A Proof-of-Concept Study on the Theranostic Potential of 177 Lu-labeled Biocompatible Covalent Polymer Nanoparticles for Cancer Targeted Radionuclide Therapy.

Theranostic nanomedicine combined bioimaging and therapy probably rises more helpful and interesting opportunities for personalized medicine. In this work, 177 Lu radiolabeling and surface PEGylation of biocompatible covalent polymer nanoparticles (CPNs) have generated a new theranostic nanoformulation (177 Lu-DOTA-PEG-CPNs) for targeted diagnosis and treatment of breast cancer. The in vitro anticancer investigations demonstrate that 177 Lu-DOTA-PEG-CPNs possess excellent bonding capacity with breast cancer cells (4T1), inhibiting the cell viability, leading to cell apoptosis, arresting the cell cycle, and upregulating the reactive oxygen species (ROS), which can be attributed to the good targeting ability of the nanocarrier and the strong relative biological effect of the radionuclide labelled compound. Single photon emission computed tomography/ computed tomography (SPECT/CT) imaging and in vivo biodistribution based on 177 Lu-DOTA-PEG-CPNs reveal that notable radioactivity accumulation at tumor site in murine 4T1 models with both intravenous and intratumoral administration of the prepared radiotracer. Significant tumor inhibition has been observed in mice treated with 177 Lu-DOTA-PEG-CPNs, of which the median survival was highly extended. More strikingly, 50 % of mice intratumorally injected with 177 Lu-DOTA-PEG-CPNs was cured and showed no tumor recurrence within 90 days. The outcome of this work can provide new hints for traditional nanomedicines and promote clinical translation of 177 Lu radiolabeled compounds efficiently.

Rigidity and Flexibility: Unraveling the Role of Fulvic Acid in Uranyl Sorption on Graphene Oxide Using Molecular Dynamics Simulations.

Using molecular dynamics simulations, this work targets a molecular understanding on the rigidity and flexibility of fulvic acid (FA) in uranyl sorption on graphene oxide (GO). The simulations demonstrated that both rigid Wang's FA (WFA) and flexible Suwannee River FA (SRFA) can provide multiple sites to cooperate with GO for uranyl sorption and act as "bridges" to connect uranyl and GO to form GO-FA-U (type B) ternary surface complexes. The presence of flexible SRFA was more beneficial to uranyl sorption on GO. The interactions of WFA and SRFA with uranyl were primarily driven by electrostatics, and the electrostatic interaction of SRFA-uranyl was significantly stronger owing to the formation of more complexes. The flexible SRFA could markedly enhance the bonding strength of uranyl with GO by folding itself to provide more sites to coordinate with uranyl. The rigid WFAs tended to be adsorbed on the GO surface in parallel due to π-π interactions, whereas the flexible SRFAs took more slant configurations resulting from intermolecular hydrogen bonds. This work provides new insights into the sorption dynamics, structure, and mechanism and addresses the effect of molecular rigidity and flexibility, with great significance for FA-based remediation strategies of uranium-contaminated sites.

Biocompatible conjugated polymer nanoparticles labeled with 225Ac for tumor endoradiotherapy.

Recently, endoradiotherapy based on actinium-225 (225Ac) has attracted increasing attention, which is due to its α particles can generate maximal damage to cancer cells while minimizing unnecessary radiation effects on healthy tissues. Herein, 111In/225Ac-radiolabeled conjugated polymer nanoparticles (CPNs) coated with amphiphilic polymer DSPE-PEG-DOTA have been developed as a new injectable nano-radiopharmaceuticals for cancer endoradiotherapy under the guidance of nuclear imaging. Single photon emission computed tomography/computed tomography (SPECT/CT) using 111In-DOTA-PEG-CPNs as nano probe indicates a prolonged retention of radiolabeled nanocarriers, which was consistent with the in vivo biodistribution examined by direct radiometry analysis. Significant inhibition of tumor growth has been observed in murine 4T1 models treated with 225Ac-DOTA-PEG-CPNs when compared to mice treated with PBS or DOTA-PEG-CPNs. The 225Ac-DOTA-PEG-CPNs group experienced no single death within 24 days with the median survival considerably extended to 35 days, while all the mice treated with PBS or DOTA-PEG-CPNs died at 20 days post injection. Additionally, the histopathology studies demonstrated no obvious side effects on healthy tissues after treatment with 225Ac-DOTA-PEG-CPNs. All these results reveal that the new 225Ac-labeled DOTA-PEG-CPNs is promising as paradigm for endoradiotherapy.

Derivative of cinnamic acid inhibits T3SS of Xanthomonas oryzae pv. oryzae through the HrpG-HrpX regulatory cascade.

Bacterial leaf blight (BLB) caused by Xanthomonas oryzae pv. oryzae (Xoo) has a significant impact on rice yield and quality worldwide. Traditionally, bactericide application has been commonly used to control this devastating disease. However, the overuse of fungicides has led to a number of problems such as the development of resistance and environmental pollution. Therefore, the development of new methods and approaches for disease control are still urgent. In this paper, a series of cinnamic acid derivatives were designed and synthesized, and three novel T3SS inhibitors A10, A12 and A20 were discovered. Novel T3SS inhibitors A10, A12 and A20 significantly inhibited the hpa1 promoter activity without affecting Xoo growth. Further studies revealed that the title compounds A10, A12 and A20 significantly impaired hypersensitivity in non-host plant tobacco leaves, while applications on rice significantly reduced symptoms of bacterial leaf blight. RT-PCR showed that compound A20 inhibited the expression of T3SS-related genes. In summary, this work exemplifies the potential of the title compound as an inhibitor of T3SS and its efficacy in the control of bacterial leaf blight.

The effect of secukinumab treatment for psoriasis on serum cytokines and correlation with disease severity.

OBJECTIVE: To investigate the effects of secukinumab treatment for psoriasis on different functional cytokines and inflammatory mediators in patients' serum METHODS: Enzyme-linked immunosorbent assay was used to detect interleukin (IL)-1ß and IL-1RA associated with intrinsic immunity; IL-6, IL-18, and growth regulated oncogene alpha (GROα) associated with neutrophils; IL-12, tumour necrosis factor (TNF)-α, and interferon (IFN)-γ associated with Th1; IL-23, IL-17A, and IL-22 associated with Th17; Thymus activation regulated chemokine (TARC), IL-13, and defensin beta 2 (DEFB2) associated with Th2; Vascular endothelial growth factor (VEGF)-A and IL-10 associated with angiogenesis; and IFN-γ associated with sepsis in the peripheral blood of 12 patients with common psoriasis treated with secukinumab and 15 healthy controls. IL-23, IL-17A, IL-22 associated with Th17; TARC, IL-13, DEFB2 associated with Th2; VEGF-A, IL-10 associated with angiogenesis and procalcitonin (PCT) associated with sepsis. The differences in expression of the above cytokines before and after treatment and the correlation with psoriasis disease severityï¼»Psoriasis Area Severity Index(PASI) scoreï¼½, age, and disease duration were analyzed. RESULTS: The mean PASI score of the enrolled patients with moderate to severe psoriasis was 21.6 ± 11.0 before treatment and decreased to below 1 after treatment. Serum IL-6; IL-18, GROα, IFN-γ, TNF-α, VEGF-A, and IL-17A were significantly higher than normal. And IL-17A and IFN-γ were positively correlated with disease duration and age, and IL-18 was positively correlated with PASI score. The expression levels of IL-6, GROα, VEGF-A, IFN-γ, TNF-α, IL-17A and IL-23 were significantly lower after secukinumab treatment compared with those before treatment, but the expression levels of IFN-γ, VEGF-A, TARC, IL-13, and DEFB2 were still significantly higher than those of normal subjects after treatment CONCLUSIONS: secukinumab clears skin lesions by antagonizing IL-17A and simultaneously decreasing the expression levels of IL-6, GRO α, VEGF-A, IFN-γ, TNF-α, IL-17A, and IL-23.

Unusual uranium biomineralization induced by green algae: Behavior investigation and mechanism probe.

As a biosorbent, algae are frequently used for the biotreatment or bioremediation of water contaminated by heavy metal or radionuclides. However, it is unclear that whether or not the biomineralization of these metal or radionuclides can be induced by algae in the process of bioremediation and what the mechanism is. In this work, Ankistrodsemus sp. has been used to treat the uranium-contaminated water, and more than 98% of uranium in the solution can be removed by the alga, when the initial uranium concentration ranges from 10 to 80 mg/L. Especially, an unusual phenomenon of algae-induced uranium biomineralization has been found in the process of uranium bioremediation and its mineralization mechanism has been explored by multiple approaches. It is worth noticing that the biomineralization of uranium induced by Ankistrodsemus sp. is significantly affected by contact time and pH. Uranium is captured rapidly on the cell surface via complexation with the carboxylate radical, amino and amide groups of the microalgae cells, which provides nucleation sites for the precipitation of insoluble minerals. Uranium stimulates Ankistrodsemus sp. to metabolize potassium ions (K+), which may endow algae with the ability to biomineralize uranium into the rose-like compreignacite (K2[(UO2)6O4(OH)6]•8H2O). As the time increased, the amorphous gradually converted into compreignacite crystals and a large number of crystals would expand over both inside and outside the cells. To the best of our knowledge, this is the first investigated microalgae with a time-dependent uranium biomineralization ability and superior tolerance to uranium. This work validates that Ankistrodsemus sp. is a promising alga for the treatment of uranium-contaminated wastewater.

In Vitro Anticancer Ability of Nano Fluorescent 111 In-MIL-68/PEG-FA on Hela Cells.

In past decades, nanoscale metal-organic frameworks (NMOFs) have drawn more and more attention in multimodal imaging and targeting therapy of various malignant cancers. Here, we proposed to dope 111 In into fluorescent In-based NMOFs (In-MIL-68-NH2 ), with an attempt to prepare a new nanomedicine with great anticancer potential. As a proof of concept, the obtained NMOF (In-MIL-68/PEG-FA) with targeting motifs is able to act as a fluorescent probe to achieve Hela cell imaging. Moreover, the Auger electron emitter 111 In built in corresponding radioactive NMOF (111 In-MIL-68/PEG-FA) can bring clear damage to cancer cells, leading to a high cell killing rate of 59.3 % within 48 h. In addition, the cell cycle presented a significant dose-dependent G2/M inhibiting mode, which indicates that 111 In-MIL-68/PEG-FA has the ability to facilitate the cancer cells to enter apoptotic program. This work demonstrated the potential of 111 In-labelled NMOFs in specific killings of cancer cells, providing a new approach to develop nanomedicines with theranostic function.

Targeted Alpha Therapy of Glioma Using 211At-Labeled Heterodimeric Peptide Targeting Both VEGFR and Integrins.

Targeted radionuclide therapy based on α-emitters plays an increasingly important role in cancer treatment. In this study, we proposed to apply a heterodimeric peptide (iRGD-C6-lys-C6-DA7R) targeting both VEGFR and integrins as a new vector for 211At radiolabeling to obtain high-performance radiopharmaceuticals with potential in targeted alpha therapy (TAT). An astatinated peptide, iRGD-C6-lys(211At-ATE)-C6-DA7R, was prepared with a radiochemical yield of ∼45% and high radiochemical purity of >95% via an electrophilic radioastatodestannylation reaction. iRGD-C6-lys(211At-ATE)-C6-DA7R showed good stability in vitro and high binding ability to U87MG (glioma) cells. Systematic in vitro antitumor investigations involving cytotoxicity, apoptosis, distribution of the cell cycle, and reactive oxygen species (ROS) clearly demonstrated that 211At-labeled heterodimeric peptides could significantly inhibit cell viability, induce cell apoptosis, arrest the cell cycle in G2/M phase, and increase intracellular ROS levels in a dose-dependent manner. Biodistribution revealed that iRGD-C6-lys(211At-ATE)-C6-DA7R had rapid tumor accumulation and fast normal tissue/organ clearance, which was mainly excreted through the kidneys. Moreover, in vivo therapeutic evaluation indicated that iRGD-C6-lys(211At-ATE)-C6-DA7R was able to obviously inhibit tumor growth and prolong the survival of mice bearing glioma xenografts without notable toxicity to normal organs. All these results suggest that TAT mediated by iRGD-C6-lys(211At-ATE)-C6-DA7R can provide an effective and promising strategy for the treatment of glioma and some other tumors.

Understanding the Effect of pH on the Solubility and Aggregation Extent of Humic Acid in Solution by Combining Simulation and the Experiment.

Molecular dynamics (MD) simulations were performed to investigate the dynamics of humic acid (HA) in an aqueous solution and the influence of pH, temperature, and HA concentration. The HA model employed in MD simulations was chosen and validated using experimental chemical composition data and Fourier transform infrared (FTIR) spectra. The simulations showed that the HA molecule has a strong propensity to adopt a compact conformation in water independent of pH, while the aggregation of HA was found to be pH-dependent. At high pH, the ionized HAs assembled into a thread-like structure, maximizing contact with water. At low pH, the neutral HAs formed a droplet-like aggregate, minimizing contact with the solvent. The simulation results are consistent with experimental data from dynamic light scattering (DLS) measurements and transmission electron microscopy (TEM) imaging. This work provides new insight into the folding and aggregation of HA as a function of pH and a molecular-level understanding of the relationship between the acidity and the structure, solubility, and aggregation of HA, with direct implications for HA-based remediation strategies of contaminated sites.

In vitro and in vivo evaluation of 211At-labeled fibroblast activation protein inhibitor for glioma treatment.

Glioma is the most common primary intracranial tumor without effective treatment. Positron emission tomography tracers labeled with 68Ga targeting fibroblast activation protein (FAP) have shown favorable characteristics in the diagnosis of glioma. However, to the best of our knowledge, FAP-targeted endoradiotherapy has never been explored in glioma. Hence, in this study, we investigated the therapeutic effect of 211At-labeled fibroblast activation protein inhibitor (FAPI) for glioma in vitro and in vivo. By astatodestannylation reaction, we prepared 211At-FAPI-04 with a radiochemical yield of 45 ± 6.7% and radiochemical purity of 98%. With good stability in vitro, 211At-FAPI-04 showed fast and specific binding to FAP-positive U87MG cells, and could significantly reduce the cell viability, arrested cell cycle at G2/M phase and suppressed cell proliferative efficacy. Biodistribution studies revealed that 6-fold higher accumulation in tumor sites was achieved by intratumoral injection in comparison with intravenous injection. In U87MG xenografts, 211At-FAPI-04 obviously suppressed the tumor growth and prolonged the median survival in a dose-dependent manner without obvious toxicity to normal organs. In addition, reduced proliferation and increased apoptosis were also observed after 211At-FAPI-04 treatment. All these results suggest that targeted alpha-particle therapy (TAT) mediated by 211At-FAPI-04 can provide an effective and promising strategy for the treatment of glioma.

PET imaging of VEGFR and integrins in glioma tumor xenografts using 89Zr labelled heterodimeric peptide.

Vascular endothelial growth factor receptor (VEGFR) and integrin αv are over-expressed in angiogenesis of variety malignant tumors with key roles in angiogenesis, and have been proven as valuable targets for cancer imaging and treatment. In this study, a heterodimeric peptide targeting VEGFR and integrin was designed, and radiolabeled with zirconium-89 (89Zr) for PET imaging of glioma. 89Zr-DFO-heterodimeric peptide, a the newly developed probe, was prepared with radiochemical yield of 88.7 ± 2.4%. Targeted binding capability of 89Zr-DFO-heterodimeric peptide towards U87MG cells was investigated in murine glioma xenograft models, which shows that the designed probe has good binding ability to both targeting sites. Biodistribution indicated that kidney metabolism is the main pathway and tumor uptake of 89Zr-DFO-heterodimeric peptide reached the peak of 0.62 ± 0.10% ID/g . U87MG xenograft could be clearly visualized by microPET/CT imaging through 1 to 3 h post-injection of 89Zr-DFO-heterodimeric peptide. Importantly, the tumor radiouptake was significantly reduced after blocking, and the imaging effect of this radioactive compound was more obvious than that of monomeric peptide probes. 89Zr-DFO-heterodimeric peptide has been demonstrated to show potential as a new radiopharmaceutical probe towards glioma, and multi-target probes do have advantages in tumor imaging.

Safety and efficacy of Magnesium Sulfate in the management of Tetanus: A systematic review.

Tetanus is a rare life-threatening condition often complicated by repetitive spasms, dysautonomia and neuromuscular respiratory failure contributing to high fatality rates in its severe form. Benzodiazepines used to treat muscle spasms pose a high risk of respiratory failure requiring mechanical ventilation, which is unaffordable and inaccessible for many. Magnesium sulfate, a cheap and widely available medication in all urban and rural health centres of LMICs for the treatment of eclampsia, can be used to control muscle spasms and dysautonomia. We thus conducted a systematic review of evidence to assess the safety and efficacy of magnesium sulfate in the treatment of tetanus. Any study published before April 15, 2021, discussing the efficacy and/or safety of MgSO4 infusion in the treatment of tetanus was systemically reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Our systematic review included data from 13 studies, three were randomised, double-blind and controlled trials. The remaining ten studies were observational; six prospective and four retrospective studies. Our review showed no mortality benefit associated with the use of magnesium sulfate. However, magnesium sulfate was found to be effective in reducing spasms along with diazepam, leading to better control of dysautonomia, reduced need for mechanical ventilation and shorter hospital stay by 3-7 days. The incidence of magnesium toxicity was very low in the studies included.

Synthesis and Preliminary Evaluation of 131I-Labeled FAPI Tracers for Cancer Theranostics.

As an excellent target for cancer theranostics, fibroblast activation protein (FAP) has become an attractive focus in cancer research. A class of FAP inhibitors (FAPIs) with a N-(4-quinolinoyl)-Gly-(2-cyanopyrrolidine) scaffold were developed, which displayed nanomolar affinity and high selectivity. Compared with 90Y, 177Lu, 225Ac, and 188Re, 211At seems to be more favored as a therapeutic candidate for FAPI tracers which have fast washout and short retention in tumor sites. Thus, the current study reported the synthesis of two FAPI precursors for 211At and 131I labeling and the preliminary evaluation of 131I-labeled FAPI analogues for cancer theranostics. FAPI variants with stannyl precursors were successfully synthesized and labeled with 131I using a radioiododestannylation reaction. Two radioactive tracers were obtained with high radiochemical purity over 99% and good radiochemical yields of 58.2 ± 1.78 and 59.5 ± 4.44% for 131I-FAPI-02 and 131I-FAPI-04, respectively. Both tracers showed high specific binding to U87MG cells in comparison with little binding to MCF-7 cells. Compared to 131I-FAPI-02, 131I-FAPI-04 exhibited higher affinity, more intracellular uptake, and longer retention time in vitro. Biodistribution studies revealed that both tracers were mainly excreted through the kidneys as well as the hepatobiliary pathway due to their high lipophilicity. In addition, higher accumulation, longer dwell time, and increased tumor-to-organ ratios were achieved by 131I-FAPI-04, which was clearly demonstrated by SPECT/CT imaging. Furthermore, intratumor injection of 131I-FAPI-04 significantly suppressed the tumor growth in U87MG xenograft mice without significant toxicity observed. The above results implied that FAP-targeted alpha endoradiotherapy (specific to 211At) should be used to treat tumors in the near future, considering the chemical similarity between iodine and astatine can ensure the labeling of the latter onto the designed FAPIs.

Nanomechanics of Lignin-Cellulase Interactions in Aqueous Solutions.

Efficient enzymatic hydrolysis of cellulose in lignocellulose to glucose is one of the most critical steps for the production of biofuels. The nonproductive adsorption of lignin to expensive cellulase highly impedes the development of biorefinery. Understanding the lignin-cellulase interaction mechanism serves as a vital basis for reducing such nonproductive adsorption in their practical applications. Yet, limited report is available on the direct characterization of the lignin-cellulase interactions. Herein, for the first time, the nanomechanics of the biomacromolecules including lignin, cellulase, and cellulose were systematically investigated by using a surface force apparatus (SFA) at the nanoscale in aqueous solutions. Interestingly, a cation-π interaction was discovered and demonstrated between lignin and cellulase molecules through SFA measurements with the addition of different cations (Na+, K+, etc.). The complementary adsorption tests and theoretical calculations further confirmed the validity of the force measurement results. This finding further inspired the investigation of the interaction between lignin and other noncatalytic-hydrolysis protein (i.e., soy protein). Soy protein was demonstrated as an effective, biocompatible, and inexpensive lignin-blocker based on the molecular force measurements through the combined effects of electrostatic, cation-π, and hydrophobic interactions, which significantly improved the enzymatic hydrolysis efficiencies of cellulose in pretreated lignocellulosic substrates. Our results offer quantitative information on the fundamental understanding of the lignin-cellulase interaction mechanism. Such unraveled nanomechanics provides new insights into the development of advanced biotechnologies for addressing the nonproductive adsorption of lignin to cellulase, with great implications on improving the economics of lignocellulosic biorefinery.

Competition/Cooperation between Humic Acid and Graphene Oxide in Uranyl Adsorption Implicated by Molecular Dynamics Simulations.

Molecular dynamics (MD) simulations were performed to investigate the influence of curvature and backbone rigidity of an oxygenated surface, here graphene oxide (GO), on its adsorption of uranyl in collaboration with humic acid (HA). The planar curvature of GO was found to be beneficial in impeding the folding of HA. This, together with its rigidity that helps stabilize the extended conformation of HA, offered rich binding sites to interact with uranyl with only marginal loss of binding strength. According to our simulations, the interaction between uranyl and GO was mainly driven by electrostatic interactions. The presence of HA not only provided multiple sites to compete/cooperate with GO for adsorption of free uranyl but also interacted with GO acting as a "bridge" to connect uranyl and GO. The potential of mean force (PMF) profiles implied that HA significantly enhanced the interaction strength between uranyl and GO and stabilized the uranyl-GO complex. Meanwhile, GO could reduce the diffusion coefficients of uranyl and HA and retard their migrations in aqueous solution. This work provides theoretical hints on the GO-based remediation strategies for the sites contaminated by uranium or other heavy metal ions and oxygenated organic pollutants.

Short communication: Quantitative PCR coupled with sodium dodecyl sulfate and propidium monoazide for detection of culturable Escherichia coli in milk.

Escherichia coli has been frequently reported as a major foodborne bacterium contaminating raw milk or pasteurized milk. Therefore, the aim of this study was to explore a quantitative real-time PCR (qPCR) technique combined with sodium dodecyl sulfate (SDS) and propidium monoazide (PMA) to detect culturable E. coli in milk. An internal amplification control was also added into this reaction system as an indicator of false-negative results. The inclusivity and exclusivity of the primers were tested using DNA from 7 E. coli and 14 other bacterial strains. The concentrations of SDS and PMA were determined according to plate counts and quantitative cycle values of qPCR, respectively. A standard curve was established using series diluted E. coli DNA. The reliability and specificity of this method were further determined by the detection of E. coli in spiked milk. The results showed that the optimal concentrations of SDS and PMA were 100 µg/mL and 40 µM, respectively. A standard curve with a good linear relationship (coefficient of determination = 0.997; amplification efficiency = 100.5%) was obtained. Compared with conventional PCR and PMA-qPCR, the SDS-PMA-qPCR assay was more specific and sensitive in culturable E. coli detection. Therefore, we evaluated and improved the SDS-PMA-qPCR method for detecting culturable E. coli in milk.

Influence of Speciation of Thorium on Toxic Effects to Green Algae Chlorella pyrenoidosa.

Thorium (Th) is a natural radioactive element present in the environment and has the potential to be used as a nuclear fuel. Relatively little is known about the influence and toxicity of Th in the environment. In the present study, the toxicity of Th to the green algae Chlorella pyrenoidosa (C. pyrenoidosa) was evaluated by algal growth inhibition, biochemical assays and morphologic observations. In the cultural medium (OECD TG 201), Th(NO3)4 was transformed to amorphous precipitation of Th(OH)4 due to hydrolysis. Th was toxic to C. pyrenoidosa, with a 96 h half maximum effective concentration (EC50) of 10.4 µM. Scanning electron microscopy shows that Th-containing aggregates were attached onto the surface of the algal cells, and transmission electron microscopy indicates the internalization of nano-sized Th precipitates and ultrastructural alterations of the algal cells. The heteroagglomeration between Th(OH)4 precipitation and alga cells and enhanced oxidative stress might play important roles in the toxicity of Th. To our knowledge, this is the first report of the toxicity of Th to algae with its chemical species in the exposure medium. This finding provides useful information on understanding the fate and toxicity of Th in the aquatic environment.

Dynamics of Humic Acid and Its Interaction with Uranyl in the Presence of Hydrophobic Surface Implicated by Molecular Dynamics Simulations.

This work targeted a molecular level of understanding on the dynamics of humic acid (HA) and its interaction with uranyl in the presence of hydrophobic surface mimicked by a carbon nanotube (CNT), which also represents a potential intruder in the environment accompanying with the development of nanotechnology. In aqueous phase, uranyl and HA were observed to build close contact spontaneously, driven by electrostatic interaction, leading to a more compact conformation of HA. The presence of CNT unfolds HA via π-π interactions with the aromatic rings of HA without significant perturbation on the interaction strength between HA and uranyl. These results show that the hydrophilic uranyl and the hydrophobic CNT influence the folding behavior of HA in distinct manners, which represents two fundamental mechanisms that the folding behavior of HA may be modulated in the environment, that is, uranyl enhances the folding of HA via electrostatic interactions, whereas CNT impedes its spontaneous folding via van der Waals (vdW) interactions. The work also provides molecular level of evidence on the transformation of a hydrophobic surface into a hydrophilic one via noncovalent functionalization by HA, which in turn affects the migration of HA and the cations it binds to.

Toxicity of cerium and thorium on Daphnia magna.

Cerium (Ce) and thorium (Th) are always thought to be chemically similar and have comparable toxic properties on living organisms. In the present study, the acute and chronic toxicity of these two elements to freshwater crustacean Daphnia magna were investigated in the modified reconstituted water (6mg/L KCl, 123mg/L MgSO4·7H2O, and 294mg/L CaCl2·2H2O in Milli-Q water, pH 7.8). It seemed that Ce and Th had comparable acute toxicity on Daphnia: 24/48h EC50 for Th and Ce were 7.3/4.7µM and 16.4/10.7µM, respectively. However, Ce was present as soluble ions while all of Th was present as particulate ThO2 in the exposure medium. Considering their different chemical forms and bioavailability, the toxic mechanisms of Ce3+ and ThO2 on Daphnia would be totally different. To our knowledge, this is the first time to investigate the aquatic toxicity of thorium and cerium based on their actual chemical speciation in the exposure medium. The results also suggest that more attention should be paid on the detrimental effect of Th in the form of particulate ThO2.

Human testis-expressed sequence 101 is limitedly distributed in germinal epithelium of testis and disappears in seminoma.

BACKGROUND: Testis-expressed sequence 101 (TEX101) was found to be highly expressed in testis and involved in acrosome reaction in previous studies. Recently, the metastasis suppressor function of TEX101 in cancer was disclosed, but the comprehensive investigation of its expression has rarely been reported. In this study, the expression features of TEX101 in normal human organs and seminoma were systematically analyzed. RESULTS: Immunohistochemistry demonstrated intense staining of TEX101 in human testis tissues; however, its expression in 27 other types of normal human organs, including the ovary, was negligible. Higher expression of TEX101 was observed in the spermatocytes and spermatids of the testis, but relatively lower staining was detected in spermatogonia. Western blotting showed a single TEX101 band of 38 kDa in human testis, but it did not correspond to the predicted molecular weight of its mature form at 21 KDa. Furthermore, we examined seminoma tissues by immunohistochemistry and found that none of the 36 samples expressed TEX101. CONCLUSIONS: Our data confirmed TEX101 to be a testis protein that could be related to the maturation process of male germ cells. The lack of TEX101 in seminoma indicated its potential role in tumor progression. This characteristic expression of TEX101 could provide a valuable reference for understanding its biological functions.