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Sub-bandgap near-infrared silicon (Si) photodetectors are key elements in integrated Si photonics. We demonstrate such a Si photodetector based on a black Si (b-Si)/Ag nanoparticles (Ag-NPs) Schottky junction. This photodetector synergistically employs the mechanisms of inner photoemission, light-trapping, and surface-plasmon-enhanced absorption to efficiently absorb the sub-bandgap light and generate a photocurrent. The b-Si/Ag-NPs sample was prepared by means of wet chemical etching. Compared to those of a planar-Si/Ag thin-film Schottky photodetector, the responsivities of the b-Si/Ag-NPs photodetector were greatly enhanced, being 0.277 and 0.226 mA/W at a reversely biased voltage of 3 V for 1319- and 1550-nm light, respectively.

Our previous studies identified that the expression of microRNA‑29c (miR‑29c‑3p) was significantly increased in the serum of pregnant women carrying fetuses with congenital heart disease (CHD) compared with in that of normal pregnant women. However, the mechanism by which miR‑29c‑3p affects development of the embryonic heart remained unclear. The aim of the present study was to investigate the effect and potential molecular mechanism of miR‑29c‑3p overexpression on P19 cell proliferation, apoptosis and differentiation. miR‑29c‑3p‑overexpression and protein kinase Bγ (Akt3)‑knockdown cell lines were constructed using transfection technology. The function of miR‑29c‑3p and Akt3 in cardiomyocyte development was investigated by determining the proliferation, apoptosis and differentiation of P19 cells, which can differentiate into cardiomyocytes induced by dimethylsulfoxide. Bioinformatic analysis and luciferase assays were performed to explore the association between Akt3 and miR‑29c‑3p. The results of the present study revealed that miR‑29c‑3p overexpression and Akt3 knockdown suppressed proliferation, and promoted apoptosis and differentiation in P19 cells. Akt3 was also demonstrated to be a target of miR‑29c‑3p. Therefore, overexpression of miR‑29c‑3p may inhibit proliferation, and promote apoptosis and differentiation in P19 cells by inhibiting the expression of Akt3. miR‑29c‑3p may be a potential therapeutic target for the treatment of CHD.

Background: This study investigated the scientific research capacity and related factors of nurses with Master of Science in Nursing (MSN) degrees to provide information on hierarchical management and continuing education of nurses in China., Method: This multi-center cross-sectional study included 221 MSN hospital nurses in China., Results: Ninety-one percent of MSN nurses had good or excellent research capacity. Continuing education requirements existed regarding research practice and design. Research time, teamwork, leadership support, and retraining opportunities influenced research capacity, which decreased with increasing age and years of work, especially at 3 to 5 years after initial employment., Conclusion: Clinical managers should pay attention to factors that influence nurses' research capacity and continuing education requirements. Multiple incentives should be used for MSN nurses, especially for those with 3 to 5 years of employment, to provide more chances for self-actualization, to take advantage of their talents, and to promote the development of clinical nursing. [J Contin Educ Nurs. 2019;50(2):61-68.]., (Copyright 2019, SLACK Incorporated.)

In nature, biological machines and motors can selectively transport cargoes across the lipid membranes to efficiently perform various physiological functions via ion channels or ion pumps. It is interesting and challengeable to develop artificial motors and machines of nanodimensions to controllably regulate mass transport in compartmentalized systems. In this work, we show a system of artificial molecular motors that uses light energy to perform transmembrane molecule transport through synthetical nanochannels. After functionalizing the polymer nanochannels with azobenzene derivatives, these nanomachines exhibit autonomous selective transport behavior over a long distance upon simultaneous irradiation with UV (365 nm) and visible (430 nm) light. With new strategies or suitable materials for directed molecular movement, such device can be regarded as a precursor of artificial light-driven molecular pumps., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In nature, biological machines can perform sophisticated and subtle functions to maintain the metabolism of organisms. Inspired from these gorgeous works of nature, scientists have developed various artificial molecular motors and machines. However, selective transport of biomolecules across membrane has remained a great challenge. Here, we establish an ATP transport system by assembling photocontrolled DNA nanomachines into the artificial nanochannels. With alternant light irradiation, these ATP transport lines can selectively shepherd cargoes across the polymer membrane. These findings point to new opportunities for manipulating and improving the mass transportation and separation with light-controlled biomolecular motors, and can be used for other molecules and ions transmembrane transport powered by light.

Inspired by the delicate functions of living organisms to transport or transform nitrite ions (NO 2 - ), a bioinspired smart nanochannel that can realize harmless conversion of NO 2 - into N 2 is developed by immobilizing a NO 2 - -responsive functional molecule, p-phenylenediamine, onto a single conical polyethylene terephthalate nanochannel. Subsequently, the aromatic primary amine groups could be triggered to transform into a phenyldiazonium molecule based on the acid-activated NO 2 - -binding process. The nanochannel exhibits specific selectivity and highly ultratrace recognition of NO 2 - . Fascinatingly, the transformed phenyldiazonium molecules could be triggered to generate phenol groups and release N 2 by ultraviolet light activation, achieving NO 2 - harmless conversion. This system could provide inspiration to construct artificial nanofluidic devices for ion-sensing and nitrogen cycle fields.

Objectives: The aims of this study were to investigate whether serum levels of neurofilaments heavy chain (NfH) and light chain (NfL), neuron-specific enolase (NSE) and S100 calcium binding protein B (S100B): (1) change, (2) alleviate in post-therapy and (3) are associated with sleep quality and cognitive dysfunction, in patients with chronic insomnia disorder (CID)., Methods: Forty CID outpatients constituted free-therapy group (ft-CID), in which twenty-four patients completed follow-up after six-month treatment to form re-visiting group (rv-CID), and twenty healthy good sleepers constituted control group (HC). All subjects completed questionnaires, polysomnography, Chinese-Beijing Version of Montreal Cognitive Assessment (MoCA-C) and Nine Box Maze Test (NBMT) to assess sleep and neuropsychological function. The serum levels of NfH, NfL, NSE and S100B were detected using enzyme-linked immunosorbent assay., Results: The ft-CID had higher levels of NfH, NfL, NSE and S100B than the HC. Of note, the levels of NfH, NfL and NSE were significantly reduced in the rv-CID compared to the ft-CID, but not the level of S100B. Principal components analysis revealed that in these serum biomarkers, NfL and S100B had a substantial correlation with subjective and objective sleep parameters., Conclusions: The CID patients had elevated serum levels of NfH, NfL, NSE and S100B, indicating existence of damaged brain microstructure, including neurons, astrocytes and neuronal terminals, which were associated with the insomniac severity or/and cognitive dysfunction and could significantly reduce after effective therapy apart from the S100B., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Iron as an essential trace element in the human body participates in various biological processes. The demand for efficient and sensitive detection of Fe III has drawn wide attentions. Inspired by biological nanochannels, a high-sensitivity, economic, and recyclable Fe III detection method is proposed by using dopamine (DOPA)-modified funnel-shaped nanochannels. Along with the Fe III concentration changing, different Fe III -DOPA chelates are generated in the channel, which affect the wettability and charge distribution of the pore surface, resulting in a change of ionic current through the nanochannels. Meanwhile, the funnel-shaped nanochannel applied in this work with a narrow cylindrical segment (a diameter close to 10 nm) as the critical section can enhance the sensing ability to the ultra-trace level (down to 10 -12 M). We expound the mechanism and feasibility of this method and anticipate that the system can be a good example to design highly sensitive and stable ion detection devices.

A magnetic metal organic framework (MMOF) was synthesized and used to separate Sr2+ in aqueous solution. The shape and structure of prepared Fe3O4@UiO-66-NH2 were characterized, and the absorbed concentration of strontium was determined through inductively coupled plasma mass spectrometry. The results indicated that Fe3O4 and UiO-66-NH2 combined through chemical bonding. The experimental adsorption results for separation of Sr2+ in aqueous solution indicated that the adsorption of Sr2+ to Fe3O4@UiO-66-NH2 increased drastically from pH 11 to pH 13. The adsorption isotherm model indicated that the adsorption of Sr2+ conformed to the Freundlich isotherm model (R2 = 0.9919). The MMOF thus inherited the superior qualities of magnetic composites and metal organic frameworks, and can easily be separated under an external magnetic field. This MMOF thus has potential applications as a magnetic adsorbent for low level radionuclide 90Sr., (Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Inspired by the potassium ion channel, here, we firstly report a structure-tailorable dumbbell-shaped nanochannel with controllable ionic rectification. This system creates an ideal experimental and theoretical platform for the precision transportation of ions, which have potential applications in analytical sciences.

Water wetting behavior in nanoconfined environments plays an important role in mass transport and signal transmission of organisms. It is valuable and challenging to investigate how water behaves in such a nanometer-scale with external stimuli, in particular with electric field and light. Unfortunately, the mechanism of hydrophobic reaction inside the nanospaces is still obscure and lacks experimental support for the current electric-field- or photoresponsive nanochannels which suffer from fragility or monofunctionality. Here, we design functionalized hydrophobic nanopores to regulate ion transport by light and electric field using azobenzene-derivatives-modified polymer nanochannels. With these addressable features, we can control the pore surface wetting behavior to switch the nanochannels between nonconducting and conducting states. Furthermore, we found these hydrophobic nanochannels are rough with a contact angle of 67.3°, making them extremely different from the familiar ones with a smooth pore surface and larger contact angles (>90°). These findings point to new opportunities for studying and manipulating water behavior in nanoconfined environments.

Both B and Al have high oxygen affinity and their oxidation processes are highly exothermic, hinting at intriguing physical chemistry in ternary Al-B-O clusters. We report a combined photoelectron spectroscopy and density-functional study on the structural, electronic, and bonding properties of Al n BO 2 - and Al n BO 2 (n = 2, 3) clusters. Ground-state vertical detachment energies (VDEs) are measured to be 2.83 and 2.24 eV for Al 2 BO 2 - and Al 3 BO 2 - , respectively. A weak isomer is also observed for Al 3 BO 2 - with a VDE of 1.31 eV. Coalescence-kick global searches allow the identification of candidate structures, confirmed via comparisons with experiment. The Al 2 BO 2 - anion is V-shaped in geometry, C s ( 1 A'), with an Al center connecting to OB and OAl terminals. It can be viewed alternatively as the fusion of BOAl and AlOAl by sharing an Al atom. Al 3 BO 2 - has a C s ( 2 A'') global minimum in which an Al 2 dimer interacts with bridging boronyl (BO) and an OAl unit, as well as a low-lying C 2v ( 2 B 2 ) isomer consisting of boronyl and OAl that are doubly bridged by two Al atoms. The BO 2 block (linear O[double bond, length as m-dash]B[double bond, length as m-dash]O chain) is nonexistent in any of the anion and neutral species. Chemical bonding in these Al-B-O clusters is elucidated via canonical molecular orbitals and adaptive natural density partitioning. The cluster structures are also rationalized using the concept of sequential and competitive oxidation of B versus Al centers in Al n B. The first O atom prefers to oxidize B and form BO, whereas the second O atom has options to interact with a fresh Al/Al n /Al n B unit or a BO group. The former route wins thermodynamically, leading to the observed geometries.

The creation of an artificial solid-state ion pump that mimics the delicate ion transport behaviors of a biological protein-based ion pump is drawing more and more research attention due to its potential applications in energy conversion, biosensor, and desalination. However, the reported bioinspired double-gated ion pump systems are generally very primary and can only realize nonselective ion pumping functions with no directionality and uncontrollable ion gating functions, which are far from their biological counterparts. To make the bioinspired device "smart" in a real sense, the implementation of high-level selectivity and directionality in the ion pumping process, while achieving great controllability in the ion gating process, is a necessity. Here, we developed a bioinspired heterogeneous ion pump membrane by combining block copolymer membrane sacrificial coating and plasma grafting technique. The system has unidirectional selective ion pumping and controllable ion gating properties. The introduction of asymmetric ionic group distribution is the key reason for its novel transport behaviors. Such a heterogeneous ion pump could not only provide a basic platform that potentially sparks further efforts to simulate the smart ion transport processes in living bodies but also promote the application of artificial nanofluidic devices in energy conversion, water treatment, and biosensing.

Background: Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) has been shown to be increased in patients with acute ischemic stroke. Here, we evaluated plasma sLOX-1 levels and vascular carotid plaque LOX-1 (ie, OLR1 ) gene expression in patients with ischemic stroke and transient ischemic attack (TIA) with particular focus on their relation to time since symptom onset., Methods and Results: Plasma sLOX-1 (n=232) and carotid plaque OLR1 gene expression (n=146) were evaluated in patients who were referred to evaluation for carotid endarterectomy, as well as in healthy control plasma (n=81). Patients were categorized according to presence of acute ischemic stroke or transient ischemic attack (n=35) ≤7 days, >7 days ≤3 months (n=90), >3 months (n=40), or no reported symptoms before study inclusion (n=67). Our major findings were the following: (1) Patients with carotid atherosclerosis had increased plasma sLOX-1 levels as compared with controls. (2) Plaque OLR1 mRNA levels were increased in carotid plaques (n=146) compared with nonatherosclerotic vessels (ie, common iliac arteries of organ donors, n=10). (3) There were no differences in sLOX plasma levels or OLR1 gene expression when analyzed according to the time since relevant cerebral ischemic symptoms. (4) Also patients with severe carotid atherosclerosis without any previous ischemic events had raised sLOX-1 levels. (5) Immunostaining showed colocalization between LOX-1 and macrophages within the carotid plaques. (6) Also patients with acute stroke (within 7 days) caused by atrial fibrillation (n=22) had comparable raised sLOX-1 levels., Conclusions: sLOX-1 levels are elevated in patients with ischemic stroke and transient ischemic attack independent of cause and time since the ischemic event., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

The controllable molecule transport is crucial to realize many highly valuable applications both in vivo and in vitro. Nanoporous membranes, with nanoscopic pores, high porosity, uniform pore dimensions, and controllable surface chemical properties, hold tremendous potential to achieve this function. Herein, we report a nano-gating system for on-demand molecule transport based on a peptide-gated nanoporous membrane. Acting as gatekeeper, the peptides introduced to the nanoporous membrane provide an opportunity to realize on-demand on-off states via reversible conformational switching of the peptides. This nano-gating system offers sustained release and can be used as a sophisticated molecule transport platform for localized drug delivery with a feedback function., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The structural, electronic, and magnetic properties of FeGe n -/0 (n = 3-12) clusters were investigated by using anion photoelectron spectroscopy in combination with density functional theory calculations. For both anionic and neutral FeGe n (n = 3-12) clusters with n ≤ 7, the dominant structures are exohedral. The FeGe 8 -/0 clusters have half-encapsulated boat-shaped structures, and the opening of the boat-shaped structure is gradually covered by the additional Ge atoms to form Ge n cage from n = 9 to 11. The structures of FeGe 10 -/0 can be viewed as two Ge atoms symmetrically capping the opening of the boat-shaped structure of FeGe 8 , and those of FeGe 12 -/0 are distorted hexagonal prisms with the Fe atom at the center. Natural population analysis shows that there is an electron transfer from the Ge atoms to the Fe atom at n = 8-12. The total magnetic moment of FeGe n -/0 and local magnetic moment of the Fe atom have not been quenched.

Semi-continuous biogas production from fruit and vegetable waste by medium temperature anaerobic fermentation was conducted. Hydrogen production under different food-microorganism ratios (F/M 0.5, 0.75, 1.0, 1.5) and hydraulic retention times (HRT) (2, 3, 4 d) were investigated. The results show that in the case of a smaller F/M values (0.5 and 0.75), not all HRT stages were conducive to the continuous production of hydrogen, however, they were conducive to producing methane, especially when HRT was 3 or 4 d. Continuous hydrogen production was viable when the F/M ration was relatively higher (1.0 and 1.5), however, this was not conducive to the production of methane, with almost no methane production detected in this process. A F/M of 1.0 and a HRT of 3 d provided the best conditions for continuous hydrogen production from fruit and vegetable waste. Meanwhile, the highest and average daily volume of hydrogen production were 451.2 mL·(L·d) -1 and (186±29) mL·(L·d) -1 respectively, whereas the highest and average hydrogen production rate of volatile solids were 133 mL·g -1 and (27±5) mL·g -1 respectively. The hydrogen content was 20%-30%.

Background/aims: To investigate the prognostic significance of preoperative albumin to globulin ratio (AGR) in patients with resectable gastric cancer (GC)., Materials and Methods: According to the inclusion criteria, 269 GC patients (male:female=127:67; median age: 67 years) with a stage I through III who underwent gastrectomy with D2 lymphadenectomy and R0 resection were included. These patients were categorized into two groups, namely low AGR group and high AGR group, based on a cutoff point that was obtained using a receiver-operating characteristic curve. The correlations of preoperative AGR with the clinicopathological characteristics and overall survival were analyzed. Univariate and multivariate analysis were performed to assess the prognostic value of preoperative AGR., Results: Age, gender, tumor size, T stage, and preoperative hemoglobin were significantly different between the low and high AGR groups (p<0.05). Moreover, using binary logistic regression analysis, female gender, older age, larger tumor size, and lower preoperative hemoglobin were found to be independent risk factors of low preoperative AGR. Kaplan-Meier curves showed a significantly lower overall survival for the low AGR group (13 months; 95% confidence interval (CI), 10.9-15.1) compared to the high AGR group (17 months; 95% CI, 13.8-20.2; p=0.014). The univariate analysis of all the variables showed that overall survival was significantly related to age; tumor size; differentiation degree; T stage; N stage; tumor, node, metastasis (TNM) stage; preoperative AGR; and hemoglobin (p<0.05). Results of multivariate analysis showed that low preoperative AGR (<1.36) was an independent risk factor for poorer overall survival in GC patients (odds ratio [OR]=1.5; 95% CI, 1.0-2.1; p=0.041)., Conclusion: Preoperative AGR was significantly associated with the prognosis of GC patients in our study. In addition, preoperative AGR is suggested to be a simple but efficient prognosis predicting biomarker in patients with GC.

Background: Nasopharyngeal carcinoma (NPC) is especially prevalent in southeast Asia and southern China, but its molecular mechanisms remain poorly characterized. DNA methylation is associated with initiation and progression of tumors, including NPC. Through a genome-wide DNA methylation screening approach, we discovered ZNF154, but its methylation status and roles in NPC have not been investigated., Methods: The methylation status of ZNF154 in NPC was detected with Methylation specific-PCR (MSP) and Quantitative Sequenom MassARRAY. The invasion and migration capacities were examined by wound healing and transwell invasion assays. The role of ZNF154 in NPC metastasis was clarified with experimental metastasis assay in vivo . Western blotting analysis was used to investigate protein changes followed by ZNF154 over-expression. Kaplan-Meier analysis was performed to determine the association between ZNF154 methylation and prognosis in NPC., Results: Compared to immortalized nasopharyngeal tissues and cells, ZNF154 expression was frequently downregulated in NPC tissues and cell lines due to promoter methylation. Demethylation treatment with 5-aza-2-deoxycytidine (5-Aza) restored ZNF154 expression in NPC cell lines. Ectopic overexpression of ZNF154 in NPC cells inhibited cell migration and invasion in vitro and lung nodule formation in an in vivo tumor metastasis assay. Mechanistic investigations suggested ZNF154 inhibits Wnt/β-catenin signalling pathway activation and prevents the EMT in NPC. Furthermore, Kaplan-Meier analysis showed hypermethylation of the ZNF154 promoter was associated with significantly poorer disease-free survival (P = 0.032) and distant metastasis-free survival (P = 0.040) among patients with locoregionally advanced NPC., Conclusions: Taken together, these findings define a novel role for ZNF154 as a tumor suppressor in NPC., Competing Interests: CONFLICTS OF INTEREST The authors have no potential conflicts of interest to disclose.

In the present work, two-dimensional bismuth oxybromide (BiOBr) was synthesized and coupled with co-catalyst molybdenum disulphide (MoS 2 ) via a simple hydrothermal process. The photoactivity of the resulting hybrid photocatalyst (MoS 2 /BiOBr) was evaluated under the irradiation of 15 W energy-saving light bulb at ambient condition using Reactive Black 5 (RB5) as model dye solution. The photo-degradation of RB5 by BiOBr loaded with 0.2 wt% MoS 2 (MoBi-2) exhibited more than 1.4 and 5.0 folds of enhancement over pristine BiOBr and titanium dioxide (Degussa, P25), respectively. The increased photocatalytic performance was a result of an efficient migration of excited electrons from BiOBr to MoS 2 , prolonging the electron-hole pairs recombination rate. A possible charge transfer diagram of this hybrid composite photocatalyst, and the reaction mechanism for the photodegradation of RB5 were proposed., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The osmotic energy existing in fluids is recognized as a promising "blue" energy source that can help solve the global issues of energy shortage and environmental pollution. Recently, nanofluidic channels have shown great potential for capturing this worldwide energy because of their novel transport properties contributed by nanoconfinement. However, with respect to membrane-scale porous systems, high resistance and undesirable ion selectivity remain bottlenecks, impeding their applications. The development of thinner, low-resistance membranes, meanwhile promoting their ion selectivity, is a necessity. Here, we engineered ultrathin and ion-selective Janus membranes prepared via the phase separation of two block copolymers, which enable osmotic energy conversion with power densities of approximately 2.04 W/m 2 by mixing natural seawater and river water. Both experiments and continuum simulation help us to understand the mechanism for how membrane thickness and channel structure dominate the ion transport process and overall device performance, which can serve as a general guiding principle for the future design of nanochannel membranes for high-energy concentration cells.

A tunable ionic diode is presented that is based on biomimetic structure-tailorable nanochannels, with precise ion-transport characteristics from ohmic behavior to bidirectional rectification as well as gating properties. The forward/reverse directions of the ionic diode and the degree of rectification can be well-regulated by combining the patterned surface charge and the sophisticated structure. This system creates an ideal platform for precise transportation of ions and molecules, and potential applications in analytical sciences are anticipated., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We present a novel formulation of video stabilization in the space of geometric transformations. With the setting of the Riemannian metric, the optimized smooth path is cast as the geodesics on the Lie group embedded in transformation space. While solving the geodesics has a closed-form expression in a certain space, path smoothing can be easily implemented by using geometric interpolation, rather than optimizing any space-time energy function. Specially, by using the geodesic solution in the space of rigid transformations, our approach even gains speedup 10× faster than state-of-the-art methods for path smoothing and motion compensation, and guarantees no extra distortion drawn into the stabilized frames. The experiments demonstrate the efficiency and effectiveness of our algorithm on stabilizing a variety of shaky videos.

Background: The relative efficacy of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) versus IC followed by radiotherapy (RT) alone in locoregionally advanced NPC remains unclear., Methods: A total of 877 patients with locally advanced NPC who underwent IC/CCRT or IC/RT at four institutions in China between January 2004 and December 2010 were retrospectively assessed. IC was cisplatin-based combination chemotherapy; concurrent chemotherapy, single agent cisplatin. Two-dimensional conventional radiotherapy (2DCRT) was the radiotherapy technique. All patients were matched in an equal ratio using a pair-matched method. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), locoregional relapse-free survival (LRRFS) and toxicities were assessed., Results: Eligible patients were matched (n = 642; 321 patients per arm) based on eight clinicopathological characteristics. Five-year OS, DFS, DMFS, and LRRFS were 76%, 70%, 86%, and 88% for IC/CCRT and 75%, 70%, 90%, and 91% for IC/RT, respectively. There were no statistically significant survival differences between arms (P>0.05), even in subgroup analysis. In multivariate analysis, treatment (IC/CCRT vs. IC/RT) was not an independent prognostic factor for any survival end-point. Grade 3/4 acute gastrointestinal toxicities (vomiting, nausea) and hematological toxicities (leucopenia/neutropenia, thrombocytopenia and anemia) were significantly more common in the IC/CCRT arm than IC/RT arm during RT., Conclusion: Overall, IC/CCRT failed to demonstrate any survival advantage but higher acute toxicities over IC/RT in locoregionally advanced NPC.

Objective: To examine the effects of brucine on the invasion, migration and bone resorption of receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis., Methods: The osteoclastogenesis model was builded by co-culturing human breast tumor MDA-MB-231 and mouse RAW264.7 macrophages cells. RANKL (50 ng/mL) and macrophage-colony stimulating factor (50 ng/mL) were added to this system, followed by treatment with brucine (0.02, 0.04 and 0.08 mmol/L), or 10 μmol/L zoledronic acid as positive control. The migration and bone resorption were measured by transwell assay and in vitro bone resorption assay. The protein expressions of Jagged1 and Notch1 were investigated by Western blot. The expressions of transforming growth factor-β1 (TGF-β1), nuclear factor-kappa B (NF-κB) and Hes1 were determined by enzyme-linked immunosorbent assay., Results: Compared with the model group, brucine led to a dose-dependent decrease on migration of MDA-MB-231 cells, inhibited RANKL-induced osteoclastogenesis and bone resorption of RAW264.7 cells (P<0.01). Furthermore, brucine decreased the protein levels of Jagged1 and Notch1 in MDA-MB-231 cells and RAW264.7 cells co-cultured system as well as the expressions of TGF-β1, NF-κB and Hes1 (P<0.05 or P<0.01)., Conclusion: Brucine may inhibit osteoclastogenesis by suppressing Jagged1/Notch1 signaling pathways.

Objective: To investigate the mortality rate and the cause of death of hospitalized neonates., Methods: The clinical data of 480 neonates who died between January 2008 and December 2014 were collected. The mortality rates of neonates with different gestational ages, birth weights, sexes, and ages in days were analyzed. The abnormal perinatal factors, cause of death, and death grade were summarized., Results: Among the 41 910 hospitalized neonates, 480 (1.1%) died, and the mortality rates of preterm infants and full-term infants were 1.7% and 0.7%, respectively. The mortality rate of hospitalized neonates decreased from 1.4% in 2008 to 1.1% in 2014, and the decrease was more apparent in the preterm infants with a gestational age of <32 weeks and the neonates with a birth weight of <1 000 g. Among preterm infants and full-term infants, those with a lower gestational age tended to have a higher mortality rate, but post-term infants had an increased mortality rate. The infants with a lower birth weight tended to have a higher mortality rate. Male neonates had a significantly higher mortality rate than female neonates (1.31% vs 0.92%; P<0.05). Among the neonates who died, 61.3% had definite abnormal perinatal factors, including abnormal amniotic fluid (29.4%), premature rupture of membranes (16.9%), placental abnormality (16.9%), fetal intrauterine distress (14.0%), and abnormal umbilical cord (12.3%). Among the 480 neonates who died, 57 (11.9%) died within 24 hours after birth, 181 (37.7%) died within 2-7 days, and 242 (50.4%) died within 8-28 days. The three most common causes of death were infection, birth defect, and respiratory distress syndrome. The most common cause of death was respiratory distress syndrome in 2008-2011 and infection in 2012-2014. Respiratory distress syndrome was the most common cause of death in preterm infants with a gestational age of <32 weeks, neonates with a birth weight of <1 500 g, and neonates who died with 24 hours; infection was the most common cause of death in neonates with a gestational age of 32-42 weeks, neonates with a birth weight of 1 500-4 000 g, and neonates who died within 8-28 days. Neonatal asphyxia was the major cause of death in post-term infants. Inevitable deaths (grade 1) accounted for 54.4%, deaths that could be avoided under certain conditions (grade 2) accounted for 23.3%, and deaths caused by concerns about prognosis or economic reasons (grade 3) accounted for 22.3%., Conclusions: In recent years, the treatment of neonates has gradually improved, and the mortality rate of neonates is gradually decreasing, especially in neonates with low gestational age and birth weight. Important measures for reducing the mortality rate in neonates include enhancing perinatal management, reducing abnormal perinatal factors, preventing infection, and increasing parents' confidence in treatment.

A highly selective recognition system for zinc(II) and pyrophosphate ions is constructed using a single conical nanochannel covalently functionalized with N'-{4-[(2,2':6',2''-terpyridine)-4-yl]benzyl}ethane-1,2-diamine (TPYD). The immobilized TPYD acts as a specific coordination site for Zn 2+ to form TPYD-Zn 2+ complexes in preference over other metal ions, and subsequently, the resulting Zn 2+ -coordinated nanochannel can be used as a selective recognition element for the pyrophosphate ion based on the coordination reaction between hydroxyl oxygen atoms of pyrophosphate and Zn 2+ . Ion recognition is monitored by measuring the current-voltage curves of the solutions. The ionic current of the TPYD-functionalized system at -2.0 V undergoes a clear decrease after exposure to Zn 2+ ions and is followed with an obvious increase after subsequent treatment with a pyrophosphate solution. The change of ionic current can be primarily attributed to the variation of charge density of the nanochannel. This functionalized single nanochannel might provide a simple and universal means to recognize other targets by modifying different functional molecules onto the inner surfaces of nanochannels., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Identification of disease genes is a hot topic in biomedicine and genomics. However, it is a challenging problem because of the complexity of diseases. Inflammatory bowel disease (IBD) is an idiopathic disease caused by a dysregulated immune response to host intestinal microflora. It has been proven to be associated with the development of intestinal malignancies. Although the specific pathological characteristics and genetic background of IBD have been partially revealed, it is still an overdetermined disease and the blueprint of all genetic variants still needs to be improved. In this study, a novel computational method was built to identify genes related to IBD. Samples from two subtypes of IBD (ulcerative colitis and Crohn's disease) and normal samples were employed. By analyzing the gene expression profiles of these samples using minimum redundancy maximum relevance and incremental feature selection, 21 genes were obtained that could effectively distinguish samples from the two subtypes of IBD and the normal samples. Then, the shortest-path approach was used to search for an additional 20 genes in a large network constructed using protein-protein interactions based on the above-mentioned 21 genes. Analyses of the 41 genes obtained indicate that they are closely associated with this disease., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this article.

The Pseudorhombus dupliocellatus belongs to family Paralichthyidae of Pleuronectiformes. In this study, the complete mitochondrial genome of P. dupliocellatus is determined and described. The mitogenome is 16 621 bp in length and consists of 13 protein-coding genes, 22 tRNAs, 2 rRNAs, a control region, and a L-strand replication origin. The arrangement of the mitogenome is identical to that of the typical teleost. The overall base composition is 26.9%, 25.3%, 31.0%, and 16.8% for A, T, C, and G, respectively, with a slight bias on A+T content (52.2%). The phylogenetic tree of 13 species all in Pleuronectiformes demonstrated that P. dupliocellatus, as well as the other Paralichthyidae fishes containing Paralichthys olivaceus and Pseudorhombus cinnamoneus, clustered in a clade and had a closer relationship with Pleuronectidae species than Bothidae ones. This study is expected to contributing to the systematic evolution of Paralichthyidae and further Pleuronectiformes.

A novel CO 2 -driven ionic gate, mimicking the function of olfactory sensory neurons of mosquitoes, is successfully developed by functionalizing the walls of the nanochannels using 1-(4-amino-phenyl)-2,2,2-trifluoro-ethanone. This artificial nanochannel can switch between the ON-state and OFF-state in the presence and absence of CO 2 , with an ultrahigh gating ratio of up to 1250, and has potential applications in CO 2 -related sensing, gating, and nanofluidic systems., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Light-controlled nanochannels are fabricated through self-assembling azobenzene-incorporated DNA (Azo-DNA) strands to regulate ion transport. By switching between collapsed and relaxed states using visible and ultraviolet light alternately, the Azo-DNA channels can be opened and closed because the conformation of Azo-DNA changes, that is, Azo-DNA is used as switchable controlling unit. In addition to sharing short response time and reversibility with other photoresponsive apparatuses, the Azo-DNA-based nanochannel system has advantages in good biocompatibility and versatile design, which could potentially be applied in light-controlled drug release, optical information storage, and logic networks., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Photocatalytic CO 2 reduction over the UV-Vis-NIR broad spectrum was realized for the first time. The presence of surface oxygen vacancy defects on Bi 2 WO 6 resulted in significant photocatalytic enhancement over the pristine counterpart under UV and visible light irradiation. Meanwhile, the photocatalytic responsiveness of Bi 2 WO 6 -OV was successfully extended to the NIR region.

Asymmetric multifunctional heterogeneous membranes are demonstrated by combing a block copolymer polystyrene-block-poly(N,N-dimethylaminoethylmethacrylate) membrane with a track-etched porous poly(ethylene terephthalate) membrane. This hybrid membrane is capable of integrating pH- and temperature-cooperative high-performance ionic rectification, highly efficient cation gating, and excellent stability and controllability, which allows broad application in biosensing, energy conversion, and filtration., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Regulating and controlling the transport of water across nanochannels is of great importance in both fundamental research and practical applications because it is difficult to externally control water flow through nanochannels as in biological channels. To date, only a few hydrophobic nanochannels controlling the transport of water have been reported, all of which use exotic hydrophobic molecules. However, the effect of electrostatic charges, which plays an indispensable role in membrane proteins and dominates the energetics of water permeation across aquaporins, has not gained enough attention to control water transport through a solid-state nanochannel/nanopore. Here, we report electrostatic-charge-induced water gating of a single ion track-etched sub-10 nm channel. This system can directly realize the gating transition between an open, conductive state and a closed, nonconductive state by regulating the surface charge density through a process that involves alternating capillary evaporation and capillary condensation. Compared to the introduction of exotic hydrophobic molecules, water gating controlled by electrostatic charges is simple, convenient, and effective. Such a system anticipates potential applications including desalination, controllable valves, and drug delivery systems.

Biological ion pumps with active ionic transport properties lay the foundation for many life processes. However, few analogs have been produced because extra energy is needed to couple to this "uphill" process. We demonstrate a bioinspired artificial photo-driven ion pump based on a single polyethylene terephthalate conical nanochannel. The pumping process behaving as an inversion of zero-volt current can be realized by applying ultraviolet irradiation from the large opening. The light energy can accelerate the dissociation of the benzoic acid derivative dimers existing on the inner surface of nanochannel, which consequently produces more mobile carboxyl groups. Enhanced electrostatic interaction between the ions traversing the nanochannel and the charged groups on the inner wall is the key reason for the uphill cation transport behavior. This system creates an ideal experimental and theoretical platform for further development and design of various stimuli-driven and specific ion-selective bioinspired ion pumps, which anticipates wide potential applications in biosensing, energy conversion, and desalination.

Background: Cancer pain is an important and distressing symptom that tends to increase in frequency and intensity as the cancer advances. For people with advanced cancer, the prevalence of pain can be as high as 90%. It has been estimated that 30% to 50% of people with cancer categorise their pain as moderate to severe, with between 75% and 90% of people with cancer experiencing pain that they describe as having a major impact on their daily life. Epidemiological studies suggest that approximately 15% of people with cancer pain fail to experience acceptable pain relief with conventional management. Uncontrolled pain can lead to physical and psychological distress and can, consequently, have a drastic effect on people's quality of life., Objectives: To determine the analgesic efficacy of hydromorphone in relieving cancer pain, as well as the incidence and severity of any adverse events., Search Methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase and clinical trials registers up to April 2016. There were no language, document type or publication status limitations applied in the search., Selection Criteria: We included randomised controlled trials (RCTs) that compared hydromorphone with placebo or other active pain medication for cancer pain in both adults and children. The four main outcomes selected have previously been identified as important to people with cancer; pain no worse than mild pain, and the impact of the treatment on consciousness, appetite and thirst. We did not consider physician-, nurse- or carer-reported measures of pain., Data Collection and Analysis: Two review authors independently extracted data. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We used a random-effects model and assessed the risk of bias for all included studies. A meta-analysis was not completed on any of the primary outcomes in this review due to the lack of data. We assessed the evidence using GRADE and created two 'Summary of findings' tables., Main Results: We included four studies (604 adult participants), which compared hydromorphone to oxycodone (two studies) or morphine (two studies). Overall, the included studies were at low or unclear risk of bias, rated unclear due to unknown status of blinding of outcome assessment; we rated three studies at high risk of bias for potential conflict of interest. Data for 504 participants were available for analysis. We collected data on endpoint participant-reported pain intensity measured with a visual analogue scale (VAS) (mean ± standard deviation (SD): hydromorphone 28.86 ± 17.08, n = 19; oxycodone 30.30 ± 25.33, n = 12; scale from 0 to 100 with higher score indicating worse pain), and Brief Pain Inventory (BPI) 24 hours worst pain subscale (mean ± SD: hydromorphone 3.5 ± 2.9, n = 99; morphine 4.3 ± 3.0, n = 101, scale from 0 to 10 with higher score indicating worse pain). The data demonstrated a similar effect between groups with both comparisons. The pain intensity data showed that participants in all four trials achieved no worse than mild pain. There were several adverse events: some were the expected opioid adverse effects such as nausea, constipation and vomiting; others were not typical opioid adverse effects (for example, decreased appetite, dizziness and pyrexia, as shown in Table 1 in the main review), but generally showed no difference between groups. There were three deaths in the morphine group during the trial period, considered to be due to disease progression and unrelated to the drug. Three trials had over 10% dropout, but the reason and proportion of dropout was balanced between groups. The overall quality of evidence was very low mainly due to high risk of bias, imprecision of effect estimates and publication bias. There were no data available for children or for several participant-important outcomes, including participant-reported pain relief and treatment impact on consciousness, appetite or thirst., Authors' Conclusions: This review indicated little difference between hydromorphone and other opioids in terms of analgesic efficacy. Data gathered in this review showed that hydromorphone had a similar effect on participant-reported pain intensity as reported for oxycodone and morphine. Participants generally achieved no worse than mild pain after taking hydromorphone, which is comparable with the other drugs. It produced a consistent analgesic effect through the night and could be considered for use in people with cancer pain experiencing sleep disturbance. However, the overall quality of evidence was very low mainly due to risk of bias, imprecision of effect estimates and publication bias. This review only included four studies with limited sample size and a range of study designs. Data for some important outcomes, such as impact of the treatment on consciousness, appetite or thirst, were not available. Therefore, we were unable to demonstrate superiority or inferiority of hydromorphone in comparison with other analgesics for these outcomes. We recommend that further research with larger sample sizes and more comprehensive outcome data collection is required.

Human noroviruses are the most important viral pathogens causing epidemic acute gastroenteritis, in which the GII.4 viruses have been predominant worldwide for the past decades. During 2014-2015 winter season, a new GII.17 variant emerged as the predominant virus in China surpassing the GII.4 virus in causing significantly increased acute gastroenteritis outbreaks. Genome sequences of the new GII.17 variant was determined and compared with other GII.17 noroviruses, revealing residue substitutions at specific locations, including the histo-blood group antigen-binding site and the putative antigenic epitopes. Further study of GII.17 outbreaks focusing on host susceptibility showed that the new GII.17 variant infected secretor individuals of A, B, O and Lewis types. Accordingly, the P particles of the new GII.17 variant bound secretor saliva samples of A, B, O and Lewis types with significantly higher binding signals than those of the P particles of the previous GII.17 variants. In addition, human sera collected from the outbreaks exhibited stronger blockade against the binding of the new GII.17 P particles to saliva samples than those against the binding between the P particles of previous GII.17 variants and saliva samples. Taken together, our data strongly suggested that the new GII.17 variant gained new histo-blood group antigen-binding ability and antigenic features, which may contribute to its predominance in causing human norovirus epidemics.

Background: Acute diarrhea is one of the most serious problems in global public health that causes considerable morbidity and mortality worldwide. Human caliciviruses (HuCV) including norovirus (NoV, genogroup GI and GII) and sapovirus (SaV), is a leading cause of acute sporadic diarrhea in individuals across all age groups. However, few studies had been conducted clarifying the characteristics of HuCV in diarrhea cases across all age groups in China. Our study was aimed at assessing the HuCV-related diarrhea burden and NoV genotypes distribution in southwest China., Methods: The study was conducted in four hospitals in Kunming city, Yunnan province, from June 2014 to July 2015. Stool specimens were collected from 1,121 diarrhea cases and 319 healthy controls in outpatient departments. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect NoV (GI, GII) and SaV. Sequencing was applied to confirm the three viral infections and phylogenetic analysis was performed to determine their genotypes. A structured questionnaire was used to record the demographic information and clinical symptoms of subjects., Results: HuCV was detected at an 11.0 % infection rate in 1,121 diarrhea cases and at 3.4 % rate in 319 non-diarrhea subjects (p < 0.0001, OR = 3.5, 95 % CI 1.8-6.5). The prevalence of the NoV genogroup GII and genotype GII.4 in diarrhea cases was significantly higher than that found in healthy controls (p < 0.0001, p = 0.018, respectively). NoV GII (n = 118, 10.5 %) was the most common HuCV subtype in diarrhea cases, followed by SaV (n = 3, 0.3 %) and NoV GI (n = 2, 0.2 %). Of 118 NoV GII strains isolated from diarrhea patients. GII.4 (n = 55, 46.6 %) was the predominant strain, followed by GII.3 (n = 28, 23.7 %), GII.12 (n = 25, 21.2 %), GII.17 (n = 8, 6.8 %), and GII.5 (n = 2, 1.7 %). Of the 55 GII.4 strains, the GII.4 Sydney 2012 variant had absolutely predominant prevalence (n = 52, 94.5 %), followed by the NoV GII.4-2006b variant (n = 3, 5.5 %). The GII.4 Orleans 2009 variant was not found in diarrhea cases of the study., Conclusions: NoV GII was the major genogroup and GII.4 was the most predominant strain detected in diarrhea patients. The GII.17 is an emergent variant in sporadic diarrhea and might become the predominant strain in diarrhea cases in the near future. Rapid, accurate detection kits need to be developed to help us find and treat NoV-associated diarrhea in clinical settings in a timely manner.

A recent histopathologic study implicated human tonsillar crypt epithelium as an important site for EV71 replication in EV71-caused fatal cases. This study aimed to confirm the susceptibility of human tonsillar epithelium to EV71. Two human tonsillar epithelial cell lines (UT-SCC-60A and UT-SCC-60B) were susceptive to EV71, and PI3K/AKT, p38, ERK1/2, and JNK1/2 signal pathways were activated. Interferon-α, IL-8, IL-1β, IL-6 and IL-12p40 were induced and regulated by PI3K/AKT, p38, ERK1/2, and JNK1/2 signal pathways. PI3K/AKT pathway activation appeared to suppress the induction of TNF-α, which induced cell survival by inhibiting GSK-3β. The activation of NF-κB was observed but inhibited by these pathways in EV71 infection. Furthermore, ERK1/2 and JNK1/2 were essential for efficient EV71 replication. Human tonsillar epithelial cells support EV71 replication and display innate antiviral immunity in vitro, indicating that human tonsillar epithelial cells may be novel targets for EV71 infection and replication in vivo., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To investigate the effect of premature rupture of the membrane (PROM) on neonatal complications in premature infants., Methods: The registration information of 7684 preterm infants with gestational age <37 weeks were collected from the cooperative units in the task group between January 1, 2014 to December 31, 2014. Specially trained personnel from each cooperative units filled in the unified form in a standardized format to record the gender, gestational age, birth weight, PROM, placental abruption, antenatal corticosteroid, Apgar score, amniotic fluid pollution, and complications of the infants. The data were analyzed comparatively between the cases with PROM and those without (control)., Results: The preterm mortality rate was significantly lower but the incidences of ICH, NEC, ROP and BPD were significantly higher in PROM group than in the control group (P<0.05). The 95% confidence interval of the OR value was <1 for mortality, and was >1 for ICH, NEC, ROP and BPD. After adjustment for gestational age, birth weight, gender, mode of delivery, placental abruption, placenta previa, prenatal hormones, gestational diabetes mellitus (GDM), gestational period hypertension and 5-min Apgar score <7, the incidences of NEC, ROP and BPD were significantly different between the two groups (P<0.05) with 95% confidence interval of OR value >1, but the mortality rate and incidence of ICH were not significantly different between the two groups (P>0.05)., Conclusion: PROM is a risk factor for NEC, ROP and BPD in preterm infants, and adequate intervention of PROM can reduce the incidences of such complications as NEC, ROP and BPD in the infants.

Cynoglossus zanzibarensis (Cynoglossidae, Soleoidei) is characterized by both eyes on the left side of the body. Here we report the mitogenome of this tonguesole for the first time, which is 16,569 bp in length, with gene order reorganized. The tRNA-Gln gene is translocated from the light strand (L-strand) to the heavy strand (H-strand), accompanied by shuffling of tRNA-Ile and tRNA-Met genes with a 160-bp intergenic spacer between tRNA-Gln and tRNA-Ile. The putative control region is translocated downstream to the place between the ND1 and the tRNA-Gln genes, leaving a 25-bp trace fragment in the original position. The rest of the gene arrangement is identical to that of the typical fish.

Cynoglossus bilineatus (Cynoglossidae, Soleoidei) is characterized by both eyes on the left side of the body and with a rounded snout and a short rostral hook. Here we first report the mitogenome of this tongue sole, which is 16,454 bp in length, and gene rearrangements have been observed. Particularly, the tRNA-Gln gene encoded by the light strand (L-strand) has translocated to the heavy strand (H-strand), along with the tRNA-Ile gene shuffling. In addition, the putative control region has translocated downstream to a position between the ND1 and tRNA-Gln genes, leaving a 26-bp intergenic spacer in its original position. However, the arrangement of the rest genes is identical to that of the typical teleost. This result could contribute to a better understanding the molecular mechanisms of gene rearrangement in fish mitogenome as well as phylogenetic study of Cynoglossidae and Pleuronectiformes.

The enhanced stability and controllability of an ionic diode system based on funnel-shaped nanochannels with a much longer critical region is reported. The polarity of ion transport switching from anion/cation-selective to ambipolar can be controlled by tuning the length and charge of the critical region. This nanofluidic structure anticipates potential applications in single-molecule biosensing, water resource monitoring, and healthcare., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Cynoglossus abbreviatus (Cynoglossidae, Soleoidei) is characterized by a bilaterally asymmetrical with both eyes on the left side. In this study, the complete mitogenome of this tongue sole has been reported for the first time. The gene order in C. abbreviatus mitogenome possesses a novel rearrangement like other tonguefish. The tRNA-Gln gene moves from the light strand to the heavy strand, accompanied by tRNA-Ile gene shuffling, leaving a large non-coding region (88 bp) between these two tRNAs. Additionally, the control region translocates to the place between ND1 and tRNA-Gln genes. The total length is 16,417 bp, with 30.9%, 29.5%, 24.9% and 14.7% for A, T, C and G, respectively (60.4% for AT content). These molecular data will provide useful information about the mechanism of gene reorganization in Cynoglossidae mitogenome and further phylogenetic study on Pleuronectiformes.

Background: Mice lacking glycosylated lysosomal membrane protein (Glmp (gt/gt) mice) have liver fibrosis as the predominant phenotype due to chronic liver injury. The Glmp (gt/gt) mice grow and reproduce at the same rate as their wild-type siblings. Life expectancy is around 18 months., Methods: Wild-type and Glmp (gt/gt) mice were studied between 1 week and 18 months of age. Livers were analyzed using histological, immunohistochemical, biochemical, and qPCR analyses., Results: It was shown that Glmp (gt/gt) mice were not born with liver injury; however, it appeared shortly after birth as indicated by excess collagen expression, deposition of fibrous collagen in the periportal areas, and increased levels of hydroxyproline in Glmp (gt/gt) liver. Liver functional tests indicated a chronic, mild liver injury. Markers of inflammation, fibrosis, apoptosis, and modulation of extracellular matrix increased from an early age, peaking around 4 months of age and followed by attenuation of these signals. To compensate for loss of hepatocytes, the oval cell compartment was activated, with the highest activity of the oval cells detected at 3 months of age, suggesting insufficient hepatocyte proliferation in Glmp (gt/gt) mice around this age. Although constant proliferation of hepatocytes and oval cells maintained adequate hepatic function in Glmp (gt/gt) mice, it also resulted in a higher frequency of liver tumors in older animals., Conclusions: The Glmp (gt/gt) mouse is proposed as a model for slowly progressing liver fibrosis and possibly as a model for a yet undescribed human lysosomal disorder.