Our previous study showed that chromium malate improved the regulation of blood glucose in mice with alloxan-induced diabetes. The present study was designed to evaluate the effect of chromium malate on glycometabolism, glycometabolism-related enzymes and lipid metabolism in type 2 diabetic rats. Our results showed that fasting blood glucose, serum insulin level, insulin resistance index and C-peptide level in the high dose group had a significant downward trend when compared with the model group, chromium picolinate group and chromium trichloride group. The hepatic glycogen, glucose-6-phosphate dehydrogenase, glucokinase, Glut4, phosphor-AMPKβ1 and Akt levels in the high dose group were significantly higher than those of the model, chromium picolinate and chromium trichloride groups. Chromium malate in a high dose group can significantly increase high density lipoprotein cholesterol level while decreasing the total cholesterol, low density lipoprotein cholesterol and triglyceride levels when compared with chromium picolinate and chromium trichloride. The serum chromium content in chromium malate and chromium picolinate group is significantly higher than that of the chromium trichloride group. The results indicated that the curative effects of chromium malate on glycometabolism, glycometabolism-related enzymes and lipid metabolism changes are better than those of chromium picolinate and chromium trichloride. Chromium malate contributes to glucose uptake and transport in order to improved glycometabolism and glycometabolism-related enzymes.

Photocatalytic hydrogen (H2) production was performed by visible-light-driven (VLD) ternary photocatalyst, zinc oxysulfide (ZnO0.6S0.4) in the presence of sulfide/sulfite (S22-/SO32-) sacrificing system, with simultaneous azo-dye Reactive Violet 5 (RV5) degradation. Enhancement in both RV5 degradation and H2 production was achieved, with the promotion of H2 production after decolorization of RV5. The effect of initial concentration of RV5 was found to be influential on the enhancement of H2 during the simultaneous processes, with a maximum of 110% increase of H2 produced. The mechanism of the simultaneous system was investigated by scavenger study and intermediate analysis, including Fourier transform-infrared (FTIR) spectroscopy and total organic carbon (TOC) analysis. It was confirmed that the partial degradation of RV5 and presence of dynamic organic intermediates contributed to the enhancement in H2 production. The present study revealed the feasibility of developing VLD photocatalysis as a sustainable and environmentally friendly technology for concurrent organic pollutant degradation with energy generation.

Despite the initial evidence on the role of zinc and zinc transporters in cancer prevention, little attention has been paid to the zinc-derived compounds. In the present work, we reported a strategy to prepare a kind of zinc-releasing container with enhanced biocompatibility and release dynamics using ZIF-8 nanocrystals as the sacrificial templates. Transmission electron microscopy (TEM) analysis demonstrated that the ZIF-8 nanocrystals were gradually etched out in the aqueous media within 48 h, resulting in hollow nanocapsules. Notably, we found the self-polymerization of dopamine can form nanoshells around the ZIF-8 nanocrystals, which served as a type of functional membranes during the release of zinc. More interestingly, PDA@ZIF-8⁻based nanohybrids expressed stronger inhibition to the cancer cell growth, which implied that the nanohybrids could be a drug carrier for chemotherapy. This study broadens the biomedical application of ZIF-8 and also provides a versatile strategy toward the development of multifunctional delivery system.

Bioscaffolds are widely used for tissue engineering, but failed and inconsistent preclinical results have hampered the clinical use of bioscaffolds for tissue engineering. We aimed to construct a cellular remodelling landscape and to identify the key cell subpopulations and important genes driving bladder remodelling.

This study reports on interactions between low dose toxic and essential metals. Low dose Pb (0.01mg/L), Hg (0.001mg/L), Cd (0.005mg/L) and As (0.01mg/L) were administered singly to four groups of 3-week old mice for 120 days. Pb exposure increased brain Mg and Cu by 55.5% and 266%, respectively. Increased brain Mg resulted from metabolic activity of brain to combat insults, whiles Cu overload was due to alteration and dysfunction of CTR1 and ATP7A molecules. Reduction of liver Ca by 56.0% and 31.6% (on exposure to As and Cd, respectively) resulted from inhibition of Ca-dependent ATPase in nuclei and endoplasmic reticulum through binding with thiol groups. Decreased kidney Mg, Ca and Fe was due to uptake of complexes of As and Cd with thiol groups from proximal tubular lumen. At considerably low doses, the study establishes that, toxic metals disturb the homeostasis of essential metals.

The aim of this work was to study the effects of paclitaxel-loaded nanobubbles targeting pro-gastrin-releasing peptide, designated as paclitaxel targeting nanobubbles, on small cell lung cancer (SCLC).

We report a study on the synthesis of TiO2/Fe2O3 (TF) nanocomposites and their photocatalytic performance under visible-light irradiation. The characterization of structure and morphology shows that hematite Fe2O3 was deposited on anatase TiO2 nanoparticles with particle sizes in the range of 20-100 nm. In contrast to pure TiO2 and pure Fe2O3, the nanocomposites exhibited remarkable photocatalytic activity. For example, the photoreduction efficiency of TF0.5 reaches 100% for a 100 ppm Cr(vi) solution within 160 minutes. The photochemical properties were studied by various methods. Finally, we conclude that the excellent performance of the photocatalysts is mainly attributed to two aspects: the enhanced absorption of visible light and the synergistic effect of an internal electric field at the heterojunction and citric acid for promoting the separation of electron-hole pairs.

Inconvenient dual-laser irradiation and tumor hypoxic environment as well as limited judgment of treating region have impeded the development of combined photothermal and photodynamic therapies (PTT and PDT). Herein, Bi2Se3@AIPH nanoparticles (NPs) are facilely developed to overcome these problems. Through a one-step method, free radical generator (AIPH) and phase transition material (lauric acid, LA, 44-46 °C) are encapsulated in hollow bismuth selenide nanoparticles (Bi2Se3 NPs). Under a single 808-nm laser irradiation at the tumor area, hyperthermia produced by Bi2Se3 not only directly leads to cell death, but also promotes AIPH release by melting LA and triggers free radical generation, which could further eradicate tumor cells in hypoxic environments. Moreover, Bi2Se3 with high X-ray attenuation coefficient endows the NPs with high computed tomography (CT) imaging capability, which is important for treating area determination. The results exhibit that Bi2Se3@AIPH NPs possesses 31.2% photothermal conversion efficiency for enhanced PTT, ideal free radical generation for oxygen-independent PDT, and 37.77 HU mL mg-1 X-ray attenuation coefficient for CT imaging with high quality. Most importantly, the tumor growth inhibition rate by synergistic PTT, PDT, and following immunotherapy is 99.6%, and even one tumor disappears completely, which demonstrates excellent cascaded synergistic effect of Bi2Se3@AIPH NPs for the tumor therapy.

Many drugs are effective in the early stage of treatment, but patients develop drug resistance after a certain period of treatment, causing failure of the therapy. An important example is Herceptin, a popular monoclonal antibody drug for breast cancer by specifically targeting human epidermal growth factor receptor 2 (Her2). Here we demonstrate a quantitative binding kinetics analysis of drug-target interactions to investigate the molecular scale origin of drug resistance. Using a surface plasmon resonance imaging, we measured the in situ Herceptin-Her2 binding kinetics in single intact cancer cells for the first time, and observed significantly weakened Herceptin-Her2 interactions in Herceptin-resistant cells, compared to those in Herceptin-sensitive cells. We further showed that the steric hindrance of Mucin-4, a membrane protein, was responsible for the altered drug-receptor binding. This effect of a third molecule on drug-receptor interactions cannot be studied using traditional purified protein methods, demonstrating the importance of the present intact cell-based binding kinetics analysis.

Cadmium (Cd) is a nonessential heavy metal with potentially deleterious effects on different organisms. The organisms have evolved sophisticated defense system to alleviate heavy metal toxicity. Hydrogen sulfide (H2S) effectively alleviates heavy metal toxicity in plants and reduces oxidative stress in mammals. However, the function of H2S for alleviating heavy metal toxicity in aquatic organisms remains less clear. Tetrahymena thermophila is an important model organism to evaluate toxic contaminants in an aquatic environment. In this study, the molecular roles of exogenously H2S application were explored by RNA sequencing under Cd stress in T. thermophila.

Cysteine is implicated in important biological processes. It is synthesized through two different pathways. Cystathionine β-synthase and cystathionine γ-lyase participate in the reverse transsulfuration pathway, while serine acetyltransferase and cysteine synthase function in the de novo pathway. Two evolutionarily related pyridoxal 5'-phosphate-dependent enzymes, cystathionine β-synthase TtCBS1 (TTHERM_00558300) and cysteine synthase TtCSA1 (TTHERM_00239430), were identified from a freshwater protozoan Tetrahymena thermophila. TtCbs1 contained the N-terminal heme binding domain, catalytic domain, and C-terminal regulatory domain, whereas TtCsa1 consisted of two α/β domains. The catalytic core of the two enzymes is similar. TtCBS1 and TtCSA1 showed high expression levels in the vegetative growth stage and decreased during the sexual developmental stage. TtCbs1 and TtCsa1 were localized in the cytoplasm throughout different developmental stages. His-TtCbs1 and His-TtCsa1 were expressed and purified in vitro. TtCbs1 catalyzed the canonical reaction with the highest velocity and possessed serine sulfhydrylase activity. TtCsa1 showed cysteine synthase activity with high Km for O-acetylserine and low Km for sulfide and also had serine sulfhydrylase activity toward serine. Both TtCbs1 and TtCsa1 catalyzed hydrogen sulfide producing. TtCBS1 knockdown and TtCSA1 knockout mutants affected cysteine and glutathione synthesis. TtCbs1 and TtCsa1 are involved in cysteine synthesis through two different pathways in T. thermophila.

Silver/copper-filament-based resistive switching memory relies on the formation and disruption of a metallic conductive filament (CF) with relatively large surface-to-volume ratio. The nanoscale CF can spontaneously break after formation, with a lifetime ranging from few microseconds to several months, or even years. Controlling and predicting the CF lifetime enables device engineering for a wide range of applications, such as non-volatile memory for data storage, tunable short/long term memory for synaptic neuromorphic computing, and fast selection devices for crosspoint arrays. However, conflictive explanations for the CF retention process are being proposed. Here we show that the CF lifetime can be described by a universal surface-limited self-diffusion mechanism of disruption of the metallic CF. The surface diffusion process provides a new perspective of ion transport mechanism at the nanoscale, explaining the broad range of reported lifetimes, and paving the way for material engineering of resistive switching device for memory and computing applications.

The high-mobility-group (HMG)-box domain represents a very versatile protein domain that mediates the DNA-binding of non-sequence-specific and sequence-specific proteins. HMG-box proteins are involved in various nuclear functions, including modulating chromatin structure and genomic stability. In this study, we identified the gene HMGB3 in Tetrahymena thermophila. The predicted HmgB3p contained a single HMG-box, an SK-rich-repeat domain and a neutral phosphorylated C-terminal. HMGB3 was expressed in the growth and starvation stages. Furthermore, HMGB3 showed a higher expression levels during the conjugation stage. HMGB3 knockout strains showed no obvious cytological defects, although initiation of HMGB3 knockout strain mating was delayed and maximum mating was decreased. HA-HmgB3p localized on the micronucleus (MIC) during the vegetative growth and starvation stages. Furthermore, HA-HmgB3p specially decorated the meiotic and mitotic functional MIC during the conjugation stage. Truncated HMGB3 lacking the HMG box domain disappeared from MICs and diffused in the cytoplasm. Overexpressed HmgB3p was abnormally maintained in newly developing macronuclei and affected the viability of progeny. Taken together, these results show that HmgB3p is a germline micronuclear-specific marker protein. It may bind to micronucleus-specific DNA sequences or structures and is likely to have some function specific to micronuclei of T. thermophila.

The present study was designed to evaluate the effect of chromium malate on glycometabolism, glycometabolism-related enzyme levels and lipid metabolism in type 2 diabetic rats, and dose-response and curative effects.

Conjugation in Tetrahymena thermophila involves a developmental program consisting of three prezygotic nuclear divisions, pronuclear exchange and fusion, and postzygotic and exconjugant stages. The conjugation junction structure appears during the initiation of conjugation development, and disappears during the exconjugant stage. Many structural and functional proteins are involved in the establishment and maintenance of the junction structure in T. thermophila. In the present study, a zinc finger protein-encoding gene ZFR1 was found to be expressed specifically during conjugation and to localize specifically to the conjugation junction region. Truncated Zfr1p localized at the plasma membrane in ordered arrays and decorated Golgi apparatus located adjacent to basal body. The N-terminal zinc finger and C-terminal hydrophobic domains of Zfr1p were found to be required for its specific conjugation junction localization. Conjugation development of ZFR1 somatic knockout cells was aborted at the pronuclear exchange and fusion conjugation stages. Furthermore, Zfr1p was found to be important for conjugation junction stability during the prezygotic nuclear division stage. Taken together, our data reveal that Zfr1p is required for the stability and integrity of the conjugation junction structure and essential for the sexual life cycle of the Tetrahymena cell.

Inulin is a kind of polysaccharide that can be obtained various biomass. Inulooligosaccharides (IOS), a kind of oligosaccharides that can be obtained from inulin by enzymatic hydrolysis using inulinases, have been regarded as the functional food ingredients. Commercially available inulinases produced by natural Aspergillus niger contained both endo- and exo-inulinase activities. For IOS production from inulin, it is desirable to use only endo-inulinase as exo-inulinase would produce mainly the monosacchairde fructose from inulin. In the present study, a simple inulin-mediated ethanol precipitation method was developed to separate endo- and exo-inulinases present in natural inulinases. IOS production from inulin using the enriched endo-inulinase was then optimized in process conditions including pH and temperature, achieving a high yield of ∼94%. The resultant IOS products had a degree of polymerization ranging from 2 to 7. The study demonstrated a novel method for obtaining partially purified or enriched endo-inulinase for IOS production from inulin in an efficient process.

Bone defects are often combined with the risk of infection in the clinic, and artificial bone substitutes are often implanted to repair the defective bone. However, the implant materials are carriers for bacterial growth, and biofilm can form on the implant surface, which is difficult to eliminate using antibiotics and the host immune system. Magnesium (Mg) was previously reported to possess antibacterial potential.

Adjusting biomaterial degradation profiles to match tissue regeneration is a challenging issue. Herein, biodegradable hyperbranched poly(β-amino ester)s (HP-PBAEs) were designed and synthesized via "A2 + B4" Michael addition polymerization, and displayed fast gelation with thiolated hyaluronic acid (HA-SH) via a "click" thiol-ene reaction. HP-PBAE/HA-SH hydrogels showed tunable degradation profiles both in vitro and in vivo using diamines with different alkyl chain lengths and poly(ethylene glycol) diacrylates with varied PEG spacers. The hydrogels with optimized degradation profiles encapsulating ADSCs were used as injectable hydrogels to treat two different types of humanized excisional wounds - acute wounds with faster healing rates and diabetic wounds with slower healing and neo-tissue formation. The fast-degrading hydrogel showed accelerated wound closure in acute wounds, while the slow-degrading hydrogel showed better wound healing for diabetic wounds. The results demonstrate that the new HP-PBAE-based hydrogel in combination with ADSCs can be used as a well-controlled biodegradable skin substitute, which demonstrates a promising approach in the treatment of various types of skin wounds.

The repair of critical-sized bone defects is always a challenging problem. Electromagnetic fields (EMFs), used as a physiotherapy for bone defects, have been suspected to cause potential hazards to human health due to the long-term exposure. To optimize the application of EMF while avoiding its adverse effects, a combination of EMF and tissue engineering techniques is critical. Furthermore, a deeper understanding of the mechanism of action of EMF will lead to better applications in the future.

This study is to investigate whether liposome-loaded nanobubbles (NBs) have the potentials to carry anti-pro-gastrin releasing peptide (proGRP) antibody and enhance ultrasound imaging of small cell lung cancer (SCLC).