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Engraulis japonicus , an important fishery resource, is a key species in ecosystem trophodynamics studies. In this study, we examined stomach content of E. japonicusby stable isotope analyses, with samples collected from the East China Sea in 2008-2009 and 2020. The aim of this study was to demonstrate their diet composition, diel and ontogenetic changes in feeding habits and trophic level. Results of the stomach content analysis showed that E. japonicus mainly fed on planktonic crustaceans and small fish. The main prey species were Euphausia pacifica [index of relative importance (IRI)=87.6%; frequency( F )=57.6%], Paracalanus parvus (IRI=3.2%, F =15.3%), and Themisto gracilipes (IRI=2.1%, F =13.1%). Results of the stable isotope analysis showed that Copepoda were the main food source of E. japonicus , followed by Euphausiacea, and the contribution rate of Amphipoda was the least, which was less than 1%. There was significant diel change in diet composition. Feeding intensity was higher in the daytime than at night, with the highest in the dusk and the lowest at midnight. Ontogenetic change in feeding habit occurred when fork length reached 90 mm, over which the fish fed both zooplankton and small fishes. The δ 13 C of E. japonicus was between -21.66‰ and -18.14‰, with an average of (-19.92±0.86)‰. The δ 15 N of E. japonicus ranged from 4.07‰ to 10.78‰, with an average of (8.14±2.48)‰. Both δ 13 C and δ 15 N values were positively correlated with fork length. Trophic level of the fish was 3.4 with stomach content analysis and 2.7 with stable isotope analysis. The results would provide important reference for understanding nutritional status of pelagic small fish, and offer some basic data to establish ecopath model.

A novel ratiometric electrochemical biosensing strategy based on T7 exonuclease (T7 Exo)-assisted homogenous target recycling coupling hairpin assembly triggered dual-signal output was proposed for the accurate and sensitive detection of microRNA-141 (miRNA-141). Concretely, in the presence of target miRNA, abundant signal transduction probes were released via the T7 Exo-assisted homogenous target recycling amplification, which could be captured by the specially designed ferrocene-labeled hairpin probe (Fc-H1) on -electrode interface and triggered the nonenzymatic catalytic hairpin assembly (Fc-H1 + MB-H2) to realize the cascade signal amplification and dual-signal output. Through such a conformational change process, the electrochemical signal of Fc (IFc) and MB (IMB) is proportionally and substantially decreased and increased. Therefore, the signal ratio of IMB/IFc can be employed to accurately reflect the true level of original miRNA. Benefiting from the efficient integration of the T7 Exo-assisted target recycle, nonenzymatic hairpin assembly and dual-signal output mode, the proposed sensor could realize the amplified detection of miRNA-141 effectively with a wide detection range from 1 fM to 100 pM, and a detection limit of 200 aM. Furthermore, it exhibits outstanding sequence specificity to discriminate mismatched RNA, acceptable reproducibility and feasibility for real sample. This strategy effectively integrated the advantages of multiple amplification and ratiometric output modes, which could provide an accurate and efficient method in biosensing and clinical diagnosis.

Explorations of new types of borates are important because of their promising application in diverse fields. A new bismuth-containing boroselenite, Bi 2 [B 2 (SeO 3 ) 6 ], has been obtained through high-temperature solid-state reaction in a closed system. Bi 2 [B 2 (SeO 3 ) 6 ] possesses a zero-dimensional [B 2 (SeO 3 ) 6 ] 6- anionic group that does not belong to any types of reported boroselenites. Besides, Bi 2 [B 2 (SeO 3 ) 6 ] is the first boroselenite with lone-pair electrons containing a metal ion as the countercation. More interestingly, on the basis of the first-principles calculations, this compound displays a large birefringence (0.090) at 1064 nm.

Two new antimonous phosphates, namely Ba 3 Sb 2 (PO 4 ) 4 and Cd 3 Sb 2 (PO 4 ) 4 (H 2 O) 2 , have been successfully prepared through mild hydrothermal reactions. Ba 3 Sb 2 (PO 4 ) 4 features a 1D [Sb(PO 4 ) 2 ] 3- chain structure separated by Ba 2+ cations while Cd 3 Sb 2 (PO 4 ) 4 (H 2 O) 2 presents a 2D [Sb(PO 4 ) 2 ] 3- layered structure with Cd 2+ located at the interlayer space. The [Sb(PO 4 ) 2 ] 3- chain in Ba 3 Sb 2 (PO 4 ) 4 is the first example of 1D antimonous phosphate structure, and Cd 3 Sb 2 (PO 4 ) 4 (H 2 O) 2 represents the first d 10 transition metal antimonous phosphate. Based on UV-vis-NIR spectra, both Ba 3 Sb 2 (PO 4 ) 4 and Cd 3 Sb 2 (PO 4 ) 4 (H 2 O) 2 can display large optical band gaps (4.30 and 4.36 eV, respectively). But their transparent ranges are quite different because of the coordination water of Cd 3 Sb 2 (PO 4 ) 4 (H 2 O) 2 (500-2000 and 500-1300 nm for Ba and Cd compounds). The anhydrous Ba 3 Sb 2 (PO 4 ) 4 shows high thermal stability in the nitrogen atmosphere (900 °C). Because of the incorporation of the lone pair cation of Sb(III), the birefringence of Ba 3 Sb 2 (PO 4 ) 4 and Cd 3 Sb 2 (PO 4 ) 4 (H 2 O) 2 has been enhanced to 0.086 and 0.053 at 532 nm, respectively.

Nonlinear optical (NLO) crystals assembled with conventional non-π-conjugated tetrahedral functional building units (FBUs), generally referring to [PO 4 ] and [BO 4 ], usually exhibit weak nonlinearity and poor birefringence. It is currently proposed that partially substituting oxygen atoms with fluoride atoms in these FBUs could enhance these crucial properties. Hence, we investigated for the first time the NLO-related properties of NH 4 BAsO 4 F (ABAF), which was constructed from tetrahedral [BO 3 F] and [AsO 4 ] FBUs, and enhancements of these properties were observed in this material, that is large second-harmonic generation (SHG) response (2 × KDP) and improved birefringence (0.03 at 1064 nm). Notably, both SHG coefficient and birefringence of ABAF exceeded those of a great majority of phosphates, sulfates, or boron phosphates and achieved a preferable balance. It is interesting that ABAF shows vast structural similarities to the typical NLO crystals Sr 2 Be 2 B 2 O 7 (SBBO) and KBe 2 BO 3 F 2 (KBBF), which might be the partial reason why it showed improvement in these vital properties. This work may afford some inspiration for enhancing the key performances of NLO crystals assembled with non-π-conjugated tetrahedra., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

Objective: To study the metabolic derangements in the second half of pregnancy caused by gestational diabetes mellitus(GDM), on the short term neurodevelopment of infants., Design: A prospective cohort study of 555 mother-child pairs were recruited, which included 177 GDM patients and 378 pregnant women with normal glucose tolerance as controls. Clinical and demographic characteristics were obtained at enrollment, birth and follow-up. Neurodevelopment was examined with the Bayley Scales of Infant Development V.1 mental development index (MDI) and psychomotor development index (PDI). Fatty acids (FA) were analyzed by gas chromatography mass spectrometry (GC-MS)., Results: Statistically significant differences were found between the two groups in fasting plasma glucose (FPG) and triglyceride (TG). The scores of MDI and PDI of control group were higher than those of GDM group. The regression analysis showed that maternal age and saturated fatty acid (SFA) were independently associated with lower scores on the MDI whereas gestational age and docosahexaenoic acid (DHA) were associated with higher scores; in addition, lower scores on the PDI were associated with FPG and neonatal weigh associated with higher scores., Conclusion: SFA, DHA and FPG as indicators of lipid metabolism were associated with neurodevelopmental outcome at 1 year in offspring of women with gestational diabetes mellitus. Control the level of blood glucose and lipid during pregnancy and the appropriate supplementation of DHA during pregnancy in the second half of pregnancy may be beneficial to the neurodevelopment of infants.

Large birefringence (Δn = 0.277 at 546 nm) and strong second-harmonic generation (SHG) intensity (4.3 × KDP) achieved a remarkable balance in a potential ultraviolet nonlinear optical crystal: 2(C 3 H 7 N 6 ) + ·2Cl - ·H 2 O. Theoretical calculations showed that planar benzene-like π-conjugated [C 3 N 6 ] groups had important optical properties.

We report a new strongly birefringent material, [Al(H 2 O) 6 ](IO 3 ) 2 (NO 3 ) (AINO). Based on a detailed analysis, we concluded that its enhanced birefringence (0.253 at 546 nm) predominantly resulted from a synergy of the effects of its (NO 3 ) - and (IO 3 ) - functional motifs, combined with an equally important and indispensable optimal arrangement of these two groups in the structure. This work has provided insight for discovering new birefringent materials.

Selective pumping and probing of highly excited states of molecules are essential in various studies but are also challenging because of high density of states, weak transition moments, and lack of precise spectroscopy data. We develop a comb-locked cavity-assisted double-resonance spectroscopy (COCA-DR) method for precision measurements using low-power continuous-wave lasers. A high-finesse cavity locked with an optical frequency comb is used to enhance both the pumping power and the probing sensitivity. As a demonstration, Doppler-free stepwise two-photon absorption spectra of CO 2 were recorded by using two milliwatt diode lasers (1.60 and 1.67 μm), and the rotation energies in a highly excited state (CO-stretching quanta = 8) were determined with an unprecedented accuracy of a few kilohertz.

We aimed to establish a discriminative gene-expression-based classifier to predict survival outcomes of T-cell lymphoblastic lymphoma (T-LBL) patients. After exploring global gene-expression profiles of progressive (n = 22) vs. progression-free (n = 28) T-LBL patients, 43 differentially expressed mRNAs were identified. Then an eleven-gene-based classifier was established using LASSO Cox regression based on NanoString quantification. In the training cohort (n = 169), high-risk patients stratified using the classifier had significantly lower progression-free survival (PFS: hazards ratio 4.123, 95% CI 2.565-6.628; p < 0.001), disease-free survival (DFS: HR 3.148, 95% CI 1.857-5.339; p < 0.001), and overall survival (OS: HR 3.790, 95% CI 2.237-6.423; p < 0.001) compared with low-risk patients. The prognostic accuracy of the classifier was validated in the internal testing (n = 84) and independent validation cohorts (n = 360). A prognostic nomogram consisting of five independent variables including the classifier, lactate dehydrogenase levels, ECOG-PS, central nervous system involvement, and NOTCH1/FBXW7 status showed significantly greater prognostic accuracy than each single variable alone. The addition of a five-miRNA-based signature further enhanced the accuracy of this nomogram. Furthermore, patients with a nomogram score ≥154.2 significantly benefited from the BFM protocol. In conclusion, our nomogram comprising the 11-gene-based classifier may make contributions to individual prognosis prediction and treatment decision-making.

This study investigated how visual feedback of virtual error reduction (ER) modified the visuomotor performance of older adults with limited attentional capacity. Error structures of young and older adults during birhythmic force tracking were contrasted when the visualized error size was exact or half of the actual size. As compared with full-size error feedback, ER feedback improved the force tracking symmetry of older adults, but undermined that of young adults. Extended Poincaré analysis revealed that young adults presented greater short-term error variability (mean value of κ-lagged SD1 of the error signal) with ER feedback, which led to a smaller mean value of κ-lagged SD1 of the error signal for older adults. The ER-related task improvement of the older adults was negatively correlated with the size of the tracking errors with real error feedback and positively correlated with ER-related increases in force spectral symmetry and decreases in the mean value of κ-lagged SD1 of the error signal. ER feedback could advance visuomotor tasks for older adults who perform worse with full-size visual feedback by the enhancement of self-efficacy and stabilization of negative internal feedback.

Purpose: Adults with T-cell lymphoblastic lymphoma (T-LBL) generally benefit from treatment with acute lymphoblastic leukemia (ALL)-like regimens, but approximately 40% will relapse after such treatment. We evaluated the value of CpG methylation in predicting relapse for adults with T-LBL treated with ALL-like regimens., Experimental Design: A total of 549 adults with T-LBL from 27 medical centers were included in the analysis. Using the Illumina Methylation 850K Beadchip, 44 relapse-related CpGs were identified from 49 T-LBL samples by two algorithms: least absolute shrinkage and selector operation (LASSO) and support vector machine-recursive feature elimination (SVM-RFE). We built a four-CpG classifier using LASSO Cox regression based on association between the methylation level of CpGs and relapse-free survival in the training cohort ( n = 160). The four-CpG classifier was validated in the internal testing cohort ( n = 68) and independent validation cohort ( n = 321)., Results: The four-CpG-based classifier discriminated patients with T-LBL at high risk of relapse in the training cohort from those at low risk ( P < 0.001). This classifier also showed good predictive value in the internal testing cohort ( P < 0.001) and the independent validation cohort ( P < 0.001). A nomogram incorporating five independent prognostic factors including the CpG-based classifier, lactate dehydrogenase levels, Eastern Cooperative Oncology Group performance status, central nervous system involvement, and NOTCH1 / FBXW7 status showed a significantly higher predictive accuracy than each single variable. Stratification into different subgroups by the nomogram helped identify the subset of patients who most benefited from more intensive chemotherapy and/or sequential hematopoietic stem cell transplantation., Conclusions: Our four-CpG-based classifier could predict disease relapse in patients with T-LBL, and could be used to guide treatment decision., (©2020 American Association for Cancer Research.)

SETD2, the histone H3 lysine 36 methyltransferase, previously identified by us, plays an important role in the pathogenesis of hematologic malignancies, but its role in myelodysplastic syndromes (MDSs) has been unclear. In this study, low expression of SETD2 correlated with shortened survival in patients with MDS, and the SETD2 levels in CD34+ bone marrow cells of those patients were increased by decitabine. We knocked out Setd2 in NUP98-HOXD13 (NHD13) transgenic mice, which phenocopies human MDS, and found that loss of Setd2 accelerated the transformation of MDS into acute myeloid leukemia (AML). Loss of Setd2 enhanced the ability of NHD13+ hematopoietic stem and progenitor cells (HSPCs) to self-renew, with increased symmetric self-renewal division and decreased differentiation and cell death. The growth of MDS-associated leukemia cells was inhibited though increasing the H3K36me3 level by using epigenetic modifying drugs. Furthermore, Setd2 deficiency upregulated hematopoietic stem cell signaling and downregulated myeloid differentiation pathways in the NHD13+ HSPCs. Our RNA-seq and chromatin immunoprecipitation-seq analysis indicated that S100a9, the S100 calcium-binding protein, is a target gene of Setd2 and that the addition of recombinant S100a9 weakens the effect of Setd2 deficiency in the NHD13+ HSPCs. In contrast, downregulation of S100a9 leads to decreases of its downstream targets, including Ikba and Jnk, which influence the self-renewal and differentiation of HSPCs. Therefore, our results demonstrated that SETD2 deficiency predicts poor prognosis in MDS and promotes the transformation of MDS into AML, which provides a potential therapeutic target for MDS-associated acute leukemia., (© 2020 by The American Society of Hematology.)

The search of novel second-harmonic generation crystals in gallium selenite systems results in three new compounds of MGa 2 (SeO 3 ) 4 (M = Sr, Pb) and BiGa(SeO 3 ) 3 . The isostructural MGa 2 (SeO 3 ) 4 (M = Sr, Pb) are centrosymmetric ( P 1̅, no. 2). The structures represent a complicated three-dimensional skeleton containing two different types of Ga 4 Se 4 8-member polyhedral ring tunnels with the counter cations located at the broad ones. When the divalent counter cations were substituted by a trivalent lone pair cation of Bi(III), a novel noncentrosymmetric compound of BiGa(SeO 3 ) 3 was achieved. BiGa(SeO 3 ) 3 displays a 3D gallium selenite framework with 1D bismuth oxide chains filling in the 12-member polyhedral ring tunnels. Frequency doubling measurements showed that BiGa(SeO 3 ) 3 presented an apparent SHG signal comparable to the commercial KDP and can realize phase matching. The lone pair anionic groups of SeO 3 2- made the major contribution according to the SHG density analyses. BiGa(SeO 3 ) 3 exhibits a wide transparent range and large optical bandgap (3.90 eV). The laser-induced damage threshold of BiGa(SeO 3 ) 3 was estimated to be 98.68 MW/cm 2 , about 44 × AGS.

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Ubiquitin-specific peptidase 10 (USP10) stabilizes both tumor suppressors and oncogenes in a context-dependent manner. However, the nature of USP10's role in non-small cell lung cancer (NSCLC) remains unclear. By analyzing The Cancer Genome Atlas (TCGA) database, we have shown that high levels of USP10 are associated with poor overall survival in NSCLC with mutant p53, but not with wild-type p53. Consistently, genetic depletion or pharmacological inhibition of USP10 dramatically reduces the growth of lung cancer xenografts lacking wild-type p53 and sensitizes them to cisplatin. Mechanistically, USP10 interacts with, deubiquitinates, and stabilizes oncogenic protein histone deacetylase 6 (HDAC6). Furthermore, reintroducing either USP10 or HDAC6 into a USP10-knockdown NSCLC H1299 cell line with null-p53 renders cisplatin resistance. This result suggests the existence of a "USP10-HDAC6-cisplatin resistance" axis. Clinically, we have found a positive correlation between USP10 and HDAC6 expression in a cohort of NSCLC patient samples. Moreover, we have shown that high levels of USP10 mRNA correlate with poor overall survival in a cohort of advanced NSCLC patients who received platinum-based chemotherapy. Overall, our studies suggest that USP10 could be a potential biomarker for predicting patient response to platinum, and that targeting USP10 could sensitize lung cancer patients lacking wild-type p53 to platinum-based therapy.

In this study, we investigated if subunit displacement and/or alterations in proteasome biosynthesis are responsible for the changes in the levels of constitutive proteasomes (c-20S), immunoproteasomes (i-20S) and the activators PA28 and PA700 in neurons and astrocytes cultured with a cytokine mixture (IFN-γ/TNF-α/IL-1β). Exposure of both cell types to cytokines for 24 h increases mRNA and protein expression of the i-20S-specific subunit β5i and PA28α/β, and leads to a decline in the amount of the c-20S-specific subunit β5. Since β5 mRNA levels are unchanged by the cytokine treatment, it is fair to conclude that displacement of constitutive β-subunits with inducible β5i subunits is likely the mechanism underlying the decrease in c-20S. As expected, the increase in the amount of the IFN-γ-inducible subunits coincides with elevated expression of phospho-STAT-1 and interferon regulatory factor-1 (IRF-1). However, inhibition of NF-κB signaling in cytokine-treated astrocytes reduces IRF-1 expression without affecting that of i-20S, c-20S and PA28. This suggests that STAT-1 is capable of increasing the transcription of i20S-specific subunits and PA28α/β by itself. The lack of a decrease in proteasome β5 mRNA expression is consistent with the fact that Nrf1 (Nfe2l1) and Nrf2 (Nfe2l2) levels are not reduced by pro-inflammatory cytokines. In contrast, we previously found that there is a significant Nrf1 dysregulation and reduced β5 mRNA expression in the spinal cords of mice with experimental autoimmune encephalomyelitis (EAE). Thus, there are stressors in EAE, other than a pro-inflammatory environment, that are not present in cytokine-treated cells.

The first alkali-metal vanadium iodate fluoride, CsVO 2 F(IO 3 ), with a novel 3D anionic framework, has been rationally designed and hydrothermally synthesized. The 3D [VO 2 F(IO 3 )] - framework in CsVO 2 F(IO 3 ) is built from 0D Λ-shaped cis-[VO 3 F(IO 3 ) 2 ] 4- polyanions via corner-sharing of oxo anions and bridging of the iodate groups. CsVO 2 F(IO 3 ) displays both a strong second-harmonic generation (SHG) 1.1 times as strong as KTiOPO 4 (KTP) under 2.05 μm laser radiation and high laser-induced damage threshold (LIDT) of 107.9 MW cm -2 . This work provides a new route to design SHG crystals with stable 3D anionic structures from low-dimensional structural building units., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Platelets (PLTs) are involved in tumor growth, metabolism and vascular activation. PLT-based models have been reported to have significant value on the recurrence of malignant hepatic tumors. The present study aimed to investigate the effect of PLT count and 18 PLT-based models on the prognosis of patients with malignant hepatic tumors. The clinical data from 189 patients with malignant hepatic tumors were retrospectively analyzed and used to calculate the scores of the 18 PLT-based models. Receiver operating characteristic curve was used to determine the suitable cut-off values of mortality and recurrence in patients with malignant hepatic tumors. The overall survival and cumulative recurrence rates of patients were calculated using Kaplan-Meier survival curves and the difference was analyzed using log-rank test. Multivariate analysis was performed to determine the independent risk factors of recurrence-free survival and overall survival. In the present study, 11 models were considered as predictors of mortality (P<0.05) and six models were considered as predictors of recurrence (P<0.05). The results from multivariate analysis demonstrated that vascular cancer embolus, uric acid >231 µmol/l, hemoglobin >144 g/l and the Lok index model >0.695 were considered as independent risk factors of mortality (P<0.05). Furthermore, vascular cancer embolus, PLT to lymphocyte ratio (PLR) >175 and fibrosis-4 (FIB-4) >4.82 were independent factors of recurrence (P<0.05). In addition, the results from this study indicated that the Lok-index could be considered as a predictor of the overall survival rate. In conclusion, the FIB-4 and PLR model may be valuable for predicting the recurrence-free rate of patients with malignant hepatic tumors., (Copyright: © Hu et al.)

The goal of this study was to determine if subunit displacement and/or alterations in proteasome biosynthesis could explain the changes observed in the levels of constitutive proteasomes (c-20S) and immunoproteasomes (i-20S) in the spinal cords of mice with experimental autoimmune encephalomyelitis (EAE). To this end, EAE was induced in C57BL/6 mice by immunization with MOG 35-55 peptide. Spinal cords were collected at different times during the disease course and used for western blotting, RNA analysis, and immunohistochemistry. The results show that, as expression of i-20S and the activator PA28 rise in EAE, there is a concomitant decline in that of c-20S at the mRNA and protein level. These changes are observed in neurons and astrocytes but not in oligodendrocytes. The increased amounts of the i-20S-specific subunit β5i and PA28α/β in EAE correlate with the levels of interferon-γ and its downstream effectors p-signal transducer and activator of transcription 1 and interferon regulatory factor-1, but not with those of nuclear factor kappa-light-chain-enhancer of activated B cells. This suggests that the signal transducer and activator of transcription 1/interferon regulatory factor-1 pathway is solely responsible for the induction of these subunits. The decrease in the mRNA and protein levels corresponding to the c-20S-specific subunit β5 may also be due to reduced expression of the nuclear factor (erythroid-derived 2)-like-1 (Nrf1 or Nfe2l1), specifically Nrf1α and Nrf1β. Low Nfe2l1 mRNA expression is unlikely caused by reduced mammalian target of rapamycin signaling but could be the result of diminished pre-B-cell leukemia homeobox-1 transcription factor levels. Together, these findings suggest that a combination of subunit displacement and reduced Nrf1 expression may be responsible for c-20S impairment in EAE. The present work provides insights into the dynamics of proteasome expression in the CNS of EAE mice and is the first to explore Nrf1 signaling in an inflammatory demyelinating disorder., (© 2019 International Society for Neurochemistry.)

Introduction: The recurrence of cholecystolithiasis after choledochoscopic gallbladder-preserving surgery is a major problem. It is unclear whether the recurrence of cholecystolithiasis is due to the limitations of the operation itself or to the selection of inappropriate candidates., Aim: To analyze the recurrence of cholecystolithiasis after choledochoscopic gallbladder-preserving surgery and to provide guidance for the treatment of cholecystolithiasis by choledochoscopic gallbladder-preserving surgery., Material and Methods: A total of 145 patients who had undergone choledochoscopic gallbladder-preserving surgery were studied from January 2012 to January 2018. The recurrence rate, recurrence time, and risk factors were evaluated., Results: Of these 145 patients, 14 (9.66%) experienced recurrence with a mean follow-up time of 39.72 ±24.44 months. The mean time to recurrence was 30.07 ±21.21 months. Univariate analysis showed that pregnancy history (p = 0.008), the uniformity of gallstones (p = 0.002), preoperative inflammation (p = 0.022), postoperative oral drugs (p = 0.022) and the regularity of diet (p = 0.001) were significantly related to recurrence. The uniformity of gallstones (odds ratio (OR) = 0.079; 95% confidence interval (CI): 0.010-0.590; p = 0.013) and the regularity of diet (OR = 0.074; 95% CI: 0.010-0.528; p = 0.009) were independent prognostic factors for recurrence according to multivariate analysis., Conclusions: Nonuniform gallstones combined with an irregular diet are significant risk factors that predict cholecystolithiasis recurrence., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2019 Fundacja Videochirurgii.)

Six spirobiflavonoid stereoisomers including two new ones, spiropensilisols A (1) and B (2), were isolated from a mass-limited trunk barks of Glyptostrobus pensilis, an endangered conifer endemic to China. The new structures featuring a benzofuran-containing spirolactone and their absolute configurations were determined by extensive spectroscopic methods. All the isolates showed significant inhibitory activities against the human protein tyrosine phosphatase 1B (PTP1B) enzyme, a potential therapeutic target for diabetes and obesity, with IC 50 values ranging from 3.3 to 17.1 µM. A preliminary SAR analysis with assistance of the molecular modeling approach was performed for the most potent compound (i.e., 1), to understand the nature of interactions governing the binding mode of spirobiflavonids within the active site of the PTP1B enzyme., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Due to the intriguing chemical variability and structure-property flexibility, molecular materials with striking multifunctional characteristics, including tunable physical, chemical, optical, and electronic properties, have aroused wide attention. Recently, great advances have also been made in designing molecular ferroelastics with optoelectronic properties. However, the band gaps of the most typical ferroelastics are far in excess of 2.0 eV, which severely hinder their further applications. And this corresponds to the inherent incompatibility of ferroelastics. Herein we report an organometallic compound, ferrocenium tetrachloroferrate ( 1 ), undergoing a ferroelastic phase transition at 407.7 K with a large spontaneous strain of 0.1088. To the best of our knowledge, this is the first molecular ferroelastic with such a high Curie temperature ( T c ) and narrow band gap of 1.61 eV. UV-vis absorption spectra and density-functional theory (DFT) calculation confirm this band gap. The band gap of 1 is determined by both the ferrocenium and the tetrachloroferrate components. The ideal semiconducting characteristic makes a breakthrough in the inherent incompatibility with ferroelastics. This will inspire an intriguing and further research in molecular ferroelastics with ideal semiconductor characteristics and hold great potential for the utilization in optoelectronic devices, especially the photovoltaic applications.

Quantitative determination of atmospheric CO 2 concentration by remote sensing relies on accurate line parameters. Lamb dips of the lines up to J'' = 72 in the 30013-00001 band at 1605 nm were measured using a comb-locked cavity ring-down spectrometer, and the positions were determined with an accuracy of a few kHz. A simple effective Hamiltonian model can fit the rotational energies in the 30013 state ideally within the experimental accuracy, indicating that the vibrational state is well-isolated and can be regarded as free from perturbations. From a comparison between other bands using a similar analysis, we conclude that the transitions in the 30013-00001 band could be more suitable as reference lines for sensing applications with the potentially improved line parameter accuracy.

The first divalent-metal iodate-phosphate, Pb 2 (IO 3 )(PO 4 ), has been prepared via the strategy of introducing (IO 3 ) - into phosphate. The structure features a unique 3D network where [Pb(IO 3 )] ∞ + and [Pb(PO 4 )] ∞ - layers are alternatively interconnected. The birefringence of Pb 2 (IO 3 )(PO 4 ) is greatly increased to 0.060 at 1064 nm.

Objective: The aim of our meta-analysis was to explore whether overweight and obesity was associated with preeclampsia or not., Design: Three databases were systematically reviewed and reference lists of relevant articles were checked. Meta-analysis of published cohort studies comparing whether overweight and obesity was associated with preeclampsia and adjusting for potential confounding factors. Calculations of pooled estimates were conducted in random-effects models. Heterogeneity was tested by using Chi-square test with Cochrane and heterogeneity was explored with meta-regression. Publication bias was estimated from Egger's test (linear regression method) and Begg's test (rank correlation method)., Results: Nineteen studies met the inclusion criteria. The meta-analysis showed that overweight and obesity was associated with an increased risk of preeclampsia. The aOR calculated for 13 studies (compared overweight to normal weight) was 1.71, 95% CI (1.52, 1.91) for random-effects models and 19 studies (compared obesity to normal weight) was 2.48, 95% CI (2.05, 2.90) for random-effects models, stratified analyses showed no differences regarding quality grade, location of study and period of anthropometric measurement. There was no indication of a publication bias either from the result of Egger's test or Begg's test., Conclusions: Our results suggested that prepregnancy maternal overweight and obesity are significantly associated with an increased risk of preeclampsia., (Copyright © 2020 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Given the limitations of existing therapeutic agents for treatment of postmenopausal osteoporosis, there still remains a need for more options with both efficacy and less adverse effects. Cistanche deserticola Y. C. Ma is known as a popular tonic herb traditionally used to treatment deficiency of kidney energy including muscle weakness in minority area of Asian counties. Based on the theory of "kidney dominate bone," an ovariectomized (OVX) rat model of postmenopausal osteoporosis was used to evaluate the therapeutic effect of C. deserticola extract (CDE) on bone loss. Forty eight female Sprague-Dawley rats, aged about 12 weeks, were randomly assigned into six groups including sham group orally administrated with 0.5% carboxymethyl cellulose sodium (CMC-Na) (sham), positive group treated with 1 mg/kg of estradiol valerate (EV), low, moderate, and high dosage groups orally administrated with 200, 400, and 800 mg/kg/day of CDE, respectively. After 3 months of continuous intervention, CDE exhibited significant anti-osteoporotic activity evidenced by the enhanced total bone mineral density, ameliorated bone microarchitecture; increased alkaline phosphatase activity; decreased deoxypyridinoline, cathepsin K, tartrate-resistant acid phosphatase, and malondialdehyde levels; whereas the body, uterus, and vagina weights in OVX rats were not influenced by CDE intervention. In addition, a seemed contradictory phenomenon on levels of calcium and phosphorus between OVX and sham rats were observed and elucidated. Mechanistically, CDE significantly down-regulated the levels of TRAF6, RANKL, RANK, NF-κB, IKKβ, NFAT2, and up-regulated the phosphatidylinositol 3-kinase (PI3K), AKT, osteoprotegerin, and c-Fos expressions, which implied CDE could suppress RANKL/RANK-induced activation of downstream NF-κB and PI3K/AKT pathways, and ultimately, preventing activity of the key osteoclastogenic proteins NFAT2 and c-Fos. All of the data suggested CDE possessed potential anti-osteoporotic activity and this effect was, at least in part, involved in modulation of RANKL/RANK/TRAF6-mediated NF-κB and PI3K/AKT signaling as well as c-Fos and NFAT2 levels. Therefore, CDE may represent a useful promising remedy candidate for treatment of postmenopausal osteoporosis., (Copyright © 2019 Zhang, Yang, Ding, Liu, Dong, Li, Li, Zhao, Hu, Jiang and Ma.)

A cesium bismuth germanate, Cs 2 Bi 2 O(Ge 2 O 7 ) (CBGO), was synthesized by a traditional high-temperature solid-state reaction. Its structure features a 3D network composed of a 1D chains composed of Bi 2 O 8 dimers that are further bridged by Ge 2 O 7 dimers, forming tunnels of seven member rings (MRs) that are filled by the Cs + cations. CBGO exhibits extraordinary larger second harmonic generation (SHG) response of about 13.7 times that of KDP (KH 2 PO 4 ) under 1064 nm laser radiation and 1.1 times that of KTP (KTiOPO 4 ) under 2.05 μm laser radiation, which is the highest among all of the metal germanates reported so far. CBGO possesses a moderate birefringence (0.073 at 1064 nm) and is phase matchable. Furthermore, CBGO melts congruently and exhibits high thermal stability., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

An excellent second harmonic generation (SHG) material, LiMg(IO 3 ) 3 (LMIO), has been elaborately designed from Li 2 M IV (IO 3 ) 6 (M IV = Ti, Sn, and Ge) by aliovalent substitution of the central M IV cation followed by Wyckoff position exchange. The new structure sustains the ideal-alignment of (IO 3 ) - groups. Importantly, LMIO exhibits an extremely strong SHG effect of roughly 24 × KH 2 PO 4 (KDP) under 1064 nm laser radiation or 1.5 × AgGaS 2 (AGS) under 2.05 μm laser radiation, which is larger than that of α-LiIO 3 (18 × KDP). The replacement of M IV with Mg 2+ without d-d electronic transitions induces an obviously larger band gap (4.34 eV) with a short absorption edge (285 nm). This study shows that single-site aliovalent substitution provides a new synthetic route for designing SHG materials., (This journal is © The Royal Society of Chemistry 2019.)

New prognostic factors are needed to establish indications for haematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) for T-cell lymphoblastic lymphoma (T-LBL) patients. We used microarray to compare T-LBL tissue samples (n = 75) and fetal thymus tissues (n = 20), and identified 35 differentially expressed miRNAs. Using 107 subjects as the training group, we developed a five-miRNA-based classifier to predict patient survival with LASSO Cox regression: lower risk was associated with better prognosis (disease-free survival (DFS): hazard ratio (HR) 4.548, 95% CI 2.433-8.499, p < 0.001; overall survival (OS): HR 5.030, 95% CI 2.407-10.513, p < 0.001). This classifier displayed good performance in the internal testing set (n = 106) and the independent external set (n = 304). High risk was associated with more favorable response to HSCT (DFS: HR 1.675, 95% CI 1.127-2.488, p = 0.011; OS: HR 1.602, 95% CI 1.055-2.433, p = 0.027). When combined with ECOG-PS and/or NOTCH1/FBXW7 status, this classifier had even better prognostic performance in patients receiving HSCT (DFS: HR 2.088, 95% CI 1.290-3.379, p = 0.003; OS: HR 1.996, 95% CI 1.203-3.311, p = 0.007). The five-miRNA classifier may be a useful prognostic biomarker for T-LBL adults, and could identify subjects who could benefit from HSCT.

In response to ever-increasing application requirements in lighting and displays, a tremendous emphasis is being placed on single-component white-light emission. Single-component inorganic borates doped with rare earth metal ions have shown prominent achievements in white-light emission. The first environmentally friendly defect-induced white-light emitting crystalline inorganic borate, Ba 2 [Sn(OH) 6 ][B(OH) 4 ] 2 , has been prepared. Additionally, it is the first borate-stannate without a Sn-O-B linkage. Notably, Ba 2 [Sn(OH) 6 ][B(OH) 4 ] 2 shows Commission Internationale de l'Eclairage (CIE) chromaticity coordinates of (0.42, 0.38), an ultrahigh color rendering index (CRI) of 94.1, and an appropriate correlated color temperature (CCT) of 3083 K. Such a promising material will provide a new approach in the development of white-light emitting applications., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: To investigate the prognostic value of 17 platelet-based prognostic scores in patients with malignant hepatic tumors after TACE therapy., Methods: In total, 92 patients were divided into death group and survival group according to long-term follow-up results. The AUC was calculated to determine the optimal cut-off values for predicting prognosis. To determine better prognostic models, platelet-based models were analyzed separately after being showed as binary according to cut-off values. Cumulative survival rates of malignant hepatic tumors were calculated using Kaplan-Meier curves and differences were analyzed by the log-rank test. Univariate and multivariate analyses were performed to identify platelet-based prognostic scores associated with overall survival., Results: Univariate analysis showed that APGA, APRI, FIB-4, FibroQ, GUCI, King's score, Lok index, PAPAS, cirrhosis, number of tumors, vascular cancer embolus, AFP, ALP and APTT were significantly related to prognosis. A multivariate analysis showed that the APGA, number of tumors, ALP and APTT were independently associated with overall survival., Conclusion: This study showed that the APGA, a platelet-based prognostic score, was an independent marker of prognosis in patients with malignant hepatic tumors after TACE and was superior to the other platelet-based prognostic scores in terms of prognostic ability.

The first examples of rare-earth polyiodates, namely, REI 5 O 14 (RE=Y and Gd), have been prepared by hydrothermal reactions of RE 2 O 3 and H 5 IO 6 in H 3 PO 4 (≥85 wt % in H 2 O), with extremely high yields (>95 %). They crystalize in the polar space group Cm and feature a brand-new semicircle-shaped [I 5 O 14 ] 3- pentameric polyiodate anion composed of two IO 3 and three IO 4 polyhedra. Remarkably, both compounds exhibit very large second-harmonic generation (SHG) signals (14× and 15×KH 2 PO 4 (KDP) upon 1064 nm laser radiation for Y and Gd compounds, respectively). Our work shows that the hydrothermal reaction in a phosphoric acid medium facilitates the formation of rare-earth polyiodates., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A new ultraviolet nonlinear optical material, namely LiHgPO 4 , was synthesized using the mild hydrothermal method. The structure of LiHgPO 4 features novel double layers constructed by severely distorted HgO 6 octahedra and PO 4 tetrahedra, which are further interconnected by LiO 4 tetrahedra to form a three-dimensional structure. LiHgPO 4 exhibits a very strong second harmonic generation (SHG) response of 11.0 times that of KH 2 PO 4 and a relatively large birefringence (0.068 at 1064 nm) among the reported SHG-active phosphates. Theoretical calculations revealed that the introduction of the Hg 2+ in a highly distorted HgO 6 octahedral geometry is crucial to produce the strong SHG response and large birefringence.

The present study aimed to assess whether the Acute Physiology And Chronic Health Evaluation (APACHE) II score may be used to predict whether critically ill patients benefit from continuous blood purification (CBP) treatment. A total of 115 critically ill patients were retrospectively reviewed and grouped according to their baseline APACHE II scores. Each group was further divided into 2 groups based on whether they received CBP or not. At 72 h after CBP treatment, clinical indicators comprising the plasma levels of inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8, as well as endotoxin and procalcitonin (PCT), and severity scores (APACHE II, multiple organ dysfunction syndrome and systemic inflammatory response syndrome), were analyzed in all patients. It was observed that while CBP slightly reduced the severity scores in all patients, it significantly improved those in patients with an APACHE II score of 20-29 (P<0.05). Similarly, the plasma levels of TNF-α, IL-6, IL-8, endotoxin and PCT were significantly lower in patients receiving CBP than in those without CBP when the APACHE II score was 20-29 (P<0.05). Furthermore, CBP treatment significantly decreased the fatality rate and length of stay at the intensive care unit (ICU) for critically ill patients with an APACHE II score of 20-29 (P<0.05). In conclusion, CBP significantly decreases the inflammatory response, shortens the length of stay at the ICU and improves the prognosis for critically ill patients with an APACHE II score of 20-29 points. This observation suggests that the APACHE II score is an important clinical indicator to determine the potential benefit of CBP therapy in critically ill patients.

Background: Frey syndrome is a common complication after parotidectomy. This study aimed to investigate the potential predictors for developing severe Frey syndrome after parotidectomy and to identify patients who may benefit from additional preventive maneuvers., Methods: A total of 485 patients received parotidectomy because of parotid tumors at the Otolaryngology Department of the National Cheng Kung University Hospital, from July 2009 to November 2015. Only 115 of 485 patients were included in this study and to fill in a questionnaire to determine the occurrence and severity of Frey syndrome., Results: A total of 115 parotidectomies were identified. 84 (73%, 84/115) patients were aware of the discomfort and were thus considered symptomatic. 39 (34%, 39/115) patients considered the symptoms apparently affected their quality of life. MSI tests showed that 56 (49%, 56/115) patients had a positive MSI test. By combining the results from symptom questionnaire and MSI test, 23 patients (20%, 23/115) had a severe form of Frey syndrome. Among all clinicopathological variables, the resected specimen size was the only significant predictor of the severe Frey syndrome group (P = 0.04). Disease pathology, tumor size, and adjuvant radiotherapy did not correlate with the severe Frey syndrome. Using receiver operating curve analysis, the best cutoff value of the resected specimen size (in largest dimension) for predicting severe Frey syndrome was 40 mm(sensitivity: 71.7%, specificity: 42.0%; area under the curve = 0.6483). The odds ratio of severe Frey syndrome with every 10 mm increase in the largest diameter of resected specimen was 1.30 (95% confidence interval, 1.01-1.68; P = 0.04)., Conclusions: Resected specimen size is the only significant predictor of developing severe Frey syndrome after parotidectomy. Preventive interventions may have to be considered in high-risk patients whose resected specimen size (in largest dimension) is greater than 40 mm., (© 2019 Wiley Periodicals, Inc.)

By using hydrofluoric acid as a solubilizer, the first alkali-metal niobium iodate and an alkali-earth metal niobium iodate, i.e. (H3O)HCs2Nb(IO3)9 and SrNbO(IO3)5, have been obtained. An obvious cation-controlled polarity shift is observed in the Ae/A-Nb5+-IO3 system. (H3O)HCs2Nb(IO3)9 gives a strong second harmonic generation (SHG) signal about 6 times that of KH2PO4 (KDP), making it a promising nonlinear optical (NLO) material.

Purpose: The aim of our meta-analysis was to explore whether advanced maternal age (AMA) is regarded as an important risk factor for predicting macrosomia or not., Methods: Three databases were systematically reviewed and reference lists of relevant articles were checked. Meta-analysis of published cohort studies was done comparing whether AMA was associated with macrosomia and adjusting for potential confounding factors. Calculations of pooled estimates were conducted in random-effects models. Heterogeneity was tested by using chi-square test and I 2 statistics. Publication bias was estimated from Egger's test (linear regression method) and Begg's test (rank correlation method)., Results: Twelve cohort studies met the inclusion criteria. The meta-analysis showed that AMA was associated with macrosomia as an important risk factor. The adjusted odds ratio calculated for 12 studies (compared aged 35-39 years to aged <30 years) was 1.42, 95% confidence interval (CI) (1.25-1.60) for random-effect model and 6 studies (compared aged ≥40 years to aged <30 years) was 1.40, 95% CI (1.02-1.78) for random-effect model. There was no indication of a publication bias either from the result of Egger's test or Begg's test., Conclusion: Regardless of the underlying mechanism, our finding indicated that AMA should be considered as an important risk factor for macrosomia. To adequately evaluate the clinical evolution of AMA, the effect of AMA on macrosomia need to be carefully assessed and monitored.

Two new barium polyiodate compounds in the alkali-earth system, namely, HBa 2.5 (IO 3 ) 6 (I 2 O 5 ) ( Fdd2) and HBa(IO 3 )(I 4 O 11 ) ( P1̅) have been obtained through hydrothermal reaction. Interestingly, the structures of both compounds feature different polyiodate groups, i.e., I 2 O 5 and I 4 O 11 groups. HBa 2.5 (IO 3 ) 6 (I 2 O 5 ) can be depicted as an alternative stacking of two-dimensional (2D) [Ba 4 (IO 3 ) 8 (I 2 O 5 ) 2 ] and [Ba(IO 3 ) 4 (I 2 O 5 ) 2 ] 2- layers with the I 2 O 5 and IO 3 group serving as linkers. HBa(IO 3 )(I 4 O 11 ) can be depicted as a 3D network with 2D [Ba(I 4 O 11 )] layers being interconnected by IO 3 groups. The 0D I 4 O 11 polyiodate group can be seen also viewed as formed by an I 3 O 8 group further corner-sharing with an IO 3 group or an I 2 O 5 group further corner-sharing with two IO 3 groups. Powder second harmonic generation (SHG) measurements show that HBa 2.5 (IO 3 ) 6 (I 2 O 5 ) crystals display a moderate SHG efficiency of ∼1.6 times that of KH 2 PO 4 (KDP) and are phase-matchable. Optical properties measurements, thermal analyses, and laser damage threshold (LDT) measurements have been performed. Results of theoretical calculation show that the formation of I 4 O 11 2- is thermodynamically much easier than I 3 O 8 - and I 2 O 5 , because of the lower reaction energy. Our studies shed light on exploring alkali-earth polyiodates as potential NLO materials.

Neutrophil extracellular traps (NETs) are net-like chromatin fibers that can trap and kill microorganisms. Although several anti-inflammatory effects of intravenous anesthetics have been reported, it has not been investigated whether intravenous anesthetics influence NET formation., Aims: To compare the effects of four intravenous anesthetics (propofol, thiamylal sodium, midazolam, and ketamine) on phorbol myristate acetate (PMA)-induced NET formation and analyze the associated signaling pathways., Materials and Methods: PMA-stimulated NETs formed in the absence or presence of intravenous anesthetics were stained with SYTOX Green and then quantified. Inhibitors were applied to investigate the related mechanism, which was confirmed by western blotting, and ROS were detected., Key Findings: The neutrophils incubated with propofol showed the lowest degree of NET formation compared with those incubated with the other intravenous anesthetics. Propofol significantly reduced the level of myeloperoxidase (MPO)-derived HOCl but not that of superoxide. Aminopyrine, an MPO inhibitor, markedly decreased the number of PMA-induced NETs, indicating the involvement of HOCl in the inhibitory effect of propofol on NET formation. According to western blotting results, the level of p-ERK was reduced by propofol during PMA-induced NET formation. The ERK inhibitor PD98059 decreased NET formation but did not inhibit PMA-induced HOCl generation, and aminopyrine did not reduce ERK phosphorylation., Significance: Through this study, we define a new anti-inflammatory effect of intravenous anesthetics. Of the four intravenous anesthetics tested, propofol was the most potent inhibitor of NET formation. Moreover, propofol resulted in a decrease in PMA-induced NET formation by two independent mechanisms: inhibition of HOCl and p-ERK., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

The first examples of bismuth fluoride selenites with d 0 -TM/Te VI polyhedrons, namely, Bi 4 TiO 2 F 4 (SeO 3 ) 4 (1), Bi 4 NbO 3 F 3 (SeO 3 ) 4 (2), Bi 4 TeO 4 F 2 (TeO 3 ) 2 (SeO 3 ) 2 (3), Bi 2 F 2 (MoO 4 )(SeO 3 ) (4) and Bi 2 ZrO 2 F 2 (SeO 3 ) 2 (5) have been successfully synthesized under hydrothermal reactions by aliovalent substitution. The five new compounds feature three different types of structures. Compounds 1-3, containing Ti IV , Nb V and Te VI respectively, are isostructural, exhibiting a new 3D framework composed of a 3D bismuth oxyfluoride architecture, with intersecting tunnels occupied by d 0 -TM/Te VI octahedrons and selenite/tellurite groups. Interestingly, compound Bi 4 TeO 4 F 2 (TeO 3 ) 2 (SeO 3 ) 2 (3) is the first structure containing Se IV and mixed-valent Te IV /Te VI cations simultaneously. Compound 4 features a new 3D structure formed by a 3D bismuth oxyfluoride network with MoO 4 tetrahedrons and selenites groups imbedded in the 1D tunnels. Compound 5 displays a novel pillar-layered 3D open framework, consisting of 2D bismuth oxide layers bridged by the [ZrO 2 F 2 (SeO 3 ) 2 ] 6- polyanions. Theoretical calculations revealed that the five compounds displayed very strong birefringence. The birefringence values of compounds 1-3, especially, are above 0.19 at 1064 nm, which are larger than the mineral calcite. Based on the structure and property analysis, it was found that the asymmetric SeO 3 groups (and TeO 3 in compound 3) displayed the largest anisotropy, compared with the bismuth cations and the d 0 -TM/Te polyhedra, which is beneficial to the birefringence., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

(+)-Borneol, a bicyclic monoterpene, has been shown to possess valuable biological properties and potential as a pharmaceutical agent due to anti-inflammatory, anti-oxidant and GABA receptor-enhancing functions; it also enhances the permeability of the blood brain barrier to improve the efficacy of CNS drugs. In this study, we have developed a simple, selective, and rapid liquid chromatography-tandem mass spectrometry method for the assay of (+)-borneol in rat plasma. Verapamil was used as an internal standard. Plasma samples were deproteinized using methanol. The analyte was detected by a mass spectrometer with positive atmospheric pressure chemical ionization by multiple reaction monitoring mode for transitions at m/z [M + H] + 137.2 → 81.0 for (+)-borneol and 455.2 → 165.1 for verapamil. The method has been fully validated to ensure good selectivity, a satisfactory lower limit of quantification at 10.0 ng/mL, acceptable intra- and inter-day accuracy, and high precision. The method was used for the pharmacokinetic evaluation of (+)-borneol in Sprague-Dawley rats after intravenous, oral, and sublingual administration. The results indicate that oral bioavailability of (+)-borneol was extremely low but sublingual administration yielded rapid absorption and favorable bioavailability of (+)-borneol., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Although error amplification (EA) feedback has been shown to improve performance on visuomotor tasks, the challenge of EA is that it concurrently magnifies task-irrelevant information that may impair visuomotor control. The purpose of this study was to improve the force control in a static task by preclusion of high-oscillatory components in EA feedback that cannot be timely used for error correction by the visuomotor system. Along with motor unit behaviors and corticomuscular coherence, force fluctuations (Fc) were modeled with non-linear SDA to contrast the reliance of the feedback process and underlying neurophysiological mechanisms by using real feedback, EA, and low-frequency error amplification (LF-EA). During the static force task in the experiment, the EA feedback virtually potentiated the size of visual error, whereas the LF-EA did not channel high-frequency errors above 0.8 Hz into the amplification process. The results showed that task accuracy was greater with the LF-EA than with the real and EA feedback modes, and that LF-EA led to smaller and more complex Fc. LF-EA generally led to smaller SDA variables of Fc (critical time points, critical point of Fc, the short-term effective diffusion coefficient, and short-term exponent scaling) than did real feedback and EA. The use of LF-EA feedback increased the irregularity of the ISIs of MUs but decreased the RMS of the mean discharge rate, estimated with pooled MU spike trains. Beta-range EEG-EMG coherence spectra (13-35 Hz) in the LF-EA condition were the greatest among the three feedback conditions. In summary, amplification of low-frequency errors improves force control by shifting the relative significances of the feedforward and feedback processes. The functional benefit arises from the increase in the common descending drive to promote a stable state of MU discharges.

Three new acentric Sc-based borates, K 6 ACaSc 2 (B 5 O 10 ) 3 (A = Li, Na, Li 0.7 Na 0.3 ; space group R32), have been obtained and characterized. They are isostructural, and all exhibit three-dimensional [Sc 2 (B 5 O 10 ) 3 ] 9- anionic architecture composed of B 5 O 10 clusters and ScO 6 octahedra with the alkali- and alkaline-earth-metal cations occupying the cavities and keeping the charge balance. These compounds possess moderate second-harmonic-generation (SHG) responses (∼0.2×β-BaB 2 O 4 at 532 nm and ∼0.4×KH 2 PO 4 at 1064 nm) with phase-matching abilities and importantly display short cutoff edges below 200 nm. Furthermore, the relationship between the crystal structure and the SHG property has also been discussed based on the theoretical calculations.

Two mixed-metal gallium iodate fluorides, namely, α- and β-Ba 2 [GaF 4 (IO 3 ) 2 ](IO 3 ) (1 and 2), have been designed by the aliovalent substitutions of α- and β-Ba 2 [VO 2 F 2 (IO 3 ) 2 ](IO 3 ) (3 and 4) involving one cationic and two anionic sites. Both 1 and 2 display large second-harmonic generation responses (≈6×KH 2 PO 4 (KDP)), large energy band gaps (4.61 and 4.35 eV), wide transmittance ranges (≈0.27-12.5 μm), and high relevant laser-induced damage thresholds (29.7× and 28.3×AgGaS 2 , respectively), which indicates that 1 and 2 are potential second-order nonlinear optical materials in the ultraviolet to mid-infrared. Our studies propose that three-site aliovalent substitution is a facile route for the discovery of good NLO materials., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Glutathione peroxidase 4 (GPx4) is the only enzyme capable of reducing toxic lipid hydroperoxides in biological membranes to the corresponding alcohols using glutathione as the electron donor. GPx4 is the major inhibitor of ferroptosis, a non-apoptotic and iron-dependent programmed cell death pathway, which has been shown to occur in various neurological disorders with severe oxidative stress. In this study, we investigate whether GPx4 expression is altered in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). The results clearly show that mRNA expression for all three GPx4 isoforms (cytoplasmic, mitochondrial and nuclear) decline in multiple sclerosis gray matter and in the spinal cord of MOG 35-55 peptide-induced EAE. The amount of GPx4 protein is also reduced in EAE, albeit not in all cells. Neuronal GPx4 immunostaining, mostly cytoplasmic, is lower in EAE spinal cords than in control spinal cords, while oligodendrocyte GPx4 immunostaining, mainly nuclear, is unaltered. Neither control nor EAE astrocytes and microglia cells show GPx4 labeling. In addition to GPx4, two other negative modulators of ferroptosis (γ-glutamylcysteine ligase and cysteine/glutamate antiporter), which are critical to maintain physiological levels of glutathione, are diminished in EAE. The decrease in the ability to eliminate hydroperoxides was also evidenced by the accumulation of lipid peroxidation products and the reduction in the proportion of the docosahexaenoic acid in non-myelin lipids. These findings, along with presence of abnormal neuronal mitochondria morphology, which includes an irregular matrix, disrupted outer membrane and reduced/absent cristae, are consistent with the occurrence of ferroptotic damage in inflammatory demyelinating disorders., (© 2018 International Society for Neurochemistry.)

The AML1-ETO fusion protein, generated by the t(8;21) chromosomal translocation, is causally involved in nearly 20% of acute myeloid leukemia (AML) cases. In leukemic cells, AML1-ETO resides in and functions through a stable protein complex, AML1-ETO-containing transcription factor complex (AETFC), that contains multiple transcription (co)factors. Among these AETFC components, HEB and E2A, two members of the ubiquitously expressed E proteins, directly interact with AML1-ETO, confer new DNA-binding capacity to AETFC, and are essential for leukemogenesis. However, the third E protein, E2-2, is specifically silenced in AML1-ETO-expressing leukemic cells, suggesting E2-2 as a negative factor of leukemogenesis. Indeed, ectopic expression of E2-2 selectively inhibits the growth of AML1-ETO-expressing leukemic cells, and this inhibition requires the bHLH DNA-binding domain. RNA-seq and ChIP-seq analyses reveal that, despite some overlap, the three E proteins differentially regulate many target genes. In particular, studies show that E2-2 both redistributes AETFC to, and activates, some genes associated with dendritic cell differentiation and represses MYC target genes. In AML patients, the expression of E2-2 is relatively lower in the t(8;21) subtype, and an E2-2 target gene, THPO , is identified as a potential predictor of relapse. In a mouse model of human t(8;21) leukemia, E2-2 suppression accelerates leukemogenesis. Taken together, these results reveal that, in contrast to HEB and E2A, which facilitate AML1-ETO-mediated leukemogenesis, E2-2 compromises the function of AETFC and negatively regulates leukemogenesis. The three E proteins thus define a heterogeneity of AETFC, which improves our understanding of the precise mechanism of leukemogenesis and assists development of diagnostic/therapeutic strategies., Competing Interests: Conflict of interest statement: S.D.N. has coauthored papers with J.L. and O.A.-W. but has not collaborated directly with them. R.G.R. and J.L. are both investigators on a program grant but on separate projects.

Three new cadmium(II) tartratoborates, namely, Cd 5 [(C 4 H 2 O 6 ) 2 B] 2 (H 2 O) 8 ·3H 2 O (1), K 2 Cd 4 [(C 4 H 2 O 6 ) 2 B] 2 (H 2 O) 2 (2), and Li 0.92 K 1.08 Cd 1.5 [(C 4 H 2 O 6 ) 2 B](H 2 O) 2 (3), have been successfully synthesized by the hydrothermal method. Compounds 1-3 belong to centric C2/ c, acentric Pc, and the polar C2, respectively. Through based on the same hybrid borate-tartrate [(C 4 H 2 O 6 ) 2 B] 5- anions, they exhibit different structures. The [(C 4 H 2 O 6 ) 2 B] 5- anion is composed of two tartrate anions and a B(OH) 4 - unit. Compound 1 features a novel 3D network formed by 2D {Cd 3 [(C 4 H 2 O 6 ) 2 B] 2 (H 2 O) 2 } 4- anionic layers and [Cd 2 O 10 ] dimers, forming tunnels of large 14-MRs which are filled by the non-coordination water molecules. Compound 2 has a characteristic 3D network based on {Cd 2 [(C 4 H 2 O 6 ) 2 B]} - units interlinked via carboxylate groups, forming tunnels of 11-MRs, half of which stuffed with the K + ions. Compound 3 features 2D {Cd 4 [(C 4 H 2 O 6 ) 4 B]} 3+ layers which are separated by K/Li ions. Luminescent studies suggest that they emit blue light. Compounds 2 and 3 display phase-matchable second harmonic generation signs of about 3.2× and 1.5× KH 2 PO 4 , respectively.