Tunable Multivalent Aptamer-Based DNA Nanostructures To Regulate Multiheteroreceptor-Mediated Tumor Recognition.

Precise mapping and regulation of cell surface receptors hold immense significance in disease treatment, such as cancer, infection, and neurodisorders, but also face enormous challenges. In this study, we designed a series of adjustable multivalent aptamer-based DNA nanostructures to precisely control their interaction with receptors in tumor cells. By profiling surface receptors on 12 cell lines using 10 different aptamers, we generated a heatmap that accurately distinguished between various tumor types based on multiple markers. We then incorporated these aptamers onto DNA origami structures to regulate receptor recognition, with patch-like structures demonstrating a tendency to be trapped on the cell surface and with tube-like structures showing a preference for internalization. Through precise control of aptamer species, valence, and geometric patterns, we found that multiheteroreceptor-mediated recognition not only favored the specific binding of nanostructures to tumor cells but also greatly enhanced intracellular uptake by promoting clathrin-dependent endocytosis. Specifically, we achieved over 5-fold uptake in different tumor cells versus normal cells using tube-like structures modified with different diheteroaptamer pairs, facilitating targeted drug delivery. Moreover, patch-like structures with triheteroaptamers guided specific interactions between macrophages and tumor cells, leading to effective immune clearance. This programmable multivalent system allows for the precise regulation of cell recognition using multiple parameters, demonstrating great potential for personalized tumor treatment.

Effects of microplastics on typical macrobenthos in sargassum ecosystems.

Recently, microplastics (MPs) have attracted extensive attention to their wide distribution and potential toxicity in ecosystems. However, there was a lack of research focused on MPs in seaweed bed ecosystems. This study investigated the distribution and toxicity of MPs in macrobenthos in Sargassum ecosystem. According to the in-situ investigation results, the abundance of MPs in the sediment was 0.9-2.3 items/g, the indoor microcosmic experiment was constructed. After exposure to MPs (0, 2, and 20 items/g) for 30 days, the abundance of MPs in macrobenthos exhibits a concentration-dependent increase. However, there was no significant bioaccumulation of MPs at the trophic level. The indoor toxicity test revealed that MPs induced oxidative stress and altered intestinal microflora composition in macrobenthos, even at actual environmental concentrations (2 items/g). It may result in a perturbation of the organism's homeostatic equilibrium. High-concentration (20 items/g) MPs had a greater impact on alkaline phosphatase (AKP) in Mollusks. The increase in AKP activity could be indicative of an adaptive mechanism in some macrobenthos while the decline in AKP activity might signal a decrease in their survival. These results elucidated the fate of MPs in ecosystem and the ecological risks of MPs to large benthic animals on model environmental conditions.

Advancements of the Fluidized Bed Fenton (FBF) Technology for wastewater treatment: Mechanism, mass and heat transfer.

Fluidized Bed Fenton (FBF) technology, a fusion of the Fenton method and fluidized bed reactor, has emerged as a superior alternative to conventional Fenton technology for treating organic industrial wastewater. This innovative approach has garnered significant attention from researchers in recent years. While earlier studies primarily focused on pollutant degradation in simulated wastewater and catalyst development, there has been a growing interest in examining the alterations in mass or heat transfer performance attributed to fluidized beds. This paper explores the factors that contribute to the effectiveness of Fluidized Bed Fenton technology in efficiently degrading various challenging organic pollutants, while also reducing iron sludge production and expanding the applicable pH range, through an analysis of reaction kinetics. Meanwhile, combined with the related work of fluid dynamics, the research related to mass and heat transfer inside the reactor of Fluidized Bed Fenton technology is summarized, and it is proposed that the use of computers to establish a suitable model of Fluidized Bed Fenton and solve it with the assistance of computational fluid dynamics (CFD) and other software will help to further explore the process of mass and heat transfer inside the fluidized bed, which will provide the basis for the future of the Fluidized Bed Fenton from the laboratory to the actual industrial application.

Synthetic Approaches and Clinical Application of Representative Small-Molecule Inhibitors of Cyclin-Dependent Kinase for Cancer Therapy.

The regulation of the cancer cell cycle heavily relies on cyclin-dependent kinases (CDKs). Targeting CDKs has been identified as a promising approach for effective cancer therapy. In recent years, there has been significant attention paid towards developing small-molecule CDK inhibitors in the field of drug discovery. Notably, five such inhibitors have already received regulatory approval for the treatment of different cancers, including breast tumors, lung malignancies, and hematological malignancies. This review provides an overview of the synthetic routes used to produce 17 representative small-molecule CDK inhibitors that have obtained regulatory approval or are currently being evaluated through clinical trials. It also discusses their clinical applications for treating CDK-related diseases and explores the challenges and limitations associated with their use in a clinical setting, which will stimulate the further development of novel CDK inhibitors. By integrating therapeutic applications, synthetic methodologies, and mechanisms of action observed in various clinical trials involving these CDK inhibitors, this review facilitates a comprehensive understanding of the versatile roles and therapeutic potential offered by interventions targeting CDKs.

Programmable Circular Multivalent Nanobody-Targeting Chimeras (mNbTACs) for Multireceptor-Mediated Protein Degradation and Targeted Drug Delivery.

Multispecific therapeutics hold significant promise in drug delivery, protein degradation, and cell recruitment to address clinical issues of tumor heterogeneity, resistance, and immune evasion. However, their modular engineering remains challenging. We developed a targeted degradation platform, termed multivalent nanobody-targeting chimeras (mNbTACs), by encoding diverse nanobody codons on a circular template using DNA printing technology. The homo- or hetero- mNbTACs specifically recognized membrane targets in a multivalent manner and simultaneously recruited scavenger receptors to favor clathrin-/caveolae-dependent endocytosis and lysosomal degradation of multiple proteins with high efficiency and selectivity. We demonstrated that a bispecific doxorubicin-loaded mNbTAC, named Doxo-mvNbsPPH, passively accumulated at tumor sites, specifically interacted with PD-L1 and HER2 targets, and was rapidly transported into lysosome, inducing potent immunogenic cell death and alleviating immune checkpoint evasion. The synergistic boosting of innate and adaptive immunity promoted the infiltration and proliferation of CD8+ T cells in tumor microenvironment (an 11-fold increase) with high toxicity and low exhaustion, eventually enhancing antitumor efficacy. Our mNbTAC platform provides multispecific therapeutics with variable valences and programmed species, whereas it induces targeted protein degradation through multireceptor-mediated endocytosis and lysosomal degradation without the need for lysosome-targeting receptors, representing a general and modular tool to harness extracellular proteome for disease treatment.

Nanoparticle Tracking in Single-Antiresonant-Element Fiber for High-Precision Size Distribution Analysis of Mono- and Polydisperse Samples.

Accurate determination of the size distribution of nanoparticle ensembles remains a challenge in nanotechnology-related applications due to the limitations of established methods. Here, a microstructured fiber-assisted nanoparticle tracking analysis (FaNTA) realization is introduced that breaks existing limitations through the recording of exceptionally long trajectories of rapidly diffusing polydisperse nanoparticles, resulting in excellent sizing precision and unprecedented separation capabilities of bimodal nanoparticle mixtures. An effective-single-mode antiresonant-element fiber allows to efficiently confine nanoparticles in a light-guiding microchannel and individually track them over more than 1000 frames, while aberration-free imaging is experimentally confirmed by cross-correlation analysis. Unique features of the approach are (i) the highly precise determination of the size distribution of monodisperse nanoparticle ensembles (only 7% coefficient of variation) and (ii) the accurate characterization of individual components in a bimodal mixture with very close mean diameters, both experimentally demonstrated for polymer nanospheres. The outstanding performance of the FaNTA realization can be quantified by introducing a new model for the bimodal separation index. Since FaNTA is applicable to all types of nano-objects down to sub-20 nm diameters, the method will improve the precision standard of mono- and polydisperse nanoparticle samples such as nano-plastics or extracellular vesicles.

Tunable KTA Stokes laser based on stimulated polariton scattering and its intracavity frequency doubling.

This paper presents the tunable Stokes laser characteristics of KTiOAsO4 (KTA) crystal based on stimulated polariton scattering (SPS). When the pumping laser wavelength is 1064.2 nm, the KTA Stokes wave can be discontinuously tuned from 1077.9 to 1088.4 nm with four gaps from 1079.0 to 1080.1 nm, from 1080.8 to 1082.8 nm, from 1083.6 to 1085.5 nm, and from 1085.8 to 1086.8 nm. When a frequency doubling crystal LiB3O5 (LBO) is inserted into the Stokes laser cavity, the frequency-doubled wave can be discontinuously tuned from 539.0 to 539.5 nm, from 540.1 to 540.4 nm, from 541.3 to 541.8 nm, from 542.7 to 542.9 nm and from 543.4 to 544.2 nm. With a pumping pulse energy of 130.0 mJ and an output coupler reflectivity of about 30%, the obtained maximum Stokes laser pulse energy at 1078.6 nm is 33.9 mJ and the obtained maximum frequency-doubled laser pulse energy at 543.8 nm is 15.7 mJ. By using the most probably coupled transverse optical modes obtained from the literature, the polariton refractive indexes, and the simplified polariton Sellmeier equations, the polariton dispersion curve is obtained. The formation of the Stokes frequency gaps is explained.

Tunable Stokes laser generation based on the stimulated polariton scattering in KTiOPO4 crystal.

The tunable Stokes laser characteristics based on the stimulated polariton scattering in KTiOPO4 (KTP) crystal and the intracavity frequency doubling properties for the Stokes laser are investigated for the first time. When the pumping laser wavelength is 1064.2 nm, and the angle between the pumping and Stokes beams outside the KTP crystal changes from 1.875° to 6.750°, the obtained tunable Stokes laser wavelength varies discontinuously from 1076.5 nm to 1091.4 nm with four gaps. When the pumping pulse energy is 120.0 mJ, the maximum Stokes pulse energy is 46.5 mJ obtained at the wavelength of 1086.6 nm. By inserting a LiB3O5 (LBO) crystal into the cavity, the obtained frequency-doubled laser wavelength is inconsecutive tunable from 538.5 nm to 543.8 nm. The maximum frequency-doubled laser pulse energy is 15.9 mJ at the wavelength of 543.5 nm.

Cephalopods' Skin-Inspired Design of Nanoscale Electronic Transport Layers for Adaptive Electrochromic Tuning.

Cephalopods can change their skin color by using high-speed electron transduction among receptors, neural networks, and pigmentary effectors. However, it remains challenging to realize a neuroelectrical transmission system like that found in cephalopods, where electrons/ions transmit on nanoscale, which is crucial for fast adaptive electrochromic tuning. Inspired by that, hereby an ideal, rapidly responsive, and multicolor electrochromic biomimetic skin is introduced. Specifically, the biomimetic skin comprises W18O49 nanowires (NWs) that are either colorless or blue, Au nanoparticles@polyaniline (Au NPs@PANI) ranging from green to pink, and a flexible conductive substrate. As the applied voltage changes from 0.4 V to -0.7 V and back to 0 V, the color of the biomimetic skin transforms from green to blue and ultimately to pink. This color change is attributed to the electrically induced redox reaction of Au NPs@PANI and W18O49 NWs, triggered by the transfer of electrons and ions. Furthermore, the high versatility and adaptability of electrical stimulus enable the creation of a highly interactive electrochromic biomimetic skin system through the integration of sensitive acoustic sensors, providing a perfect environment-responsive platform. This work provides a biomimetic multicolor electrochromic skin that depends on electron/ion transfer on nanoscale, expands potential uses for camouflage skin.

Fiddler crabs (Tubuca arcuata) as bioindicators of microplastic pollution in mangrove sediments.

In recent years, microplastics (MPs) have been widely found in the environment and pose potential risks to ecosystems, which attracted people's attention. Using bioindicators has been a great approach to understanding the pollution levels, bioavailability, and ecological risks of pollutants. However, only few studies have investigated MPs in mangrove ecosystems, with few bioindicators of MPs. Herein, the distribution of MPs in mangrove sediments and fiddler crabs (Tubuca arcuata) in mangroves was investigated. Results showed that the abundance values of MPs are 1160‒12,120 items/kg and 11-100 items/ind. in mangrove sediments and fiddler crabs, respectively. The dominant shape of MPs detected in mangrove sediments and fiddler crabs was fragments with sizes of 20‒1000 µm, larger MPs of 50-1000 µm were found in abundance. Polypropylene (PP), which is one of the most commonly used plastic materials, was the main polymer type. The distribution of MPs in fiddler crabs closely resembled that in surface mangrove sediments with a strong linear correlation (R2 > 0.8 and p < 0.05) between their abundance. Therefore, the MP contamination level in mangrove sediments can be determined by studying MP pollution in fiddler crabs. Moreover, the results of the target group index (TGI) indicated that fiddler crabs prefer feeding specific MPs in mangrove sediments. Our findings demonstrate the suitability of fiddler crabs as bioindicators for assessing MP pollution in mangrove sediments.

Efficient treatment of surfactant containing wastewater by photocatalytic ozonation with BiPO4 nanorods.

In this study, monoclinic BiPO4 nanorods were fabricated by one-pot solvothermal method. Its catalytic capability in photocatalytic ozonation process was tested by degradation and mineralization of sodium dodecyl benzene sulfonate (SDBS) solution. The results demonstrated that the TOC removal rate was dramatically improved to 90.0% at 75 min for UV/O3/BiPO4 process, which was 4.9 and 3.8 times more than that of UV/BiPO4 and O3. Moreover, the pseudo-first-order kinetic constant (0.337 min-1) and mineralization rate (90.0%) for SDBS degradation using BiPO4 in UV/O3 process were 1.6 and 1.3 times as great as that of conventional TiO2 photocatalyst (0.206 min-1, 67.3%). The influence of BiPO4 dosage, O3 concentration initial pH and coexisted ions on SDBS degradation in UV/O3/BiPO4 process were also investigated. The outcome of quenching studies illustrated both ·OH and h+ contributed prominently to SDBS degradation in UV/O3/BiPO4 process, implying that high valence band position of BiPO4 could promote the synergism between photocatalysis and ozonation. The degradation pathway of SBDS was proposed by combination of intermediates analysis and DFT calculation. Real carwash wastewater was chosen as typical surfactant containing wastewater to explore the practical application of UV/O3/BiPO4 technology. During 30 min, COD and LAS removal efficiency reached 59.7% and 70.6%, respectively. The quality indices of effluent could meet the requirements for reuse of carwash water in Water Quality Standard for Urban Miscellaneous Use in China. Energy consumption in the process was calculated as 13.9 kW h m-3, which was about 3.6 and 2.2 times less than that of UV/BiPO4 and O3 process, respectively. The results suggest that UV/O3/BiPO4 system has an application potential for surfactant containing wastewater treatment or recycle.

Overexpression of Calcineurin B-like Interacting Protein Kinase 31 Promotes Lodging and Sheath Blight Resistance in Rice.

A breakthrough "Green Revolution" in rice enhanced lodging resistance by using gibberellin-deficient semi-dwarf varieties. However, the gibberellic acid (GA) signaling regulation on rice disease resistance remains unclear. The resistance test showed that a positive GA signaling regulator DWARF1 mutant d1 was more susceptible while a negative GA signaling regulator Slender rice 1 (SLR1) mutant was less susceptible to sheath blight (ShB), one of the major rice diseases, suggesting that GA signaling positively regulates ShB resistance. To isolate the regulator, which simultaneously regulates rice lodging and ShB resistance, SLR1 interactors were isolated. Yeast two-hybrid (Y2H), bimolecular fluorescence complementation (BiFC), and Co-IP assay results indicate that SLR1 interacts with Calcineurin B-like-interacting protein kinase 31 (CIPK31). cipk31 mutants exhibited normal plant height, but CIPK31 OXs showed semi-dwarfism. In addition, the SLR1 level was much higher in CIPK31 OXs than in the wild-type, suggesting that CIPK31 OX might accumulate SLR1 to inhibit GA signaling and thus regulate its semi-dwarfism. Recently, we demonstrated that CIPK31 interacts and inhibits Catalase C (CatC) to accumulate ROS, which promotes rice disease resistance. Interestingly, CIPK31 interacts with Vascular Plant One Zinc Finger 2 (VOZ2) in the nucleus, and expression of CIPK31 accumulated VOZ2. Inoculation of Rhizoctonia solani AG1-IA revealed that the voz2 mutant was more susceptible to ShB. Thus, these data prove that CIPK31 promotes lodging and ShB resistance by regulating GA signaling and VOZ2 in rice. This study provides a valuable reference for rice ShB-resistant breeding.

Ganoderic Acid A Mitigates Inflammatory Bowel Disease through Modulation of AhR Activity by Microbial Tryptophan Metabolism.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a complex gastrointestinal condition influenced by genetic, microbial, and environmental factors, among which the gut microbiota plays a crucial role and has emerged as a potential therapeutic target. Ganoderic acid A (GAA), which is a lanostane triterpenoid compound derived from edible mushroom Ganoderma lucidum, has demonstrated the ability to modulate gut dysbiosis. Thus, we investigated the impact of GAA on IBD using a dextran sodium sulfate (DSS)-induced colitis mouse model. GAA effectively prevented colitis, preserved epithelial and mucus layer integrity, and modulated the gut microbiota. In addition, GAA promoted tryptophan metabolism, especially 3-IAld generation, activated the aryl hydrocarbon receptor (AhR), and induced IL-22 production. Fecal microbiota transplantation validated the mediating role of the gut microbiota in the IBD protection conferred by GAA. Our study suggests that GAA holds potential as a nutritional intervention for ameliorating IBD by influencing the gut microbiota, thereby regulating tryptophan metabolism, enhancing AhR activity, and ultimately improving gut barrier function.

The Impacts of COVID-19 Shock on Intergenerational Income Mobility: Evidence from China.

The COVID-19 crisis has caused a huge negative shock to economic activities worldwide, leading to a reduction in income and changes in income distribution. Intergenerational mobility is an important indicator of sustainable social development. This paper explores the short-term impacts of the sudden COVID-19 pandemic on intergenerational income mobility and personal income in China. Using the variation in the number of confirmed cases across provinces, we construct a province-level pandemic intensity index and combine it with individual data from the China Family Panel Studies (CFPS). We apply a general difference-in-difference strategy to identify the causal effect of the pandemic on intergenerational income mobility. We find that personal income is positively related to parental income, and that the COVID-19 crisis has caused a decline in individual income and exacerbated intergenerational income persistence. A more intense COVID-19 pandemic shock is associated with a larger increase in intergenerational income elasticity and intergenerational income rank-rank slope. We found that with one standard deviation increase in local pandemic intensity, the intergenerational income elasticity increases by 0.315 and the intergenerational income rank-rank slope increases by 0.198 on average. The mechanism testing suggests that heterogeneous effects among different groups are the force underlying the results. Low-income, low-skilled, and low-parental-income individuals have suffered a more severe impact from the pandemic shock.

The macro-economic and CO2 emissions impacts of COVID-19 and recovery policies in China.

The outbreak and ongoing evolution of the COVID-19 pandemic have dramatically impacted economic development and CO2 emissions. China is under simultaneous pressure to recover from the outbreak and meet its carbon reduction targets, and the government is endeavouring to stimulate economic recovery through fiscal and monetary policies. This paper uses a computable general equilibrium model to measure the impact on China's economic recovery and carbon emissions by incorporating the pandemic shock and related economic recovery policies of loan prime rate (LPR) and value-added tax (VAT) reduction. The study found that COVID-19 led to a simultaneous shock on China's supply and demand sides in which GDP dropped by 2.62% and carbon emissions fell by 2.53%, compared to the period prior to COVID-19. Although the LPR and VAT reduction effectively mitigated economic loss, the combined LPR and VAT reduction had a more substantial effect on boosting GDP than the single policies. The VAT cut expands production and was used to overcome supply-side shocks, while lowering LPR mitigates the damage of demand-side shocks. Compared to the VAT reduction policy, reduced LPR has smaller carbon emissions per unit of GDP output. Consequently, we recommend that the government concentrate on a combination of policies to navigate pandemic shocks, as the two economic stimulus policies are confirmed to complement one another in terms of strengths and shortcomings.

Research on real time detection of departure angle for the laser beam through atmospheric channels.

The precision of departure angle detection for the laser beam can be improved by optimizing algorithms by which the high precision and stability of the laser beam pointing and tracking would be obtained, namely, improving the performance and accommodation of the free space optical communications. Atmospheric turbulence-induced optical intensity scintillations have a strong impact on the location precision of the laser spot through the atmospheric channels. Consequently, new requests come into view for the optimization of the algorithms. In the paper, the advantages and disadvantages of the traditional centroid method are analyzed. In terms of variations of laser spot, combined with the requests for real-time detection of departure angle, we proposed a new detection method. The edge of the laser spot on the detection sensor was redefined, and then the redefined spot was used to calculate the departure angle of the laser beam. The results of the simulations and experiments show that the precision of departure angle detection has been improved by more than 16%, which could reduce the effect of detection errors on the tracking procedure.

Three-dimensional tracking of nanoparticles by dual-color position retrieval in a double-core microstructured optical fiber.

Elastic light scattering-based three-dimensional (3D) tracking of objects at the nanoscale level is essential for unlocking the dynamics of individual species or interactions in fields such as biology or surface chemistry. In this work, we introduce the concept of dual-color 3D tracking in a double-core microstructured optical fiber that for the first time allows for full 3D reconstruction of the trajectory of a diffusing nanoparticle in a water-filled fiber-integrated microchannel. The use of two single-mode cores provides two opposite decaying evanescent fields of different wavelengths within the microchannel, bypassing spatial domains of ambiguous correlation between the scattered intensity and position. The novelty of the fiber design is the use of two slightly different single-mode cores, preventing modal crosstalk and thus allowing for longitudinally invariant dual-color illumination across the entire field of view. To demonstrate the capabilities of the scheme, a single gold nanosphere (80 nm) diffusing in the water-filled microchannel was tracked for a large number of images (about 32 000) at a high frame rate (1.389 kHz) over a long time (23 s), with the determined hydrodynamic diameters matching expectations. The presented 3D tracking approach yields unique opportunities to unlock processes at the nanoscale level and is highly relevant for a multitude of fields, particularly within the context of understanding sophisticated interaction of diffusing species with functionalized surfaces within the context of bioanalytics, nanoscale materials science, surface chemistry or life science.

Role of the biochar modified with ZnCl2 and FeCl3 on the electrochemical degradation of nitrobenzene.

The Zn/Fe-modified biochar on nitrobenzene (NB) removal during the electrolysis was investigated in this study. Both the Fe and Zn-modified biochar enhanced the NB adsorption compared with the un-modified biochar due to their greater specific surface area and more abundant surface function groups, respectively. The electrolysis under 2-11 V with the assist of both Fe/Zn-modified biochar achieved effective NB removal (>93%). The removal rate under 2 V using Zn/Fe-modified biochar (∼94%) was higher than that of the un-modified biochar (∼80%), whereas the removal was similar for those under 5, 8 and 11 V. The NB removal under 2 and 5 V was attributed to both adsorption and electrochemical decomposition of NB molecules. Electrolysis under 5 V by Fe-modified biochar had a higher degree of NB mineralisation than that using un-modified and Zn-modified biochar. This was likely that the Fe-modified biochar exhibited higher electrocatalytic properties, facilitating the further NB mineralisation. The ∙OH played significant roles in the degradation of NB by Fe-modified and un-modified biochar but did not significantly participated for the test using Zn-modified biochar. This was possibly because the Zn-modified biochar could adsorb greater amounts of ∙OH into the inner pores of Zn-modified biochar via its greater porosity and specific surface area, which may prevent the contact between ∙OH and NB molecules.

Pharmacokinetics, plasma protein binding, and metabolism of a potential natural chemosensitizer from Marsdenia tenacissima in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Marsdenia tenacissima (Roxb.) Wight et Arn is a medicinal plant mainly distributed in southwest China. It is used in folk medicine for the treatment of tumors and is synergistic with chemotherapies. In our previous study, 11α-O-2-methybutyryl-12ß-O-tigloyl-tenacigenin B (MT2), a main steroid aglycone isolated from the total aglycones of M. tenacissima, significantly enhanced the in vivo antitumor effect of paclitaxel in mice bearing human tumor xenografts, showing its potential as a chemosensitizer. However, the pharmacokinetic characteristics, plasma protein binding rate, and metabolic profile of MT2 remain unclear. AIM OF THE STUDY: To elucidate the pharmacokinetic characteristics, plasma protein binding rate, and metabolic profile of MT2 in rats. MATERIALS AND METHODS: MT2 in rat plasma and phosphate-buffered saline was quantified using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method, while the MT2 metabolites in rat liver microsomes were analyzed using UPLC-triple time-of-flight MS/MS. RESULTS: For intravenously administered MT2, the maximum plasma concentration and the area under the plasma concentration-time curve indicated dose dependency, while the elimination half-life time, the mean residence time, apparent volume of distribution and total apparent clearance values remained relatively unchanged in both the 5 mg/kg and 10 mg/kg groups. For orally administered MT2, the bioavailability was 1.08-1.11%. In rat plasma, MT2 exhibited a protein binding rate of 93.84-94.96%. In rat liver microsomes, MT2 was metabolized by oxidation alone or in combination with demethylation, and five MT2 metabolites were identified. CONCLUSION: MT2 has low oral bioavailability and a high plasma protein binding rate in rats. After administration, MT2 is transformed into oxidative metabolites in the liver. To achieve a high blood concentration of MT2, it should be administered intravenously. These findings would serve as a reference for further MT2-based pharmacological study and drug development.

Challenge for the detection of microplastics in the environment.

As an emerging contaminant in the environment, microplastics have attracted worldwide attention. Although research methods on microplastics in the environment have been reported extensively, the data on microplastics obtained cannot be comparable due to different methods. In this work, we critically reviewed the analytical methods of microplastics, including sample collection, separation, identification, and quantification. Manta trawl and tweezers or cassette corers are used to collect water samples and sediments, respectively. For biota sample, internal organs need to be dissected and separated to obtain microplastics. Density differences are often used to separate microplastics from the sample matrix. Visual classification is one of the most common methods for identifying microplastics, and it can be better detected by combining it with other instruments. However, they are not suitable for detection nanoplastics, which may lead to underestimation of risk. The abundance of microplastics varies with the detection method. Thus, the analytical methods for microplastics need to be standardized as soon as possible. Meanwhile, new methods for analyzing nanoplastics are urgently needed. PRACTITIONER POINTS: Sampling, separation, identification, and quantification are important procedures. The sampling and separation methods for microplastics need to be standardized. The organic matter can be removed by digestion to facilitate identification. Combine microscope with analytical instruments to better identify microplastics. There is still a challenge to quantification of smaller-sized plastic particles.