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Gait disturbance is a vital characteristic of motor manifestation in α– synucleinopathies, especially Parkinson’s disease. Subtle gait alterations are present in isolated rapid eye movement sleep behavior disorder (iRBD) patients before phenoconversion; it is yet unclear, if gait analysis may predict phenoconversion. To investigate subtle gait alterations and explore whether gait analysis using wearable sensors is associated with phenoconversion of iRBD to α-synucleinopathies. Thirty-one polysomnography-confirmed iRBD patients and 33 healthy controls (HCs) were enrolled at baseline. All participants walked for a minute while wearing 6 inertial sensors on bilateral wrists, ankles, and the trunk (sternal and lumbar region). Three conditions were tested: (i) normal walking, (ii) fast walking, and (iii) dual-task walking. Decreased arm range of motion and increased gait variation (stride length, stride time and stride velocity) discriminate converters from HCs at baseline. After an average of 5.40 years of follow-up, 10 patients converted to neurodegenerative diseases (converters). Cox regression analysis showed higher value of stride length asymmetry under normal walking condition to be associated with an early conversion of iRBD to α– synucleinopathies (adjusted HR 4.468, 95% CI 1.088– 18.349, p = 0.038). Stride length asymmetry is associated with progression to α– synucleinopathies in patients with iRBD. Gait analysis with wearable sensors may be useful for screening, monitoring, and risk stratification for disease-modifying therapy trials in patients with iRBD.

Butyrophilin (BTN) molecules are emerging as key regulators of T cell immunity; however, how they trigger cell-mediated responses is poorly understood. Here, the crystal structure of a gamma-delta T cell antigen receptor (γδTCR) in complex with BTN2A1 revealed that BTN2A1 engages the side of the γδTCR, leaving the apical TCR surface bioavailable. We reveal that a second γδTCR ligand co-engages γδTCR via binding to this accessible apical surface in a BTN3A1-dependent manner. BTN2A1 and BTN3A1 also directly interact with each other in cis, and structural analysis revealed formation of W-shaped heteromeric multimers. This BTN2A1–BTN3A1 interaction involved the same epitopes that BTN2A1 and BTN3A1 each use to mediate the γδTCR interaction; indeed, locking BTN2A1 and BTN3A1 together abrogated their interaction with γδTCR, supporting a model wherein the two γδTCR ligand-binding sites depend on accessibility to cryptic BTN epitopes. Our findings reveal a new paradigm in immune activation, whereby γδTCRs sense dual epitopes on BTN complexes.

Despite the effective microbial inactivation of high pressure processing (HPP), too intensive pressurization can cause undesirable quality changes in fish muscle. Combination treatments can be applied to retain sensory attributes after HPP for ready-to-eat fishery products. This present study thus investigated the impacts of different initial sample temperatures (− 18, 2, 20, and 55 °C) on raw grass carp slices under 300, 400, and 500 MPa, followed by microbiological, sensorial, chemical, and structural analyses. Increasing the pressure level at 20 °C led to whitening, hardening, and decreases in water holding capacity of grass carp. For example, 400 MPa induced a L*increase from 59.6 to 80.7, loss in muscle transparency, 5.1% of weight loss, and a hardness increase from 390.2 to 540.5 g. Correspondingly, fiber shrinkage and the compaction of tissue structure were observed in pressurized fish muscle. When grass carp were pressurized at a low initial temperature (2 °C), the appearance remained semi-transparent under 300 MPa, and the changes in physicochemical quality were similar to the treatments at 20 °C. HPP treatments at a subzero (− 18 °C) or mild-heated (55 °C) initial temperature caused greater quality changes when compared to other temperature conditions, e.g., L*> 70 under 300 MPa, and hardness > 700 g under 400 MPa. The myofibrillar protein contents dropped more significantly as the initial temperature increased. Overall, a better understanding of the impacts of pressurization temperatures would thus help to monitor fish quality and develop appropriate means for novel ready-to-eat fish-based products.

Isoflavones, a class of polyphenols commonly found in the human diet, are known for their beneficial effects on the gastrointestinal health. However, their precise effect on intestinal motility remains unclear. This study explored the effects of genistein, puerarin, formononetin, and daidzein on intestinal motility in a rat model of ulcerative colitis induced by dextran sulfate sodium (DSS). Our results showed that isoflavone treatment significantly improved colonic morphology, reduced fecal water content, and regulated the intestinal transit time, thereby effectively reducing diarrhea. Mechanistic insights indicated that these isoflavones increased the expression of serotonin reuptake transporter (SERT) and decreased the levels of 5-hydroxytryptamine (5-HT), which led to a reduction in colonic peristaltic stimulation. Furthermore, they increased the expression of c-kit, a marker of interstitial cells of Cajal (ICCs), potentially alleviating motility dysfunction. Molecular docking studies corroborated these findings, demonstrating that isoflavones enhance 5-HT reuptake by facilitating the stable binding of 5-HT to SERT, a mechanism consistent with the observed reduction in 5-HT levels in vivo. These findings suggest that isoflavones have therapeutic potential for treating intestinal motility disorders associated with colitis, and lay the groundwork for further investigation of their biological activities.

The mechanism of phthalic acid, a dicarboxylic acid collector, in flotation separation of fluorite and rare earth (RE) was studied in this paper. The experimental data of flotation show that phthalic acid, as the collector, can realize highly efficient separation of fluorite and rare earth under weakly acidic conditions. The adsorption mechanism of phthalic acid on the surface of fluorite and bastnaesite was analyzed in this paper by means of the zeta potential measurement, the Fourier transform infrared (FT-IR), the X-ray photoelectron spectroscopy (XPS) and the stability constant measurement of active metal ion and phthalic acid coordination complex. According to the zeta potential testing results, the surfaces of fluorite adsorb the collector phthalate ion with negative charge under weakly acidic conditions which, in turn, increases its electronegativity and results in the motion of its potential. After the reaction between phthalic acid and fluorite ores under weakly acidic conditions, the peak of the fluorite ores is found to have significant changes in the FT-IR results, indicating strong chemical adsorption on the surfaces of phthalic acid and fluorite ores. According to the XPS analysis, the peak of benzene ring of phthalic acid is as high as 2% on the surface of fluorite, while no obvious characteristic peak of benzene ring is found on the surface of bastnaesite. According to the pH potentiometric titration results, the stability constant Ktotalof calcium phthalate complex within the acid range is higher than the stability constant Ktotal' of cerium phthalate complex, indicating that the complex generated between phthalic acid and Ca2+is more stable than the complex generated between phthalic acid and Ce3+. The possible reason is that Ca2+, with the highest reticular density, plays a prevailing role in the octahedron structure of fluorite amidst the acidic media. As the active point of flotation, Ca2+works with the carboxyl groups of the collector phthalic acid (–C=O–) to form polycyclic calcium phthalate complex.

The Ca2+-activated TRPM5 channel plays essential roles in taste perception and insulin secretion. However, the mechanism by which Ca2+regulates TRPM5 activity remains elusive. We report cryo-EM structures of the zebrafish TRPM5 in an apo closed state, a Ca2+-bound open state, and an antagonist-bound inhibited state. We define two novel ligand binding sites: a Ca2+site (CaICD) in the intracellular domain and an antagonist site in the transmembrane domain (TMD). The CaICDsite is unique to TRPM5 and has two roles: modulating the voltage dependence and promoting Ca2+binding to the CaTMDsite, which is conserved throughout TRPM channels. Conformational changes initialized from both Ca2+sites cooperatively open the ion-conducting pore. The antagonist NDNA wedges into the space between the S1–S4 domain and pore domain, stabilizing the transmembrane domain in an apo-like closed state. Our results lay the foundation for understanding the voltage-dependent TRPM channels and developing new therapeutic agents.

Destruction in intestinal barrier is concomitant with the intestinal diseases. There is growing evidence that tryptophan-derived intestinal bacterial metabolites play a critical role in maintaining the balance of intestinal mucosa. In this study, the Caco-2/HT29 coculture model was used to evaluate the effect of indole-3-propionic acid (IPA) on the intestinal barrier and explore its underlying mechanism. We found that IPA increased transepithelial electrical resistance and decreased paracellular permeability which was consistent with the increase in tight junction proteins (claudin-1, occludin, and ZO-1). Furthermore, IPA strengthened the mucus barrier by increasing mucins (MUC2 and MUC4) and goblet cell secretion products (TFF3 and RELMβ). Additionally, IPA weakened the expression of LPS-induced inflammatory factors. These discoveries provide new views for understanding the improvement of intestinal barrier by gut microbial metabolites of aromatic amino acids.

The proton-activated chloride channel (PAC) is active across a wide range of mammalian cells and is involved in acid-induced cell death and tissue injury1–3. PAC has recently been shown to represent a novel and evolutionarily conserved protein family4,5. Here we present two cryo-electron microscopy structures of human PAC in a high-pH resting closed state and a low-pH proton-bound non-conducting state. PAC is a trimer in which each subunit consists of a transmembrane domain (TMD), which is formed of two helices (TM1 and TM2), and an extracellular domain (ECD). Upon a decrease of pH from 8 to 4, we observed marked conformational changes in the ECD–TMD interface and the TMD. The rearrangement of the ECD–TMD interface is characterized by the movement of the histidine 98 residue, which is, after acidification, decoupled from the resting position and inserted into an acidic pocket that is about 5 Å away. Within the TMD, TM1 undergoes a rotational movement, switching its interaction partner from its cognate TM2 to the adjacent TM2. The anion selectivity of PAC is determined by the positively charged lysine 319 residue on TM2, and replacing lysine 319 with a glutamate residue converts PAC to a cation-selective channel. Our data provide a glimpse of the molecular assembly of PAC, and a basis for understanding the mechanism of proton-dependent activation.

The colonic mucus barrier serves as a primary defense against enteric pathogens; destruction of this mucus layer has been observed in ulcerative colitis patients. This study aims to investigate the possibility of rebuilding the colon mucus layer through puerarin supplementation, which can stimulate mucin secretion and goblet cells differentiation. After puerarin supplementation, the thickness of colon mucus layer was increased and the permeability was reduced. The erosion of intestinal epithelium by bacteria was blocked, and the loss of epithelial integrity was alleviated. Puerarin also altered the composition of mucin-utilizing bacteria, which influenced the mucus permeability. Levels of short-chain fatty acids (SCFAs) were increased after puerarin supplementation, which as a direct source of energy for the proliferation of epithelia and goblet cells. This study demonstrated that enhancement of mucin secretion to relieve ulcerative colitis (UC) by puerarin supplementation is feasible, and the regulation of mucin-utilizing bacteria and the increased levels of SCFAs may be the main reasons.

Diarrhea is considered to be associated with microbial dysbiosis caused by infection of pathogens but poorly understood. We herein characterized the colonic microbiota of diarrheal early-weaning piglets infected with porcine circovirus type 2 (PCV2) and Campylobacter. Campylobacterinfection significantly decreased species richness and Shannon diversity index of colonic microbiota together with a significant increase in the proportion of Campylobacterand Enterobacteriaceae, whereas no significant difference on the above indexes was observed in piglets infected with PCV2 compared with healthy piglets. PCV2 and Campylobacterinfection could disturb the homeostasis of colonic microbiota through deterioration of ecological network within microbial community, and specially Campylobacterperformed as a module hub in ecological networks. The microbial dysbiosis caused metabolic dysfunction and led to a remarkable reduction in production of short chain fatty acids, following by a higher pH level in colon cavity. Campylobacterinfection disturbed the function of colonic tract barrier observed in terms of significant lower relative expression of claudin-1, occluding, and zonula occludens protein-1 genes, and PCV2 infection induced intestinal inflammation together with a higher permeability of colon. Generally, these results suggested that PCV2 and Campylobacterinfection could induce microbial dysbiosis and metabolic dysfunction, and cause intestinal disorder, all of which finally were associated to contribute to the diarrhea of early-weaning piglets.

Pannexin 1 (PANX1) is an ATP-permeable channel with critical roles in a variety of physiological functions such as blood pressure regulation1, apoptotic cell clearance2and human oocyte development3. Here we present several structures of human PANX1 in a heptameric assembly at resolutions of up to 2.8 angström, including an apo state, a caspase-7-cleaved state and a carbenoxolone-bound state. We reveal a gating mechanism that involves two ion-conducting pathways. Under normal cellular conditions, the intracellular entry of the wide main pore is physically plugged by the C-terminal tail. Small anions are conducted through narrow tunnels in the intracellular domain. These tunnels connect to the main pore and are gated by a long linker between the N-terminal helix and the first transmembrane helix. During apoptosis, the C-terminal tail is cleaved by caspase, allowing the release of ATP through the main pore. We identified a carbenoxolone-binding site embraced by W74 in the extracellular entrance and a role for carbenoxolone as a channel blocker. We identified a gap-junction-like structure using a glycosylation-deficient mutant, N255A. Our studies provide a solid foundation for understanding the molecular mechanisms underlying the channel gating and inhibition of PANX1 and related large-pore channels.

Supplemental Digital Content is available in the text.

Near-infrared (NIR) photodynamic therapy (PDT) is a promising antitumor strategy under NIR light irradiation to kill cancer cells. Mitochondria has a critical function in sustaining cellular viability and death, which is the ideal organelle for PDT. Here, we reported a tetraphenylporphine (TPP)-conjugated amphiphilic copolymer and an iodinated boron dipyrromethene photosensitizer (BDPI) with high singlet oxygen yield to form nanoparticles (PBDPI-TPP), which could realize mitochondria-targeting and improve the NIR imaging-guided PDT. The as-prepared mitochondria-targeting nanoplatform could show effective subcellular localization and bring about significant irreversible mitochondrial injury for enhanced PDT. Both in vitro and in vivo experiments revealed that the mitochondria-targeting PDT system could achieve a remarkable therapeutic effect, indicating that it is a promising nanoplatform for NIR imaging-guided PDT in cancer therapeutics.

Fermented foods represent an important segment of current food markets, especially traditional or ethnic food markets. The demand for efficient utilization of agrowastes, together with advancements in fermentation technologies (microbial- and enzyme-based processing), are stimulating rapid growth and innovation in the fermented food sector. In addition, the health-promoting benefits of fermented foods are attracting increasingly attention. The microorganisms contained in many common fermented foods can serve as “microfactories” to generate nutrients and bioactives with specific nutritional and health functionalities. Herein, recent research relating to the manufacture of fermented foods are critically reviewed, placing emphasis on the potential health benefits of fermentation-enabled wellness foods. The importance of the correct selection of microorganisms and raw materials and the need for precise control of fermentation processes are explored. Major knowledge gaps and obstacles to fermented food production and market penetration are discussed. The importance of integrating multidisciplinary knowledge, communicating with consumers, establishing regulatory frameworks specifically for fermentation-enabled wellness foods and functional fermented foods, are highlighted.

Image-guided photothermal therapy (PTT) is an attractive strategy to improve the diagnosis accuracy and treatment outcomes by monitoring the accumulation of photothermal agents in tumors in real-time and determining the best treatment window. Taking advantage of the superior imaging quality of NIR-II fluorescence imaging and remote-controllable phototherapy modality of PTT, we developed a facile macromolecular fluorophore (PF) by conjugating a small-molecule NIR-II fluorophore (Flav7) with an amphiphilic polypeptide. The PF can form uniform micelles in aqueous solution, which exhibit a slight negative charge. In vitroexperimental results showed that the PF nanoparticles showed satisfactory photophysical properties, prominent photothermal conversion efficiency (42.3%), excellent photothermal stability, negligible cytotoxicity, and photothermal toxicity. Meanwhile, the PF can visualize and feature the tumors by NIR-II fluorescence imaging owing to prolonged blood circulation time and enhanced accumulation in tumors. Moreover, in vivostudies revealed that the PF nanoparticles achieved an excellent photothermal ablation effect on tumors with a low dose of NIR-II dye and light irradiation, and the process can be traced by NIR fluorescence imaging.

A new substitution pattern of BF2azadipyrromethene (azaBODIPY) dyes was obtained by phenanthrene fusion through a key palladium-catalyzed intramolecular C–H activation reaction. These [a]-phenanthrene-fused azaBODIPYs have a near planar structure of the phenanthrene-fused azadipyrromethene core in the crystalline state. The chromophore absorbs (log ε > 5) and fluoresces (ϕ = 0.32–0.38) strongly above 700 nm with excellent photostability and may be used as an attractive bright NIR bioimaging agent.

Iron deficiency, one of the most common nutritional deficient disorders, frequently affects infants, adolescents and pregnant women and impairs growth, development and immune responses. Iron deficiency may also be secondary to gastrointestinal conditions such as gastrectomy and inflammatory bowel disease, as well as cancer and chronic uremia. Iron supplementation is the most commonly selected treatment option for iron deficiency. This review summarizes the iron compounds currently recommended for the iron fortification of foods and for clinical use. Additionally, this review discusses and compares the important aspects of high-quality iron compounds/products and classes of compounds that enhance iron bioavailability. The development of efficient iron fortification methods remains the most cost-effective and long-term approach to the treatment of iron deficiency or related anemia. To date, no orally administered options for iron fortification can sufficiently replace the parenteral administration of iron supplements, which includes the intramuscular injection of iron-dextran to neonatal piglets and intravenous injection of iron supplements to patients with gastrointestinal disorders. Iron bioavailability may be enhanced by encouraging customers to ingest iron-enriched foods together with dietary sources of vitamin C, folic acid and/or oligosaccharides.

NIR photosensitizer is attractive for photodynamic therapy (PDT). Low-power light irradiation and imaging-guided PDT makes it possible to increase tissue penetration depth. The pyrrole-substituted iodinated BODIPY (BDPI) molecule was designed and synthesized, and it possesses an intense NIR absorption and emission band, and exhibits a high singlet oxygen quantum yield (ΦΔ= 0.80) which leads remarkable cytotoxicity upon low power illumination (IC50 = 0.60 μg/mL, 6.1 mW/cm2). After being encapsulated with biocompatibility polypeptide PEG–PLys, polymeric micelles nanoparticles (PBDPI NPs) was obtained that are water-dispersed and passively tumor-targetable. Such enhanced accumulation in tumor area makes it easily traced in vivodue to its NIR fluorescence. In addition, such nanoparticles offer an unprecedented photodynamic therapeutic effect by using a low-power irradiation light, which makes it possible to kill cancer cells in deep tissue efficiently.

Precise detection of the tumor environment for cancer diagnosis has been strongly demanded for further therapies. Here, a redox-responsive fluorescence switch off/on system PCQ was designed and synthesized conjugated with near-infrared (NIR) cyanine dyes (Cy5.5) and relevant quencher (FQ) in mixed polymeric micelles (PCy and PFQ). The mixed PCQ micelles were prepared with two kinds of polymers with poly(oligo (ethylene glycol) methacrylate) (POEGMA) as the hydrophilic shell, in which fluorescence emission was quenched by fluorescence resonance energy transfer (FRET) effect. The FQ was conjugated with POEGMA by disulfide linkage, which could be broken with a redox environment such as high glutathione (GSH) concentration in tumor cells. After the PCQ micelles got into tumor cells, PFQ blocks in PCQ would be disassembled to recompose PCy micelles. During that process, drugs like doxorubicin (DOX) could be loaded inside and formed PCQ@DOX nanoparticles and then released for accurate NIR bioimaging and drug delivery instantly.

Photobleaching and biotoxicity are the main bottlenecks for organic fluorescent dyes applied in real-time dynamic monitoring of living cells. Here, an unnatural amino acid, 4-nitro-3-phenyl-l-alanine (NPA), was used as a scaffold to covalently link a near-infrared fluorophore Cy5.5 and an amphiphilic polypeptide, poly[oligo(ethylene glycol) methyl ether methacrylate]-block-poly[2-amino-N4-(2-diisopropylamino-ethyl)-l-aspartic acid] (P(OEGMA)21-P(Asp)16-iPr), was then conjugated for increasing the photostability and improving the biocompatibility simultaneously. The protective agent of NPA can service as an effective triplet state quenching by intramolecular electron transfer between Cy5.5 and NPA. The less sensitivity of the electron-transfer process for molecular oxygen makes it an ideal photostabilized strategy for fluorophores applied in live-cell imaging. Bonding to copolymer is a common way for hydrophobic dyes to expand their application in biomedical imaging and increase their functionality, depending on the delivery system. The results indicate that Cy5.5–NPA-linked polypeptide copolymer exhibited an enhanced photostability and an excellent biocompatibility, which means this scaffolding strategy has a potential application in fluorescence-guided surgery, lived-cell imaging, and super-resolution microscopy.

The catalytic activation of protein kinases requires precise positioning of key conserved catalytic and regulatory motifs in the kinase core. The Regulatory Spine (RS) is one such structural motif that is dynamically assembled upon kinase activation. The RS is also a mutational hotspot in cancers; however, the mechanisms by which cancer mutations impact RS assembly and kinase activity are not fully understood. In this study, through mutational analysis of patient derived mutations in the RS of EGFR kinase, we identify an activating mutation, M766T, at the RS3 position. RS3 is located in the regulatory αC-helix, and a series of mutations at the RS3 position suggest a strong correlation between the amino acid type present at the RS3 position and ligand (EGF) independent EGFR activation. Small polar amino acids increase ligand independent activity, while large aromatic amino acids decrease kinase activity. M766T relies on the canonical asymmetric dimer for full activation. Molecular modeling and molecular dynamics simulations of WT and mutant EGFR suggest a model in which M766T activates the kinase domain by disrupting conserved autoinhibitory interactions between M766 and hydrophobic residues in the activation segment. In addition, a water mediated hydrogen bond network between T766, the conserved K745-E762 salt bridge, and the backbone amide of the DFG motif is identified as a key determinant of M766T-mediated activation. M766T is resistant to FDA approved EGFR inhibitors such as gefitinib and erlotinib, and computational estimation of ligand binding free energy identifies key residues associated with drug sensitivity. In sum, our studies suggest an unusual mode of RS assembly and oncogenic EGFR activation, and provide new clues for the design of allosteric protein kinase inhibitors.

pH-Sensitive doxorubicin conjugated polymeric micelles entrapped with near infrared (NIR) photosensitizer BODIPY (which works as an imaging agent at the same time) were designed and synthesized by ring opening polymerization of N-carboxyanhydride with mPEG-NH2as the initiator, following reaction with doxorubicin to form the hydrazone-bond linker for pH responsiveness. Then the NIR dye (BODIPY) was loaded in the micelles for both bioimaging and photodynamic therapy (PDT). A significant cytotoxicity of NIR imaging-guided combined PDT and chemotherapy could be found by MTT assays, which was also confirmed with a fluorescence microscope, indicating a new kind of polymeric nanoparticle for potential theranostic treatment of cancers. In addition, the energy density of the laser for the PDT is extremely low.

A 60-days feeding trial was conducted to determine the effect of dietary supplementation of Lonicera macranthoidesleaf (LML) on growth performance, meat quality, and free amino acid profiles in growing-finishing pigs. L. macranthoidesleaves were harvested, air-dried and milled to powder. A total of 288 crossbred barrows (Large White × Landrace) with an average initial BW of 54.0 ± 3.4 kg were randomly allocated to 3 treatment groups and fed either a basal diet or a diet supplemented with 0.5% or 1.0% LML powder. Results showed that diet supplemented with LML powder did not affect average daily feed intake (ADFI) and feed: gain ratio (P > 0.05) in growing-finishing pigs. Moreover, diet supplemented with LML powder showed no significant effects on carcass traits (P > 0.05) including dressing percentage, backfat thickness and loin muscle area, and meat quality traits (P > 0.05) including meat color, intramuscular fat and cooking loss. However, diet supplemented with LML powder significantly improved free amino acid profiles in serum and longissimus thoracis muscle in growing-finishing pigs. Most importantly, dietary LML powder increased total free amino acids content (P < 0.001) and essential free amino acid content (P < 0.001) in longissimus thoracis muscle. These results indicate that LML has the potential to improve the nutritional value of meat through improving free amino acid profiles.

Dietary polyphenols are thought to be beneficial for human health by acting as antioxidants. Chlorogenic acid (CGA) is abundant in plant-based foods as an ester of caffeic acid and quinic acid. In this study, we investigated the effects of CGA on mitochondrial protection. Our results demonstrated that pretreatment with CGA ameliorated the intestinal mitochondrial injury induced by H2O2; membrane potential was increased, mitochondrial swelling, levels of reactive oxygen species, contents of 8-hydroxy-2-deoxyguanosine, and cytochrome creleased were decreased. The beneficial effects of CGA were accompanied by an increase in antioxidant and respiratory-chain complex I, IV, and V activities. In trinitrobenzene-sulfonic acid-induced colitic rats indicated that CGA supplementation improved mitochondria ultrastructure and decreased mitochondrial injury. Our results suggest a promising role for CGA as a mitochondria-targeted antioxidant in combating intestinal oxidative injury. Daily intake of diets containing CGA, such as coffee and honeysuckle, may be useful for prevention of intestinal diseases.

An efficient pH-responsive multifunctional polypeptide micelle for simultaneous imaging and in vitro photodynamic therapy (PDT) has been prepared. The goal here is to detect and treat cancer cells by near-infrared fluorescence (NIRF) imaging and PDT synchronously. A photosensitizer BODIPY-Br2with efficient singlet oxygen generation was synthesized at first which owns both seductive abilities in fluorescence emission and reactive oxygen species (ROS) generation under light irradiation. Then, amphiphilic copolymer micelles pH-triggered disassembly were synthesized from N-carboxyanhydride (NCA) monomer via a ring-opening polymerization and click reaction for the loading of BODIPY-Br2by hydrophobic interaction, and the driving force is the protonation of the diisopropylethylamine groups conjugated to the polypeptide side chains. In vitro tests performed on HepG2 cancer cells confirm that the cell suppression rate was improved by more than 40% in the presence of light in the presence of an extremely low energy density (12 J/cm2) with very low concentration of 5.4 μM photosensitizer. At the same time, the internalization of the nanoparticles by cells can also be traced by NIRF imaging, indicating that the NIR nanoparticles presented imaging guided photodynamic therapy properties. It provides the potential of using polypeptide as a biodegradable carrier for NIR image-guided photodynamic therapy.

Near infrared (NIR) imaging-guided photodynamic therapy (PDT) is attractive, especially the utilization of one dye as both a photosensitizer and fluorescent probe, and the as-synthesized BODIPY-Br2molecule is a candidate. Here, a galactose targeted amphiphilic copolymer of a polypeptide was synthesized and its micelles work as nanocarriers for BODIPY for targeting the NIR imaging-guided PDT of hepatoma cancer cells. At the same time, BODIPY could light up the cytoplasm for real-time imaging and kill cancer cells when the light was switched on. In vitrotests performed on both HepG2 and HeLa cells confirmed that the as-prepared PMAGP-POEGMA-PLys-B micelles showed efficient cell suppression of the cells with galactose receptors in the presence of light under an extremely low energy density (6.5 J cm−2). This protocol highlights the potential of polypeptides as biodegradable carriers for NIR image-guided and confined targeting photodynamic therapy.

Some oligosaccharides have immunoregulatory and anti-inflammatory functions in the intestine. This study investigated the immunoregulatory effect of lactosucrose (LS) on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitic rats. Alkaline phosphatase activity was increased but myeloperoxidase activity was decreased in the LS-TNBS group, as compared with the TNBS group (colitis rats without receiving LS). LS supplementation stimulated IL-4 and IL-10 production, while up-regulating CD86 expression in dendritic cells. LS supplementation reduced the ratio of CD80/CD86 and the ratio of IFN-γ/IL-4 compared to the TNBS group. Moreover, IFN-γ was significantly correlated with CD80 (r = 0.764, p < 0.01), whereas IL-4 was significantly correlated with CD86 (r = 0.489, p < 0.05). These results indicated that LS attenuated colitis by promoting the production of Th2-type cytokines and rebalancing the ratio of Th1/Th2 and that enhanced IL-4 production is correlated with enhanced CD86 expression in the gut. Therefore, LS is a functional food for patients with inflammatory bowel disease.

With high optical transparency and electrical conductivity, ITO thin films were fabricated by DC magnetron sputtering. Series of research and exploration are presented on DC magnetron sputtering method for preparing ITO thin film. With substrate temperature of 60 °C, sputtering power of 200W,sputtering pressure of 1 mTorr, water pressure of 2×10-5Torr, the sheet resistance of the ITO conductive substrate is 53 Ω/□ and the transmittance is 83%.

Split Hopkinson Tensile Bar (SHTB) apparatus is widely used in experimentally investigating the mechanical properties of materials. The experimental results are significantly depended on the amplitude, the shape and the wave length of incident wave. However, theres no research on the effect of incident wave especially the influence of parts of the SHTB equipment has been put forward. The solid Hopkinson bar has faced many problems. The hollow Hopkinson Bar has more advantages than the solid Hopkinson bar. The mechanism of the overlying and the amplitude of incident wave by FEM has been analyzed, which can give much help for the theory basis of SHTB apparatus development and design to some extend.

An environmentally benign method termed ionic liquid extraction technique coupled with IC-UV/vis has been successfully applied in the determination of spices such as vanillin, ethyl vanillin and ethyl maltol in food samples.

Neonates with intrauterine growth retardation (IUGR) are prone to suffer from delayed postnatal growth and development during the early stages of life. Ferulic acid (FA) is a phenolic compound that is abundantly present in fruits and vegetables and has various health benefits. Hence, we explored whether FA supplementation could favorably affect the growth performance, antioxidant capacity, and intestinal development of piglets with IUGR. In total, eight normal-birth-weight (NBW) piglets and 16 piglets with IUGR (age, 7 d) were assigned to be fed either basic formula milk (NBW and IUGR groups, respectively) or basic formula milk supplemented with 100 mg/kg FA (IUGR + FA group) for 21 d. At necropsy, the serum and intestinal tissues were collected. FA supplementation increased (P< 0.05) the feed conversion ratio and serum total superoxide dismutase and catalase activities in piglets with IUGR. Moreover, FA supplementation elevated (P< 0.05) the duodenal lactase and maltase activities, jejunal villus height and jejunal maltase activity but reduced (P< 0.05) the duodenal crypt depth and duodenal and jejunal cell apoptosis, cleaved cysteinyl aspartic acid protease-3 (caspase-3) content and cleaved caspase-9 content in piglets with IUGR. In summary, FA supplementation could elevate antioxidant capacity and facilitate intestinal development, thus resulting in increased feed efficiency in piglets with IUGR.Intrauterine growth retardation (IUGR) impairs postnatal growth and development in neonatal piglets. Ferulic acid (FA) is a ubiquitous phenolic compound that is present in numerous fruits and vegetables and possesses various biological activities. However, little is known about whether FA supplementation has beneficial effects on the growth performance, antioxidant capacity, and intestinal development of piglets with IUGR. Our findings provide important implications for treating piglets with IUGR after birth by stimulating intestinal development with FA supplementation.The present findings are significant for providing new strategies for regulating the growth of piglets with IUGR and highlighting the potential applications of this phytochemical in swine production.

In this paper, a model of energy-environment-economic model based on dynamic CGE model is constructed after the linkage of dynamic CGE model and energy technology model, the choices of policy of energy conservation and carbon reduction to deal with the change of climate are analysed. Besides the improvement of technology of energy, if carbon taxation is employed, the goal to reduce its carbon intensity by 40% by 2020 compared with 2005 need to levy a tax of 60yuan per tonne, the simulations of this tax to carbon reduction, economic and income of residents are analysed under different circumstances, the results shows that there is a great impact on income of residents and reduction-intensive industries with a higher tax burden level.