Lipid-Sorting Specificity Encoded in K-Ras Membrane Anchor Regulates Signal Output.

K-Ras is targeted to the plasma membrane by a C-terminal membrane anchor that comprises a farnesyl-cysteine-methyl-ester and a polybasic domain. We used quantitative spatial imaging and atomistic molecular dynamics simulations to examine molecular details of K-Ras plasma membrane binding. We found that the K-Ras anchor binds selected plasma membrane anionic lipids with defined head groups and lipid side chains. The precise amino acid sequence and prenyl group define a combinatorial code for lipid binding that extends beyond simple electrostatics; within this code lysine and arginine residues are non-equivalent and prenyl chain length modifies nascent polybasic domain lipid preferences. The code is realized by distinct dynamic tertiary structures of the anchor on the plasma membrane that govern amino acid side-chain-lipid interactions. An important consequence of this specificity is the ability of such anchors when aggregated to sort subsets of phospholipids into nanoclusters with defined lipid compositions that determine K-Ras signaling output.

Removal of Cd from solution and in-situ remediation of Cd-contaminated soil by a mercapto-modified cellulose/bentonite intercalated nanocomposite.

A novel intercalated nanocomposite of mercapto-modified cellulose/bentonite (LCS-BE-SH) was synthesized by high-speed shearing method in one step at room temperature, and was applied to remove Cd from solution and remediate Cd-contaminated soil. Results revealed that cellulose long-chain molecules have intercalated into bentonite nanolayers and interlayer spacing was increased to 1.411 nm, and grafting -SH groups improved adsorption selectivity, which enabled LCS-BE-SH to have distinct capability of Cd adsorption (qmax = 147.21 mg/g). Kinetic and thermodynamics showed that Cd adsorption onto LCS-BE-SH was well fitted by pseudo-second-order and Langmuir adsorption isotherm. Characterizations of the adsorbents revealed that synergistic effect of complexation (e.g., CdS, CdO) and precipitation (e.g., Cd(OH)2, CdCO3) mechanism played a major role in Cd removal. In soil remediation, application of LCS-BE-SH was most effective (67.31 %) in Cd immobilization compared to the control (8.85 %), which reduced exchangeable Cd from 37.03 % to 11.44 %. Meanwhile, soil pH, soil organic matter, available phosphorus, and enzyme activities (catalase, urease, and dehydrogenase) were improved LCS-BE-SH treatment. The main immobilization mechanism in soil included complexation (e.g., CdS, CdO) and precipitation (e.g., Cd(OH)2, Cd-Fe-hydroxide). Overall, this work applied a promising approach for Cd removal in aqueous and Cd remediation in soil by using an effective eco-friendly LCS-BE-SH nanocomposites.

Landfill leachate treatment by graphite engineered anaerobic membrane bioreactor: Performance enhancement and membrane fouling mitigation.

Low efficiency of anaerobic digestion and membrane fouling, treating landfill leachate, are big barriers in the application of anaerobic membrane bioreactor (AnMBR). Anaerobic digestion enhancement and membrane fouling mitigation of AnMBR with graphite addition, treating landfill leachate, were investigated in this study. The effect of graphite on organics removal, biogas production, methane content in biogas, membrane fouling, microbial responses and foulant compositions were analyzed. With the graphite addition, chemical oxygen demand (COD) removal of 78% was achieved for influent COD concentration of 3000 mg/l, which was significantly higher than the stage without graphite addition (65%) for influent COD concentration of 2000 mg/l. Similarly, methane content in biogas with graphite addition was 56%, while without graphite addition it was 46%. These digestion improvements were due to the promotion of organics degradation, facilitated by direct interspecies electron transfer (DIET) mechanism via graphite addition in AnMBR. The graphite addition prolonged membrane cleaning cycle from 13 days to 30 days. Protein content in loosely bound extracellular polymeric substance (LB-EPS) was the main fouling agent, which decreased with the graphite addition. The main mechanism behind membrane fouling mitigation was the protein content reduction in LB-EPS, which was biodegraded by Trichococcus being increased in relative abundance with the graphite addition. Furthermore, abundance of Denitratisoma decreased in anaerobic sludge and its accumulation reduced on membrane surface, subsequently membrane fouling was mitigated. Overall, graphite addition in AnMBR is a potential eco-innovative approach that efficiently removes pollutants from landfill leachate, enhances biogas quality and mitigates membrane fouling.

Eco-Corona vs Protein Corona: Effects of Humic Substances on Corona Formation and Nanoplastic Particle Toxicity in Daphnia magna.

Despite many studies on the toxicity of nanoplastic particles (NPPs) to aquatic invertebrates, the effects of ecological constituents such as humic substances (HSs) are often neglected. In our study, Daphnia magna was used to evaluate the effects of three HSs, natural organic matter (NOM), fulvic acid (FA), and humic acid (HA), on NPP toxicity and corona formation. Acute toxicities of NPPs were reduced by all HSs at environmentally relevant concentrations. NPPs elicited the upregulation of all genes related to detoxification, oxidative stress, and endocrine activity after 7 days of exposure. The presence of NOM or HA resulted in the mitigation of gene expression, whereas significantly higher upregulation of all of the genes was observed with FA. The presence of FA led to increased protein adsorption on NPPs in D. magna culture medium (eco-corona, EC) and homogenates (protein corona, PC), while there was less adsorption in the presence of HA. The highly abundant proteins identified in EC are involved in immune defense, cell maintenance, and antipredator response, while those in PC are responsible for lipid transport, antioxidant effects, and estrogen mediation. Our findings revealed the key influence of HSs on the toxicity of NPPs and provide an analytical and conceptual foundation for future study.

New ingol-type diterpenes from the latex of Euphorbia resinifera.

Two new ingol-type diterpenes, euphoresins A-B (1-2), have been isolated from the methanol extract of Euphorbium, the latex of Euphorbia resinifera Berg. Their structures were established on the basis of extensive analyses of their HR-ESI-MS, IR, UV, 1D, and 2D NMR spectra. The absolute configurations were confirmed by Mosher's method and circular dichroism (CD) analyses. The two compounds were tested for their cytotoxic activities against MCF-7, U937, and C6 cancer cell lines, but they both exhibited little cytotoxic effect.

Spectrum of Enterovirus Serotypes Causing Uncomplicated Hand, Foot, and Mouth Disease and Enteroviral Diagnostic Yield of Different Clinical Samples.

Background: Hand, foot, and mouth disease (HFMD) represents a substantial disease burden in the Western Pacific region. We investigated the spectrum of causative enteroviruses of HFMD, and evaluated different clinical samples' diagnostic yield for enteroviruses. Methods: We enrolled pediatric patients hospitalized for HFMD among 6 hospitals in Anhua County, Hunan Province, China between October 2013 and September 2016. Throat swabs and stool samples (or rectal swabs) were collected to detect the enterovirus serotypes by real-time reverse-transcription polymerase chain reaction (PCR) or nested PCR. Results: Among the 2836 patients, only 1 developed severe illness. Seventeen serotypes were identified in 2401 patients (85%), with the most frequently detected being CV-A16 (29% [814]), CV-A6 (28% [784]), EV-A71 (17% [491]), CV-A10 (4% [114]), and CV-A4 (2% [53]). Children were younger in CV-A6, CV-A10, and CV-A4 infections (median, 12 months; interquartile range [IQR], 12-24 months) than EV-A71 and CV-A16 infections (median, 24 months; IQR, 12-36 months; P < .05). The predominant enterovirus serotype shifted between CV-A16 and CV-A6 during the 3 years. Stool had a higher diagnostic yield (89%) than rectal (77%) and throat swabs (74%). Detection rates reached 93% when testing stools followed by throat swabs if stools were negative, and 89% when testing rectal swabs followed by throat swabs if rectal swabs were negative. Conclusions: Our results provide a virological benchmark for future surveillance and diagnostics. Continuous comprehensive virological surveillance is essential, especially after implementation of the EV-A71 vaccine in China, to monitor serotype replacement and the vaccine's impact.

Egalitarianism in Biofilms.

Microbial biofilms are multicellular communities of sessile microorganisms encased by the hydrated polymeric matrix. They have significant influences on both aquatic/terrestrial ecosystem and anthropogenic activities. Taking advantage of the governing features of selective stress (Tan and Ng in Water Res 42:1122-1132, 2008; Wei in Water Res 45:863-871, 2011; Dereli in Water Res 59C:11-22, 2014), the evenness of microbial communities in a membrane-centered mesocosm was successfully manipulated. By measuring the biofilm growing rates under different evenness levels of communities, an evenly distributed community favors the formation of biofilms was observed. This finding is not only a new evidence linking biofilm diversity to its functionality but also a clear suggestion on controlling a biofilm-based process via a simple and smart way.

[Triterpenoids from Uygur medicine latex of Euphorbia resinifera].

Ten triterpenes compounds were isolated from the methanol extraction of the latex of Euphorbia resinifera by means of various chromatographic methods such as silica gel, ODS and semi-preparative HPLC, Their structures were identified by spectroscopic methods and physicochemical properties. These isolated compounds were identified as 3ß-hydroxy-25,26,27-trinor eupha-8-ene-24-oate (1), iso-maticadienediol (2), 25,26,27-trinorTirucall-8-ene-3ß-ol-4-acid (3), dammarendiol Ⅱ (4), eupha-8,24-diene-3-ol-26-al (5), lnonotusane C (6), eupha-8,24-diene-3ß-ol-7,11-dione (7), inoterpene A (8), inoterpene B (9), and eupha-24-methylene-8-ene-3ß-ol-7,11-dione (10). Among them, compound 1 was a new natural product, compounds 2-4 were firstly isolated from the Euphorbiaceae and compounds 5 and 6 were isolated from the genus Euphorbia for the first time. The cytotoxicity of the compounds 1-10 against MCF-7, U937 and C6 cancer cell lines was evaluated, but none of the compounds was active.

Semipermeable Functional DNA-Encapsulated Nanocapsules as Protective Bioreactors for Biosensing in Living Cells.

The development of functional DNA-based nanosensors in living cells has experienced some design challenges, including, for example, poor cellular uptake, rapid nuclease degradation, and high false positives. Herein, we designed selectively permeable poly(methacrylic acid) (PMA) nanocapsules to encapsulate functional DNAs for metal ions and small-molecules sensing in living cells. Since functional DNAs are concentrated in the nanocapsules, an increasing reaction rate is obtained in vitro. During endocytosis, polymeric capsules simultaneously improve cellular uptake of functional DNAs and preserve their structural integrity inside the confined capsule space. More importantly, selective shell permeability allows for the free diffusion of small molecular targets through capsule shells but limits the diffusion of large biomolecules, such as nuclease and nonspecific protein. Compared to the free DNAzyme, PMA nanocapsules could reduce false positives and enhance detection accuracy. Furthermore, PMA nanocapsules are biocompatible and biodegradable. Through the controllability of wall thickness, permeability, and size distribution, these nanocapsules could be expanded easily to other targets, such as microRNAs, small peptides, and metabolites. These nanocapsules will pave the way for in situ monitoring of various biological processes in living cells and in vivo.

Poly(N-phenylglycine)-Based Nanoparticles as Highly Effective and Targeted Near-Infrared Photothermal Therapy/Photodynamic Therapeutic Agents for Malignant Melanoma.

Malignant melanoma is a highly aggressive tumor resistant to chemotherapy. Therefore, the development of new highly effective therapeutic agents for the treatment of malignant melanoma is highly desirable. In this study, a new class of polymeric photothermal agents based on poly(N-phenylglycine) (PNPG) suitable for use in near-infrared (NIR) phototherapy of malignant melanoma is designed and developed. PNPG is obtained via polymerization of N-phenylglycine (NPG). Carboxylate functionality of NPG allows building multifunctional systems using covalent bonding. This approach avoids complicated issues typically associated with preparation of polymeric photothermal agents. Moreover, PNPG skeleton exhibits pH-responsive NIR absorption and an ability to generate reactive oxygen species, which makes its derivatives attractive photothermal therapy (PTT)/photodynamic therapy (PDT) dual-modal agents with pH-responsive features. PNPG is modified using hyaluronic acid (HA) and polyethylene glycol diamine (PEG-diamine) acting as the coupling agent. The resultant HA-modified PNPG (PNPG-PEG-HA) shows negligible cytotoxicity and effectively targets CD44-overexpressing cancer cells. Furthermore, the results of in vitro and in vivo experiments reveal that PNPG-PEG-HA selectively kills B16 cells and suppresses malignant melanoma tumor growth upon exposure to NIR light (808 nm), indicating that PNPG-PEG-HA can serve as a very promising nanoplatform for targeted dual-modality PTT/PDT of melanoma.

High resolution fluorescence bio-imaging upconversion nanoparticles in insects.

Imaging fluorescent markers with brightness, photostability, and continuous emission with auto fluorescence background suppression in biological samples has always been challenging due to limitations of available and economical techniques. Here we report a new approach, to achieve high contrast imaging inside small and difficult biological systems with special geometry such as fire ants, an important agricultural pest, using a homemade cost-effective optical system. Unlike the commonly used rare-earth doped fluoride nanoparticles, we utilized nanoparticles with a high upconversion efficiency in water. Specifically Y2O3:Er+3,Yb+3 nanoparticles (40-50 nm diameter) were fed to fire ants as food and then a simple illuminating experiment was conducted at 980 nm wavelength at relatively low pump intensity8 kW.cm-2. The locations were further confirmed by X-ray tomography, where most particles aggregated inside the ant's mouth. High resolution, fast, and economical optical imaging system opens the door for studying more complex biological systems.

Attomolar detection of proteins via cascade strand-displacement amplification and polystyrene nanoparticle enhancement in fluorescence polarization aptasensors.

Extremely sensitive and accurate measurements of protein markers for early detection and monitoring of diseases pose a formidable challenge. Herein, we develop a new type of amplified fluorescence polarization (FP) aptasensor based on allostery-triggered cascade strand-displacement amplification (CSDA) and polystyrene nanoparticle (PS NP) enhancement for ultrasensitive detection of proteins. The assay system consists of a fluorescent dye-labeled aptamer hairpin probe and a PS NP-modified DNA duplex (assistant DNA/trigger DNA duplex) probe with a single-stranded part and DNA polymerase. Two probes coexist stably in the absence of target, and the dye exhibits relatively low FP background. Upon recognition and binding with a target protein, the stem of the aptamer hairpin probe is opened, after which the opened hairpin probe hybridizes with the single-stranded part in the PS NP-modified DNA duplex probe and triggers the CSDA reaction through the polymerase-catalyzed recycling of both target protein and trigger DNA. Throughout this CSDA process, numerous massive dyes are assembled onto PS NPs, which results in a substantial FP increase that provides a readout signal for the amplified sensing process. Our newly proposed amplified FP aptasensor enables the quantitative measurement of proteins with the detection limit in attomolar range, which is about 6 orders of magnitude lower than that of traditional homogeneous aptasensors. Moreover, this sensing method also exhibits high specificity for target proteins and can be performed in homogeneous solutions. In addition, the suitability of this method for the quantification of target protein in biological samples has also been shown. Considering these distinct advantages, the proposed sensing method can be expected to provide an ultrasensitive platform for the analysis of various types of target molecules.

Highly Stable, Protein-Resistant Surfaces via the Layer-by-Layer Assembly of Poly(sulfobetaine methacrylate) and Tannic Acid.

Zwitterionic materials have received great attention because of the non-fouling property. As a result of the electric neutrality of zwitterionic polymers, their layer-by-layer (LBL) assembly is generally conducted under specific conditions, such as very low pH values or ionic strength. The formed multilayers are unstable at high pH or in a high ionic strength environment. Therefore, the formation of highly stable multilayers of zwitterionic polymers via the LBL assembly process is still challenging. Here, we report the LBL assembly of poly(sulfobetaine methacrylate) (PSBMA) with a polyphenol, tannic acid (TA), for protein-resistant surfaces. The assembly process was monitored by a quartz crystal microbalance (QCM) and variable-angle spectroscopic ellipsometry (VASE), which confirms the formation of thin multilayer films. We found that the (TA/PSBMA)n multilayers are stable over a wide pH range of 4-10 and in saline, such as 1 M NaCl or urea solution. The surface morphology and chemical composition were characterized by specular reflectance Fourier transform infrared spectroscopy (FTIR/SR), X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). Furthermore, (TA/PSBMA)n multilayers show high hydrophilicity, with a water contact angle lower than 15°. A QCM was used to record the dynamic protein adsorption process. Adsorption amounts of bovine serum albumin (BSA), lysozyme (Lys), and hemoglobin (Hgb) on (TA/PSBMA)20 multilayers decreased to 0.42, 52.9, and 37.9 ng/cm(2) from 328, 357, and 509 ng/cm(2) on a bare gold chip surface, respectively. In addition, the protein-resistance property depends upon the outmost layer. This work provides new insights into the LBL assembly of zwitterionic polymers.

Bile acids modulate signaling by functional perturbation of plasma membrane domains.

Eukaryotic cell membranes are organized into functional lipid and protein domains, the most widely studied being membrane rafts. Although rafts have been associated with numerous plasma membrane functions, the mechanisms by which these domains themselves are regulated remain undefined. Bile acids (BAs), whose primary function is the solubilization of dietary lipids for digestion and absorption, can affect cells by interacting directly with membranes. To investigate whether these interactions affected domain organization in biological membranes, we assayed the effects of BAs on biomimetic synthetic liposomes, isolated plasma membranes, and live cells. At cytotoxic concentrations, BAs dissolved synthetic and cell-derived membranes and disrupted live cell plasma membranes, implicating plasma membrane damage as the mechanism for BA cellular toxicity. At subtoxic concentrations, BAs dramatically stabilized domain separation in Giant Plasma Membrane Vesicles without affecting protein partitioning between coexisting domains. Domain stabilization was the result of BA binding to and disordering the nonraft domain, thus promoting separation by enhancing domain immiscibility. Consistent with the physical changes observed in synthetic and isolated biological membranes, BAs reorganized intact cell membranes, as evaluated by the spatial distribution of membrane-anchored Ras isoforms. Nanoclustering of K-Ras, related to nonraft membrane domains, was enhanced in intact plasma membranes, whereas the organization of H-Ras was unaffected. BA-induced changes in Ras lateral segregation potentiated EGF-induced signaling through MAPK, confirming the ability of BAs to influence cell signal transduction by altering the physical properties of the plasma membrane. These observations suggest general, membrane-mediated mechanisms by which biological amphiphiles can produce their cellular effects.

[Yimusake Tablet: safe and efficacious for premature ejaculation].

OBJECTIVE: To objectively evaluate the efficacy and safety of Yimusake Tablet in the treatment of premature ejaculation (PE) through a multi-centered large-sample trial. METHODS: We conducted a multi-centered, open, fixed-dose, and self-compared clinical trial among 300 patients with diagnosed PE. The trial lasted 12 weeks, including 4 weeks without any medication and 8 weeks of treatment with Yimusake Tablet, 2 pills (1 g) per night. We observed the intravaginal ejaculation latency time (IELT) before and after treatment, evaluated the safety of medication, and performed a questionnaire investigation on the patients' satisfaction. RESULTS: Of the 300 PE patients, 288 accomplished the clinical trial. The patients ranged in age from 22 to 60 years, averaging at 31.6 years. The mean IELT of the patient was 62.5 seconds at baseline, 168.9 seconds after 4 weeks of treatment with Yimusake Tablet, and 222.2 seconds after 8 weeks of medication. Among the 157 patients with normal erectile function (IIEF >21), the mean IELT was 71.4 seconds before treatment, 147.4 seconds after 4 weeks of medication, and 172.5 seconds after 8 weeks of medication. The patients' satisfaction was significantly increased after treatment. Those complicated by mild to moderate erectile dysfunction achieved different degrees of improvement in the IIEF-5 score, with a mean increase of 3.8. Only a few patients experienced mild adverse events, including constipation, dry mouth, nose bleeding, abdominal pain, and lumbosacral pain, which were all relieved without drug withdrawal. CONCLUSION: Yimusake Tablet is a safe and effective medicine for the treatment of PE.

Pharmacokinetic and safety profiles of mesalazine enema in healthy Chinese subjects: A single- and multiple-dose study.

Mesalazine is a well-established treatment for ulcerative colitis by oral or topical administration. However, the pharmacokinetic (PK) and safety profiles of mesalazine administered by an enema has not been clarified in Chinese population. We conducted an open-label study to assess the PK and safety profiles of mesalazine in 11 healthy Chinese subjects after receiving mesalazine enema (1 g/100 mL) once daily for 7 consecutive days. Blood and urine samples were collected for assay of mesalazine and N-acetyl mesalazine by liquid chromatography-tandem mass spectrometry. The PK and safety data were summarized using descriptive statistics. The mean (standard deviation) maximum plasma concentration (Cmax), area under plasma drug concentration-time curve from time 0 to the last measurable plasma concentration time point (AUC0-t) and elimination half-life (t1/2) of mesalazine were 1007.64 (369.00) ng/mL, 9608.59 (3533.08) h·ng/mL and 3.33 (1.99) h, respectively after the first dose administration. In multiple-dose study, the estimated accumulation factor of mesalazine was 1.09. The cumulative urinary excretion rate of parent and major metabolite of mesalazine was 27.77%. After the last doe administration, 2.21% of the administered dose was excreted as mesalazine and 24.47% as N-acetyl mesalazine in urine within 24 h. Overall, 9 adverse events (AEs) were reported in 4 of the 11 subjects (36.4%), including oral ulcer, toothache, upper respiratory tract infection (1 each) and laboratory abnormalities (6 cases). All AEs were mild and recovered spontaneously without treatment, and were not considered as related to mesalazine. Mesalazine enema (1 g/100 mL) was safe and well tolerated in healthy Chinese subjects. These findings support further clinical trials in Chinese patients. Trial registration: This trial was registered to Chinese Clinical Trial Registry (ChiCTR) at https://www.chictr.org.cn (registration number: ChiCTR2300073148).

Mainstream deammonification at ambient temperature treating real sewage by a plug-flow fixed-bed reactor based on zeolite/tourmaline-modified polyurethane carriers.

A plug-flow fixed-bed reactor (PFBR) with zeolite/tourmaline-modified polyurethane (ZTP) carriers (PFBRZTP) was constructed to realize mainstream deammonification for real domestic sewage treatment. The PFBRZTP and PFBR were operated for 111 days treating aerobically pretreated sewage in parallel. A higher nitrogen removal rate of 0.12 kg N·(m3·d)-1 was achieved in PFBRZTP despite lowering the temperature (16.8-19.7 °C) and fluctuating water quality. Meanwhile, it was indicated that anaerobic ammonium oxidation dominated (64.0 ± 13.2%) in PFBRZTP, by nitrogen removal pathway analysis and high anaerobic ammonium-oxidizing bacteria (AnAOB) activity (2.89 mg N·(g VSS·h)-1). And, the lower protein/polysaccharides (PS) ratio further indicated a better biofilm structure in PFBRZTP owing to a higher abundance of microorganisms relevant to PS and cryoprotective EPS secretion. Furthermore, partial denitrification was an important nitrite supply process in PFBRZTP based on low AOB activity/AnAOB activity ratio, higher Thauera abundance and a remarkably positive correlation between Thauera abundance and AnAOB activity.

In-situ membrane fouling control and performance improvement by adding materials in anaerobic membrane bioreactor: A review.

Anaerobic membrane bioreactor (AnMBR) is a promising treatment technique for various types of wastewaters, and is preferred over other conventional aerobic and anaerobic methods. However, membrane fouling is considered a bottleneck in AnMBR system, which technically blocks membrane pores by numerous inorganics, organics, and other microbial substances. Various materials can be added in AnMBR to control membrane fouling and improve anaerobic digestion, and studies reporting the materials addition for this purpose are hereby systematically reviewed. The mechanism of membrane fouling control including compositional changes in extracellular polymeric substances (EPSs) and soluble microbial products (SMPs), materials properties, stimulation of antifouling microbes and alteration in substrate properties by material addition are thoroughly discussed. Nonetheless, this study opens up new research prospects to control membrane fouling of AnMBR, engineered by material, including compositional changes of microbial products (EPS and SMP), replacement of quorum quenching (QQ) by materials, and overall improvement of reactor performance. Regardless of the great research progress achieved previously in membrane fouling control, there is still a long way to go for material-mediated AnMBR applications to be undertaken, particularly for materials coupling, real scale application and molecular based studies on EPSs and SMPs, which were proposed for future researches.

Developing a Ruthenium(III) Complex to Trigger Gasdermin E-Mediated Pyroptosis and an Immune Response Based on Decitabine and Liposomes: Targeting Inhibition of Gastric Tumor Growth and Metastasis.

To develop next-generation metal drugs with high efficiency and low toxicity for targeting inhibition of gastric tumor growth and metastasis, we not only optimized a series of ruthenium (Ru, III) 2-hydroxy-1-naphthaldehyde thiosemicarbazone complexes to obtain a Ru(III) complex (4b) with remarkable cytotoxicity in vitro but also constructed a 4b-decitabine (DCT)/liposome (Lip) delivery system (4b-DCT-Lip). The in vivo results showed that 4b-DCT-Lip not only had a stronger capacity to inhibit gastric tumor growth and metastasis than 4b-DCT but also addressed the co-delivery problems of 4b-DCT and improved their targeting ability. Furthermore, we confirmed the mechanism of 4b-DCT/4b-DCT-Lip inhibiting the growth and metastasis of a gastric tumor. DCT-upregulated gasdermin E (GSDME) was cleaved by 4b-activated caspase-3 to afford GSDME-N terminal and then was aggregated to form nonselective pores on the cell membrane of a gastric tumor, thereby inducing pyroptosis and a pyroptosis-induced immune response.

In Situ Polymerization of Aniline Derivative in Vivo for NIR-II Phototheranostics of Tumor.

Natural biopolymers can be controllably in situ synthesized in organisms and play important roles in biological activities. Inspired by this, the manipulation of in situ biosynthesis of functional polymers in vivo will be an important way to obtain materials for meeting biological requirements. Herein, in situ biosynthesis of functional conjugated polymer at the tumor site was achieved via the utilization of specific tumor microenvironment (TME) characteristics for the first time. Specially, a water-soluble aniline dimer derivative (N-(3-sulfopropyl) p-aminodiphenylamine, SPA) was artfully in situ polymerized into polySPA (PSPA) nanoparticles at the tumor site, which was activated via the catalysis of hydrogen peroxide (H2O2) overexpressed in TME to produce hydroxyl radical (•OH) by coinjected horseradish peroxidase (HRP). Benefiting from outstanding near-infrared (NIR)-II absorption of PSPA, the in situ polymerization process can be validly monitored by photoacoustic (PA) signal at the NIR-II region. Meanwhile, in situ polymerization would induce the size of polymeric materials from small to large, improving the distribution and retention of PSPA at the tumor site. On the combination of NIR-II absorption of PSPA and the size variation induced by polymerization, such polymerization can be applied for tumor-specific NIR-II light mediated PA image and photothermal inhibition of tumors, enhancing the precision and efficacy of tumor phototheranostics. Therefore, the present work opens the way to manipulate TME-activated in situ biosynthesis of functional conjugated polymer at the tumor site for overcoming formidable challenges in tumor theranostics.