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Purpose To predict the change of retinal sensitivity using optical coherence tomography (OCT) parameters in eyes with central serous chorioretinopathy (CSC). Methods Twenty-three eyes of 23 patients with CSC were enrolled. Retinal sensitivity was measured twice with a microperimetry in all examined eyes. OCT measurement was simultaneously conducted. The relationship between retinal sensitivities and the thicknesses of i) retinal nerve fiver layer + ganglion cell layer (RNFL+GCL), ii) inner nuclear layer (INL) iii) outer nuclear layer (ONL) and iV) serous retinal detachment height (SRDH) were investigated in a point-wise manner. We also investigated the association between the change of retinal sensitivity and OCT parameters at baseline. Results The mean age of participants was 49.8 ± 10.7 years. The mean SRDH was significantly lower (p

Benefited from the fast switching speed, Gallium nitride (GaN) high electron mobility transistors (HEMTs) have been widely used in high switching frequency converters. However, due to the significant correlation between the turn-off time and operating conditions (more than 20 times difference of the turn-off time between the high load current and small load current for GaN HEMTs), using a fixed dead time will introduce extra dead-time losses in inverters where the output voltage and current are constantly varying. Therefore, this paper proposes a high-efficiency adaptive method to dynamically adjust the GaN-inverter dead-time with operating conditions. An improved transient model including the parasitic inductance and output voltage with bidirectional solution flow has been proposed for GaN HEMTs to increase the accuracy of dead-time adjustment. Based on this model, the dynamic dead-time adjustment can be realized without extra sensors for GaN-inverters. Using the dynamic dead-time adjustment, the experimental results show a peak efficiency of 98.25% in a 1200W inverter with triangular current mode modulation. Compared with using the fixed dead-time, the dynamic dead-time method can reduce the power loss by 26.7% under full load and 49.14% under light load.

Dearomatization of indole is a useful strategy to access indolimines: a motif widely exists in biologically active molecules and natural products. Herein, an efficient method for the dearomatization of 2,3-disubstituted indoles to generate diverse indolimines with tetrasubstituted allenes is described. This work accomplishes dearomatization of 2,3-disubstituted indoles through 1,8-addition of (aza)-para-quinone methides, which are generated in situ from propargylic alcohols. A series of synthetically useful indolimines containing quaternary carbon centers and tetrasubstituted allenes can be accessed in good yields (up to 99%). Additionally, the separability of product isomers, diversified product transformations, and easy scale-up of the reaction demonstrate the potential application of this method.

The Tibetan chicken (Gallus gallus) provides high quality protein and iron for humans, which shows many phenotypic adaptations to the low oxygen. Study of the genetic mechanisms of circular RNAs (circRNAs) in hypoxia adaptation has not been reported. Four embryonic heart tissue samples from Tibetan chickens and Daheng broilers were collected. Differentially expressed circRNAs (DEcircRNAs) were identified via high-throughput sequencing. Bioinformatic analysis was used to indicate the functions and pathways of the DEcircRNAs. A total of 29 DEcircRNAs were identified between 4 Tibetan chickens and 4 Daheng broilers, including 15 upregulated and 14 downregulated DEcircRNAs in Tibetan chickens. GO analysis revealed that the DEcircRNAs were mainly involved in lung development or oxygen metabolism, such as ubiqunegative regulation of mesenchymal cell proliferation involved in lung development, oxidoreductase activity, and peroxisome. Pathway analysis showed that DEcircRNAs were mainly enriched in oxidative phosphorylation, tight junction, VEGF/MAPK/PPAR/Ras/PI3K-Akt signaling pathway. We also constructed a circRNA-miRNA-mRNA-pathway network to visualize the regulatory relationship associated with hypoxia adaptation of the tight junction pathways. The circRNA expression profile was obtained to complement the current Tibetan chicken circRNA database and provides new information for future studies into biological adaptation to hypoxic stress in the Tibetan chicken.

Medicine has been a great beneficiary of the nanotechnology revolution. Nanotechnology involves the synthesis of functional materials with at least one size dimension between 1 and 100 nm. Advances in the field have enabled the synthesis of bio-nanoparticles that can interface with physiological systems to modulate fundamental cellular processes. One example of a diverse acting nanoparticle-based therapeutic is synthetic high-density lipoprotein (HDL) nanoparticles (NP), which have great potential for treating diseases of the ocular surface. Our group has developed a spherical HDL NP using a gold nanoparticle core. HDL NPs: (i) closely mimic the physical and chemical features of natural HDLs; (ii) contain apoA-I; (iii) bind with high-affinity to SR-B1, which is the major receptor through which HDL modulates cell cholesterol metabolism and controls the selective uptake of HDL cargo into cells; (iv) are non-toxic to cells and tissues; and (v) can be chemically engineered to display nearly any surface or core composition desired. With respect to the ocular surface, topical application of HDL NPs accelerates re-epithelization of the cornea following wounding, attenuates inflammation resulting from chemical burns and/or other stresses, and effectively delivers microRNAs with biological activity to corneal cells and tissues. HDL NPs will be the foundation of a new class of topical eye drops with great translational potential and exemplify the impact that nanoparticles can have in medicine.

A novel Bronsted acid catalyzed 1,8-addition mediated (3 + 4)-annulation of in situ generated propargylic p-quinone methides with 2-indolylmethanols is described. This method provides a convenient and mild approach to structurally interesting and synthetically important polysubstituted indole-fused oxepines in high yields. Moreover, 2-indolylmethanols as four-atom synthons in the (3 + 4)-annulations under Bronsted acid conditions have been explored for the first time.

Herein, we describe a highly effective 1,8-conjugate-addition-mediated formal (3+3)-annulation of (aza)-para-quinone methides in situ generated from propargylic alcohols with 4-hydroxycoumarins and 1,3-dicarbonyl compounds under the catalysis of a Bronsted acid. This methodology affords efficient and practical access to synthetically important and highly functionalized pyranocoumarins and pyrans in excellent yields under mild conditions. Importantly, these products exhibit impressive inhibitory activity toward α-glucosidase.

Primary hippocampal neuronal cells were used to establish cell model of cerebral ischemia under oxygen-glucose deprivation (OGD) treatment. After the cell model was pre-treated with short hairpin (sh)-circ_NLRP1 or mmu-miR-199b-3p inhibitor, LDH release and cell apoptosis were detected by LDH kit and TUNEL staining, respectively, while the expression of NLRP3 pyroptosis-related makers was analyzed through immunofluorescence (IF) assay and Western blot, respectively. The binding sites between circ_NLRP1 and mmu-miR-199b-3p were predicted and further validated by Dual Luciferase Reporter assay. Additionally, mitogen-activated protein kinase (MAPK) pathway was also analyzed by means of Western blot assay. Neuronal cells under OGD conditions released less lactate dehydrogenase (LDH) and showed less apoptosis status by silencing circ_NLRP1. In addition, gasdermin D (GSDMD)-N immunofluorescence staining showed weaker fluorescence intensity and decreased expression of pyroptosis-related mediators. We further found that mmu-miR-199b-3p-inhibitor could alter the effects of sh-circ_NLRP1 on hippocampal neuronal cells. In addition, in this process, extracellular signal-regulated kinase (ERK)/EGR1 pathway was also significantly affected. In conclusion, OGD stimulation induced neuronal damage and pyroptosis through enhancing circ_NLRP1 expression and further downregulating mmu-miR-199b-3p levels. The present study provided a novel insight for understanding the potential mechanism of ischemia-induced neuronal damage and for developing new drugs for treating brain ischemia damage., Graphical Abstract

Friction stir lap welding (FSLW) was employed to weld dissimilar joints of zirconium and stainless steel for the first time. The microstructure, evolution mechanism of intermetallic compounds (IMCs) and mechanical properties of joint were investigated. Discontinuous dynamic recrystallization (DDRX) and continuous dynamic recrystallization (CDRX) occurred in zirconium, while DDRX occurred in stainless steel during FSLW. The formation sequence of IMCs at the interface was FeZr3, FeZr2, Fe2Zr, and Fe23Zr6. The crack nucleated at the hook zone on the advancing side (HookAS), and IMCs in the Zr/SS mixed zone accelerated crack propagation. The fracture surface exhibited ductile-brittle mixed fracture characteristic.

Cadmium pollution is serious heavy metal pollution in environmental pollution and impacts on livestock productivity. However, the effect and mechanisms of cadmium toxicity on the broiler remain unclear. This study aimed to explore the liver oxidative damage and reveal the related long non-coding RNA (lncRNA) expression patterns in the broiler liver with cadmium exposure. The broilers were fed with diets containing CdCl2 and detected the oxidative stress indexes in the liver tissues. Transcriptome sequencing of broiler liver was performed to identify cadmium exposure-related differentially expressed lncRNAs (DElncRNAs). The functions and pathways of DElncRNAs were analyzed by GO and KEGG. The sequencing results were verified by the quantitative real-time polymerase chain reaction. Cadmium exposure induced tissue structure disorder, focal hemorrhage, and irregular hepatocytes in the broiler liver, and significantly decreased GSH level and enzyme activities, and increased MDA expression in the liver. A total of 74 DElncRNAs were obtained in cadmium group compared with the control group, which were enriched in the GO terms, including intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator, branched-chain amino acid biosynthetic process. The enriched KEGG pathways, including lysine biosynthesis, valine, leucine and isoleucine biosynthesis, and pantothenate and CoA biosynthesis, were related to oxidative stress. PCR analysis indicated that the changes in ENSGALG00000053559, ENSGALG00000053926, and ENSGALG00000054404 expression were consistent with sequencing. Our results provide novel lncRNAs involved in oxidative stress in the broiler liver with cadmium exposure.

Herein, we report an efficient Bronsted acid-catalyzed formal (3+3)-annulation of (aza)-para-quinone methides generated in situ from propargylic alcohols with naphthol derivatives, which involves a 1,8-conjugate addition/6-endo annulation process. This protocol provides an effective method for preparing important functionalized pyranocoumarins under mild conditions.

Autophagy is a multistage catabolic process that mediates stress responses. However, the role of autophagy in epidermal proliferation, particularly under conditions when the epidermis becomes “activated” (hyperproliferative), remains unclear. We have shown that inhibition of Beclin 1, a key activator in the initiation phase of autophagy, attenuates imiquimod (IMQ)-induced epidermal hyperplasia in adult mice as well as naturally occurring hyperproliferation in neonatal mouse epidermis. Inhibition of Beclin 1 did not change the levels of several key inflammatory molecules or the numbers of immune cells in lesional skins. This indicates that autophagy does not affect inflammatory regulators in IMQ-treated mouse skin. Bioinformatic analysis combined with gene expression quantitative assays, revealed that a deficiency in autophagy decreases the expression of PDZ Binding Kinase (PBK), a regulator of the cell cycle, in mouse epidermis and human epidermal keratinocytes (HEKs). Interestingly, the decrease in PBK results in inhibition of proliferation in HEKs and such reduced proliferation can be rescued by activation of p38, the downstream signaling of PBK. Collectively, autophagy plays a positive role in epidermal proliferation, which is in part via regulating PBK expression.

Gallium nitride (GaN) high-electron-mobility transistor (HEMT) has the advantages of high switching speed and low ON-resistance, which make it widely used in high-frequency applications to realize high power density. Triangular current mode (TCM) modulation has been used in GaN-based converters to simultaneously achieve high power density and high efficiency through full-range zero voltage switching (ZVS). However, as switching frequency increases, the effect of dead time becomes more significant. Meanwhile, because of the junction capacitors of GaN HEMTs, the optimum dead time changes greatly with the turn-off current. Inappropriate dead time will induce extra loss that goes against the further improvement of power density. In order to minimize the dead-time loss in GaN HEMT-based TCM converter, this article proposes a strategy of adaptive dead-time control. An accurate turn-off transient model is proposed to calculate optimal dead time with consideration of the nonlinear capacitors. Based on this model, a loss model is established to evaluate the effect of dead time involving the short circuit in dead time. A new method of drive signal generation in TCM is proposed to increase the accuracy of dead-time control and reduce the current ripple. By reusing the detection signal in TCM, the adaptive dead-time control is realized without extra sensors. The proposed model is verified by a dual-pulse test, which shows the maximum error between the calculated and the experimental turn-off time is below 3 ns. The proposed adaptive dead-time control is implemented in a GaN HEMT-based boost converter. The experimental results show that the adaptive dead-time control can improve the efficiency over all operation conditions compared with using the fixed dead time, and the total loss is reduced by 26.7% at 800-W load and 70.8% at 50-W load.

An efficient and straightforward Lewis-acid-mediated stereoselective (4 + 3)-cyclization of indole-substituted alkylidene malonates and donor-acceptor cyclopropanes has been developed involving the Friedel-Crafts/Michael addition cyclization cascade. This reaction provides a mild and effective method for the construction of synthetically and structurally interesting functionalized cycloheptannelated indoles.

Radix isatidis (R. isatidis) is a commonly used traditional Chinese herbal medicine, which has been used for thousands of years in China and is believed to have the pharmacological properties of heat-clearing and detoxification. Heat-clearing and detoxification are theories of traditional Chinese medicine meaning that R. isatidis could treat febrile disease by clearing heat and reducing swelling. Polysaccharides isolated from R. isatidis by water extraction and alcohol precipitation have exhibited numerous biological activities, including antiviral and immunomodulatory effects. The present study was performed to investigate the immunomodulatory effects of water-soluble R. isatidis polysaccharides (RIPs) on RAW264.7 macrophages and murine splenocytes, and attempt to preliminarily identify the mechanism of immunomodulation. In vitro, RIPs had a low cytotoxicity, as shown by CellTiter 96® AQueous One Solution Cell Proliferation Assay. RAW264.7 cells treated with different concentrations of RIP displayed different morphological changes, from a round shape and aggregation to polygonal shape and dispersion in a dose-dependent manner. In the 5 mg/ml RIP-treated group, the changes of morphology were as same as the lipopolysaccharide-treated group. RIP also significantly enhanced the release of nitric oxide as shown by Griess method, and the secretion of TNF-α and IL-6 in RAW264.7 cells was confirmed by ELISA assay. Western blotting revealed a significant increase of toll-like receptor-4 (TLR-4) in RIP-treated RAW264.7, suggesting that TLR-4 may be associated with the immunomodulatory mechanism of RIP. Animal experiments also demonstrated through ELISA assays a significant increase in IFN-γ and IL-10 levels after the splenocytes of RIP-immunized mice were stimulated by inactivated herpes simplex virus type 2. The immune function of RIP-immunized mice was improved. The present study suggested that RIP could be potentially used as a novel immunomodulator.

Purpose To understand the relationship between ciliogenesis and autophagy in the corneal epithelium. Methods siRNAs for EphA2 or PLD1 were used to inhibit protein expression in vitro. Morpholino-anti-EphA2 was used to knockdown EphA2 in Xenopus skin. An EphA2 knockout mouse was used to conduct loss of function studies. Autophagic vacuoles were visualized by contrast light microscopy. Autophagy flux, was measured by LC3 turnover and p62 protein levels. Immunostaining and confocal microscopy were conducted to visualize cilia in cultured cells and in vivo. Results Loss of EphA2 (i) increased corneal epithelial thickness by elevating proliferative potential in wing cells, (ii) reduced the number of ciliated cells, (iii) increased large hollow vacuoles, that could be rescued by BafA1; (iv) inhibited autophagy flux and (v) increased GFP-LC3 puncta in the mouse corneal epithelium. This indicated a role for EphA2 in stratified epithelial assembly via regulation of proliferation as well as a positive role in both ciliogenesis and end-stage autophagy. Inhibition of PLD1, an EphA2 interacting protein that is a critical regulator of end-stage autophagy, reversed the accumulation of vacuoles, and the reduction in the number of ciliated cells due to EphA2 depletion, suggesting EphA2 regulation of both end-stage autophagy and ciliogenesis via PLD1. PLD1 mediated rescue of ciliogenesis by EphA2 depletion was blocked by BafA1, placing autophagy between EphA2 signaling and regulation of ciliogenesis. Conclusion Our findings demonstrate a novel role for EphA2 in regulating both autophagy and ciliogenesis, processes that are essential for proper corneal epithelial homeostasis.

In this paper, the influence of temperature on the bonding strength of aluminum alloy joints under the full temperature field is studied. Based on the service temperature range of vehicle bonding structures, the failure strength of aluminum alloy joints at different temperature points, namely −40 °C, −20 °C, 0 °C, 25 °C (RT), 40 °C, 60 °C and 80 °C, is tested. The results showed that compared with the failure strength of the adhesive at −40 °C, it decreased by 47.69% and 68.15% at RT and 80°C, respectively, the Young’s modulus of the adhesive decreased by 57.63% and 75.42% at RT and 80°C, respectively, with the increase of temperature, the young’s modulus, tensile strength and failure strain of the adhesive decreased. In addition, the failure strength of aluminum alloy joints varied with temperature. To be specific, the stiffness of joints decreased gradually from 25 °C to 80 °C and increased gradually from −40 °C. Based on the failure strength data of bonded joints at different temperature points, the secondary stress failure criteria of bonded joints at different temperatures were obtained. Then, the surface function of failure criteria under the full temperature field was established to provide reference for failure prediction of bonded structures under different temperatures and stresses.

The present study aimed to investigate the effects of a gefitinib derivative, LPY‑9, on the proliferation, apoptosis and migration of human glioma cell line U251‑MG by CCK8, Transwell or flow cytometry, and the effect of LPY‑9 on the activity of caspase‑3 enzyme and related proteins in the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways by western blot and ELISA. It was found that LPY‑9 exhibited higher a inhibitory effect on the proliferation of U251‑MG cell lines compared with gefitinib and it also exhibited a certain dose‑dependence. Following LPY‑9 treatment, typical apoptotic morphology was observed under the microscope after Giemsa staining. LPY‑9 induced apoptosis at low concentration, and the activity of caspase‑3 enzyme increased with the increase in drug concentration, significantly inhibiting the secretion of VEGF in a dose‑dependent manner. The effect was notably more evident compared with gefitinib at the same concentration. The expression level of caspase‑3 and cleaved caspase‑3 increased with the increase in LPY‑9 concentration; however, expression levels of VEGF, EGFR, phosphorylated AKT and PI3K decreased with the increase of LPY‑9 concentration and no change was observed in the expression level of AKT. LPY‑9 inhibited the proliferation of the human glioma cell line U251‑MG, promoted apoptosis and effectively inhibited the migration of U251‑MG cells. The effect of LPY‑9 was more noticeable compared with gefitinib. The results of the present study may provide a foundation for further study and clinical research of this as an anti‑tumor drug in animal models.

Trehalose-6-phosphate (T6P) is an important signaling metabolite that is involved in many physiological processes. However, the mechanism of the biological functions of T6P is not fully understood. Quantification of T6P in plants will be beneficial to elucidate the mechanism. However, it is still a challenge to chromatographically separate and sensitively detect T6P and related sugar phosphates. In the current study, we developed a method for effective separation and sensitive detection of glucose-1-phosphate (G1P), glucose-6-phosphate (G6P), sucrose-6-phosphate (S6P) and T6P in plant tissues by chemical derivatization combined with hydrophilic interaction liquid chromatography-tandem mass spectrometry (ChD-HILIC-MS/MS). With this method, two pairs of isomers (G1P/G6P and S6P/T6P) could be well separated on a HILIC column and sensitively detected by MS with limits of detection (LODs) ranging from 0.1 to 0.6 ng mL−1. The developed method was successfully applied to the detection of endogenous G1P, G6P, S6P and T6P in small amounts of plant tissues, such as 1 mg fresh weight of Oryza sativa shoot.

In this study, the effects of slag on the properties of lightweight cement-treated soils (LCS) immersed in sodium sulfate solutions were studied. The mechanical properties of the samples after immersions were evaluated by unconfined compressive strength. Microstructural properties were investigated by using X-ray diffraction (XRD) and scanning electronic microscopy (SEM). The results show the LCS can resist sodium sulfate corrosion, and the content of slag affects the internal pore structure of the material, thus affecting the strength and thermal conductivity after corrosion. When the slag content is 10% by weight of cement, the mechanical and thermal property of the LCS after corrosion was the best.

A novel lectin (ABL) was purified from the dried fruiting bodies of Agaricus bitorquis. An efficient 3-step purification protocol involved two consecutive steps of ion exchange chromatography on Q-Sepharose and SP-Sepharose and gel filtration by FPLC on Superdex 75. ABL is a monomeric protein with the molecular mass of 27.6 kDa, which is different from other lectins from genus Agaricus. Its N-terminal amino acid sequence is EYTISIRVYQTNPKGFNRPV which is unique and sharing considerably high similarity of other mushroom lectins. The hemagglutinating activity of the lectin was inhibited by inulin. Based on hemagglutination tests, ABL prefers rabbit, human type A, and AB erythrocytes to human type B and O erythrocytes. The lectin inhibits the activity of HIV-1 reverse transcriptase and the proliferation of leukemia cell (L1210) with an IC50 value of 4.69 and 4.97 μM, respectively. Furthermore, ABL demonstrates the highest mitogenic activity with a response of 24177.7 ± 940.6 [3H-methyl] thymidine counts per minute (CPM) at a concentration of 0.91 μM.

RNA modification has recently been proposed to play important roles in biological regulation. The detection and quantification of RNA modifications generally are challenging tasks since most of the modifications exist in low abundance in vivo. Here we developed an on-line trapping/capillary hydrophilic-interaction liquid chromatography/electrospray ionization-mass spectrometry (on-line trapping/cHILIC/MS) method for sensitive and simultaneous quantification of RNA modifications of N6-methyladenosine (m6A) and 5-methylcytosine (5-mC) from human blood. The hydrophilic organic-silica hybrid monolith was prepared using sol-gel combined with “thiol-ene” click reaction for the separation of nucleosides. A poly(MAA-co-EGDMA) monolithic capillary was used as the on-line trapping column. With the developed on-line trapping/cHILIC/MS analytical platform, the detection limits of m6A and 5-mC can reach to 0.06 fmol and 0.10 fmol. We then investigated the contents of m6A and 5-mC in human blood RNA from healthy persons at the age of 6–14 and 60–68 years. Our results showed that both m6A and 5-mC contents were significantly decreased in elder persons, suggesting the RNA modifications of m6A and 5-mC are correlated to aging.

Cutaneous inflammation from UV radiation exposure causes epidermal damage, cellular infiltration, and secretion of pro-inflammatory mediators that exacerbate tissue destruction. Recovery is mediated chiefly by anti-inflammatory M2 macrophages that suppress inflammation and augment epidermal regeneration. Vitamin D enables anti-inflammation to promote tissue repair in response to injury. Since vitamin D enhances cellular macroautophagy/autophagy, we investigated the role of autophagy in vitamin D protection of UV-mediated sunburn and inflammation. Using a UV-mediated acute skin injury mouse model, we demonstrate that a single dose of vitamin D resolves injury with sustained inhibition of inflammatory cytokines associated with enhanced autophagy in myeloid anti-inflammatory M2 macs. Increased MAP1LC3B/LC3 expression corroborated with complete autolysosome formation detected by electron microscopy and correlated with degradation of SQSTM1/p62 in the skin following vitamin D treatment. Specifically, pharmacological inhibition of autophagy increased UV-induced apoptosis, suppressed M2 macs recruitment, and prevented vitamin D downregulation of Tnf and Mmp9 in the skin. Furthermore, selective deletion of autophagy in myeloid cells of atg7 cKO mice abrogated vitamin D-mediated protection and recapitulated UV-induced inflammation. Mechanistically, vitamin D signaling activated M2-autophagy regulators Klf4, Pparg, and Arg1. Lastly, analysis of UV-exposed human skin biopsies detected a similar increase in macrophage autophagy following vitamin D intervention, identifying an essential role for autophagy in vitamin D-mediated protection of skin from UV damage. Abbreviations: ARG1: arginase 1; ATG7 cKO: autophagy related 7 conditional knockout; HPF: high powered field; KLF4: Kruppel like factor 4; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; macs: macrophage; 3-MA: 3-methyladenine; MMP9: matrix metallopeptidase 9; NOS2: nitric oxide synthase 2, inducible; PPARG: peroxisome proliferator activated receptor gamma; SQSTM1/p62: sequestosome 1; TNF: tumor necrosis factor; UV: ultraviolet; VD: vitamin D, 25-hydroxy vitamin D3; 1,25-VD: 1, 25-dihydroxy vitamin D3

The industrial effluents discharge including heavy metals drain into the river, which has given rise to many problems of hazarding aquatic ecosystems and human health. Biosorption serves as the adsorption of heavy metals onto a natural adsorbent, it is becoming a potential alternative for toxic metals removal from industrial effluents in the last decades. The objectives of present research were to investigate the biosorption behaviors and the mechanisms of copper (Cu), zinc (Zn), cadmium (Cd) and chromium (Cr) ions, respectively onto foxtail millet shell as a new natural biosorbent in aqueous solution. The effects of pH (2.0–6.0), contact time (5.0–240.0 min), initial metal ions concentration (25.0–300.0 mg/L), particle size (0.25–2.0 mm) and biosorbent dosage (1.0–6.0 g/L) on the adsorption efficiency of the target metals using foxtail millet shell were evaluated in batch experiments. The models of isotherms and kinetics were used to assess the removal behaviors of Cu, Zn, Cd and Cr ions from aqueous solution by foxtail millet shell. The results showed that the best fitting equilibrium isotherm models for Cu, Zn, Cd and Cr ions were Freundlich (Cu and Zn) and Langmuir (Cd and Cr), respectively under the proper adsorption conditions. The maximum biosorption capacities were 11.89, 10.59, 12.48 and 11.70 mg g−1 of Cu, Zn, Cd and Cr, respectively by terms of Langmuir model. The kinetics of biosoption the target metal ions processes were best explained by pseudo-second-order kinetic model. Furthermore, pseudo-second-order and intraparticle diffusion models were cooperative mechanism during the whole biosorption. In addition, the pores on the surface of the shell were covered and then became smooth after biosorption through Scanning electron microscope (SEM) revealed, which demonstrated that the target metal ions were adsorbed by foxtail millet shell. The results of Energy dispersive spectrometer (EDS) further gave evidences that Cu, Zn, Cd and Cr ions were adsorbed onto surface of the adsorbent, respectively. Analysis of Fourier transform infrared spectroscopy (FTIR) demonstrated that various functional groups, such as C—H, C˭O, C˭C, C—O, O—S—O and Si—O groups were engaged in the interaction between foxtail millet shell and Cu, Zn, Cd and Cr ions. This paper provided evidences that foxtail millet shell was a potential and efficient biosorbent on removal of Cu, Zn, Cd and Cr ions from aqueous solutions, due to its high biosorption availability, capacity and low cost.

Cone-rod dystrophy (CORD) is one of the inherited retinal diseases that result in central visual field deterioration and decreased visual acuity (VA). In CORD patients, impaired photoreceptor cells are observed as the disruption of ellipsoid zone (EZ) on optical coherence tomography (OCT) images. In the present study, we calculated the index of residual EZ (rEZ) to quantify the function of photoreceptor cells and investigated the correlation between rEZ index and visual functions. Twenty-six eyes of 13 patients with clinical suspicion of CORD were examined. Visual field was tested with the Humphrey Visual Field Analyzer (HFA 10-2 program). We simultaneously obtained OCT images and calculated the area of decreased EZ intensity (EZa). Using the binarized OCT images, the percentage of the rEZ in a 3 × 3 mm area surrounding the macula was analyzed. To clarify interrator reproducibility, intraclass correlation coefficient (ICC) was calculated. Moreover, we investigated the association between OCT parameters and VA as well as the mean deviation (MD) value measured with HFA. The mean age of the patients was 48.5 ± 16.9 years. The mean central retinal thickness was 122.7 ± 73.2 μm. The mean EZa and rEZ were 22.2 ± 23.6 μm2 and 0.35 ± 0.31, respectively. The ICC of each rEZ index was 0.91 (95% CI: 0.89

The photolyases PHR1 and PHR2 enable photorepair of fungal DNA lesions in the forms of UV-induced cyclobutane pyrimidine dimer (CPD) and (6-4)-pyrimidine-pyrimidone (6-4PP) photoproducts but their regulation remains mechanistically elusive. Here, we report that the white collar proteins WC1 and WC2 mutually interacting to form a light-responsive transcription factor regulate photolyase expression required for fungal UV resistance in the insect-pathogenic fungus Metharhizum robertsii. Conidial UVB resistance decreased by 54% in Δwc1 and 67% in Δwc2. Five-hour exposure of UVB-inactivated conidia to visible light resulted in photoreactivation rates of 30% and 9% for the Δwc1 and Δwc2 mutants, contrasting to 79-82% for wild-type and complemented strains. Importantly, abolished transcription of phr1 in Δwc-2 and of phr2 in Δwc1 resulted in incapable photorepair of CDP and 6-4PP DNA lesions in UVB-impaired Δwc2 and Δwc1 cells respectively. Yeast two-hybrid assays revealed interactions of either WC protein with both PHR1 and PHR2. Therefore, the essential roles for WC1 and WC2 in both photorepair of UVB-induced DNA lesions and photoreactivation of UVB-inactivated conidia rely upon their interactions with, and hence transcriptional activation of, PHR1 and PHR2. These findings uncover a novel WC-cored pathway that mediates filamentous fungal response and adaptation to solar UV irradiation. This article is protected by copyright. All rights reserved.

Chaga (Inonotus obliquus) is an edible herbal mushroom extensively distributed in the temperate to frigid regions of the Northern hemisphere, especially the Baltic and Siberian areas. Chaga parasites itself on the trunk of various angiosperms, especially birch tree, for decades and grows to be a shapeless black mass. The medicinal/nutraceutical use of chaga mushroom has been recorded in different ancient cultures of Ainu, Khanty, First Nations, and other Indigenous populations. To date, due to its prevalent use as folk medicine/functional food, a plethora of studies on bioactive compounds and corresponding compositional analysis has been conducted in the past 20 years. In this contribution, various nutraceutical and pharmaceutical potential, including antioxidant, anti-inflammatory, anti-tumor, immunomodulatory, antimutagenic activity, anti-virus, analgesic, antibacterial, antifungal, anti-hyperglycemic, and anti-hyperuricemia activities/effects, as well as main bioactive compounds including phenolics, terpenoids, polysaccharides, fatty acids, and alkaloids of chaga mushroom have been thoroughly reviewed, and tabulated using a total 171 original articles. However, only key bioactivities and bioactives are selectively discussed. Besides, the up-to-date toxicity concerns and risk assessment about the misuse of chaga, which limit its acceptance and use as medicinal/nutraceutical products, have also been clarified.

To study the effects of deep-ocean water concentrate (DOWC) on sake quality, Taichung No. 10 indica rice (Oryza sativa subsp. indica) and Tainan No. 11 japonica rice (O. sativa subsp. japonica) were used as raw materials, and basic physicochemical property parameters in shochu were analyzed differentially. Sake fermentation mash analysis results revealed that DOWC addition did not significantly affect the basic physicochemical properties during sake brewing, but it significantly reduced citric acid and malic acid contents in Taichung No. 10 indica rice sake sample by 52&ndash, 66% and 73&ndash, 93%, respectively. DOWC addition significantly increased citric acid content in Tainan No. 11 japonica rice sake sample by 32&ndash, 202%. Rice shochu analysis results revealed that DOWC addition significantly increased isoamyl acetate, ethyl hexanoate, and ethyl octanoate contents in shochu made from japonica rice and indica rice, respectively. The results indicate that rice variety directly affects the types of volatile compounds in rice shochu. Principal component analysis and sensory evaluation results revealed that DOWC addition affected the composition of volatile compounds in the two types of rice shochu and resulted in differences in flavor evaluation. DOWC addition affects yeast metabolites and directly changes the volatile compound composition and flavor of rice shochu.

Short wavelength automated perimetry (SWAP) is known for detecting the early reduction of retinal sensitivity (RS) in glaucoma. It’s application in retinal diseases have also been discussed previously. We investigated the difference in RS measured between standard white-on-white automated perimetry (WW) and blue-on-yellow SWAP in central serous chorioretinopathy (CSC). The overall RS (W-RS, S-RS) as well as the RS inside and outside of the serous retinal detachment (SRD) region were investigated in 26 eyes of 26 CSC patients using WW and SWAP. The central retinal thickness, central choroidal thickness, SRD area (SRDa), and SRD height at the fovea were measured using optic coherence tomography. RS inside the SRD region was lower than that of outside for both perimetries (both p

The overexpression of EGFR and/or ErbB2 occurs frequently in ovarian cancers and is associated with poor prognosis. The purpose of this study was to examine the anticancer effects and molecular mechanisms of berberine on human ovarian cancer cells with different levels of EGFR and/or ErbB2. We found that berberine reduced the motility and invasiveness of ovarian cancer cells. Berberine depleted both EGFR and ErbB2 in ovarian cancer cells. Furthermore, berberine suppressed the activation of the EGFR and ErbB2 downstream targets cyclin D1, MMPs, and VEGF by down-regulating the EGFR-ErbB2/PI3K/Akt signaling pathway. The berberine-mediated inhibition of MMP-2 and MMP-9 activity could be rescued by co-treatment with EGF. Finally, we demonstrated that berberine induced ErbB2 depletion through ubiquitin-mediated proteasome degradation. In conclusion, the suppressive effects of berberine on the ovarian cancer cells that differ in the expression of EGFR and ErbB2 may be mediated by the dual depletion of EGFR and/or ErbB2.

A new strategy for preparing amphibious ZnO quantum dots (QDs) with blue fluorescence within hyper-branched poly(ethylenimine)s (HPEI) was proposed in this paper. By changing [Zn2+]/[OH−] molar ratio and heating time, ZnO QDs with a quantum yields (QY) of 30% in ethanol were obtained. Benefiting from the amphibious property of HPEI, the ZnO/HPEI nanocomposites in ethanol could be dissolved in chloroform and water, acquiring a QY of 53%, chloroform and 11% in water. By this strategy, the ZnO/HPEI nano-composites could be applied in not only in optoelectronics, but also biomedical fields (such as bio-imaging and gene transfection). The bio-imaging application of water-soluble ZnO/HPEI nanocomposites was investigated and it was found that they could easily be endocytosed by the COS-7 cells, without transfection reagent, and they exhibited excellent biological imaging behavior.

Background. Visceral hypersensitivity is a common occurrence of gastrointestinal diseases such as irritable bowel syndrome (IBS), wherein early-life stress (ELS) may have a high predisposition to the development of visceral hypersensitivity in adulthood, with the specific underlying mechanism still elusive. Herein, we assessed the potential effect of small-conductance calcium-activated potassium channel subtype 2 (SK2) in the spinal dorsal horn (DH) on the pathogenesis of visceral hypersensitivity induced by maternal separation (MS) in mice. Methods. Neonatal mice were subjected to the MS paradigm, an established ELS model. In adulthood, the visceral pain threshold and the abdominal withdrawal reflex (AWR) were measured with an inflatable balloon. The elevated plus maze, open field test, sucrose preference test, and forced swim test were employed to evaluate the anxiety- and depression-like behaviors. The expression levels of SK2 in the spinal DH were determined by immunofluorescence and western blotting. The mRNA of SK2 and membrane palmitoylated protein 2 (MPP2) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Electrophysiology was applied to evaluate the neuronal firing rates and SK2 channel-mediated afterhyperpolarization current (IAHP). The interaction between MPP2 and SK2 was validated by coimmunoprecipitation. Results. In contrast to the naïve mice, ethological findings in MS mice revealed lowered visceral pain threshold, more evident anxiety- and depression-like behaviors, and downregulated expression of membrane SK2 protein and MPP2 protein. Moreover, electrophysiological results indicated increased neuronal firing rates and decreased IAHP in the spinal DH neurons. Nonetheless, intrathecal injection of the SK2 channel activator 1-ethyl-2-benzimidazolinone (1-EBIO) in MS mice could reverse the electrophysiological alterations and elevate the visceral pain threshold. In the naïve mice, administration of the SK2 channel blocker apamin abated IAHP and elevated spontaneous neuronal firing rates in the spinal DH neurons, reducing the visceral pain threshold. Finally, disruption of the MPP2 expression by small interfering RNA (siRNA) could amplify visceral hypersensitivity in naïve mice. Conclusions. ELS-induced visceral pain and visceral hypersensitivity are associated with the underfunction of SK2 channels in the spinal DH.

The preparation of various types of miktoarm star polymers with precisely controlled structures (A2B, ABC, AB2C2, etc.) has made significant progress due to the considerable advances in the synthetic strategies, including multistep protections/deprotections, orthogonality, and integration of different polymerization techniques. However, compared to the well-developed synthesis methodologies, the investigations on miktoarm star copolymers as drug delivery vehicles remain relatively unexplored, especially for the relationship of their branched structures and properties as drug delivery systems. To elucidate this structure–property relationship of amphiphilic miktoarm star polymers, we prepared four different amphiphilic miktoarm star copolymers with the respectively identical molecular weights (MWs) of hydrophilic and hydrophobic moieties but different star structures using heteroinitiators that were synthesized by protection/deprotection strategies for integrated ring-opening polymerization of hydrophobic ...

Polymeric prodrugs with precisely controlled drug loading content (DLC) and rapid intracellular destabilization generally require complicated chemistry that hinders large-scale manufacture. For this purpose, we reported in this study a facile construction of reduction-sensitive amphiphilic polyprodrugs with an anticancer drug, 10-hydroxycamptothecin (HCPT), and a hydrophilic poly(ethylene oxide) (PEG) moiety as the alternating building blocks of the multiblock copolymer using Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAc) click coupling between azide-SS-HCPT-SS-azide and alkyne-PEG-alkyne. Adoption of PEGs with two different molecular weights (MWs) of 400 and 1450 Da (PEG400 and PEG1450) afforded two polyprodrugs with different DLCs. Both formulations can self-assemble into spherical micelles with hydrodynamic diameter smaller than 200 nm, and exhibit glutathione (GSH)-triggered degradation for promoted drug release. A further comparison study revealed that the PEG1450-based polyprodrug is a better formulation than the analogue constructed from PEG400 in terms of in vitro drug release behaviors, and cytotoxicity. This work thus provides a facile yet efficient strategy toward polymeric prodrugs with precisely controlled DLC and reduction-triggered degradation for enhanced anticancer drug delivery.

Ganoderma is classified as a top grade traditional Chinese medicine for promoting human health by regulating 'vital energy'. Its potency towards metabolism and energy homeostasis, particularly, metabolic adaptations of adipocytes, needs to be re-evaluated through an evidence-based study. Here, the triterpenoid-rich Ganoderma tsugae ethanol extract (GTEE) was found to contribute towards adipogenesis accompanied with elevated intracellular lipid metabolic flux. Additionally, proteomic profiling revealed GTEE-upregulated mitochondrial remodeling and chemical energy redox modifications, which display UCP1-positive browning fat-selective features and a NADH-mediated adaptive mechanism. GTEE-treated mice with diet-induced obesity also resulted in the amelioration of white adipocyte hypertrophy and the appearance of UCP1-positive browning adipocytes. Our novel findings unravel that GTEE could promote intracellular metabolic flexibility and plasticity followed by the induction of adipocyte browning.

By establishing a chemical labeling method in combination with liquid chromatography-mass spectrometry analysis, we reported the widespread existence of various modified nucleoside triphosphates in eukaryotes., DNA and RNA contain diverse chemical modifications that exert important influences in a variety of cellular processes. In addition to enzyme-mediated modifications of DNA and RNA, previous in vitro studies showed that pre-modified nucleoside triphosphates (NTPs) can be incorporated into DNA and RNA during replication and transcription. Herein, we established a chemical labeling method in combination with liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) analysis for the determination of endogenous NTPs in the mammalian cells and tissues. We synthesized 8-(diazomethyl)quinoline (8-DMQ) that could efficiently react with the phosphate group under mild condition to label NTPs. The developed method allowed sensitive detection of NTPs, with the detection limits improved by 56–137 folds. The results showed that 12 types of endogenous modified NTPs were distinctly determined in the mammalian cells and tissues. In addition, the majority of these modified NTPs exhibited significantly decreased contents in human hepatocellular carcinoma (HCC) tissues compared to tumor-adjacent normal tissues. Taken together, our study revealed the widespread existence of various modified NTPs in eukaryotes.

A polyvinylpyrrolidone (PVP)/polyacrylic acid (PAA) layer-by-layer (LbL) assembled composite coating with a multilayer structure for the corrosion protection of AZ31 magnesium alloy was prepared by a novel spin-casting method. The microstructure and composition of this coating were investigated by means of SEM, XRD and FT-IR measurements. Moreover, electrochemical, immersion and scratch tests in vitro were performed to measure the corrosion performance and the adhesion strength. These results indicated that the (PVP/PAA)10 composite coating with defect-free, dense and uniform morphologies could be successfully deposited on the surface of magnesium alloy. The coating had excellent corrosion resistance and adhesion strength.

Tetrastigma hemsleyanum leaves (THL), a popular anticancer functional food in China, are used as nutrient or dietary supplement. However, the anticancer effects and the underlying mechanism of THL are still unknown. Thus, the phenolic profiles and anticancer activities of THL purified extract were investigated by a combination of chemical assays, LC-QTOF-MS/LC-QqQ-MS techniques, cell cultures and tumor-bearing mice model. It has been indicated that the TPC/TFC (421.63 and 343.38 mg/g DW) of THL extract were obviously increased after SPE purification, and the main phenolic components were apigenin and luteolin glycosides. Besides, THL could induce apoptosis by both of extrinsic death receptor pathway and intrinsic mitochondria pathway in HepG2 cells as well as inhibit the tumor growth, regulate Bcl-2 family proteins, and active the caspase family proteins in H22 tumor-bearing mice. Summarily, the findings clearly demonstrated that THL could be a potential functional food for the treatment and prevention of liver cancer.

DNA and RNA contain diverse chemical modifications that exert important influences in a variety of cellular processes. In addition to enzyme-mediated modifications of DNA and RNA, previous in vitro studies showed that pre-modified nucleoside triphosphates (NTPs) can be incorporated into DNA and RNA during replication and transcription. Herein, we established a chemical labeling method in combination with liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) analysis for the determination of endogenous NTPs in the mammalian cells and tissues. We synthesized 8-(diazomethyl)quinoline (8-DMQ) that could efficiently react with the phosphate group under mild condition to label NTPs. The developed method allowed sensitive detection of NTPs, with the detection limits improved by 56-137 folds. The results showed that 12 types of endogenous modified NTPs were distinctly determined in the mammalian cells and tissues. In addition, the majority of these modified NTPs exhibited significantly decreased contents in human hepatocellular carcinoma (HCC) tissues compared to tumor-adjacent normal tissues. Taken together, our study revealed the widespread existence of various modified NTPs in eukaryotes.

Taking advantage of the excellent barrier properties of reduced graphene oxide (rGO) sheets and the loading capacity of mesoporous silica (SiO2), silane-functionalized rGO/SiO2 nanocontainers are synthesized and, after loaded with benzotriazole (BTA), composite corrosion protection coatings are prepared. The XRD, FTIR, XPS, SEM, and TEM are used to confirm the successful preparation of silane-functionalized rGO/SiO2 nanocontainers, and BET and UV–visible measurements are used to estimate the loading and release behavior of BTA. Dispersion stability of the nanocontainers is observed, the surface morphology, wettability, and water absorption of coatings are characterized by SEM, water contact angle, and weight method, respectively. The corrosion behavior of pristine and scratched composite coatings is characterized by EIS, the effect of released BTA is further confirmed. The results show that silane-functionalized rGO/SiO2 nanocontainers possess excellent dispersibility and load capacity, reduce defects and micropores in composite coatings, and provide improved permeability resistance, corrosion resistance, and self-repairing performance.

A 28-day experiment was conducted to investigate the temporal variations in cellular energy allocation (CEA), oxygen consumption rate (OCR) and activities of energy metabolism related enzymes in discus fish ( Symphysodon aequifasciatus ) exposed to decreased water temperatures. The steady temperature decrease (1 °C/day) from control (28 °C) to low temperatures (24 or 20 °C) significantly reduced the initial energy reserves (mainly lipids and carbohydrates) while significantly increased the energy consumption (respiratory electron transport system (ETS) activity) in the muscle tissue. Accordingly, on day 0 the CEA was slightly reduced with decreased temperatures. After 28 days of cold acclimation, however, the initial differences in energy reserves, ETS activity and CEA between treatments were decreased. Concurrently, the OCR was reduced with decreased temperatures, suggesting a decreased metabolic rate. During cold acclimation, however, activities of hepatic alkaline phosphatase (ALP), lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were generally increased with decreased temperatures, indicating a compensation for the decreased metabolic rate. Linear discriminant analysis (LDA) showed that the fish exposed to 24 °C only on day 14 was separated from the initial day 0 while those exposed to 20 °C on both days 14 and 28 were separated from the initial day 0, with LDH and ALP activities being the two most discriminant factors. Moreover, after cold acclimation the fish exposed to 24 °C showed comparable growth rates with those exposed to 28 °C. These findings reveal that S. aequifasciatus could recover from the initial energy disturbances resulted from decreased temperatures. The enhanced metabolic activity in response to 24 °C was well within the homeostatic range. It might be promising to culture the juvenile S. aequifasciatus at water temperature as low as 24 °C.

Growing body of evidence shows that extra adiposity influences on the progression of multiple cancers, including breast cancer. The aim of this study is to investigate whether obesity correlates with mammary tumor development in vitro and in vivo. We found that obesity-related mediators, 3T3-L1 adipocyte conditioned medium, enhanced formation of cancerous foci induced by the carcinogen 7,12-Dimethylbenz[a]anthracene (DMBA) in NIH/3T3 fibroblasts, in vitro. Additionally, we tested the effect of obesity in mouse model of DMBA-induced breast cancer. C57BL/6J female mice were fed a low fat (LF), or high fat (HF) diet, and DMBA was administered by oral gavage (LF plus DMBA [LFD] and HF plus DMBA [HFD]). Our results indicated that HFD mouse developed a tumor which weight was 169mg, whereas the LFD mouse developed a tumor weight of 77mg. Histological analysis of the mammary tumor from HFD group showed morphological aggressiveness and multiple cell type infiltration compared to LFD group. The epididymal adipose tissue from the DMBA groups showed more macrophage infiltration, polarized towards an M1 phenotype compared to the non-DMBA mice. HF mice showed less accumulation of M2 macrophages in the adipose tissue. In summary, obese mediators enhanced DMBA induced tumorigenesis in vitro and in vivo.