid, is crucial for understanding superfluidity and elucidating critical phenomena. Here, we report the observation of second sound attenuation in a homogeneous Fermi gas of lithium-6 atoms at unitarity by performing Bragg spectroscopy with high energy resolution in the long-wavelength limit. We successfully obtained the temperature dependence of second sound diffusivity [Formula: see text] and thermal conductivity κ. Furthermore, we observed a sudden rise-a precursor of critical divergence-in both [Formula: see text] and κ at a temperature of about 0.95 superfluid transition temperature [Formula: see text]. This suggests that the unitary Fermi gas has a much larger critical region than does liquid helium. Our results pave the way for determining the universal critical scaling functions near quantum criticality.

A facile strategy for preparation of strong tough poly(lactic acid) foam with a unique microfibrillated bimodal micro/nano cellular structure.

This work reports the design and fabrication of strong tough poly(lactic acid) (PLA) foam by combining pressure-induced-flow (PIF) processing with supercritical CO2 foaming. PIF processing widened the foaming window of PLA to 40-120 °C, while supercritical CO2 foaming released the undesired internal stress of PLA samples with PIF processing (P-PLA). The prepared PLA foams displayed a unique microfibrillated bimodal micro/nano cellular structure which is strongly affected by saturation temperature (Ts). Both micron and nano cells showed decreasing cells size and increasing cell density as Ts elevated. The orientation factor as well as internal stress of PLA foams decreased with increased Ts. Compared with P-PLA samples, PLA foam prepared at Ts of 40 °C showed negligible reduction of orientation from 0.45 to 0.41 and release of internal stress characterized by the rightward shift of Raman peak (stretching vibration of CO bond from 1763 to 1766 cm-1). Furthermore, PLA foam prepared at Ts of 40 °C presented excellent impact strength (32.3 kJ/m2), tensile strength (42.0 MPa), and ductility (14.2%). The combination of PIF processing and supercritical CO2 foaming provides a facile and effective method to prepare strong tough PLA foam that has immense potential in biomedical, aerospace, automotive, and other structural applications.

Evaluation of chemical similarity among rhizome, pseudo stem and leaf of Musa basjoo by UPLC-ELSD fingerprint combined with chemo metrics methods.

Rhizoma Musa (the Rhizome of Musa basjoo Sied.et Zucc.) is used as a traditional medical herb of Miao nationality in Guizhou province, in China. It has the efficacy of clearing heat and detoxifying, quenching thirst, diuresis, etc. Modern pharmacological studies have shown that it has hypoglycemic, inhibition of α-glucosidase, and anti-inflammatory activity. However, when the rhizomes of Musa basjoo are dug up, the rhizomes are unable regenerate, and the pseudostem and leaf are discarded, which not only pollutes the environment, but also causes a huge waste of herb resources. In this study, a UPLC-ELSD fingerprint analysis with chemometric method was applied for the evaluation of chemical similarity among rhizome, pseudostem and leaf of Musa Basjoo. The results indicated that the combined method could efficiently analyze and compare the chemical similarity among rhizome, pseudostem, and leaf of Musa Basjoo. The proposed method provides the foundation for the resource substitution of the rhizome, pseudostem, and leaf of Musa Basjoo.

Synthesis of Transition Metal Complexes and Their Effects on Combustion Properties of Semi-Rigid Polyvinyl Chloride.

Using introduction of MoO42- and Fe3+, Cu2+, or Zn2+ into amphiphilic polymers (DN) via an ion-exchange reaction, different transition metal complexes, as retardants and smoke suppressants, including (DN)Mo, Fe(DN)Mo, Cu(DN)Mo, and Zn(DN)Mo were synthesized. Combined with the results of X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR), it could be determined that ionic bonding of these ions with DN occurred. Subsequently, the influence of flame-retardant, smoke-suppression, and mechanical properties of (DN)Mo, Fe(DN)Mo, Cu(DN)Mo, and Zn(DN)Mo on polyvinyl Chloride (PVC) were tested. It was demonstrated that transition metal complexes of three metal elements, Fe(DN)Mo, Cu(DN)Mo, and Zn(DN)Mo, showed better flame retardancy, smoke suppression, and thermal stability as confirmed by microcalorimetry, limiting oxygen index (LOI), smoke density, and thermogravimetric analysis (TGA) tests, in which Cu(DN)Mo worked best due to the Lewis acid mechanism and reductive coupling mechanism. Scanning electron microscopy (SEM) showed that the addition of (DN)Mo, Fe(DN)Mo, Cu(DN)Mo, and Zn(DN)Mo promoted the formation of a dense carbon layer on the PVC surface during combustion, which could protect the interior PVC. The addition of these transition metal complexes hardly impaired the mechanical properties of PVC.

Expression profile of PU.1 in CD4+T cells from patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with complex genetic predisposing factors involved. PU.1 is an important member of the ETS transcription factors family which has diverse functions such as regulating the proliferation, differentiation of immune cells and multiple inflammatory cytokines. Previous studies preliminary explored the relation between PU.1 and SLE. To further explain the potential role of PU.1 in the pathogenesis of SLE, 40 SLE patients and 20 age-sex matched healthy controls (HC) were recruited in this study. Flow cytometry was used to test the percentages of CD4+PU.1+T cells in peripheral blood mononuclear cells (PBMCs) from patients with SLE and HC. Expression levels of PU.1 mRNA in CD4+T cells from SLE patients and HC were analyzed by real-time transcription-polymerase chain reaction. Expression levels of plasma IL-1ß, IL-9, IL-18, IL-6, IFN-α, TNF-α, IL-10 and TGF-ß1 were measured by enzyme-linked immunosorbent assay. The percentage of CD4+PU.1+T cells in PBMCs from patients with SLE was significantly higher than that from HC (P < 0.001). In addition, the PU.1 mRNA expression in CD4+T cells from SLE patients was increased than that from HC (P = 0.002). In SLE patients, no significant correlation was found between the percentage of CD4+PU.1+T cells and the expression of PU.1 mRNA in CD4+T cells (P > 0.05). Associations of PU.1 mRNA expression in CD4+T cells with major clinical and laboratory parameters of SLE patients were also analyzed, but no significant correlations were found. Consistent with previous studies, SLE patients had increased IL-1ß, IL-18, IL-6, IFN-α, TNF-α and IL-10 plasma concentrations than HC (P < 0.01). The expression level of plasma TGF-ß1 was significantly decreased in SLE patients than in HC (P < 0.001). In SLE patients, the expression level of IL-1ß was positive correlated with PU.1 mRNA expression in CD4+T cells (P = 0.001). Our study first time evaluated the expression profile of PU.1 in CD4+T cells from SLE patients confirming that PU.1 may participate in the pathogenesis of SLE.

Universal Dynamical Scaling of Quasi-Two-Dimensional Vortices in a Strongly Interacting Fermionic Superfluid.

Vortices play a leading role in many fascinating quantum phenomena. Here we generate a large number of vortices by thermally quenching a fermionic superfluid of ^{6}Li atoms in an oblate optical trap and study their annihilation dynamics and spatial distribution. Over a wide interaction range from the attractive to the repulsive side across the Feshbach resonance, these quasi-two-dimensional vortices are observed to follow algebraic scaling laws both in time and space, having exponents consistent with the two-dimensional universality. We further simulate the classical XY model on the square lattice by a Glauber dynamics and find good agreement between the numerical and experimental behaviors. Our work provides a direct demonstration of the universal 2D vortex dynamics.

A CT-based nomogram for predicting the malignant potential of primary gastric gastrointestinal stromal tumors preoperatively.

PURPOSE: To develop and validate a computerized tomography (CT)-based nomogram for predicting the malignant potential of primary gastric gastrointestinal stromal tumors (GISTs). METHODS: The primary and validation cohorts consisted of 167 and 39 patients (single center, different time periods) with histologically confirmed primary gastric GISTs. Clinical data and preoperative CT images were reviewed. The association of CT characteristics with malignant potential was analyzed using univariate and stepwise logistic regression analyses. A nomogram based on significant CT findings was developed for predicting malignant potential. The predictive accuracy of the nomogram was determined by the concordance index (C-index) and calibration curves. External validation was performed with the validation cohort. RESULTS: CT imaging features including tumor size, tumor location, tumor necrosis, growth pattern, ulceration, enlarged vessels feeding or draining the mass (EVFDM), tumor contour, mesenteric fat infiltration, and direct organ invasion showed significant differences between the low- and high-grade malignant potential groups in univariate analysis (P < 0.05). Only tumor size (> 5 cm vs ≤ 5 cm), location (cardiac/pericardial region vs other), EVFDM, and mesenteric fat infiltration (present vs absent) were significantly associated with high malignant potential in multivariate logistic regression analysis. Incorporating these four independent factors into the nomogram model achieved good C-indexes of 0.946 (95% confidence interval [CI] 0.899-0.975) and 0.952 (95% CI 0.913-0.977) in the primary and validation cohorts, respectively. The cutoff point was 0.33, with sensitivity, specificity, and diagnostic accuracy of 0.865, 0.915, and 0.780, respectively. DISCUSSION: Primary gastric GISTs originating in the cardiac/pericardial region appear to be associated with higher malignant potential. The nomogram consisting of CT features, including size, location, EVFDM, and mesenteric fat infiltration, could be used to accurately predict the high malignant potential of primary gastric GISTs.

Analysis of Health Service Utilization and its Influencing Factors among Patients with Pneumoconiosis in China.

Pneumoconiosis, an interstitial lung disease that occurs from breathing in certain kinds of damaging dust particles, is a major occupational disease in China. Patients diagnosed with occupational pneumoconiosis can avail of free medical treatment, whereas patients without a diagnosis of occupational diseases cannot not claim free medical treatment in most provinces from the government before 2019. This study aimed to analyze the priority of medical facility selection and its influencing factors among patients with pneumoconiosis. A total of 1,037 patients with pneumoconiosis from nine provinces in China were investigated. The health service institutions most frequently selected by the patients were county-level hospitals (37.5%). The main reason for the choice was these hospitals' close distance to the patients' homes (47.3%). The factors for the choice of health care institutions were living in the eastern region ( OR = 2.91), living in rural areas ( OR = 2.10), silicosis diagnosis ( OR = 2.44), employment in private enterprises ( OR = 2.91), smoking ( OR = 2.69), and quit smoking ( OR = 3.98). The diagnosis, treatment, and rehabilitation therapy of pneumoconiosis should be enhanced in primary medical institutions.

Rapid Onset of Efficacy of Baricitinib in Chinese Patients with Moderate to Severe Rheumatoid Arthritis: Results from Study RA-BALANCE.

INTRODUCTION: Baricitinib is an oral, selective inhibitor of Janus kinase which demonstrates clinical efficacy in patients with rheumatoid arthritis (RA). This report aims to analyze the onset time of baricitinib in Chinese patients with moderately to severely active RA who had an inadequate response to methotrexate. METHODS: This post hoc analysis evaluated clinical improvements of Chinese patients treated with baricitinib 4 mg once daily compared with placebo, based on data from a phase 3 study RA-BALANCE. Efficacy measures including American College of Rheumatology 20% (ACR20) response, ACR core set values, Disease Activity Score modified to include the 28 diarthrodial joint count (DAS28) using high-sensitivity C-reactive protein (hsCRP), DAS28-erythrocyte sedimentation rate, Simplified Disease Activity Index, Clinical Disease Activity Index, DAS28-hsCRP ≤ 3.2 response (low disease activity), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were evaluated at weeks 1, 2, 4, 8, 12, 14, 16, 20, and 24 (except for FACIT-F evaluated every 4 weeks). A logistic regression model and an analysis of covariance model were used to analyze treatment comparisons of categorical and continuous measures, respectively. RESULTS: Statistically significant (p ≤ 0.05) improvements were observed as early as week 1 or 2 for the baricitinib group compared to placebo in almost all main efficacy measures. For other outcomes including 66 swollen joint count, 68 tender joint count, FACIT-F, and DAS28-hsCRP ≤ 3.2 response rate, differences were evident (p ≤ 0.05) by week 4 in the baricitinib group compared with placebo. Significant improvements in all efficacy measures were sustained through 24 weeks. CONCLUSIONS: Baricitinib demonstrated a rapid onset of efficacy on ACR20 response, ACR core set values, disease activity, and patient-reported outcome improvements in Chinese patients from RA-BALANCE. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02265705.