Methylparaben toxicity and its removal by microalgae Chlorella vulgaris and Phaeodactylum tricornutum.

The widespread occurrence of methylparaben (MPB) has aroused great concern due to its weak estrogenic endocrine-disrupting property and potential toxic effects. However, the degradation potential and pathway of MPB by microalgae have rarely been reported. Here, microalgae Chlorella vulgaris and Phaeodactylum tricornutum were used to investigate their responses, degradation potential and mechanisms towards MPB. MPB showed low-dose stimulation (by 86.02 ± 0.07% at 1 mg/L) and high-dose inhibition (by 60.17 ± 0.05% at 80 mg/L) towards the growth of C. vulgaris, while showed inhibition for P. tricornutum (by 6.99 ± 0.05%-20.14 ± 0.19%). The degradation efficiencies and rates of MPB were higher in C. vulgaris (100%, 1.66 ± 0.54-5.60 ± 0.86 day-1) than in P. tricornutum (4.3-34.2%, 0.04 ± 0.01-0.08 ± 0.00 day-1), which could be explained by the significantly higher extracellular enzyme activity and more fluctuation of the protein ratio for C. vulgaris, indicating a higher ability of C. vulgaris to adapt to pollutant stress. Biodegradation was the main removal mechanism of MPB for both the two microalgae. Furthermore, two different degradation pathways of MPB by the two microalgae were proposed. MPB could be mineralized and completely detoxified by C. vulgaris. Overall, this study provides novel insights into MPB degradation by microalgae and strategies for simultaneous biodegradation and detoxification of MPB in the environment.

Revealing drug release and diffusion behavior in skin interstitial fluid by surface-enhanced Raman scattering microneedles.

Microneedle (MNs), as a novel dermal drug delivery formulation, have drawn a lot of attention in recent years. Drug release and diffusion behavior in dermal interstitial fluid (ISF) determines the pharmacokinetics and effectiveness of MNs, which have not been clearly elucidated until now. Herein, we develop surface-enhanced Raman scattering (SERS)-based detection MNs (D-MNs) for the sensitive analysis of model drugs in ISF. The surface of the D-MNs was deposited with a high density of hotspot-rich core-satellite gold nanoparticles, which would generate a sensitive SERS signal of a model drug (3,3'-diethylthiatricarbocyanine, DTTC) released by therapeutic MNs (T-MNs). Furthermore, the D-MNs produced an internal-standard signal for drug signal calibration, increasing the accuracy of detection. Taking advantage of the D-MNs, the release and diffusion behavior of the drug from T-MNs in the ISF of living mice was systematically studied. It was found that DTTC diffused without directional preference in ISF up to a distance of 1.5 cm. The intensities at diffusion sites decreased sharply with increasing distance from the release site (less than 0.3% at 1.5 cm). These results indicated that drug concentration gradient rather than ISF fluidity was a major driving force for the diffusion. Moreover, the application of water-soluble MN polymers, hydrophilic model drugs in T-MNs, as well as a heating or cupping treatment of mouse skin, enhanced drug diffusion in ISF. This work provides a new tool for in situ and real-time detection of molecules in ISF, which would be beneficial for the development and evaluation of MN-based therapeutic systems.

Source identification and weathering processes of tar ball deposited Qinhuangdao coast along the Bohai Sea, China.

Deposition of tar balls on the Qinhuangdao beaches along the coasts of the Bohai Sea (China) could affect people's leisure activities and tourism, and even affect the marine ecosystem. In 2020, representative tar balls collected from Qinhuangdao beaches, fingerprint analysis based on diagnostic ratios suggested that these tar balls were all very similar and may belong to the same source. Source identification by cross plot and principal component analysis (PCA), showed that the tar balls were likely from Penglai 19-3 crude oil. The weathering characterizations based on polycyclic aromatic hydrocarbons (PAHs), alkanes parameters and unresolved complex mixture (UCM), indicated that the tar balls had been significantly influenced by natural weathering processes such as evaporation, biodegradation and photooxidation. The study of this leakage provides a powerful support for determining the leakage source, evaluating the potential weathering mechanism and determining the accident liability. This is the first time to use fingerprint technology to identify the source of tar balls in Qinhuangdao coastal zone in the Bohai Sea.

Microplastics exposure as an emerging threat to ancient lineage: A contaminant of concern for abnormal bending of amphioxus via neurotoxicity.

Growing inputs of microplastics into marine sediment have increased significantly the needs for assessment of their potential risks to the marine benthos. A knowledge gap remains with regard to the effect of microplastics on benthos, such as cephalochordates. By employing amphioxus as a model benthic chordate, here we show that exposure to microplastics for 96 h at doses of 1 mg/L and 100 mg/L results in evident accumulation of the polyethylene microplastics. The accumulated microplastics are as much as 0.027% of body weight upon high-dose exposure, causing an abnormal body-bending phenotype that limits the locomotion capability of amphioxus. Mechanistic insight reveals that microplastics can bring about histological damages in gill, intestine and hepatic cecum; In-depth assay of relevant biomarkers including superoxide dismutase, catalase, glutathione, pyruvic acid and total cholesterol indicates the occurrence of oxidative damage and metabolic disorder; Further, microplastics exposure depresses the activity of acetylcholinesterase while allowing the level of acetylcholine to rise in muscle, suggesting the emergence of neurotoxicity. These consequences eventually contribute to the muscle dysfunction of amphioxus. This study rationalizes the abnormal response of the vulnerable notochord to microplastics, signifying the dilemma suffered by the ancient lineage under the emerging threat. Given the enrichment of microplastics through marine food chains, this study also raises significant concerns on the impact of microplastics to other marine organisms, and eventually human beings.

Seasonal and spatial variations in nutrients under the influence of natural and anthropogenic factors in coastal waters of the northern Yellow Sea, China.

Analysis of the common and most influential natural and anthropogenic activities on the spatiotemporal variation in nutrients at a multiannual scale is important. Eleven cruises from 2015 to 2017 were carried out to better elucidate the seasonal and spatial variations in nutrients, as well as the impact factors on dissolved inorganic nitrogen (DIN), phosphorus (DIP) and silicate (DSi). Both nutrient concentrations and forms showed similar and significant seasonal variations over the 3 years, and were closely related to the biomass and species of phytoplankton. Terrestrial inputs had significant effects on the spatial distribution of nutrients throughout the year, especially in the surface water, which showed DIN > DIP>DSi. In summer, shellfish aquaculture and hypoxia jointly affected the spatial distribution of nutrients. The bottom water nutrient concentrations in the aquaculture area were 1.1-2.3 times higher than those outside of the aquaculture area. Seasonal hypoxia can increase the release of DSi and NH4+ from the sediment to the water. In summary, anthropogenic activities and physical conditions jointly influenced the nutrient distributions.

A ratiometric fluorescent probe for detecting the endogenous biological signaling molecule superoxide anion and bioimaging during tumor treatment.

Tumor resistance and drug-induced nephrotoxicity pose great challenges to the clinical treatment of tumors, and they also limit the clinical application of oncology drugs. Finding an effective adjuvant, which can sensitize tumor treatment, is an effective method for tumor treatment. Here, we developed a ratiometric fluorescent probe, TP-Tfs, for superoxide anion (O2˙-) detection in living cells and in vivo during the process of tumor treatment for the first time. TP-Tfs with simple synthesis steps and high yields can detect O2˙- sensitively and selectively, and the detection limit was determined to be 37 nM. Using TP-Tfs, we found that cis-diaminodichloroplatinum(ii) (DDP) was effective in treating tumors by inducing O2˙- burst. Curcumin (cum) can sensitize tumor treatment effectively by inducing more severe O2˙- burst. These results indicated that the probe TP-Tfs was a promising candidate for drug screening and tumor treatment evaluation.

Self-assembly of nanoparticles by human serum albumin and photosensitizer for targeted near-infrared emission fluorescence imaging and effective phototherapy of cancer.

Photodynamic therapy (PDT) and photothermal therapy (PTT) are effective cancer treatments, and photosensitizers play the most important role in the treatment. However, photosensitizers are insufficient for in vivo tumor treatment. Herein, we develop a small molecule fluorophore Cy-HPT as a novel photosensitizer, which possesses the advantages of near-infrared (NIR) emission, high photothermal conversion efficiency and high singlet oxygen generation efficiency. Moreover, a nanoplatform of HSA@Cy-HPT was synthesized by self-assembly of Cy-HPT and human serum albumin (HSA) in aqueous solution. Compared to Cy-HPT, HSA@Cy-HPT possesses more stable spectral properties, enhances the effect of PDT/PTT, and exhibits more satisfactory in vivo metabolism. HSA@Cy-HPT demonstrates outstanding tumor targeting in subcutaneous tumor xenograft models owing to its enhanced permeability and retention in tumor tissue. Furthermore, HSA@Cy-HPT was successfully utilized in tumor xenograft models and tumor tissue growth was clearly inhibited without any regrowth, extending survival rate of the models. Also, no distinct damage of the normal tissue of tumor xenograft models was observed using hematoxylin & eosin staining. This study presents a promising therapeutic agent for the synergetic PDT and PTT cancer treatment.

In situ microbial remediation of crude oil-soaked marine sediments using zeolite carrier with a polymer coating.

Marine oil spill pollution is an important environmental problem in the world, especially crude oil-soaked marine sediments, because they are difficult to be remediated. In this study, in situ bioremediation of oil-soaked sediment was performed in the middle of the Bohai Sea. Oil-degrading bacteria were adsorbed on powdery zeolite (PZ)/granular zeolites (GZ) surfaces and then wrapped with poly-γ glutamic acid (γ-PGA). Settling column and wave flume experiments were conducted to model marine conditions and to select appropriate biological reagents. The optimal conditions were as follows: the average diameter of GZ 3 mm, mass ratio of GZ/PZ 2:1, and concentration of γ-PGA 7%. After bioremediation, over 50% of most oil-spilled pollutants n-alkanes (C12 to C27) and polycyclic aromatic hydrocarbons were degraded in 70 days. This work resulted in a successful trial of in situ bioremediation of oil-soaked marine sediments.

A ratiometric fluorescent probe for imaging and quantifying anti-apoptotic effects of GSH under temperature stress.

Hypothermia and hyperthermia are cell stressed states resulting from environmental temperature changes, which can abnormally decrease intracellular glutathione (GSH) concentrations and induce apoptosis. As the most abundant intracellular non-protein biothiol, GSH can protect cells from apoptosis. Considering the important roles of GSH in the anti-apoptotic process in cells and in vivo, we strive to develop a powerful chemical tool for the direct detection of GSH concentration changes under temperature stress. Herein, we report a ratiometric fluorescent probe (CyO-Dise) based on a selenium-sulfur exchange reaction for the qualitative and quantitative detection of GSH concentration fluctuations in cells and in vivo. The probe has been successfully used to assess the changes of GSH levels in HepG2 and HL-7702 cells using the stimulations of hypothermia and hyperthermia. In terms of the anti-apoptotic effect of GSH under hypothermic and hyperthermic conditions, human normal liver HL-7702 cells have stronger abilities to fight against temperature stress than human liver carcinoma HepG2 cells. Hypothermia and hyperthermia can also improve the drug resistance of cis-dichlorodiamineplatinum(ii) (DDP)-resistant HepG2/DDP cells. The CyO-Dise probe has been employed to image GSH concentration changes in HepG2 and HepG2/DDP xenografts on nude mice. With the adjuvant therapy effects of hypothermia and hyperthermia, the chemotherapy drug DDP exhibits good ability for the treatment of HepG2 and HepG2/DDP xenografts. The above applications make our probe a potential new candidate for the accurate diagnosis of cancer and efficacy evaluation of treatment.

Mesoporous titania based yolk-shell nanoparticles as multifunctional theranostic platforms for SERS imaging and chemo-photothermal treatment.

Recently surface-enhanced Raman scattering (SERS) imaging guided theranostic nanoplatforms have attracted considerable attention. Herein, we developed novel yolk-shell gold nanorod@void@mesoporous titania nanoparticles (AuNR@void@mTiO2 NPs) for simultaneous SERS imaging and chemo-photothermal therapy. Our work showed three highlighted features: first, we proposed a facile and versatile "up to down" SERS labeling strategy for the drug delivery system, in which "empty carriers" were pre-synthesized, followed by co-loading of Raman reporters on AuNR and anti-cancer drug doxorubicin (DOX) in mTiO2 in sequence. The acquired SERS signal was strong enough for tracking NPs at both living cells and mice levels. Second, we selected mTiO2 as a novel drug loading material instead of the widely used mesoporous silica (mSiO2). The mTiO2 shared satisfactory drug loading and release behavior as mSiO2 but it was chemically inert. This property not only provided a facile way to form a yolk-shell structure but also rendered it with superior structural stability in a biological system. Third, the near infrared (NIR) light absorbing property of the AuNR SERS substrate was also explored for drug release regulation and photothermal treatment. Significantly greater MCF-7 cell killing was observed when treated together with DOX-loaded NPs and NIR laser irradiation, attributable to the synergistic chemo-thermal therapeutic effect. Our results indicated the established SERS labeled yolk-shell NP as a promising theranostic platform and suggested its potential in vivo applications.

Fluorescent probes for hydrogen sulfide detection and bioimaging.

In comparison with other biological detection technologies, fluorescence bioimaging technology has become a powerful supporting tool for intracellular detection, and can provide attractive facilities for investigating physiological and pathological processes of interest with high spatial and temporal resolution, less invasiveness, and a rapid response. Due to the versatile roles of hydrogen sulfide (H2S) in cellular signal transduction and intracellular redox status regulation, fluorescent probes for the detection of this third signalling gasotransmitter have rapidly increased in number in recent years. These probes can offer powerful means to investigate the physiological actions of H2S in its native environments without disturbing its endogenous distribution. In this feature article, we address the synthesis and design strategies for the development of fluorescent probes for H2S based on the reaction type between H2S and the probes. Moreover, we also highlight fluorescent probes for other reactive sulfur species, such as sulfane sulfurs and SO2 derivatives.

Sensitive near-infrared fluorescent probes for thiols based on Se-N bond cleavage: imaging in living cells and tissues.

Cy-NiSe and Cy-TfSe were designed and synthesized as sensitive near-infrared (NIR) fluorescent probes for detecting thiols on the basis of Se-N bond cleavage both in cells and in tissues. Since a donor-excited photoinduced electron transfer (d-PET) process occurs between the modulator and the fluorophore, Cy-NiSe and Cy-TfSe have weak fluorescence. On titration with glutathione, the free dye exhibits significant fluorescence enhancement. The two probes are sensitive and selective for thiols over other relevant biological species. They can function rapidly at pH 7.4, and their emission lies in the NIR region. Confocal imaging confirms that Cy-NiSe and Cy-TfSe can be used for detecting thiols in living cells and tissues.

Quercetin molecularly imprinted polymers: preparation, recognition characteristics and properties as sorbent for solid-phase extraction.

Molecular imprinted polymers (MIPs) were prepared through thermal polymerization by using quercetin as the template molecule, acrylamide (AA) as the functional monomer and ethylene glycol dimethacrylate (EDMA) as the cross-linker in the porogen of tetrahydrofuran (THF). The synthesized MIPs were identified by both Fourier transform infrared (FTIR) and scanning electron microscope (SEM). Systematic investigations of the influences of key synthetic conditions, including functional monomers, porogens and cross-linkers, on the recognition properties of the MIPs were conducted. Scatchard analysis revealed that the homogeneous binding sites were formed in the polymers. Besides quercetin, two structurally similar compounds of rutin and catechol were employed for molecular recognition specificity tests of MIPs. It was observed that the MIPs exhibited the highest selective rebinding to quercetin. Accordingly, the MIPs were used as a solid-phase extraction (SPE) sorbent for the extraction and enrichment of quercetin in cacumen platycladi samples, followed by HPLC-UV analysis. The application of MIPs with high affinity and excellent stereo-selectivity toward quercetin in SPE might offer a novel method for the enrichment and determination of flavonoid compounds in the natural products.

Off-line comprehensive two-dimensional high-performance liquid chromatography system with size exclusion column and reverse phase column for separation of complex traditional Chinese medicine Qingkailing injection.

A comprehensive two-dimensional liquid chromatography system was constructed on the combination of size exclusion chromatography (SEC) and reverse phase liquid chromatography (RPLC). The first dimension used a SEC column with 300 mm x 8mm i.d., packed with Toyopearl HW-40S. The column was eluted with 0.05 mol/l Tris-HCl (pH 6.9) at a flow rate of 0.4 ml/min. The second dimension used a RPLC column with 100 mm x 4.6mm i.d., which was operated in gradient form at a flow rate of 1.0 ml/min. An automatic switching valve was used to collect the effluent of the SEC column every 3 min, and the effluent was automatically injected into the RPLC column. Mass spectrometer was used for peak identification. This system was used to separate Qingkailing injection, a traditional Chinese medicine (TCM). The result showed that the total peak capacity of this system could reach 1134 and the qualitative analysis of seven chemical components of the Qingkailing injection was accomplished by this system. The results show that comprehensive two-dimensional liquid chromatography system is of great importance and high value in the separation of complex TCM.

[HPLC fingerprint for the Corydalis saxicola Bunting injection].

AIM: To establish the fingerprint of Corydalis saxicola Bunting injection. METHODS: It was performed by HPLC Kromasil column was used with acetonitrile and H2O as mobile phase. The flow rate was 0.5 mL x min(-1). The detection wavelength was 254 nm. The mass spectrometry detection was performed on a trap equipped with an ESI interface and operated in positive-ionization mode. RESULTS: Eleven components of Corydalis saxicola Bunting were identified by LC-MS and 7 of them were quantified. CONCLUSION: The fingerprint chromatogram could represent the characteristics of Corydalis saxicola Bunting injection. Evaluation of resemblances and results of precision were satisfactory. This method could be used as quality and quantity control.

[Determination of alkaloids from Coptis chinensis Franch. and Phellodendron amurense Rupr. Decocted together in baitouweng decocta by high performance capillary electrophoresis].

A rapid and accurate method for determining alkaloids from Coptis chinensis Franch, and Phellodendron amurense Rupr, decocted together in Baitouweng decocta was established. Experiments were carried out on a self-assembled capillary electrophoresis system. The experimental conditions were as follows: 75 microns i.d. x 50 cm fused silica capillary, 0.05 mol/L Na2B4O7-CH3OH (85:15, V/V) as buffer, applied voltage 14 kV and detection wavelength 232 nm. In addition, the concentration of ethanol in the extraction solvent was optimized. Experimental results showed that ethanol-water (30:70, V/V) was the ideal solvent to extract the main effective ingredients from Coptis chinensis Franch. and Phellodendron amurense Rupr. decocted together in Baitouweng decocta. Berberine and palmatine had good linearities in the range of 15.0 mg/L-65.0 mg/L and 12.5 mg/L-50.0 mg/L respectively, and their average recoveries were 95.5%-104% (RSD 2.7%-6.9%) and 92.1%-103% (RSD 4.5%-6.7%) respectively.