MiR-494-mediated Effects on the NF-κB Signaling Pathway Regulate Lipopolysaccharide-Induced Acute Kidney Injury in Mice.

OBJECTIVE: To explore the effects of miR-494 inhibition through the NF-κB signaling pathway on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) mouse model. METHODS: The AKI mice induced by LPS were treated with miR-494 antagomir, and the kidney parameters and indicators of oxidative stress were detected. HE and TUNEL staining were performed to observe the kidney histopathology and the apoptosis in renal tubular epithelial cells (RTECs), respectively. The ROS level was measured using dihydroethidium (DHE) staining. In addition, qRT-PCR, western blotting, immunohistochemistry (IHC), and ELISA were also used to detect gene or protein expression. RESULTS: LPS-induced AKI mice injected with the miR-494 antagomir showed reduced blood urea nitrogen (BUN) and serum creatinine (Cr) with improved kidney histopathology. The expression levels of p-IKKα/ß, p-IκBα and p65 NF-κB in the nucleus were increased in kidney tissues from the LPS-induced AKI mice, and they were decreased by the miR-494 antagomir. Moreover, the results of IHC showed that the miR-494 antagomir downregulated p65 NF-κB in kidney tissues from the LPS-induced AKI mice, accompanied by decreased levels of TNF-α, IL-1ß, IL-6, MDA, NO, and ROS but increased levels of SOD and GSH. In addition, the LPS-induced AKI mice had increased apoptosis in RTECs, as well as increased Caspase-3 and Bax and decreased Bcl-2, which were reversed by the miR-494 antagomir. CONCLUSIONS: The inhibition of miR-494 could reduce inflammatory responses and improve oxidative stress in kidney tissues from LPS-induced AKI mice by blocking the NF-κB pathway accompanying by reduced apoptosis in RTECs.

[The role and molecular mechanism of miR-494 in disease development and progression].

MicroRNA-494 (miR-494) is a small non-coding RNA located in chromosome 14q32.31 and regulates post-transcriptional gene expression by promoting the degradation of its target mRNAs via binding to the 3' untranslated regions (3'UTR). It has been reported that miR-494 plays an important role in the occurrence, development and prognosis of various diseases. Several signaling pathways modulated by miR-494 including the PTEN/PI3K/AKT, nuclear factor κ-B (NF-κB), mitogen-activated protein kinase (MAPK), transforming growth factor-ß (TGF-ß)/SMAD, and Wnt/ß-catenin are associated with physiological regulation and pathological process in many diseases. The stably expression of miR-494 in the blood stream suggests its potential as a biological marker for disease diagnosis, treatment, and prognosis. Based on recent research, we summarize the role and molecular mechanism of miR-494 in disease development and progression. We also discuss its potential as a marker for clinical diagnosis and prognosis of various diseases.

Discovery of Guanidine Derivatives from Buthus martensii Karsch with Metal-Binding and Cholinesterase Inhibition Properties.

Two rare guanidine-type alkaloids, Buthutin A (1) and Buthutin B (2), along with two other compounds (3, 4), were isolated from Buthus martensii Karsch, and determined using extensive spectroscopic data analysis and high resolution-mass spectrometry. Compound 1 showed the most potent inhibition on AChE and BChE with IC50 values of 7.83 ± 0.06 and 47.44 ± 0.95 µM, respectively. Kinetic characterization of compound 1 confirmed a mixed-type of AChE inhibition mechanism in accordance with the docking results, which shows its interaction with both catalytic active (CAS) and peripheral anionic (PAS) sites. The specific binding of compound 1 to PAS domain of AChE was also confirmed experimentally. Moreover, compounds 1 and 3 exhibited satisfactory biometal binding abilities toward Cu2+, Fe2+, Zn2+ and Al3+ ions. These results provide a new evidence for further development and utilization of B. martensii in health and pharmaceutical products.

New 4-N-phenylaminoquinoline derivatives as antioxidant, metal chelating and cholinesterase inhibitors for Alzheimer's disease.

A series of new 4-N-phenylaminoquinoline derivatives were designed, synthesized, and their anticholinesterase activities, 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, metal-chelating ability were tested. Among them, compounds 11j, 11k and 11l had comparable inhibition activities to reference drug galantamine both in AChE and in BChE. Especially, compound 11j revealed the most potent inhibition to eeAChE and eqBChE with IC50 values of 1.20 µM and 18.52 µM, respectively. Furthermore, both kinetic analysis of AChE inhibition and molecular docking study indicated that compound 11j was mixed-type inhibitor, binding simultaneously to the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE, and propidium iodide displacement assay showed significant displacement of propidium iodide with compound 11k (25.80%) from PAS of eeAChE. More importantly, compound 11l displayed excellent DPPH radical scavenging activity (84% at 1 mg/mL), and its EC50 value was 0.328 µM. In addition, compounds 11a, 11j, 11k and 11l exhibited obvious biometal chelating abilities toward Al3+, Fe2+, Cu2+ and Zn2+ ions. Taken together, 4-N-phenylaminoquinoline derivatives targeting multiple pathogenetic factors deserve further investigation for treatment of AD.

Bone marrow-derived mesenchymal stem cells promote hepatic regeneration after partial hepatectomy in rats.

OBJECTIVES: Our goal was to study the ability of mesenchymal stem cells (MSCs) to stimulate liver regeneration after partial hepatectomy in rats. METHODS: MSCs were isolated from bone marrow and cultured in vitro. Their characteristics were analyzed by flow cytometry. After 70% partial hepatectomy, Sprague-Dawley rats were randomly divided into three groups: a control group that was injected with saline, animals that received bone marrow-derived MSCs (BM-MSCs) by tail vein injection (the BM-MSC-TV group) and animals that received BM-MSCs by portal vein injection (the BM-MSC-PV group). The injected BM-MSCs were traced by labeling with 4',6-diamidino-2-phenylindole, and cell proliferations were determined by immunohistochemical staining with Ki-67 and 5-bromo-2'-deoxyuridine. RESULTS: After the third passage, the cultured BM-MSCs had a fibroblast-like morphology and expressed high levels of stem cell markers CD29 and CD90. The levels of albumin rose significantly in the BM-MSC-TV and BM-MSC-PV groups compared with the control group. The number of 4',6-diamidino-2-phenylindole-positive liver cells in the BM-MSC-PV group was significantly higher than in the BM-MSC-TV group. The levels of Ki-67 and 5-bromo-2'-deoxyuridine were significantly higher in the BM-MSC-TV and the BM-MSC-PV groups than in the controls. CONCLUSION: Taken together, these results indicate that BM-MSC injections enhance liver regeneration after partial hepatectomy in rats.

Bis{1-[(1H-benzimidazol-1-yl)meth-yl]-1H-imidazole-κN (3)}bis-(3,5-dicarb-oxy-benzoato-κ(2) O (1),O (1'))nickel(II) octa-hydrate.

In the title complex, [Ni(C9H5O6)2(C11H10N4)2]·8H2O, the Ni(II) ion exhibits site symmetry 2. It has a distorted octa-hedral coordination defined by two N atoms from two symmetry-related 1-[(1H-benzimidazol-1-yl)meth-yl]-1H-imidazole ligands and four O atoms from two symmetry-related 3,5-dicarb-oxy-benzoate anions. In the crystal, the complex mol-ecules and solvent water mol-ecules are linked via O-H⋯O, O-H⋯N and N-H⋯O hydrogen bonds, forming a three-dimensional structure. There are also a number of C-H⋯O inter-actions present.

[Quality of life of inpatients with coal workers' pneumoconiosis and its influential factors].

OBJECTIVE: To investigate the quality of life ( QOL) of inpatients with coal workers' pneumoconiosis( CWP) and analyse its influential factors, and to provide a theoretical basis for effective control measures. METHODS: Eighty-eight CWP patients in a hospital were included in the study. A questionnaire survey was conducted in them using a self-designed QOL scale. A database was established by software EpiData3.1, and the obtained data were statistically analyzed by software SPSS 16.0. RESULTS: Of the 88 patients, 73( 82.9%) had middle-level QOL, with a mean QOL loss rate of 36.2%; the loss rates of physical function and somatic sensation were the highest ( 44.2% and 41.5%). The patients with stage II CWP had significantly lower physical function than those with stage I and III CWP; the physical function and social function of patients significantly decreased with age; the personal income, household income, and housing condition of the patients had a marked impact on their physical and psychological functions, and the housing condition and education level had a marked impact on their social function. The multivariate analysis showed that old age, low income,and poor housing condition were the main adverse factors for the QOL of inpatients with CWP. CONCLUSION: The QOL of inpatients with CWP declines significantly, and their QOL is related to the age, income, and satisfaction with housing condition.

Insight into mixed chlorine/chloramines conversion and associated water quality variability in drinking water distribution systems.

Mixed chlorine/chloramines are common in drinking water distribution systems (DWDSs); however, their transformation and impact on chemical and microbial characteristics are not well understood. We systematically investigated water quality parameters associated with mixed chlorine/chloramine species conversion in 192 samples (including raw, finished, and tap water) collected throughout the year in a city in East China. Various chlorine/chloramine species (free chlorine, monochloramine [NH2Cl], dichloramine [NHCl2], and organic chloramines [OC]) were detected in both chlorinated and chloraminated DWDSs. NHCl2 + OC increased with transport distance along the pipeline network. The maximum proportion of NHCl2 + OC in over total chlorine in tap water reached 66 % and 38 % from chlorinated and chloraminated DWDSs, respectively. Both free chlorine and NH2Cl showed a rapid decay in the water pipe systems, but NHCl2 and OC were more persistent. Correlations between chlorine/chloramine species and physicochemical parameters were established. Models for predicting the sum of chloroform/TCM, bromodichloromethane/BDCM, chlorodibromomethane/CBDM, and bromoform/TBM (THM4) (R2 = 0.56) and haloacetic acids (HAAs) (R2 = 0.65) exhibited greater accuracy based on machine learning tuned with chlorine/chloramine species, particularly NHCl2 + OC. The predominant bacterial communities in mixed chlorine/chloramine systems were those resistant to chlorine or chloramine such as proteobacteria. NH2Cl was the most significant explanatory factor (28.1 %) for the variation in microbial community assemblage in chloraminated DWDSs. Although residual free chlorine and NHCl2 + OC, accounted for a smaller proportion of chlorine species in chloraminated DWDSs, they played an essential role (12.4 % and 9.1 %, respectively) in the microbial community structure.

[Silica induced α-SMA expression in HBE cell line by targeting the PI3K/Akt pathway].

OBJECTIVE: To explore the role of the phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) pathway in silica-induced α-SMA (α smooth muscle actin) expression in HEB (human bronchial epithelial) cell. METHODS: The cultured HBE cells were divided into 5 groups: control, silica, PI3K inhibitor (Ly294002), both PI3K inhibitor (Ly294002) and silica at the same time and the inhibitor 24 h ahead of silica. The final concentrations of PI3K inhibitor and silica were 10 µmol/L and 100 µg/ml, respectively. Western blots were used to detect protein expressions of Akt, p-Akt, TGF-ß and α-SMA. The location and expression of α-SMA were measured by immunofluorescence assay. RESULTS: HBE cell line exposed to silica can induce Akt phosphorylation, in which expressions of p-Akt were up regulated 1 times at 48 and the highest at 72 h. The expressions of TGFß increased remarkably at 12 h and the peak at 48 h after silica exposure, while the expressions of α-SMA increased at 24 h and the highest at 72 h. However, the PI3K inhibitor (Ly294002) significantly down regulated α-SMA expression. When the cell line exposed to the PI3K inhibitor ahead of silica 24 h, the expressions of p-Akt and α-SMA were more remarkably down regulated which were decreased 1.5 times and 7.6 times respectively compare to silica exposure group. But no significant changes were found for TGFß expressions. The immunofluorescence assay showed that silica can induce α-SMA expression, which located in cytoplasma, and PI3K inhibitor can decrease the expression. CONCLUSIONS: Silica induced α-SMA expression in HBE cell line is by targeting the PI3K/Akt pathway and PI3K inhibitor can repress α-SMA expression.

Evidence for two types of Aquilegia ecalcarata and its implications for adaptation to new environments.

Spurs have played an important role in the radiation of the genus Aquilegia, but little is known about how the spurless state arose in A. ecalcarata. Here we aim to characterize the genetic divergence within A. ecalcarata and gain insights into the origin of this species. A total of 19 populations from A. ecalcarata and 23 populations from three of its closest relatives (Aquilegia kansuensis, Aquilegia rockii and Aquilegia yabeana) were sampled in this study. We sequenced fifteen nuclear gene fragments across the genome and three chloroplast loci to conduct phylogenetic, PCoA and STRUCTURE analyses. Our analyses indicate that A. ecalcarata may not be monophyletic and can be divided into two distinct lineages (A. ecalcarata I and A. ecalcarata II). A. ecalcarata I is genetically close to A. kansuensis, whereas A. ecalcarata II is close to A. rockii. Isolation-with-migration analysis suggested that historical gene flow was low between A. ecalcarata I and A. rockii, as well as between A. ecalcarata II and A. kansuensis. The two distinct lineages of A. ecalcarata show significant divergence in 13 floral traits and also have distinct distributions. In addition, both A. ecalcarata I and II are adapted to a stony environment that differs from that of their closest relatives, indicating a habitat shift may have driven new adaptations. Our findings enrich the understanding of how floral evolution contributes to species diversification.

Bioactive prenylated phenolic compounds from the aerial parts of Glycyrrhiza uralensis.

In this work, a bioassay-guided fractionation strategy was used to isolate 26 phenolic compounds from the ethyl acetate partition of an ethanol extract of the aerial parts of Glycyrrhiza uralensis Fisch. ex DC. Among them, 8 prenylated phenolic compounds (glycyuralins Q-X) were described for the first time. The two enantiomers of glycyuralin Q were purified and their absolute configurations were established by ECD spectral calculations. (1″R, 2″S)-glycyuralin Q and (1″S, 2″R)-glycyuralin Q showed significant inhibitory activities against SARS-CoV-2 virus proteases 3CLpro with IC50 values of 1.5 ± 1.0 and 4.0 ± 0.3 µM, and PLpro with IC50 values of 2.4 ± 0.2 and 1.9 ± 0.1 µM, respectively. Four compounds showed potent cytotoxic activities against A549, Huh-7, and HepG2 human cancer cells with IC50 values ranging from 0.5 to 2.5 µM.

[Studies on flavonoids from the leaves of Lindera aggregata].

OBJECTIVE: To investigate the chemical constituents in the leaves of Lindera aggregate. METHODS: Compounds were separated by column chromatography with silica gel and ODS. The structures were identified by physicochemical properties and spectral analysis (1H-NMR, 13C-NMR). RESULTS: Eight compounds were isolated and identified as: quercetin-3-O-L-rhamnoside(1), kaempferol-3-O-L-rhamnoside(2), kaempferol(3), dihydrokaempferol-3-O-L-rhamnoside (4), quercetin (5), quercetin-3-O-alpha-D-arabinofuranoside (6), quercetin-3-O-alpha-D-glucopyranoside(7), kaempferol-3-O-D-glucopyranoside(8). CONCLUSION: Compounds 2,4 and 8 are obtained from Lindera aggregata for the first time.

Accessory sex glands of male mice have the ability to synthesize taurine via the cysteine sulfinate decarboxylase pathway.

Our previous study showed that cysteine sulfinate decarboxylase (CSD) is expressed in the testis, epididymis, and ductus deferens. However, the expression of CSD and taurine concentration in the male accessory sex glands remain unknown. Therefore, we conducted immunohistochemical analysis, semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), and western blotting in order to examine CSD expression in the seminal vesicle; bulbourethral gland; and prostate gland, including the dorsolateral prostate, ventral prostate, and anterior prostate. We also analyzed the tissue taurine concentration by using high-performance liquid chromatography (HPLC). Immunohistochemical analysis revealed that CSD is expressed in the tall columnar cells of the seminal vesicle, the glandular epithelium of the bulbourethral gland, and the epithelial cells of the intermediate segments of prostate gland. The taurine concentrations in the dorsolateral prostate, ventral prostate, and anterior prostate; seminal vesicle; and bulbourethral gland in terms of micromoles per gram wet weight were 6.09+/-0.67, 6.62+/-0.43, 4.14+/-0.05, 12.55+/-1.03, and 7.50+/-0.64, respectively; these values are similar to the relative expression levels of the CSD protein. These results demonstrate that CSD is expressed in the accessory sex glands of mice, and they confirm our hypothesis that male accessory sex glands are able to synthesize taurine through the CSD pathway.

Research progress of vagus nerve stimulation in the treatment of epilepsy.

The International League Against Epilepsy (ILAE) defined drug-resistant epilepsy (DRE) that epilepsy seizure symptoms cannot be controlled with two well-tolerated and appropriately chosen antiepileptic drugs, whether they are given as monotherapy or in combination. According to the WHO reports, there is about 30%-40% of epilepsy patients belong to DRE. These patients need some treatments other than drugs, such as epilepsy surgery, and neuromodulation treatment. Traditional surgical approaches may be limited by the patient's clinical status, pathological tissue location, or overall prognosis. Thus, neuromodulation is an alternative choice to control their symptoms. Vagus nerve stimulation (VNS) is one of the neuromodulation methods clinically, which have been approved by the Food and Drug Administration (FDA). In this review, we systematically describe the clinical application, clinical effects, possible antiepileptic mechanisms, and future research directions of VNS for epilepsy.

[Effects of Cyclical Temperature Fluctuations on Organic Carbon Mineralization in Purple Soil].

In the natural state, the soil temperature changes periodically throughout the day, but there is no unified opinion on whether the daily variation of soil temperature affects the mineralization of soil organic carbon. Therefore, the effect of cyclical temperature fluctuations on organic carbon mineralization of purple soil, widely distributed in southwest China, was studied by an incubation experiment in the laboratory. These soils were incubated at three constant temperatures (15, 20, and 25℃) with cyclically fluctuating temperatures (the range was within 15/25℃) and two moisture levels (70% water holding capacity (WHC) and submerged condition). In the entire incubation period (66 d), aerobic and submerged condition, variable temperature (15/25℃) cultivation of purple soil, SOC cumulative mineralization and the mineralization intensity had no obvious differences with constant temperature of 20℃. This indicated that the periodic variable temperature treatment (15/25℃) of SOC mineralization of purple soil with the same accumulated temperature of constant temperature processing (20℃). In addition, except for constant temperature of 15℃, the temperature processing of submerged condition of purple soil SOC cumulative mineralization was significantly higher than 70% WHC treatment (P<0.05). During the entire incubation period, soil microorganism carbon content could not reflect the SOC mineralization differences under constant temperature and cyclically fluctuating temperature. According to two-pool first-order model, the submerged condition can effectively increase the labile SOC pool size of purple soil, but the cyclically fluctuating temperature cannot effectively affect the labile SOC pool size of purple soil.

High-Energy Density Li metal Dual-Ion Battery with a Lithium Nitrate-Modified Carbonate-Based Electrolyte.

Lithium (Li) metal is a favorable anode for most energy storage equipment, thanks to its higher theoretical specific capacity. However, nonuniform Li nucleation/growth results in large-sized and irregular dendrites generated from the Li anode, which causes rapid capacity fade and serious safety hazard, hindering its widespread practical applications. In this paper, with the aid of a lithium nitrate (LiNO3) additive in a carbonate-based electrolyte, the Li anode shows low hysteresis for in excess of 1000 h at a current density of 0.5 mA cm-2. At the same time, a Li-graphite dual-ion battery exhibits an outstanding cycling stability at 5C; after 1000 cycles, 81% of the capacity is retained. After calculation, the Li-graphite dual-ion battery shows a competitive specific energy density of 243 Wh kg-1 at a power density of 234 W kg-1. Moreover, the linear sweep voltammetry test was first performed to analyze the Li nucleation/growth mechanism and explain the effect of the LiNO3 additive. The superior electrochemical properties of the Li-graphite dual-ion battery are ascribed to the formation of smooth Li composed of Li nanoparticles and a steady solid electrolyte interface film.

Bioaccumulation of endocrine disrupting compounds in fish with different feeding habits along the largest subtropical river, China.

Endocrine disrupting compounds (EDCs) are becoming an increasing concern regarding bioaccumulation in aquatic biota. However, the effects of regional pollution levels and specific feeding habits on the bioaccumulation of EDCs in fish are rarely reported. 4-Nonylphenol (4-NP), bisphenol A (BPA), 4-tert-octylphenol (4-t-OP), triclocarban (TCC) and triclosan (TCS) were determined in abiotic compartments [water, sediment, suspended particulate matter (SPM)] and fish with different feeding habits along the Pearl River, China. EDCs in abiotic compartments exhibited significant (p < 0.05) spatial variations, forming five zones clustered based on site-specific EDC concentrations. 4-NP was the dominant compound, contributing 58-98% of the EDCs in fish, followed by BPA (<41%), 4-t-OP (<13%), and TCC and TCS (<4.7%). The concentrations of 4-NP and 4-t-OP, BPA, and TCC and TCS were the highest in brackish carnivorous, planktivorous, and detritivorous fish, respectively. The bioaccumulation factors (BAFs) showed that 4-NP accumulated (BAF > 5000) in all fish except for suck-feeding detritivores, while 4-t-OP and TCC accumulated in filter-feeding planktivores. The concentration of 4-NP in carnivores was significantly higher than that in detritivores, indicating the potential biomagnification of 4-NP along food chains. EDCs in sediment and SPM and those in water were most positively correlated with those in detritivores and planktivores, respectively, suggesting the potential of fish with these two feeding habits to act as bioindicators of EDC pollutants.

Comparison of intravitreal ganciclovir monotherapy and combination with foscarnet as initial therapy for cytomegalovirus retinitis.

AIM: To compare the effectiveness between multiple intravitreal injections of ganciclovir alone and combined with foscarnet as initial treatment for patients with newly-onset cytomegalovirus retinitis (CMVR). METHODS: The retrospective study observed 37 patients (58 eyes) who suffered from CMVR onset between 2013 and 2015. Among them, 35 eyes underwent 4 weekly intravitreal injections of 3.0 mg ganciclovir, and 23 eyes underwent 4 weekly injections of 3.0 mg ganciclovir combined with 2.4 mg foscarnet. Visual acuity, intraocular pressure and viral load of cytomegalovirus (CMV) in aqueous humor measured by real-time polymerase chain reaction were compared before and after each injection. RESULTS: CMV-DNA copies in aqueous humor decreased remarkably in both groups. The average of CMV-DNA copies in patients' aqueous decreased from 38.3×104 copies/mL at baseline to 2.2×104 copies/mL after the 4th injection in patients who were treated with ganciclovir monotherapy, and decreased from 76.9×104 copies/mL to 11.3×104 copies/mL after 4 continuous injections of ganciclovir combined with foscarnet. No significant difference was found in reduction of viral load, change of visual acuities or intraocular pressures between monotherapy or combined therapy. CONCLUSION: Results of this study show that the initial effectiveness of treating CMVR after 4 weekly intravitreal injections is not significantly different from ganciclovir alone or combined with foscarnet. Continuous injection of ganciclovir alone is sufficient in treating immunosuppressive patients with newly-onset CMVR.

Protective effects of enhanced minor ginsenosides in Lactobacillus fermentum KP-3-fermented ginseng in mice fed a high fat diet.

Lactobacillus fermentum KP-3 was isolated from Korean pickle and used to ferment ginseng. The changes in the minor ginsenosides in the fermented ginseng were analyzed and the material was evaluated in high fat diet-fed mice. Total ginsenosides increased from 0.746 mg g-1 to 0.939 mg g-1 after fermentation, and the levels of minor ginsenosides (Rg2, Rg3, Rh1, Rh2, F2, and Ro) increased from 0.186 mg g-1 to 0.704 mg g-1. In an animal study, the serum TC and LDL levels in the HFD group were significantly higher than those of the control group. Compared with the HFD group, the probiotic-fermented ginseng significantly decreased the serum TC and LDL levels. In addition, the serum and liver ALT and AST levels were dramatically increased in the HFD group, but these increases were significantly inhibited by treatment with the probiotic-fermented ginseng. Furthermore, fermented ginseng reduced high fat diet-induced liver lipid accumulation. Overall, fermentation with L. fermentum KP-3 enhanced minor ginsenosides in ginseng and this probiotic-fermented ginseng ameliorated hyperlipidemia and liver injury induced by a high fat diet.