An optimized short-term steroid therapy for chronic drug-induced liver injury: A prospective randomized clinical trial.

BACKGROUND AND AIMS: The use of corticosteroids in chronic drug-induced liver injury (DILI) is an important issue. Our previous randomized controlled trial showed that patients with chronic DILI benefited from a 48-week steroid stepwise reduction (SSR) regimen. However, it remains unclear whether a shorter course of therapy can achieve similar efficacy. In this study, we aimed to assess whether a 36-week SSR can achieve efficacy similar to that of 48-week SSR. METHODS: A randomized open-label trial was performed. Eligible patients were randomly assigned to the 36- or 48-week (1:1) SSR group. Liver biopsies were performed at baseline and at the end of treatment. The primary outcome was the proportion of patients with relapse rate (RR). The secondary outcomes were improvement in liver histology and safety. RESULTS: Of the 90 participants enrolled, 84 (87.5%) completed the trial, and 62 patients (68.9%) were women. Hepatocellular damage was observed in 53.4% of the cohort. The RR was 7.1% in the 36-week SSR group but 4.8% in the 48-week SSR group, as determined by per-protocol set analysis (p = 1.000). Significant histological improvements in histological activity (93.1% vs. 92.9%, p = 1.000) and fibrosis (41.4% vs. 46.4%, p = .701) were observed in both the groups. Biochemical normalization time did not differ between the two groups. No severe adverse events were observed. CONCLUSIONS: Both the 36- and 48-week SSR regimens demonstrated similar biochemical response and histological improvements with good safety, supporting 36-week SSR as a preferable therapeutic choice (ClinicalTrials.gov, NCT03266146).

[Protective Effect of Mesenchymal Stem Cell Transplantation on Intestinal Injury in Septic Mice and Its Mechanism].

Objective: To explore the protective effect of placenta-derived mesenchymal stem cells (P-MSCs) transplantation on intestinal injury in septic mice and its mechanism. Methods: A total of 24 mice were randomly assigned to 3 groups, a sham operation group, a sepsis group that underwent cecal ligation and puncture (CLP) procedure, and a group that received CLP and P-MSCs treatment. Hereinafter, the three groups are referred to as the Sham group, the CLP group, and the CLP+P-MSCs group. For the mice in the Sham group, the abdomen was cut open and the cecum was exposed and then placed back in the abdomen. CLP was performed in the other two groups to establish the sepsis model. Mice in the Sham and the CLP groups received 0.1 mL of 0.9% NaCl injection in the tail vein 1 hour after operation, while mice in the CLP+P-MSCs group received 2×10 5 P-MSCs infusion 1 hour after operation. Intestinal and blood specimens were collected from the mice in each group 24 hours after P-MSCs transplantation. Hematoxylin and eosin (HE) staining of the intestinal tissue was performed for pathological evaluation. The serum concentrations of D-lactic acid, diamine oxidase (DAO), endotoxin, interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, IL-10, and transforming growth factor (TGF)-ß were determined by enzyme linked immunosorbent assay (ELISA). The gene expression of the relevant inflammatory factors in the small intestinal tissue was determined by real-time fluorescence polymerase chain reaction. The expression of zonula occludens protein-1 (ZO-1) and occludin protein in the intestine was determined by Western blot, the infiltration of intestinal macrophages was determined by immunohistochemical method, and the polarization of macrophages was determined by immunofluorescence. Results: The exogenous transplantation of P-MSCs could form colonies in the injured intestines of septic mice. Compared with those of the CLP group, the intestinal injury of the CLP+P-MSCs group was significantly alleviated, the serum concentrations of D-lactic acid, DAO, endotoxin, IL-1ß, IL-6, and TNF-α were significantly decreased ( P<0.05), while the serum concentrations of IL-10 and TGF-ß were significantly increased ( P<0.05), the expression levels of IL-1 ß, TNF-α and IL-6 genes in the intestinal tissue were significantly decreased ( P<0.05), while the expression levels of IL-10 and TGF-ß genes were significantly increased ( P<0.05), and the expression of ZO-1 and occludin proteins in the intestine was also significantly increased ( P<0.05). In addition, the distribution of macrophages in the intestinal tissue of the CLP+P-MSCs group decreased significantly and the macrophages showed a tendency for M2 polarization. Conclusion: Exogenous transplantation of P-MSCs can significantly reduce inflammatory injury and improve the intestinal barrier function in septic mice with intestinal injury. Reduction in the infiltration of macrophages and promotion of the polarization of macrophages from M1 to M2 may be the mechanisms underlying the reduction of inflammation.

MiR-125 family improves the radiosensitivity of head and neck squamous cell carcinoma.

BACKGROUND: MiRNAs can affect the radiosensitization of head and neck squamous cell carcinoma (HNSCC). We aimed to analyze the function of miR-125 family members in HNSCC using The Cancer Genome Atlas (TCGA) and determine their effect on radiation in laryngeal squamous cell cancer (LSCC). METHODS: First, we systematically analyzed the role of the miR-125 family in HNSCC using the TCGA database and found that miR-125a-5p is associated with radiotherapy. We then performed comprehensive enrichment analysis of miR-125a-5p and predicted target genes. Then, we performed transfection, cell proliferation assays, reverse transcription polymerase chain reaction, apoptosis assays, micronucleus tests, and western blotting on hep-2 cells selected with puromycin. RESULTS: MiR-125 family members exhibited significantly different expression in HNSCC. They were significantly associated with tumor-node-metastasis staging, clinical stages, and histological grades. Radiation therapy had a statistically effect on miR-125 family members, except miR-125a-3p. Moreover, miR-125a-5p was related to overall survival in LSCC. Thus, we predicted 110 target genes and seven hub genes of miR-125a-5p. The proliferation rate of cells transfected with lentivirus vector expressing miR-125a-5p was significantly reduced compared to the other groups. The radiation effect was enhanced in cells transfected with miR-125a-5p. The ratio of apoptotic cells transfected and exposed to X-rays (10 Gy) was distinctly higher than that of the Ad-control group. Western blotting analysis revealed that miR-125a-5p upregulated the apoptotic regulators P53 and rH2AX. Thus, miR-125a-5p may increase radiosensitivity in LSCC via upregulation of pro-apoptotic genes. CONCLUSIONS: MiR-125 family members could be prognostic biomarkers of HNSCC and improve HNSCC sensitivity to radiotherapy by activating P53. Upregulating miR-125a-5p via lentivirus vectors may be a novel strategy to strengthen the effect of radiotherapy on LSCC.

Genome-wide map of N6-methyladenosine circular RNAs identified in mice model of severe acute pancreatitis.

BACKGROUND: Severe acute pancreatitis (SAP) is a deadly inflammatory disease with complex pathogenesis and lack of effective therapeutic options. N6-methyladenosine (m6A) modification of circRNAs plays important roles in physiological and pathological processes. However, the roles of m6A circRNA in the pathological process of SAP remains unknown. AIM: To identify transcriptome-wide map of m6A circRNAs and to determine their biological significance and potential mechanisms in SAP. METHODS: The SAP in C57BL/6 mice was induced using 4% sodium taurocholate salt. The transcriptome-wide map of m6A circRNAs was identified by m6A-modified RNA immunoprecipitation sequencing. The biological significance of circRNAs with differentially expressed m6A peaks was evaluated through gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis. The underlying mechanism of m6A circRNAs in SAP was analyzed by constructing of m6A circRNA-microRNA networks. The expression of demethylases was determined by quantitative polymerase chain reaction and western blot to deduce the possible mechanism of reversible m6A process in SAP. RESULTS: Fifty-seven circRNAs with differentially expressed m6A peaks were identified by m6A-modified RNA immunoprecipitation sequencing, of which 32 were upregulated and 25 downregulated. Functional analysis of these m6A circRNAs in SAP found some important pathways involved in the pathogenesis of SAP, such as regulation of autophagy and protein digestion. In m6A circRNA-miRNA networks, several important miRNAs participated in the occurrence and progression of SAP were found to bind to these m6A circRNAs, such as miR-24-3p, miR-26a, miR-92b, miR-216b, miR-324-5p and miR-762. Notably, the total m6A level of circRNAs was reduced, while the demethylase alkylation repair homolog 5 was upregulated in SAP. CONCLUSION: m6A modification of circRNAs may be involved in the pathogenesis of SAP. Our findings may provide novel insights to explore the possible pathogenetic mechanism of SAP and seek new potential therapeutic targets for SAP.

A novel 3-D lead-iodide polymer based on the linkage of rare binuclear [Pb2I]3+ cations and anionic bis(pyrazinyl)-trizole bridges.

A novel 3-D lead-iodide polymer [Pb2I(µ-bpt-z)3]n (1, Hbpt-z = 3,5-bis(pyrazinyl)-1,2,4-trizole) has been hydrothermally prepared and structurally characterized. 1 offers the first example of a 3-D lead-iodide polymer built up from the linkage of rare binuclear [Pb2I]3+ cations and anionic bis(pyrazinyl)-trizole bridges. 1 exhibits photoluminescent and photocurrent response properties, and its density functional theory calculation was also studied.

Two Organic Hybrid Iodoplumbates Directed by a Bifunctional Bis(pyrazinyl)triazole.

The two novel organic hybrid iodoplumbates [Hhbpt]2[H2hbpt][H4hbpt][Pb5I18]·9H2O (1, hbpt = 1H-3,5- bis(pyrazinyl)-1,2,4-triazole) and [Pb2I(bpt)2(H2O)3(I3·1/2I2)] (2) were synthesized under hydrothermal conditions. 1 contains a new type of pentanuclear cluster [Pb5I18]8- anion, while 2 comprises an unprecedented 2-D polyiodoplumbate layer. Both 1 and 2 are potential semiconductors with narrow absorption edges of 1.98 eV for 1 and 1.38 eV for 2. 2 also shows photocurrent response and photoluminescent properties.

Analysis of the Relationship Between Modic Change and Spinopelvic Parameters in the Sagittal Plane.

BACKGROUND This study explored relationship between Modic change and spinopelvic parameters in the sagittal plane. MATERIAL AND METHODS We divided 80 patients into 4 groups: 60 subjects diagnosed with Modic changes (MC) were enrolled in the MC groups (MC1, MC2, and MC3) with each MC type consisting of 20 subjects, and 60 healthy subjects were enrolled in the control group. Spinopelvic parameters in the sagittal plane were calculated to assess their associations with MC. Multivariate logistic regression was used to explore possible risk factors for MC. RESULTS PI and LL in the MC groups were significant smaller than in the control group (p<0.05). PI, SS, and PT were significantly correlated with LL with a correlation coefficient of 0.75PI, 0.71SS and 0.69PT (p<0.05). Multivariate logistic regression of the significant variables showed that PI (less than 43.2°) is an independent significant risk factor for MC. ROC analysis showed that moderate diagnostic value was obtained for the significant variable, with an area under the curve (AUC) of 0.80 (p>0.05). CONCLUSIONS We concluded that PI is risk factor for MC, and smaller PI is associated with higher incidence of MC.

[The protective effects of vitamin E on lung injury caused by high temperature and PM2.5 in COPD rats].

OBJECTIVE: To investigate the effects of vitamin E on the respiratory function impairment in rats with chronic obstructive pulmonary disease (COPD) after exposed to high temperature and PM2.5. METHODS: Fifty-four 7-week-old SPF male Wistar rats were randomly divided into 9 experimental groups (n=6). The rat COPD model was established by lipopolysaccharide (LPS) and smoke exposure. After modeled, the rats were tracheal instilled with PM2.5 (0 mg/ml, 3.2 mg/ml) and intraperitoneally injected with vitamin E at the dose of 40 mg/kg (20 mg/ml). Part of rats (high temperature groups) were then exposed to high temperature (40℃), once (8 h) a day for three consecutive days. After the last exposure, the lung function of rats was detected. The expression levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1) were detected by corresponding ELISA kits. RESULTS: Compared with the control group, exposure of high temperature and PM2.5 could inhibit the lung function of COPD rats significantly (P＜0.05); the level of MCP-1 was increased significantly in PM2.5-exposure groups (P＜0.05); iNOS was increased significantly in the groups of high temperature (P＜0.05). Compared with the single-PM2.5 exposure groups, TNF-α in lung was decreased in the normal temperature health group and high temperature COPD group (P＜0.05) after treated with vitamin E; MCP-1 was decreased in all vitamin E-treated groups (P＜0.05); the decreased iNOS only appeared in the group of high temperature with vitamin E treatment. CONCLUSION: High temperature and PM2.5 could aggravate the inflammation of COPD rats. As an antioxidant, vitamin E may protect the lung from the damage effects.

Nonmonotonic strain dependence of lattice thermal conductivity in monolayer SiC: a first-principles study.

An increasing number of two-dimensional (2D) materials have already been achieved experimentally or predicted theoretically, which have potential applications in nano- and opto-electronics. Various applications of electronic devices are closely related to their thermal transport properties. In this work, the strain dependence of phonon transport in monolayer SiC with a perfect planar hexagonal honeycomb structure is investigated by solving the linearized phonon Boltzmann equation. It is found that the room-temperature lattice thermal conductivity (κL) of monolayer SiC is two orders of magnitude lower than that of graphene. The low κL is due to small group velocities and short phonon lifetimes, which can also be explained by the polarized covalent bond due to large charge transfer from Si to C atoms. In a considered strain range, it is proved that the SiC monolayer is mechanically and dynamically stable. With increased tensile strain, the κL of the SiC monolayer shows an unusual nonmonotonic up-and-down behavior, which is due to the competition between the change of phonon group velocities and phonon lifetimes of low frequency phonon modes. At low strain values (<8%), the phonon lifetime enhancement induces the increased κL, while at high strain values (>8%) the reduction of group velocities as well as the decrease of the phonon lifetimes are the major mechanisms responsible for decreased κL. Our works further enrich the studies on the phonon transport properties of 2D materials with a perfect planar hexagonal honeycomb structure, and motivate further experimental studies.

Advanced Anti-Fouling Membranes for Osmotic Power Generation from Wastewater via Pressure Retarded Osmosis (PRO).

A facile and versatile approach was demonstrated for the fabrication of low-fouling pressure retarded osmosis (PRO) membranes for osmotic power generation from highly polluted wastewater. A water-soluble zwitterionic random copolymer with superior hydrophilicity and unique chemistry was molecularly designed and synthesized via a single-step free-radical polymerization between 2-methacryloyloxyethyl phosphorylcholine (MPC) and 2-aminoethyl methacrylate hydrochloride (AEMA). The P[MPC- co-AEMA] copolymer was then chemically grafted onto the surface of PES/Torlon hollow fibers via amino groups coupling of poly(AEMA) with the polyimide structures of Torlon, leaving the zwitterions of poly(MPC) in the feed solution. Because of the outstanding hydrophilicity, unique cationic and anionic groups, and electrical neutrality of the zwitterionic brush, the newly developed membrane showed great resistances to both inorganic scaling and organic fouling in PRO operations. When using a real wastewater brine comprising multifoulants as the feed, the P[MPC- co-AEMA] modified membrane exhibits a much lower flux decline of 37% at Δ P = 0 bar after 24-h tests and a smaller power density decrease of 28% at Δ P = 15 bar within 12-h tests, compared to 61% and 42% respectively for the unmodified one. In addition to the low fouling tendency, the modified membrane shows outstanding performance stability and fouling reversibility, where the flux is almost fully recovered by physical backwash of water at 15 bar for 0.5 h. This study provides valuable insights and strategies for the design and fabrication of effective antifouling materials and membranes for PRO osmotic power generation.

Down-regulated miR-448 relieves spinal cord ischemia/reperfusion injury by up-regulating SIRT1.

MicroRNAs play a crucial role in the progression of spinal cord ischemia/reperfusion injury (SCII). The role of miR-448 and SIRT1 in SCII was investigated in this study, to provide further insights into prevention and improvement of this disorder. In this study, expressions of miR-448 and SIRT1 protein were determined by qRT-PCR and western blot, respectively. Flow cytometry was used to analyze cell apoptosis. The endogenous expression of genes was modulated by recombinant plasmids and cell transfection. Dual-luciferase reporter assay was performed to determine the interaction between miR-448 and SIRT1. The Basso, Beattie, and Bresnahan score was used to measure the hind-limb function of rat. The spinal cord ischemia reperfusion injury model of adult rats was developed by abdominal aorta clamping, and the nerve function evaluation was completed by motor deficit index score. In SCII tissues and cells treated with hypoxia, miR-448 was up-regulated while SIRT1 was down-regulated. Hypoxia treatment reduced the expression of SIRT1 through up-regulating miR-448 in nerve cells. Up-regulation of miR-448 induced by hypoxia promoted apoptosis of nerve cells through down-regulating SIRT1. Down-regulated miR-448 improved neurological function and hind-limb motor function of rats with SCII by up-regulating SIRT1. Down-regulated miR-448 inhibited apoptosis of nerve cells and improved neurological function by up-regulating SIRT1, which contributes to relieving SCII.

A DFT study of the catalytic pyrolysis of benzaldehyde on ZnO, γ-Al2O3, and CaO models.

The catalytic pyrolysis pathways of carbonyl compounds in coal were systematically studied using density functional theory (DFT), with benzaldehyde (C6H5CHO) employed as a coal-based model compound and ZnO, γ-Al2O3, and CaO as catalysts. The results show that the products of both pyrolysis and catalytic pyrolysis are C6H6 and CO. However, the presence of any of the catalysts changes the reaction pathway and reduces the energy barrier, indicating that these catalysts promote C6H5CHO decomposition. Graphical abstract The presence of catalysts changes the reaction pathway and the energy barrier decreases in the order Ea (no catalyst)> Ea (CaO)> Ea (γ-Al2O3)> Ea (ZnO), indicating that these catalysts promote C6H5CHO decomposition.

[Hydrochemical Characteristics of Groundwater and the Origin in Alluvial-proluvial Fan of Qinhe River].

To study the hydrochemical characteristics of groundwater and the factors controlling the alluvial-proluvial fan of the Qinhe River, 60 samples were collected including 9 surface water samples and 51 groundwater samples. The distribution characteristics of the hydrochemistry and major controlling factors of hydrochemical evolution processes of surface water and groundwater in the study area were analyzed by using mathematical statistics, the Schakerev classification, Piper diagrams, Schoeller diagrams, Gibbs plots, and ion ratios. The results show that:① the major anions and cations of surface water and groundwater in the study area are Ca2+, Mg2+, SO42-, and HCO3-. The recharge sources of surface water and groundwater are closely related; ② the major hydrochemical types of the groundwater are HCO3-Ca, HCO3-Ca·Mg, and HCO3·SO4-Ca·Mg, while the major hydrochemical type of surface water is HCO3·SO4-Ca·Mg; and ③ the major ions of surface water and groundwater are affected by carbonate mineral weathering and dissolution, ion exchange, and evaporation. Sulfuric acid and carbonic acid were involved in carbonate mineral weathering and dissolution.

Down-regulated miR-448 relieves spinal cord ischemia/reperfusion injury by up-regulating SIRT1

MicroRNAs play a crucial role in the progression of spinal cord ischemia/reperfusion injury (SCII). The role of miR-448 and SIRT1 in SCII was investigated in this study, to provide further insights into prevention and improvement of this disorder. In this study, expressions of miR-448 and SIRT1 protein were determined by qRT-PCR and western blot, respectively. Flow cytometry was used to analyze cell apoptosis. The endogenous expression of genes was modulated by recombinant plasmids and cell transfection. Dual-luciferase reporter assay was performed to determine the interaction between miR-448 and SIRT1. The Basso, Beattie, and Bresnahan score was used to measure the hind-limb function of rat. The spinal cord ischemia reperfusion injury model of adult rats was developed by abdominal aorta clamping, and the nerve function evaluation was completed by motor deficit index score. In SCII tissues and cells treated with hypoxia, miR-448 was up-regulated while SIRT1 was down-regulated. Hypoxia treatment reduced the expression of SIRT1 through up-regulating miR-448 in nerve cells. Up-regulation of miR-448 induced by hypoxia promoted apoptosis of nerve cells through down-regulating SIRT1. Down-regulated miR-448 improved neurological function and hind-limb motor function of rats with SCII by up-regulating SIRT1. Down-regulated miR-448 inhibited apoptosis of nerve cells and improved neurological function by up-regulating SIRT1, which contributes to relieving SCII.

Lower lattice thermal conductivity in SbAs than As or Sb monolayers: a first-principles study.

Phonon transport in group-VA element (As, Sb and Bi) monolayer semiconductors has been widely investigated in theory, and, of them, monolayer Sb (antimonene) has recently been synthesized. In this work, phonon transport in monolayer SbAs is investigated with a combination of first-principles calculations and the linearized phonon Boltzmann equation. It is found that the lattice thermal conductivity of monolayer SbAs is lower than those of both monolayer As and Sb, and the corresponding sheet thermal conductance is 28.8 W K-1 at room temperature. To understand the lower lattice thermal conductivity in monolayer SbAs than those in monolayer As and Sb, the group velocities and phonon lifetimes of monolayer As, SbAs and Sb are calculated. The calculated results show that the group velocities of monolayer SbAs are between those of monolayer As and Sb, but that the phonon lifetimes of SbAs are smaller than those of both monolayer As and Sb. Hence, the low lattice thermal conductivity in monolayer SbAs is attributed to very small phonon lifetimes. Unexpectedly, the ZA branch has very little contribution to the total thermal conductivity, only 2.4%, which is obviously different from those of monolayer As and Sb with very large contributions. This can be explained by very small phonon lifetimes for the ZA branch of monolayer SbAs. The lower lattice thermal conductivity of monolayer SbAs compared to that of monolayer As or Sb can be understood by the alloying of As (Sb) with Sb (As), which should introduce phonon point defect scattering. We also consider the isotope and size effects on the lattice thermal conductivity. It is found that isotope scattering produces a neglectful effect, and the lattice thermal conductivity with a characteristic length smaller than 30 nm can reach a decrease of about 47%. These results may offer perspectives on tuning the lattice thermal conductivity by the mixture of multiple elements for applications of thermal management and thermoelectricity, and motivate further experimental efforts to synthesize monolayer SbAs.

Greatly enhanced light emission of MoS2 using photonic crystal heterojunction.

We present theoretical study on developing a one-dimensional (1D) photonic crystal heterojunction (h-PhC) that consists of a monolayer molybdenum disulfide (MoS2) structure. By employing the transfer matrix method, we obtained the analytical solution of the light absorption and emission of two-dimensional materials in 1D h-PhC. Simultaneously enhancing the light absorption and emission of the medium in multiple frequency ranges is easy as h-PhC has more modes of photon localization than the common photonic crystal. Our numerical results demonstrate that the proposed 1D h-PhC can simultaneously enhance the light absorption and emission of MoS2 and enhance the photoluminescence spectrum of MoS2 by 2-3 orders of magnitude.

Study of the association between hemorrhage and the position of hemorrhagic stigmata in patients with esophageal varices.

The aim of the present study was to investigate the predilection position of hemorrhagic stigmata (HS) in patients with esophageal variceal hemorrhage and provide guidance on endoscopic therapy for esophageal varices. The clinical characteristics, particularly the endoscopic manifestations of HS, in the patients who presented with gastroesophageal variceal hemorrhage and cirrhosis between January 2003 and December 2013 at our hospital were summarized and patients were grouped according to the distance of the lesion site to incisors at 35-40 and ~30 cm. The association between the location of HS and active hemorrhage was assessed. The location of hemorrhage and HS at 35-40 cm from the incisors was more common in esophageal varices patients, followed by the location at ~30 cm from the incisors (P<0.0001). The incidence of HS in esophageal varices patients in the 35-40 cm group was significantly higher than that in the ~30 cm group except for HS at 9:00 position (P<0.0001). The highest incidence of HS in the ~30 cm group was at the 3:00 position, followed by the 12:00, 6:00 and 9:00 position. Among them, there were significant differences between the 3:00 and 6:00 position, the 3:00 and 9:00 position, and the 9:00 and 12:00 position (P<0.05). The order in the 35-40 cm group was similar to that in the ~30 cm group and the incidence of HS at the 9:00 position was lowest (P<0.05). A certain association between the point of location of HS and hemorrhage was identified. HS located at 35-40 cm from the lesion site to incisors was identified to be most likely to bleed, followed by that located at ~30 cm. In addition, the incidence of HS at 9:00 position was found to be lower than that in the other positions. Therefore, HS located at ~30 cm and 35-40 cm from the lesion site to incisors should be paid attention to and the 3:00, 12:00 and 6:00 rather than the 9:00 position should be prioritized during endoscopic treatment, particularly in emergency situations.