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Gram-positive enhancer matrix (GEM) nanoparticles are often used in mucosal immunity, preparation of subunit vaccines or as an immune adjuvant due to its good immunological activities in recent years. Here, we designed and screened out a high affinity peptide ligand PL23, which could specifically target the non-epitope region of Classic Swine Fever Virus (CSFV) E2 protein, by virtual screening technology, enzyme linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) test. The OD value of PL23 at 450 nm was reached 1.982, and the KD value of it was 90.12 nM. Its binding capacity to protein was verified by SDS-PAGE as well. PL23 was subsequently conjugated to GEM nanoparticles by dehydration synthesis generating GEM-PL23 particles, and the GEM-PL-E2 particles were assembled after incubated with CSFV E2 protein. The cytotoxic test indicated that PL23, CSFV E2 protein, GEM nanoparticles, GEM-PL23 particles and GEM-PL-E2 particles were not toxic to cells and GEM nanoparticles could significantly promote the growth of APCs at high concentration for 1 h, p

Glomerulosclerosis and renal interstitial fibrosis occur with the aging kidney. In this study, we examined the expression of miR-21, peroxisome proliferator-activated receptor(PPARα), hypoxia-inducible factor(HIF-1α) in the kidney of 3-month-old rats fed ad libitum (YAL), 24-month-old rats fed ad libitum (OAL) and 24-month-old rats subjected to a 70% calorie-restricted diet for 8 months (OCR). We found long-term caloric restriction (CR) ameliorated aging and aging-related fibrosis. CR ameliorated the increment of miR-21 and HIF-1α, as well as the decrement of PPARα in old ad libitum group. Human proximal tubular cells (HPTCs) presented phenotypes of senescence and epithelial to mesenchymal transition (EMT) under high-glucose conditions, in which senescence occurred earlier than EMT. Senescent cells secreted extracellular vesicles (EVs) which contained miR-21 into the recipient cells. Inhibiting miR-21 of donor cells prevented the occurrence of EMT in recipient cells. In addition, miR-21 induced EMT through targeting PPARα protein and consequently enhancing HIF-1α expression, although other pathways cannot be ruled out. These findings demonstrated that miR-21-containing EVs derived from the senescent cells could facilitate EMT of HPTCs via PPARα-HIF-1α signaling pathway. Long-term caloric restriction and caloric restriction mimetics alleviated aging-related-fibrosis of kidney through downregulation of miR-21.

Owing to the unearthed left maxillary fragment and left lower premolar fossil in 1950s, Changyang Cave was regarded as an important hominin site where Middle Pleistocene hominins are first discovered in southern China. However, only two bovine tooth fossils have been dated to 194 + 24–20 ka and 196 + 20–17 ka by U-series dating since 1980s. In this work, the stratigraphy of Changyang Cave was re-investigated by applying U–Th dating method for eight new tooth fossils obtained from fossil layer and two carbonate crystal samples from clay cement on the wall of this cave. New dating results showed that the ages of the two carbonate crystals are 256 and 233 ka respectively, and those of the eight tooth fossils are concentrated from 193 ka to 143 ka. Considering the ages of the two previous fossils, new carbonate crystals, and new eight tooth fossils, we suggested that the age range of Changyang hominin is between 196 and 143 ka.

The clinical use of gentamicin over prolonged periods is limited because of dose and time-dependent nephrotoxicity, in which intracellular oxidative stress and heightened inflammation have been implicated. Macroautophagy/autophagy is an essential and highly conserved self-digestion pathway that plays important roles in the maintenance of cellular function and viability under stress. The aim of this study was to determine changes in autophagy in response to the antioxidant N-acetylcysteine (NAC), via its effects on oxidative stress, inflammation, apoptosis, and renal function, following treatment with gentamicin in mini pigs. Adult mini pigs were divided into isotonic saline solution, gentamicin, and gentamicin plus NAC combination treatment groups. Gentamicin-induced histopathological changes, including inflammatory cell infiltration and tubular necrosis, were attenuated by NAC. NAC ameliorated the gentamicin-induced decreases in the levels of autophagy-related proteins, such as LC3 (microtubule-associated protein 1 light chain 3), PINK1 (phosphatase and tensin homologue deleted on chromosome10-induced kinase 1), phospho-parkin, AMBRA1 (activatingmolecule in Beclin 1-regulated autophagy), p62/SQSTM1 (sequestosome protein 1), and polyubiquitinated protein aggregates. NAC also caused a significant reduction in oxidative damage markers, including 4-hydroxy-2-nonenal, protein carbonyls, γ-H2AX (gamma histone variant H2AX), and 8-hydroxy-2′-deoxyguanosine, in gentamicin-treated animals. These data show that the protective effects of NAC might be related, at least in part, to a reduced inflammatory response, as observed in animals treated with both gentamicin and NAC. These results suggest that autophagy could be a new therapeutic target for preventing gentamicin-induced kidney injury, and that NAC might ameliorate gentamicin-induced nephrotoxicity by autophagy.

Three-dimensional hollow SnO2@TiO2 spheres encapsulated in reduced graphene oxide aerogels (HSTGAs) were successfully fabricated through self-assembly from SnO2@TiO2 hollow spheres and graphene oxide nanosheets using a simple hydrothermal process. The hollow spheres possess an average size of 360 nm. The thickness of SnO2 shell is 10–15 nm, and the thickness of TiO2 shell is 20–35 nm. The TiO2 shell was anchored onto the surface of hollow SnO2 spheres to effectively limit volume change. Afterward, hollow SnO2@TiO2 spheres were wrapped in graphene oxide nanosheets to build a three-dimensional conductive structure. The applications of HSTGAs as anode for lithium ion storage were explored. Systematic electrochemical results show that HSTGAs electrode maintains a high-discharge capacity of about 668.2 mA h g−1 at 100 mA g−1 after 200 cycles. Compared with pure metal oxide hollow spheres, HSTGAs can greatly enhance the electrochemical performance due to the synergistic effects of metal oxide hollow spheres and graphene oxide nanosheets. HSTGAs are prospective multifunctional nanomaterials that can be used to solve the current energy storage issues.

Polyaniline (PANI) is a conducting polymer which has been employed as a photosensitizer for enhancing the performance of a number of photocatalysts. Herein, we describe the synthesis of organic–inorganic hybrid materials in order to enhance the photocatalytic activity of double-shell TiO2/PANI hollow spheres (TAHSs), which were fabricated by means of sol–gel and in situ polymerization processes. The physicochemical properties of the PANI-modified TiO2 hollow spheres were investigated by a variety of techniques. The effect of the PANI shell layer on the photocatalytic activity of TAHSs was elucidated. With the optimal PANI content, the resultant TiO2/PANI hybrid materials exhibited remarkably enhanced UV and visible light photocatalytic degradation of aqueous methyl orange, far exceeding the activity of bare TiO2 hollow spheres. The synergistic effect between TiO2 and PANI is explained in terms of the improved separation of photogenerated electron–hole pairs.

An immunized mouse phage display scFv library with a capacity of 3.34 × 109 CFU/mL was constructed and used for screening of recombinant anti-ciprofloxacin single-chain antibody for the detection of ciprofloxacin (CIP) in animal-derived food. After four rounds of bio-panning, 25 positives were isolated and identified successfully. The highest positive scFv-22 was expressed in E. coli BL21. Then, its recognition mechanisms were studied using the molecular docking method. The result showed the amino acid residue Val160 was the key residue for the binding of scFv to CIP. Based on the results of virtual mutation, the scFv antibody was evolved by directional mutagenesis of contact amino acid residue Val160 to Ser. After the expression and purification, an indirect competitive enzyme-linked immunosorbent assay (IC-ELISA) based on the parental and mutant scFv was established for CIP, respectively. The IC50 value of the assay established with the ScFv mutant was 1.58 ng/mL, while the parental scFv was 26.23 ng/mL, this result showed highly increased affinity, with up to 16.6-fold improved sensitivity. The mean recovery for CIP ranged from 73.80% to 123.35%, with 10.46% relative standard deviation between the intra-assay and the inter-assay. The RSD values ranged between 1.49% and 9.81%. The results indicate that we obtained a highly sensitive anti-CIP scFv by the phage library construction and directional evolution, and the scFv-based IC-ELISA is suitable for the detection of CIP residue in animal-derived edible tissues.

Introduction Renal interstitial fibrosis, an important pathological feature of kidney aging and chronic renal failure, is regulated by mesenchymal stem cells (MSCs). We have previously demonstrated low expression of miR-133b in MSC-derived extracellular vesicles (MSC-EVs) in aged rats. However, miR-133b can mediate the inhibition of epithelial-mesenchymal transition (EMT) of renal tubules induced by transforming growth factor-β1 (TGF-β1). We investigated the effect of miR-133b for the treatment of geriatric renal interstitial fibrosis and evaluated its target genes. Methods We performed real-time polymerase chain reaction to detect miR-133b expression induced during EMT of HK2 cells by TGF-β1 at different concentrations (0, 6, 8, and 10 ng/mL) and at different time points (0, 24, 48, and 72 h). The target genes of miR-133b were validated using the dual-luciferase reporter assay. In vitro experiments were performed to evaluate mRNA and protein expression of miR-133b targets, E-cadherin, α-smooth muscle actin (SMA), fibronectin, and collagen 3A1 (Col3A1), in HK2 cells transfected with miR-133b under TGF-β1 stimulation. A 24-month-old unilateral ureteral obstruction (UUO) mouse model was established and injected with transfection reagent and miR-133b into the caudal vein. The target gene of miR-133b and other parameters mentioned above such as mRNA and protein expression levels and renal interstitial fibrosis were detected at 7 and 14 days. Results miR-133b expression gradually decreased with an increase in TGF-β1 concentration and treatment time, and the miR-133b mimic downregulated connective tissue growth factor (CTGF) expression. The dual-luciferase reporter assay confirmed CTGF as a direct target of miR-133b. Transfection of the miR-133b mimic inhibited TGF-β1-induced EMT of HK2 cells; this effect was reversed by CTGF overexpression. miRNA-133b expression significantly increased (approximately 70–100 times) in mouse kidney tissues after injection of the miRNA-133b overexpression complex, which significantly alleviated renal interstitial fibrosis in mice with UUO. Conclusion miR-133b exerted targeted inhibitory effects on CTGF expression, which consequently reduced TGF-β1-induced EMT of HK2 cells and renal interstitial fibrosis in aged mice with UUO.

Tremella-like silica spheres (TSSs) and brush-like silica fibers (BSFs) with well-defined structures were synthesized using cetyltrimethylammonium bromide and sodium dodecyl sulfate aggregate as structure-directing agent and β-cyclodextrin (β-CD) as inducing agent. By controlling the amount of β-CD, the morphology of mesoporous silica was changed from TSSs to BSFs and then back to TSSs. The materials were characterized by using several techniques. The extraordinary mesoporous silica with a brush-like shape and measuring 180–220 nm wide and 6–20 μm long were formed as a result of the diameter of the U-shaped silica skeleton. These two kinds of materials can be used as fluorescent hybrid materials by immobilizing Rhodamine B (Rh B). Furthermore, the hybrid materials were well characterized by the fluorescence spectra to prove that BSFs-Rh B has excellent fluorescence property.

In this study, flower-shaped TiO2/C embedded with fish-scale-like MoS2 (TiO2/C/MoS2) microspheres were synthesized by impregnating MoS2 into the interspace of TiO2/C. The TiO2/C/MoS2 microspheres (diameter of 2–3 µm), which are composed of several homogeneous flake-shaped petals, were then applied as anode in lithium-ion batteries. MoS2 has a fish-scale shape with size of approximately 10 nm. In addition, MoS2 is connected to the TiO2 petal surface. In the flower-shaped TiO2/C/MoS2 microspheres, TiO2 acts as backbone for MoS2 that can effectively minimize the strain of volume changes. The fish-scale-like MoS2 can provide more active sites for reactions. The flower-shaped TiO2/C/MoS2 electrode exhibits a discharge capacity of 621 mA h g−1 at 100 mA g−1 after 100 cycles, which is much higher than that of TiO2/C electrode (291 mA h g−1) and pure MoS2 electrode (160 mA h g−1). Compared with TiO2/C and pure MoS2, the structural and compositional features of the TiO2/C/MoS2 microspheres enhance the specific capacity and cycling stability.

Monolithic alumina aerogels were prepared with inorganic aluminum salts as raw material by epoxide-assisted sol–gel method. The structure and morphology of the monolithic alumina aerogels doped with different lanthanum oxide concentration were investigated by X-ray diffraction, Fourier transform infrared spectroscopy, N2 adsorption–desorption method and field emission scanning electron microscope. The results indicate that the pure alumina aerogel is translucent and sky blue in color. Alumina aerogels gradually changes into opaque blocks of ivory with increasing the amount of lanthanum oxide. The addition of lanthanum oxide can increase the specific surface area of alumina aerogels and improve their thermal stability at high calcination temperature. After calcination at 1000 °C for 2 h, alumina aerogel doped with 10 wt% lanthanum oxide is still amorphous phase and its specific surface area can reach 282 m2/g, which is much higher than pure alumina aerogel.

In this study, we developed a facile one–pot strategy for fabricating flower–shaped yolk–shell SiO2 nanospheres (FYSSns) using cetyltrimethylammonium bromide–polyvinylpyrrolidone–cyclohexane–ethanol–water vesicle–microemulsion composite aggregation as templates through a simple solvothermal route. FYSSns displayed yolk–shell structures with flower-shaped yolks (260–320 nm) with ordered radial mesochannels (∼7 nm), large cavities (100–120 nm), and thin silica shells (20–30 nm). High laccase immobilization amounts were achieved using FYSSns as supporter, and the laccase–modified FYSSns were applied to the electrochemical sensor with high selectivity for detecting catechol. Under the optimized conditions, the proposed sensor showed a wide linear range from 12.5–450 μM over catechol concentration and a low detection limit of 1.6 μM. The outstanding performance was attributed to the advantages of FYSSns, such as large specific surface area and its own mesochannel structure.

In this study, anatase TiO 2 nanorods with exposed high-energy {100} and {001} facets and low-energy {101} facets were fabricated in the presence of surfactants cetyltrimethylammonium bromide, didecyldimethylammonium bromide, and ammonia via a facile hydrothermal method without the erosive reagent hydrofluoric acid. The particle size and morphology were mainly tuned by regulating the hydrothermal temperature. When the temperature was increased from 150 °C to 180 °C and 200 °C, the length of the nanorods decreased from 700-1000 nm to 400–500 nm and 100–200 nm, respectively. Concurrently, the edges and tops of the truncated tetragonal pyramid of the TiO 2 nanorods became blurry and flattened. The synthesized typical TiO 2 nanorods were then used as photocatalysts, and their performance during the direct generation of H 2 from water was evaluated. The TiO 2 nanorods obtained at 150 °C successfully produced high amounts of H 2 evolution (281.36 μmol) in the presence of methanol as a sacrificial agent under ultraviolet light irradiation for 4 h. The outstanding photocatalytic activity of the nanorods was mainly ascribed to the formation of surface heterojunctions in the edges and corners between adjacent high-energy {001} or {100} facets and low-energy {101} facets. The formed heterojunctions could facilitate charge separation through preferential carrier flow toward the specific facets.

Benzophenone-type UV filters are a group of compounds widely used to protect human skin from damage of UV irradiation. Benzophenone-4 (BP-4) was targeted to explore its transformation behaviors during chlorination disinfection treatment in the presence of iodide ions. With the help of ultra performance liquid phase chromatograph and high-resolution quadrupole time-of-flight mass spectrometer, totally fifteen halogenated products were identified, and five out of them were iodinated products. The transformation mechanisms of BP-4 involved electrophilic substitution generating mono- or di-halogenated products, which would be oxidized into esters and further hydrolyzed into phenolic derivatives. The desulfonation and decarboxylation were observed in chlorination system either. Obeying the transformation pathways, five iodinated products formed. The pH conditions of chlorination system determined the reaction types of transformation and corresponding species of products. The more important was that, the acute toxicity had significant increase after chlorination treatment on BP-4, especially in the presence of iodide ions. When the chlorination treatment was performed on ambient water spiked with BP-4 and iodide ions, iodinated by-products could be detected.

Background IgA nephropathy (IgAN) is one of the most common primary glomerular diseases worldwide, but effective therapy remains limited and many patients progress to end-stage renal disease (ESRD). Only angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin-receptor blockers (ARB) show a high level of evidence (1B level) of being of value in the treatment for IgAN according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. However, traditional Chinese medicine has raised attention in kidney disease research. Abelmoschus manihot, a single medicament of traditional Chinese medicine has shown therapeutic effects in primary glomerular disease according to the randomized controlled clinical trial that we have completed. Here, we conduct a new study to assess the efficacy and safety of Abelmoschus manihot in IgAN. Also, this study is currently the largest double-blind, randomized controlled registered clinical research for the treatment of IgAN. Methods We will conduct a multicenter, prospective, double-blind, double-dummy randomized controlled study. The study is designed as a noninferiority clinical trial. Approximately 1600 biopsy-proven IgAN patients will be enrolled at 100 centers in China and followed up for as long as 48 weeks. IgAN patients will be randomized assigned to the Abelmoschus manihot group (in the form of a huangkui capsule, 2.5 g, three times per day) and the losartan potassium group (losartan potassium, 100 mg/d). The primary outcome is the change in 24-h proteinuria from baseline after 48 weeks of treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after 48 weeks of treatment, the incidence of endpoint events (proteinuria ≥3.5 g/24 h, the doubling of serum creatinine, or receiving blood purification treatment) are the secondary outcomes. Twenty-four-hour proteinuria and eGFR are measured at 0, 4, 12, 24, 36 and 48 weeks. Discussion This study will be of sufficient size and scope to evaluate the efficacy and safety of Abelmoschus manihot compared to losartan potassium in treating patients with IgAN. The results of this study may provide a new, effective and safe treatment strategy for IgAN. Trial registration ClinicalTrials.gov, identifier: NCT02231125. Registered on 30 August 2014. Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1774-6) contains supplementary material, which is available to authorized users.

Aging is a risk factor for various acute and chronic kidney injuries. Kidney aging is accompanied by the secretion of growth factors, proteases, and inflammatory cytokines, known as the senescence-associated secretory phenotype (SASP). These factors accelerate the aging process and senescence-associated changes. Delaying kidney senescence may prevent acute and chronic kidney injury. Methionine restriction (MR) was found to be an effective intervention for delaying senescence. However, the mechanism of MR remains unclear. In this study, we investigated the effect of MR on the survival rate and renal aging of C57BL/6 mice and examined the relevant mechanisms. MR increased the survival rate and decreased the levels of senescence markers in the aging kidney. Both in vivo and in vitro, MR upregulated the transsulfuration pathway to increase H(2)S production, downregulated senescence markers and the SASP, and activated AMPK. The ability of MR to delay aging was reduced when AMPK was inhibited. These results suggest that MR may slow animal aging and kidney senescence through H(2)S production and AMPK pathway activation. Abbreviations: DR: diet restriction; MR: methionine restriction; SASP: senescence-associated secretory phenotype; AL: ad libitum; CKD, chronic kidney disease; AKI: acute kidney disease; TSP: transsulfuration pathway; CGL: cystathionine g-lyase; H(2)S: hydrogen sulfide; AMPK: AMP-activated protein kinase; mTOR: mammalian target of rapamycin; IS: indoxyl sulfate; CC: compound C.

Invited for the cover of this issue is Qinghua Gong, Guowei Zhou, and co-workers at Qilu University of Technology. The dial represents the etching time of SiOx yolk in NaOH solution and the brightness of the Chinese red lantern represents the electrochemical performance of the composites. Read the full text of the article at 10.1002/chem.202003246.

Chloroform, a regulated disinfection by-product in water, is often generated during chlorination disinfection treatment. However, the formation of chloroform is heavily dependent on the molecular structures of precursors. Moreover, compounds containing ketone moiety are ubiquitous in water environments. However, it is unclear if they can generate chloroform during chlorination. In this study, 14 benzophenones (BPs), efficient and widely used UV filters, with different substituents were selected to explore chloroform formation during chlorination. All 14 BPs generated chloroform, with yields dependent on their molecular structures and operational conditions. Compounds 2,2′,4,4′-tetrahydroxy-BP and benzophenone produced the highest and lowest chloroform of 0.313 and 0.013 g/g, respectively, corresponding to the fastest and slowest formation rate constants of 1.41 × 10−1 and 2.71 × 10−2 min−1. Alkaline conditions and high chlorine dosages were favorable to chloroform formation. Three reactions played key roles in chloroform formation from BPs: (1) chlorine initiated Baeyer–Villiger oxidation converted ketone moieties of BP molecules into esters; (2) the esters further underwent hydrolysis and formed phenolic and benzoic products; and (3) benzoic acids underwent decarboxylation and hydrolysis to form phenolic products. Subsequently, these phenolic products could further generate chloroform in the chlorination system. More importantly, BPs could generate chloroform in the ambient water matrices during practical chlorination treatment. This work emphasized the critical role of Baeyer–Villiger oxidation for chloroform formation, implying that pollutants containing aromatic ketone moieties generate chloroform during chlorination disinfection, and their potential risk should therefore be reviewed.

Aim Previous studies showed that circulating fibroblast growth factor-23 (FGF23) is a new biomarker linked to cardiovascular and kidney diseases. Here, we explored the association between serum FGF23 and aging-related cardiovascular–renal parameters in a healthy Chinese population. Methods A total of 314 healthy participants aged 36–87 years were enrolled. Cardiovascular structure and function were assessed by the left ventricular ejection fraction, the ratio of early diastolic peak flow velocity to late diastolic peak flow velocity at the mitral leaflet tips, carotid intima-media thickness, the diameter of the bilateral common carotid artery, blood systolic peak and end diastolic velocities, which were measured by M-mode ultrasonography. Glomerular filtration rate was evaluated using the Chronic Kidney Disease Epidemiology Collaboration equation and Chronic Kidney Disease Epidemiology Collaboration equation for Asians. Serum FGF23, 1, 25-dihydroxy vitamin D3 and parathyroid hormone were measured by enzyme-linked immunosorbent assay. Results For all participants, intima-media thickness/diameter of the bilateral common carotid artery gradually decreased with the progression from low to high FGF23 concentration (P

Novel series of caffeoyl benzanilide compounds as dual inhibitors of HIV-1 CCR5/IN were designed and synthesized. The biological results indicated that the acetylated compounds with double bonds were reduced, especially compound 9a, which showed potential activity against HIV-1 CCR5 tropic viruses with an EC50 value of 4.85 μM, as well as binding affinity with IN (KD 2.4 μM). Molecular modeling studies also suggested the possible binding mode of 9a with CCR5 and IN. These results indicated that 9a has the possibility of being a dual inhibitor of HIV-1.

Rationale and Objective IgA nephropathy (IgAN) is an important cause for end-stage renal disease worldwide. The treatment for IgAN remains challenging, and few randomized and controlled clinical trials have been conducted to evaluate new therapies. The present study assesses the efficacy and safety of Abelmoschus manihot (AM) in IgAN patients. Study Design Randomized, non-inferiority, double-blind, double-dummy multicenter trial. Setting and Participants This trial was designed to recruit 1,600 biopsy-proven IgAN patients (proteinuria between 0.5-3.0 g/d and estimated glomerular filtration rate [eGFR] of ≥ 45 ml/min/1.73 m2) across China. Interventions The participants were randomized at 1:1 to AM (2.5 g for three times per day) or losartan potassium (100 mg per day) for 48 weeks. Outcomes The primary outcome was the change in 24-hour proteinuria from baseline to week 48. The secondary outcomes were the change in eGFR from baseline to week 48, and the incidents of endpoint events (proteinuria ≥ 3.5 g/24 h, doubling of serum creatinine, or receiving renal replacement treatment). Results Among 1,470 randomized patients (mean age, 37.4 [SD, 10.6] years old; 777 [52.9%] were female; mean eGFR, 95.0 [SD, 24.3] mL/min/1.73 m2; mean 24-hour proteinuria, 1.2 [SD, 0.7] g/d), the mean decline in 24-h proteinuria at week 48 was 230 mg and 253 mg in the AM and losartan potassium groups, respectively (P = 0.676). The mean difference in the change in 24-h proteinuria between these two groups was -23.32 mg (95% confident interval: -123.2 to 76.6, p = 0.647). The mean decline in eGFR was 0.41 ml/min/1.73 m2 and 0.76 ml/min/1.73 m2 in the AM and losartan potassium groups, respectively (p = 0.661). The mean difference in the change in eGFR between these two groups was -0.43 ml/min/1.73 m2 (95% confident interval: -1.99 to 1.13, p = 0.589). The incidence of endpoint events was 8.6% in the AM group and 8.2% in the losartan group (p = 0.851). Limitations The results of the trial may not be generalized to IgAN patients with a proteinuria of > 3.0 g/d and an eGFR of Conclusion AM can be recommended as a promising treatment for IgAN patients.

2,4-Dihydroxybenzophenone (BP-1) is an important component and metabolite of benzophenone-type (BPs) UV filters, it is widely used in commercial products and frequently detected in environmental media and organism samples. The transformation characteristics and genotoxicity changes of BP-1 during chlorination disinfection process were explored. Nineteen transformation products were separated and tentatively identified, eleven of which were not previously reported. Most importantly, nine novel by-products including one chlorobenzoquinone, four phenyl benzoquinones, and four polycyclic aromatic hydrocarbons were formed during BP-1 chlorination. Plausible transformation pathways for BP-1 during chlorination treatment were proposed, in which chlorination substitution, Baeyer-Villiger oxidation, hydrolysis, and CC coupling reactions were involved. The CC coupling reaction is firstly observed in chlorination disinfection system. Higher pH values and chlorine doses would be a benefit for BP-1 transformation. The genotoxicity of the reaction mixture increased significantly with increasing chlorine dose under acid and neutral conditions due to the formation of benzoquinones and polycyclic aromatic hydrocarbons. It was noted that BP-1 and its chlorinated products were found in swimming pool water samples. This work inferred that BP-1 and its analogs are transformed during the chlorination disinfection process and may cause potential ecological and health risks.

A highly efficient approach to the synthesis of a series of pyrimido[b]azepines has been developed with 5-allyl-2,4,6-trichloropyrimidine as the starting material in six or seven steps via a ring-closing metathesis (RCM) reaction. The absolute configuration of the key intermediate pyrimido[4,5-b]azepine was ascertained by X-ray crystal structure analysis.

Summary Two studies have concluded that lithium exposure extends the lifespan of Caenorhabditis elegans. However, the effect of lithium on another widely used model organism, Drosophila melanogaster, remains unclear. Here, we demonstrate that chronic treatment with a low to moderate dose of lithium chloride does not extend lifespan in D. melanogaster and that the drug abolishes the female lifespan advantage in flies.

We investigated the boron isotopic composition in loess–paleosol sequences in five different profiles in the Chinese Loess Plateau. Three possible boron sources are identified: atmospheric input, carbonates, and weathered silicate rocks. Variations of [Sr], [B], δ11B and the magnetic susceptibility correlate well with the pedogenetic intensity in three out of the five studied profiles, where pedogenesis under a cold–dry climate indicates lower δ11B, lower [B], lower magnetic susceptibility and higher [Sr] values. Exceptions to the variations between the δ11B and other known proxies were observed in arenaceous soils and the Red Clay sequence: the former suggested that vertical redistribution probably occurred with the boron migration, and the latter indicated an unknown mechanism of susceptibility enhancement. A better correlation between the δ11B and magnetic susceptibility and the quantitative estimation of boron budget from each source confirms the influence of paleoenvironmental changes on boron geochemical cycle. Significant positive correlations in Sr/Ca vs. B/Ca and Mg/Ca vs. B/Ca reflect consistent enrichment behavior of those mobile elements into calcium carbonate. The preliminary results imply that boron isotopic compositions in soils can be a potential geochemical proxy to reconstruct the paleoenvironmental changes in loess–paleosol sequences.

The fossil evidence of hominins in China is crucial to understand the human evolution and dispersal in Eurasia. However, the dating of Chinese Early and Middle Pleistocene hominin record remains a serious problem. In this study, we applied coupled ESR/U-series dating method on Bailongdong hominin cave site in Hubei Province, central China, which is a key area to study early human migration between South and North China. The U-series analyses show that the fossil teeth samples from three horizons are close or beyond equilibrium, which indicate very early uptake or potential loss of uranium. Single saturation exponential fitting of 10 dose points irradiated up to 4 kGy was used for DE determination except one by double saturation exponential fitting with 16 dose points up to 63 kGy. Calculated by two uranium migration models, we obtain a weighted mean age of 509 ± 16 ka for five fossil teeth from layer 2. Combined with cosmogenic nuclides 26Al/10Be burial dating carried out on the cave deposits beneath the fossil layers in previous study, the multi-methods dating study places Bailongdong site at the early stage of Middle Pleistocene, and pinpoints the deposition of the fossil remains to the time of marine isotope stages 13. This is in agreement with the fauna composition and sedimentary characteristics which show a subtropical-tropical warm forest-grass environment. The multi-methods dating of Bailongdong site by both cosmogenic and coupled ESR/U-series methods is a good example for the future chronological studies of early human sites in China.

Two polyketides were isolated from the mangrove endophytic fungus, Penicillium sp. sk14JW2P, and one derivative with a modified structure. The structures were elucidated by spectroscopic analyses, the structure of the compound 1 was further confirmed by single-crystal X-ray diffraction, and its absolute configuration was determined. Compound 1 and 2 showed acetylcholinesterase (AchE) inhibitory activities with IC50 values of 12±0.3 and 79±2 nM, respectively.

Organic polymer solar materials are shown to exhibit better solubility in mixed solvents than in pure ones, which affects the performance of their solar cells. In this article, poly[N-9-hepta-decanyl-2,7-carbazole-alt-5,5-(4,7-di-2-thienyl-2,1,3-benzothiadiazole) (PCDTBT) and [6,6]-phenyl-C71-butyric acid methyl ester (PC71BM) are used as active layer materials in solar cells. To optimize the performance of these active materials, the ratio of chloroform (CF) to chlorobenzene used as solvents to dissolve PCDTBT, and PC71BM is varied, which is shown to affect power conversion efficiency (PCE). The solar cell that shows the best performance with a PCE as high as 6.82 % is produced using a volume ratio of CF to chlorobenzene of 1:1.

Xylanthraquinone (1), a new anthraquinone, along with three known compounds, altersolanol A (2), deoxybostrycin (3) and bostrycin (4) was isolated from the fungus Xylaria sp. 2508 from the South China Sea. The structures of these compounds were identified by NMR experiments, and the absolute configuration of compound 1 was further confirmed by single-crystal X-ray diffraction with Cu Kα radiation. Compounds 1–4 did not show inhibitory activities against Mycobacterium tuberculosis protein tyrosine phosphatase B (IC50 values more than 100 μM).

Arigsugacin I (1), a new α-pyrone meroterpene, along with two known compounds, arigsugacins F (2) and territrem B (3), were isolated from the mangrove endophytic fungus Penicillium sp. sk5GW1L from Kandelia candel. Their structures were identified through mass spectrometry and NMR experiments, and the absolute configuration of compound 1 was further confirmed by low-temperature (100 K) single crystal X-ray diffraction with Cu Kα radiation. The absolute configuration of compound 2 was first reported by using X-ray copper radiation. Compounds 1–3 showed inhibitory activities against acetylcholinesterase with IC50 values of 0.64 ± 0.08 µM, 0.37 ± 0.11 µM, and 7.03 ± 0.20 nM, respectively.

Aiming at the limited effectiveness of current clinical therapeutic effect of AIDS, novel series of compounds bearing (E)-3,4-dihydroxystyryl sulfone (or sulfoxide) and anilide fragments were designed and synthesized as dual inhibitors of HIV-1 CCR5/IN. The biological results indicated that several target compounds showed inhibitory activity against HIV-1 Bal (R5) infection in TZM-bl cells. Besides targeting the chemokine receptor on the host cell surface, they also displayed binding affinities with HIV-1 integrase using the surface plasmon resonance (SPR) binding assays. Molecular docking studies have inferred the possible binding mode of target compounds against integrase. These data demonstrate that the structure of (E)-3,4-dihydroxystyryl sulfone and sulfoxide derivatives have the potential to derive potent dual inhibitors of HIV-1 Integrase and CCR5.

Renal aging is always accompanied by increased oxidative stress. Hydrogen sulfide (H2S) can be up-regulated by 50% dietary restriction (DR) for 7-day and can block mitochondrial oxidative stress. H2S production exerts a critical role in yeast, worm and fruit fly models of DR-mediated longevity. In this study, we found that renal aging could be attenuated by 30% DR for 6-month (DR-6M) and life-long (DR-LL), but not for 6-week (DR-6W). The expressions of cystathionine-γ-lyase (CGL) and cystathionine-β- synthase (CBS) were improved by DR-6M and DR-LL. Endogenous H2S production shared the same trend with CBS and CGL, while glutathione (GSH) didn’t. When comparing efficiencies of DR for different durations, more evident production of H2S was found in DR-6M and DR-LL than in DR-6W. Finally the level of oxidative stress was improved by DR-6M and DR-LL rather than by DR-6W. It concluded that aged rats had the ability to produce enough H2S on 30% DR interventions protecting against renal aging and the effect of DR for long-term were more significant than that of DR for short-term.

The present study aimed to investigate the roles of fibrin deposition and protease activated receptor-1 (PAR-1) in renal cytokine/chemokine production and inflammatory cell infiltration in rats of different ages. Acute inflammation was induced by lipopolysaccharide (LPS) in rats which were then treated with tranexamic acid (TA), TA+urokinase (UK) or TA+low-molecular-weight heparin (HP). Fibrin deposition, inflammatory cells and expressions of PAR-1, monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule 1 (ICAM-1) were detected. A reduction in fibrin deposition and PAR-1 expression in the LPS+TA+HP group was associated with decreased infiltration of inflammatory cells and down-regulated expressions of MCP-1 and ICAM-1. In the LPS+TA+UK group, the fibrin deposition, but not the PAR-1 expression, was reduced, However, the infiltration of inflammatory cells decreased and the expressions of MCP-1 and ICAM-1 down-regulated. There were significant differences in the fibrin deposition, infiltration of inflammatory cells and expression of PAR-1, MCP-1 and ICAM-1 between young and old rats undergoing the same treatment. These findings demonstrated that fibrin deposition plays more important roles than PAR-1 dose in cytokine/chemokine production and inflammatory cell infiltration in vivo, and ageing may deteriorate the fibrin deposition-induced production of cytokines/chemokines and infiltration of inflammatory cells.

O-Trimethylsilyl (TMS)-protected diphenylprolinol-catalyzed Michael addition of a functionalized alkylidene malonate and n-butanal affords an aldehyde. This adduct can serve as the common intermediate for the assembly of secologanin tryptamine and dopamine alkaloids; this is demonstrated by the total syntheses of corynantheidol, dihydrocorynantheol, protoemetinol, and protoemetine, and the formal synthesis of mitragynine. The key steps include reductive amination of this aldehyde with tryptamine, condensation of this aldehyde with 4-methoxytryptamine, condensation of dimethoxyphenethylamine with a lactone derived from this aldehyde, and subsequent Bischler-Napieralski cyclization and reduction.

SUMMARY Aim: In order to determine the relationship between glomerular filtration rate (GFR) and age, the associated factors, and the accurate method of GFR in healthy adults, we conducted a cross-sectional study in community-dwelling adults in Beijing. Methods: Renal function of 201 clinically healthy subjects was determined using technetium-99 m-labelled diethylene triamine pentacetic acid (99mTc-DTPA). Estimated GFR was calculated with the Cockcroft–Gault (CG) equation, abbreviated Modification of Diet in Renal Disease (MDRD) equation, and plasma clearance of creatinine (Ccr). Serum cystatin C, biomarkers of inflammatory and endothelial cells were analyzed as well. Protein intake, carotid artery intima-media thickness and plaque formation were assayed as well. Results: Glomerular filtration rate was negatively associated with age and the correlation coefficient for 99mTc-GFR, CG-GFR, MDRD-GFR, Ccr were −0.643, −0.736, −0.55 and −0.619, respectively (P

Context Cathepsin B (CTSB) is an important enzyme for many physiological and pathological processes, and its activity increases with age. Here, we explored the association between serum CTSB and aging-related subclinical cardiovascular and renal status in a healthy Chinese population. Methods The study included 369 healthy individuals aged 36–87 years. Cardiovascular structure and function were assessed by the left ventricular ejection fraction, the early-diastolic peak flow velocity to late-diastolic peak flow velocity ratio at the mitral leaflet tips, carotid intima-media thickness (IMT), the diameter of the bilateral common carotid artery (D), and blood systolic peak (SPV) and end diastolic velocities, which were measured by M-mode ultrasonography. Serum CTSB, insulin-like growth factor-1 (IGF-1), 1, 25-dihydroxy vitamin D3, and parathyroid hormone (PTH) were measured by enzyme-linked immunosorbent assay. Results In men, serum CTSB was significantly related to IMT and IMT/D in the unadjusted model, and these associations were lost after age adjustment. In women, serum CTSB remained significantly associated with serum creatinine (SCr) (p = 0.009), estimated glomerular filtration rate (p = 0.048) and IMT/D (p = 0.017) following full adjustment. PTH was independently associated with SCr. IGF-1 was significantly associated with SPV in women. CTSB was correlated with metabolic and endocrine biomarkers. Conclusion Serum CTSB was associated with aging-related cardiovascular-renal parameters even in healthy people. Measurement of serum CTSB alone or in combination with metabolic and endocrine biomarkers can provide valuable information for predicting cardiovascular-renal function in healthy people, especially in elderly women.

Background: Chronic inflammation is thought to be a determinant of the aging rate and longevity. Caloric restriction (CR) attenuates age-related increases in the systemic levels of several pro-inflammatory mediators, but the anti-inflammatory mechanisms of CR in the aging process remain unclear. Methods: Fisher 344 rats in a CR group were fed an amount of food corresponding to 60% of that fed to an ad libitum-fed (AL) group for 8 months. Biochemical analyses and renal pathological grading were used to analyze physiological status. Important signaling molecules in the Toll-like receptor/nuclear factor kappa-light-chain-enhancer of activated B cells (TLR/NF-κB) pathway were also analyzed by western blotting, immunofluorescence and immunohistochemistry. Results: 1) Compared with AL feeding, CR decreased aging-mediated increases in both biochemical marker levels and renal pathological grading. 2) Single immunoglobulin IL-1 (IL-1)-related receptor (SIGIRR) expression decreased with increasing age, but CR led to overexpression. 3) The expression of TLR4 was significantly higher in the CR group than in the AL group. 4) SIGIRR overexpression decreased the expression of the adaptor molecules myeloid differentiation factor 88 (MyD88), IL-1 receptor-associated kinase 4 (IRAK4) and tumor necrosis factor receptor-associated factor 6 (TRAF6). 5) The levels of the inflammatory markers phospho-IκBa and phospho-NF-κB p65 decreased in the CR group. Conclusions: The inflammatory response might be alleviated by SIGIRR via blockade of the TLR4/NF-κB signaling pathway. Therefore, CR can decrease inflammation via SIGIRR overexpression, and SIGIRR might be a new target to delay aging.

Background Numerous studies have demonstrated the life-extending effect of caloric restriction. It is generally accepted that caloric restriction has health benefits, such as prolonging lifespan and delaying the onset and progression of CKD in various species, especially in rodent models. Although many studies have tested the efficacy of caloric restriction, no complete quantitative analysis of the potential beneficial effects of reducing caloric intake on the development and progression of CKD has been published. Methods All studies regarding the relationship between caloric restriction and chronic kidney diseases were searched in electronic databases, including PubMed/MEDLINE, EMBASE, Science Citation Index (SCI), OVID evidence-based medicine, Chinese Bio-medical Literature and Chinese science and technology periodicals (CNKI, VIP, and Wan Fang). The pooled odds ratios (OR) and 95% confidence intervals (95% CI) were calculated by using fixed- or random-effects models. Results The data from 27 of all the studies mentioned above was used in the Meta analysis. Through the meta-analysis, we found that the parameter of blood urea nitrogen, serum creatinine and urinary protein levels of the AL group was significant higher than that of the CR group, which are 4.11 mg/dl, 0.08mg/dl and 33.20mg/kg/24h, respectively. The incidence of the nephropathy in the caloric restriction (CR) group was significantly lower than that in the ad libitum—fed (AL) group. We further introduced the subgroup analysis and found that the effect of caloric restriction on the occurrence of kidney disease was only significant with prolonged intervention; the beneficial effects of CR on the 60%-caloric-restriction group were greater than on the less-than-60%-caloric-restriction group, and caloric restriction did not show obvious protective effects in genetically modified strains. Moreover, survival rate of the caloric restriction group is much higher than that of the ad libitum—fed (AL) group. Conclusions Our findings demonstrate for the first time that compared with the AL group, the caloric restriction indeed decreased urea nitrogen, creatinine, urine protein, incidence of kidney diseases and increased the survival rate on 700~800 days.

Palitantin (II) and the new analogue, 13-hydroxypalitantin (I), exhibit acetylcholinesterase (AchE) inhibitory activities.

A novel 2-pyridinone scaffold was rationally designed and synthesized based on the active anti-HIV agent 1 (LAM-trans) via an efficient method. The biological results revealed that some target compounds inhibited HIV-1 reverse transcriptase in the lower micromolar concentration range (IC50 0.089–0.68 μm). Notably, the most promising compound 25b exhibited extremely potent inhibitory activity against HIV-1 replication with an EC50 value of 0.0563 μM and the viral selectivity index amounted to 3466.8. Molecular modeling studies were performed, and some SARs were rationalized.

Low-temperature thermal conductivity (\kappa), as well as magnetization (M) and electric polarization (P), of multiferroic orthoferrite DyFeO_3 single crystals are studied with H \parallel c. When the crystal is cooled in zero field, M, P, and \kappa all consistently exhibit irreversible magnetic-field dependencies. In particular, with 500 mK < T \le 2 K, all these properties show two transitions at the first run of increasing field but only the higher-field transition is present in the subsequent field sweepings. Moreover, the ultra-low-T (T < 500 mK) \kappa(H) shows a different irreversibility and there is only one transition when the field is swept both up and down. All the results indicate a complex low-T H-T phase diagram involving successive magnetic phase transitions of the Fe^{3+} spins. In particular, the ground state, obtained with cooling to subKelvin temperatures in zero field, is found to be an unexplored phase., Comment: 9 pages, 7 figures, accepted for publication in Phys. Rev. B

The temperature and carrier concentration dependence of the thermopower (TEP) S in Bi2Sr2Ca1-xRxCu2Oy (R = Gd, Pr) single crystals were carefully studied. Upon Gd or Pr doping, the superconductivity changes systematically from overdoping to underdoping with the TEP increasing monotonically. S(T)/S(Tscale) against T/Tscale for all the underdoped crystals can be well scaled into a universal curve, where Tscale is the temperature at which S begins to deviate from T-linear behaviour. This scaling behaviour is assumed to correlate with the opening of the pseudogap. Furthermore, the temperature dependence of the TEP is analysed and discussed in terms of two different two-band models and the Nagaosa-Lee model.

A new kind of Bi-based single crystal Bi 2 Sr 1.5 Pr 2.5 Cu 2 O y was grown by a self-flux method. The crystals were characterized by energy dispersive X-ray analysis and X-ray diffraction. It was found that the crystal has an orthorhombic structure with lattice parameters a =5.491(7) A, b =5.532(8) A and c =35.68(8) A, which are close to those of the Bi 2 Sr 2 Ca 2 Cu 3 O y (Bi2223) phase, and incommensurate modulation structures along b -axis with period of 4.15. Intergrowth of other phases in some crystals were also observed.

Effects of oxygen doping and structural distortion on the superconductivity of (Bi2212) were studied by ac susceptibility and x-ray diffraction measurements for a group of high-quality single crystals. The crystals were annealed at 600 and under different oxygen pressures ranging from to 6080 Torr. It was found that the c-axis length showed a plateau at - Torr and decreased with increasing oxygen pressure above Torr, which strongly suggested that two stages of oxygen diffusion may be involved. The full width at half maximum (FWHM) of the 00 main reflection, which reflects structural distortion in the c direction, showed a peak around the optimized oxygen doping. This implies that the structural modification may be another factor that affects apart from oxygen content. On the other hand, the period of incommensurate modulation along the b direction, s, was found to have nothing to do with the oxygen content or superconductivity. Relationships between superconductivity, oxygen content and microstructure of the Bi2212 single crystal are discussed.