Calcium supplementation attenuates fluoride-induced bone injury via PINK1/Parkin-mediated mitophagy and mitochondrial apoptosis in mice.

Excessive consumption of fluoride can cause skeletal fluorosis. Mitophagy has been identified as a novel target for bone disorders. Meanwhile, calcium supplementation has shown great potential for mitigating fluoride-related bone damage. Hence, this study aimed to elucidate the association between mitophagy and skeletal fluorosis and the precise mechanisms through which calcium alleviates these injuries. A 100 mg/L sodium fluoride (NaF) exposure model in Parkin knockout (Parkin-/-) mice and a 100 mg/L NaF exposure mouse model with 1% calcium carbonate (CaCO3) intervention were established in the current study. Fluoride exposure caused the impairment of mitochondria and activation of PTEN-induced putative kinase1 (PINK1)/E3 ubiquitin ligase Park2 (Parkin)-mediated mitophagy and mitochondrial apoptosis in the bones, which were restored after blocking Parkin. Additionally, the intervention model showed fluoride-exposed mice exhibited abnormal bone trabecula and mechanical properties. Still, these bone injuries could be effectively attenuated by adding 1% calcium to their diet, which reversed fluoride-activated mitophagy and apoptosis. To summarize, fluoride can activate bone mitophagy through the PINK1/Parkin pathway and mitochondrial apoptosis. Parkin-/- and 1% calcium provide protection against fluoride-induced bone damage. Notably, this study provides theoretical bases for the prevention and therapy of animal and human health and safety caused by environmental fluoride contamination.

The modulator role of Urtica dioica on deleterious effects of retinoic acid high doses on histological parameters and fertilization of rats.

Aim: This study purposed to evaluate the modulator and protective role of Urtica dioica (UD) extract against deleterious effects of retinoic acid (RA) high doses on histological parameters and fertilization of rats. Materials and methods: For the in-vivo phase, 60 female Wistar rats were divided into 6 identical groups as 1) control, 2) 25 mg/kg RA, 3) 25 mg/kg UD extract, 4) 50 mg/kg UD extract, 5) UD extract (25 mg/kg) + RA (25 mg/kg), and 6) UD extract (50 mg/kg) + RA (25 mg/kg). Biochemical parameters, including luteinizing hormone (LH), folliclestimulating hormone (FSH), malondialdehyde (MDA) levels, superoxide dismutase (SOD), and catalase (CAT) activities, were measured. In the in-vitro phase, oocytes were obtained from 10 female rats without injection. In addition to the mentioned parameters, histological parameters (oocytes in various stages) and the results of IVM, IVF, and embryo developments were assessed and compared among the groups with the use of one-way ANOVA and Tukey's post hoc tests. Results: The high dosage of RA significantly reduced the LH and FSH levels; however, UD alone and with RA increased the hormone levels in rats. Regarding the reactive oxygen species (ROS) activity levels in rats' blood samples, RA increased the MDA and decreased the SOD and CAT levels. Treatment with UD extract (UD + RA groups) significantly improved the parameters mentioned, showing UD's antioxidant effect. The rate of oocyte maturation, 2-cell-4-cell and 4-cell-8-cell embryos, and blastocyst formation increased significantly in the groups in which UD extracts were administered compared to the control and RA groups. Furthermore, the increases were significant in the UD + RA groups compared to the RA group. Conclusion: UD extract can significantly reduce RA high doses side effects on histological parameters and fertilization of rats and has the protective potential against RA deleterious effects.

In vivo antibacterial activity of medicinal plant Sophora flavescens against Streptococcus agalactiae infection.

Streptococcosis disease caused by Streptococcus agalactiae (Group B Streptococcus, GBS) results in a huge economic loss of tilapia culture. It is urgent to find new antimicrobial agents against streptococcosis. In this study, 20 medicinal plants were evaluated in vitro and in vivo to obtain medicinal plants and potential bioactive compounds against GBS infection. The results showed that the ethanol extracts of 20 medicinal plants had low or no antibacterial properties in vitro, with a minimal inhibitory concentration ≥256 mg/L. Interestingly, in vivo tests showed that 7 medicinal plants could significantly inhibit GBS infection in tilapia, and Sophora flavescens (SF) had the strongest anti-GBS activity in tilapia, reaching 92.68%. SF could significantly reduce the bacterial loads of GBS in different tissues (liver, spleen and brain) of tilapia after treated with different tested concentrations (12.5, 25.0, 50.0 and 100.0 mg/kg) for 24 h. Moreover, 50 mg/kg SF could significantly improve the survival rate of GBS-infected tilapia by inhibiting GBS replication. Furthermore, the expression of antioxidant gene cat, immune-related gene c-type lysozyme and anti-inflammatory cytokine il-10 in liver tissue of GBS-infected tilapia significantly increased after treated with SF for 24 h. Meanwhile, SF significantly reduced the expression of immune-related gene myd88 and pro-inflammatory cytokines il-8 and il-1ß in liver tissue of GBS-infected tilapia. The negative and positive models of UPLC-QE-MS, respectively, identified 27 and 57 components of SF. The major components of SF extract in the negative model were α, α-trehalose, DL-malic acid, D- (-)-fructose and xanthohumol, while in the positive model were oxymatrine, formononetin, (-)-maackiain and xanthohumol. Interestingly, oxymatrine and xanthohumol could significantly inhibit GBS infection in tilapia. Taken together, these results suggest that SF can inhibit GBS infection in tilapia, and it has potential for the development of anti-GBS agents.

Colorectal cancer therapy mediated by nanomedicines.

Colorectal cancer is the third most malignant gastrointestinal tumor. Although traditional chemotherapy and radiotherapy have been widely used for treating colorectal cancer, the treatment effect is still unsatisfactory, resulting in a high mortality rate and a low 5-year survival rate. In recent years, with the development of molecular biology of colorectal cancer, many promising therapeutic strategies based on nanomaterials have been developed for colorectal cancer. In this review, we focus on recent advances in colorectal cancer treatment-related nanomedicines. We first discuss the exploration of stimuli-responsive drug delivery systems (DDSs) for colorectal cancer treatment using pH, hypoxia, glutathione (GSH), enzymes, light, magnetic fields (MF), and ultrasound (US) as stimuli. Moreover, the latest progress in emerging therapy for colorectal cancer is further summarized, including photothermal therapy (PTT), magnetothermal therapy (MTT), photodynamic therapy (PDT), sonodynamic therapy (SDT), and chemodynamic therapy (CDT). Finally, we explore the existing challenges and future directions for the better design and development of nanomedicines for clinical colorectal cancer treatment.

Blood-brain Barrier Permeable and Multi-stimuli Responsive Nanoplatform for Orthotopic Glioma Inhibition by Synergistic Enhanced Chemo-/Chemodynamic/Photothermal/Starvation Therapy.

Glioblastoma (GBM) is a common malignant tumor in brain, and the treatment is still a challenge owing to the high invasiveness and the existence of blood-brain barrier (BBB). Although temozolomide (TMZ) is the first line medication, its efficacy is not ideal, which is related to the defect of dose distribution and drug resistance. It is urgent to develop a novel BBB-permeable nanoagent with multiple therapeutic modalities for improving the treatment effect of GBM. In this work, we constructed an intelligent BBB-permeable nanoplatform (CTHG-Lf NPs) with hollow mesoporous copper sulfide nanoparticles (HM-CuS NPs) as temozolomide (TMZ) carrier and hyaluronic acid (HA) as gatekeeper, as well as further modification with glucose oxidase (GOx) and lactoferrin (Lf) for highly efficient synergistic therapy of orthotopic GBM. The modification of Lf endows CTHG-Lf NPs with good target and BBB-permeable ability. HA not only prevents the TMZ leakage during circulation, but also achieves responsive drug release at tumor site for effective chemotherapy (CT). GOx provides high hydrogen peroxide (H2O2) and gluconic acid for improving the treatment effect of chemodynamic therapy (CDT), and realizes the starvation therapy (ST) by consuming glucose. The good photothermal effect of CTHG-Lf NPs achieves the "mild" photothermal therapy (PTT), while enhancing the efficiency of Fenton-like reaction. The synergistic strategy with CT/CDT/PTT/ST can not only promote brain drug delivery, but also realize the combination of multiple mechanisms for effective tumor growth suppression in vivo.

Non-medicinal parts of safflower (bud and stem) mediated sustainable green synthesis of silver nanoparticles under ultrasonication: optimization, characterization, antioxidant, antibacterial and anticancer potential.

The flower of safflower is widely used in Chinese herbal preparations and the non-medicinal parts have been applied to develop a sustainable green method, where AgNPs were generated using a mixture of leaf and stem after 12 h of incubation in the dark. In this study, we intend to improve the efficiency of the reduction reaction and optimize this green method by selecting other non-medicinal parts, such as the bud and the pure stem, evaluating the biosynthesis parameters and harnessing the assistance of ultrasonication. Visual observation and UV-vis spectroscopy confirmed that both safflower stem (SS) and bud (SB) mediated AgNPs (SS-AgNPs and SB-AgNPs, respectively) could be produced rapidly over time under ultrasonication. An alkaline solution could accelerate the formation of SS-AgNPs and SB-AgNPs with greater surface loads. SS-AgNPs and SB-AgNPs of small size could be obtained at pH 8.0 and 10.0, respectively. Large concentrations of SS and SB extract are also beneficial for forming AgNPs of small size. It is in acid and neutral solutions that monodispersed SS-AgNPs and SB-AgNPs can be generated. Characterization of selectively synthesized SS-AgNPs and SB-AgNPs demonstrated their spherical shape with the actual size below 30 nm covered by anions. Both SS-AgNPs and SB-AgNPs exhibited potent antioxidant and antibacterial activity. The MIC values of SS-AgNPs for S. aureus and E. coli were 12.5 and 25.0 µg mL-1, respectively, slightly superior to SB-AgNPs. In an in vitro anticancer assay, both kinds of AgNPs show potent toxicity action against the SW620 cell line with IC50 values of 5.4 and 10.6 µg mL-1, respectively. However, only SS-AgNPs reveal an inhibitory action against the HeLa cell line, where the IC50 is found to be 26.8 µg mL-1. These results provide experimental proof that the assistance of ultrasonication and adjusting the process parameters are efficient methods for promoting the reduction reaction, and both SS and SB mediated AgNPs could serve as a promising antioxidant, antibacterial and anticancer agents.

Natural component plumbagin as a potential antibacterial agent against Streptococcus agalactiae infection.

Streptococcus agalactiae, also known as Group B Streptococcus (GBS), can infect humans, terrestrial animals and fish. The emergence of bacterial resistance of S. agalactiae to antibiotics leads to an urgent need of exploration of new antimicrobial agents. In the study, the antibacterial activity of natural component plumbagin (PLB) against S. agalactiae was investigated in vitro and in vivo. The results showed that the minimal inhibitory concentration (MIC) of PLB against S. agalactiae was 8 mg/L. The growth curve assay revealed that PLB could inhibit the growth of S. agalactiae. In addition, the time-killing curve showed that S. agalactiae was killed almost completely by 2-fold MIC of PLB within 12 h. Transmission electron microscopy results showed obvious severe morphological destruction and abnormal cells of S. agalactiae after treated with PLB. The pathogenicity of S. agalactiae to zebrafish was significantly decreased after preincubation with PLB for 2 h in vitro, further indicating the bactericidal activity of PLB. Interestingly, PLB could kill S. agalactiae without inducing resistance development. Furthermore, pretreatment and post-treatment assays suggested that PLB also exhibited the antibacterial activity against S. agalactiae infection in vivo by effectively reducing the bacterial load and improving the survival rate of S. agalactiae-infected zebrafish. In summary, PLB had potent antibacterial activity against S. agalactiae in vitro and in vivo, and it could be an excellent antimicrobial candidate to prevent and control S. agalactiae infection.

Green Fabrication of Bioactive Silver Nanoparticles Using Mentha pulegium Extract under Alkaline: An Enhanced Anticancer Activity.

Fabrication of silver nanoparticles (AgNPs) using Chinese herbal medicine is popular as the bioactive components included in them would generate potential synergistic effect with the metal nanoparticles. The leaf of Mentha pulegium, whose extract contains a range of phytochemicals and exhibits a wide spectrum of bioactivities, is used as Chinese herbal medicine after drying naturally. Thus, the green synthesis of AgNPs using Mentha pulegium has aroused interests from analysts. However, the biosynthesis of AgNPs under alkaline conditions and the biological activities remain elusive, where alkaline conditions may influence the physicochemical properties and the biological activities of biosynthesized AgNPs. In this study, we were stimulated to fabricate bioactive AgNPs using Mentha pulegium extract under alkaline conditions, accompanied by a systematic evaluation on the effect of biosynthesis parameters on the formation, average size, and polydispersity of AgNPs. Our results showed that alkaline conditions could accelerate the formation of AgNPs with a small average size but at a disadvantage to the polydispersity. Additionally, the as-prepared AgNPs had a hexagonal structure and spherical shape with an average size of 15.7 ± 0.1 nm, existing in the monodispersed form and revealing a high degree of stability. The AgNPs exhibited potent antioxidant and significant inhibitory activity for both bacterial and cancer cell lines. The MIC values of AgNPs for Staphylococcus aureus and Escherichia coli were both 50.0 µg·mL-1, and the IC50 values for HCT116, HepG2, and HeLa cells were 9.0, 14.5, and 31.5 µg·mL-1, respectively. The AgNPs biosynthesized using M. pulegium under alkaline conditions, which had a smaller size and more surface loads, are entirely different with those synthesized under acidic conditions, and the anticancer activity increased significantly. The internalization of AgNPs inside these five cells displayed a variant trend with variable AgNPs concentrations, suggesting the different mechanism of cell death. For two pathogens, HCT116 and HepG2 cancer cell lines, both cell wall and intracellular damage may be responsible for the cell death. However, for Hela cell line the cell death may be rooted in oxidative stress or intracellular penetration. These results confirmed that the AgNPs biosynthesized from M. pulegium extract under alkaline conditions would act as better anticancer agents in biomedicine.

Tumor Diagnosis and Therapy Mediated by Metal Phosphorus-Based Nanomaterials.

Metal phosphorus-based nanomaterials (Metal-P NMs) including metal phosphate nanomaterials, metal phosphide nanomaterials, and metal-black phosphorus (Metal-BP) nanocomposite are widely used in the field of biomedicine owing to their excellent physical and chemical properties, biocompatibility, and biodegradability. In recent years, metal phosphate nanomaterials and Metal-BP nanocomposite acted as medicine delivery system have made breakthroughs in tumor diagnosis including magnetic resonance imaging, fluorescence imaging, photoacoustic imaging, nuclear imaging, and therapies including chemotherapy, gene therapy, photothermal therapy, photodynamic therapy, and radiation therapy. Metal phosphate nanomaterials have good biodegradability, especially calcium-based metal phosphate nanomaterials can be dissolved into nontoxic ions and participate in the metabolisms of normal organs. Compared with metal phosphate nanomaterials, metal phosphide nanomaterials have excellent optical, magnetic, and catalytic properties, which can be used as multifunctional diagnostic nanoplatforms and therapeutic agents for chemodynamic therapy, photothermal therapy, or immunotherapy. The latest developments in Metal-P NMs, covering the range of preparation methods and biological applications, such as serving as drug carriers, tumor diagnosis, and therapy, are focused. All in all, the current trends, key issues, future prospects and challenges of Metal-P NMs are concluded and discussed, which are important for the development of this research field and shining more lights on this direction.

Rapidly clearable MnCo2O4@PAA as novel nanotheranostic agents for T1/T2 bimodal MRI imaging-guided photothermal therapy.

Integrating multi-modal imaging and therapy functions into a nanoplatform has been recognized as a promising strategy for cancer theranostics with high accuracy and efficiency. However, there are still some challenges, such as the complicated synthesis process and instability. Herein, we successfully prepared clearable MnCo2O4 nanodots modified with polyacrylic acid (MnCo2O4@PAA) as nanoagents for T1/T2 bimodal MRI imaging-guided PTT. Owing to their intrinsic magnetic properties, single MnCo2O4@PAA nanomaterials can serve as contrasts for T1/T2 bimodal MRI, providing precise diagnotic information. Moreover, excellent absorption in the NIR biowindow endows MnCo2O4@PAA with good photothermal performance, and the ultrasmall size of MnCo2O4@PAA allows them to penetrate deeply into tumors, resulting in a good anticancer effect in vitro and in vivo. What is more, MnCo2O4@PAA can almost be completely cleared from mice at 7 d postinjection, implying their negligible long-term toxicity. These findings demonstrate that MnCo2O4@PAA are promising nanoagents for cancer diagnosis and treatment, which have great potential for clinical applications.

A novel green synthesis of silver nanoparticles by the residues of Chinese herbal medicine and their biological activities.

Green synthesis of silver nanoparticles (AgNPs) by using the extracts of Chinese herbal medicines (CHMs) has attracted tremendous attention due to the potential synergistic effect between metal nanoparticles and capping agents. However, since CHMs are precious and expensive, finding other cheap and eco-friendly resources for biosynthesizing AgNPs with superior medicinal activites is necessary. Herbal medicine residues (HMRs) are the by-products of traditional Chinese herbal medicine after decoction and were identified to contain approximately 30-50% of medicinally active ingredients, which may be advantageous for green synthesis of medicinal AgNPs. Inspired by this, we present herein the preparation of AgNPs by reusing Bazheng Mixture residues and evaluate both biosynthesis parameters and bioactivities, where Bazheng Mixture is a famous Chinese patent medicine for relieving inflammation and pain, and allaying fever. The UV-visible spectrum and DLS analysis showed that the as-prepared AgNPs were sensitive to pH, material proportion and incubation time, but the yield was impervious to material proportion. TEM, HRTEM, SAED and DLS characterization found that AgNPs (pH 10.0; material proportion 1 : 1; 6 h) had a face-centered cubic (fcc) structure and spherical shape with an average size of 22.2 ± 0.5 nm covered by anions, and existed in monodispersed form with long term stability. The AgNPs displayed potent toxic effects against both cancer cell lines and pathogens, and superior antioxidant activity. The IC50 for HCT116, HepG2 and HeLa cell lines were 13.07, 19.67, and 26.18 µg mL-1, respectively. The MICs of AgNPs for E. coli and S. aureus were both 50.0 µg mL-1. The uptake analysis of AgNPs for both pathogens and cancer cell lines was performed to preliminarily illustrate the mechanism of toxic effects. These results confirm that HMRs could be a low-cost, nontoxic and eco-friendly resource for green synthesis of medicinal AgNPs, and also provide an alternative method for general recycling strategies of HMRs.

Influences of phosphorus concentration and porewater advection on phosphorus dynamics in carbonate sands around the Weizhou Island, northern South China Sea.

A series of flow-through reactor experiments were undertaken to assess the potential effect of porewater advection and dissolved inorganic phosphorus (DIP) concentration on benthic DIP dynamics in permeable sediments collected from the Weizhou Island, northern South China Sea. The flux of DIP ranged from -0.13 to 0.05 mmol m-2 h-1, and the reversal from DIP efflux to influx occurred when the DIP concentration reached a threshold. DIP release from the sediment into the seawater peaked at intermediate advection rate, which perhaps provide optimum conditions for DIP release related to CaCO3 dissolution. Phosphorus limitation in seawater could be relieved by DIP release from the sediment, and CaCO3-bound P in carbonate sands may play a major role in benthic DIP release and decrease in the molar nitrogen/phosphorus ratio in seawater around the Weizhou Island.

Evaluation of biosynthesis parameters, stability and biological activities of silver nanoparticles synthesized by Cornus Officinalis extract under 365 nm UV radiation.

Since silver nanoparticles (AgNPs) synthesized by using plant extracts revealed varied biological activities, the green synthesis of AgNPs has attracted considerable attention. Although the green synthesis of AgNPs have been accomplished by using the extracts of Cornus Officinalis, which is a traditional Chinese medicine and exhibits a wide spectrum of phytochemicals. The effects of biosynthesis parameters on reducing reaction, stability and more broad biological activities of so-prepared AgNPs did not been evaluated. In this paper, we firstly assessed the effects of UV radiation, pH, material proportion and radiation times on the green synthesis of AgNPs under 365 nm UV radiation by UV-visible spectrum and dynamic light scattering (DLS) analysis. The results showed that UV radiation could accelerate the formation of AgNPs and influence the average size below pH 7.0, and the size of so-prepared AgNPs were sensitive to the pH and material proportion, but no obvious changes to UV radiation times, offering a size-controlled synthetic method for AgNPs. The further X-ray diffraction (XRD), transmission electron microscopy (TEM) and DLS studies showed AgNPs synthesized at pH 7.0, extract: AgNO3 = 1 : 1 and after 4 h UV radiation were a face-centered cubic (fcc) structure and both spherical and polygonal in shape with average particle size of 64.5 ± 0.3 nm existed in a monodispersed form. Subsquently, the stability of AgNPs was analyzed by zeta potential (-24.8 mV) and the average size measurement after 30 days storage (63.3 ± 0.4 nm), revealing a high degree of stability. Lastly, the investigation of biological activities showed that the biosynthesized AgNPs had potent antioxidant activity, antimicrobial activity against both S. aureus and E. coli as well as anticancer activity against HCT116 and HepG2 cell lines but negligible cytotoxicity against SW620. And the internalization of biosynthesized AgNPs inside the bacterial cell was evaluated by flow cytometric analysis, where the SSC values have significant increase after treating with nanoparticles. These results confirmed that the biosynthesis parameters on the green synthesis of AgNPs by using Cornus Officinalis extract also played pivotal roles and so-prepared AgNPs would be useful for the development of new alternative antioxidant, antimicrobial and anticancer agents in biomedicine.

Plasmonic Pt Superstructures with Boosted Near-Infrared Absorption and Photothermal Conversion Efficiency in the Second Biowindow for Cancer Therapy.

Photothermal therapy triggered by near-infrared light in the second biowindow (NIR-II) has attracted extensive interest owing to its deeper penetration depth of biological tissue, lower photon scattering, and higher maximum permissible exposure. In spite of noble metals showing great potential as the photothermal agents due to the tunable localized surface plasmon resonance, the biological applications of platinum are rarely explored. Herein, a monocomponent hollow Pt nanoframe ("Pt Spirals"), whose superstructure is assembled with three levels (3D frame, 2D layered shells, and 1D nanowires), is reported. Pt Spirals exhibit outstanding photothermal conversion efficiency (52.5%) and molar extinction coefficients (228.7 m2 mol-1 ) in NIR-II, which are much higher than those of solid Pt cubes. Simulations indicate that the unique superstructure can be a significant cause for improving both adsorption and the photothermal effect simultaneously in NIR-II. The excellent photothermal effect is achieved and subsequently verified in in vitro and in vivo experiments, along with superb heat-resistance properties, excellent photostability, and a prominent effect on computed tomography (CT) imaging, demonstrating that Pt Spirals are promising as effective theranostic platforms for CT imaging-guided photothermal therapy.

Double Switch Biodegradable Porous Hollow Trinickel Monophosphide Nanospheres for Multimodal Imaging Guided Photothermal Therapy.

Due to the limitation of inorganic nanomaterials in present clinical applications induced by their inherent nonbiodegradability and latent long-term side effects, we successfully prepared double switch degradable and clearable trinickel monophosphide porous hollow nanospheres (NiP PHNPs) modified with bovine serum albumin (BSA). Attributed to their acidic and oxidative double switch degradation capacities, NiP PHNPs can be effectively excreted from mice without long-term toxicity. Moreover, because of the paramagnetic and high molar extinction coefficient property resulting from the strong absorption in the second near-infrared light (NIR II) biowindow, NiP PHNPs have potential to be used for photoacoustic imaging (PAI) and T1-weighted magnetic resonance imaging (MRI) guided photothermal ablation of tumors in the NIR II biowindow. Specifically, it is interesting that the hollow structure and acidic degradation property enable NiP PHNPs to act as intelligent drug carriers with an on-demand release ability. These findings highlight the great potential of NiP PHNPs in the cancer theranostics field and inspire us to further broaden the bioapplications of transition metal phosphides.

Effect of New Dayuan powder on methicillin-resistant Staphylococcus aureus biofilms in vitro.

OBJECTIVE: To observe the effects of New Dayuan powder (NDYP) on Methicillin-resistant Staphylococcus aureus (MRSA) biofilms and the embedded bacteria in vitro. METHODS: 2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assays were used to study the effects of NDYP on developing MRSA biofilms: 100 µL of bacterial culture and 100 µL drug solution were added to wells of 96-well plates. After 24 h of incubation, the plates were washed and XTT-phenazine methyl sulfate (PMS) was added to enable counting of the number of live bacteria in biofilms using a microplate reader. XTT assays were also used to explore the effects of NDYP on mature MRSA biofilms: 100 µL of bacterial culture were added to wells of 96-well plates. Bacteria were cultured in the plates for 24 h, and then drug solution was added. The plates were cultured for another 24 h, and then XTT-PMS was added to detect the number of live bacteria in the biofilms. Scanning electron microscopy (SEM) was used to observe the effects of NDYP on mature MRSA biofilms: washed and sterilized glass coverslips were added to 24-well plates. Bacterial culture was added. After 24 h of incubation, drug solution was added. After another 24 h of incubation, the samples were observed by SEM. RESULTS: XTT assays showed that the number of live bacteria in both developing and mature MRSA biofilms decreased significantly (P < 0.01) after the administration of NDYP. SEM images showed that NDYP could destroy the structure of the bacteria and resulted in uneven thickness of MRSA biofilms. CONCLUSION: In vitro, NDYP has obvious inhibitory effects on the formation of MRSA biofilms and on mature biofilms.

A New Co-P Nanocomposite with Ultrahigh Relaxivity for In Vivo Magnetic Resonance Imaging-Guided Tumor Eradication by Chemo/Photothermal Synergistic Therapy.

Design of new nanoagents that intrinsically have both diagnostic imaging and therapeutic capabilities is highly desirable for personalized medicine. In this work, a novel nanotheranostic agent is fabricated based on polydopamine (PDA)-functionalized Co-P nanocomposites (Co-P@PDA) for magnetic resonance imaging (MRI)-guided combined photothermal therapy and chemotherapy. The ultrahigh relaxivity of 224.61 mm-1 s-1 can enable Co-P@PDA to be applied as an excellent contrast agent for MRI in vitro and in vivo, providing essential and comprehensive information for tumor clinical diagnosis. Moreover, Co-P@PDA exhibit excellent photothermal performance owing to the strong near-infrared (NIR) absorbance of both Co-P nanocomposite and PDA. Highly effective ablation of tumors is achieved in a murine tumor model because the NIR laser not only induces photothermal effects but also triggers the chemotherapeutic drug on-demand release, which endows the Co-P@PDA with high curative effects but little toxicity and few side effects. These findings demonstrate that Co-P@PDA are promising agents for highly effective and precise antitumor treatment and warrant exploration as novel theranostic nanoagents with good potential for future clinical translation.

1H, 13C and 15N assignments of the C-terminal intrinsically disordered cytosolic fragment of the receptor tyrosine kinase ErbB2.

ErbB2 (or HER2) is a receptor tyrosine kinase that is involved in signaling pathways controlling cell division, motility and apoptosis. Though important in development and cell growth homeostasis, this protein, when overexpressed, participates in triggering aggressive HER2+ breast cancers. It is composed of an extracellular part and a transmembrane domain, both important for activation by dimerization, and a cytosolic tyrosine kinase, which activates its intrinsically disordered C-terminal end (CtErbB2). Little is known about this C-terminal part of 268 residues, despite its crucial role in interacting with adaptor proteins involved in signaling. Understanding its structural and dynamic characteristics could eventually lead to the design of new interaction inhibitors, and treatments complementary to those already targeting other parts of ErbB2. Here we report backbone and side-chain assignment of CtErbB2, which, together with structural predictions, confirms its intrinsically disordered nature.

Isolation and characterization of two novel C-type lectins from the oriental river prawn, Macrobrachium nipponense.

C-type lectins are a family of calcium-dependent carbohydrate-binding proteins which are believed to play important roles in the innate immunity of invertebrates. This study identified two novel C-type lectins, designated as MnCTLDcp2 and MnCTLDcp3, from the oriental river prawn Macrobrachium nipponense. The full-length cDNA of MnCTLDcp2 was of 1582 bp with an open reading frame (ORF) of 972 bp encoding a polypeptide of 323 amino acids. The complete nucleotide sequence of MnCTLDcp3 cDNA was 583 bp, containing a 555 bp ORF encoding a putative protein of 184 deduced amino acids. The deduced MnCTLDcp2 and MnCTLDcp3 proteins both contained a single C-type lectin-like domain (CTLD). Besides, MnCTLDcp2 contains a signal peptide and an low-density lipoprotein receptor class A (LDLa) domain. Reverse transcription PCR showed that MnCTLDcp2 was expressed in the heart, gill, nerve hepatopancreas and intestine; MnCTLDcp3 was expressed in the hepatopancreas, heart, nerve, gill and muscle. Their expression in the heart tissue was regulated following challenge with bacteria. The microbial agglutination assay showed that both MnCTLDcp2 and MnCTLDcp3 could agglutinated bacteria in the presence of calcium. All these results suggested that MnCTLDcp2 and MnCTLDcp3 functioned as pattern recognition receptors in the immune system of M. nipponense.

Detection of herb-symptom associations from traditional chinese medicine clinical data.

Background. Traditional Chinese medicine (TCM) is an individualized medicine by observing the symptoms and signs (symptoms in brief) of patients. We aim to extract the meaningful herb-symptom relationships from large scale TCM clinical data. Methods. To investigate the correlations between symptoms and herbs held for patients, we use four clinical data sets collected from TCM outpatient clinical settings and calculate the similarities between patient pairs in terms of the herb constituents of their prescriptions and their manifesting symptoms by cosine measure. To address the large-scale multiple testing problems for the detection of herb-symptom associations and the dependence between herbs involving similar efficacies, we propose a network-based correlation analysis (NetCorrA) method to detect the herb-symptom associations. Results. The results show that there are strong positive correlations between symptom similarity and herb similarity, which indicates that herb-symptom correspondence is a clinical principle adhered to by most TCM physicians. Furthermore, the NetCorrA method obtains meaningful herb-symptom associations and performs better than the chi-square correlation method by filtering the false positive associations. Conclusions. Symptoms play significant roles for the prescriptions of herb treatment. The herb-symptom correspondence principle indicates that clinical phenotypic targets (i.e., symptoms) of herbs exist and would be valuable for further investigations.