Low-Fouling Gold Nanorod Theranostic Agents Enabled by a Sulfoxide Polymer Coating.

Gold nanorods (GNRs) are widely used in various biomedical applications such as disease imaging and therapy due to their unique plasmonic properties. To improve their bioavailability, GNRs often need to be coated with hydrophilic polymers so as to impart stealth properties. Poly(ethylene glycol) (PEG) has been long used as such a coating material for GNRs. However, there is increasing acknowledgement that the amphiphilic nature of PEG facilitates its interaction with protein molecules, leading to immune recognition and consequent side effects. This has motivated the search for new classes of low-fouling polymers with high hydrophilicity as alternative low-fouling surface coating materials for GNRs. Herein, we report the synthesis, characterization, and application of GNRs coated with highly hydrophilic sulfoxide-containing polymers. We investigated the effect of the sulfoxide polymer coating on the cellular uptake and in vivo circulation time of the GNRs and compared these properties with pegylated GNR counterparts. The photothermal effect and photoacoustic imaging of these polymer-coated GNRs were also explored, and the results show that these GNRs are promising as nanotheranostic particles for the treatment of cancer.

Efficient Removal of Perfluorinated Chemicals from Contaminated Water Sources Using Magnetic Fluorinated Polymer Sorbents.

Efficient removal of per- and polyfluoroalkyl substances (PFAS) from contaminated waters is urgently needed to safeguard public and environmental health. In this work, novel magnetic fluorinated polymer sorbents were designed to allow efficient capture of PFAS and fast magnetic recovery of the sorbed material. The new sorbent has superior PFAS removal efficiency compared with the commercially available activated carbon and ion-exchange resins. The removal of the ammonium salt of hexafluoropropylene oxide dimer acid (GenX) reaches >99 % within 30 s, and the estimated sorption capacity was 219 mg g-1 based on the Langmuir model. Robust and efficient regeneration of the magnetic polymer sorbent was confirmed by the repeated sorption and desorption of GenX over four cycles. The sorption of multiple PFAS in two real contaminated water matrices at an environmentally relevant concentration (1 ppb) shows >95 % removal for the majority of PFAS tested in this study.

Antifouling Surfaces Enabled by Surface Grafting of Highly Hydrophilic Sulfoxide Polymer Brushes.

Antifouling surfaces are important in a broad range of applications. An effective approach to antifouling surfaces is to covalently attach antifouling polymer brushes. This work reports the synthesis of a new class of antifouling polymer brushes based on highly hydrophilic sulfoxide polymers by surface-initiated photoinduced electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization. The sulfoxide polymer brushes are able to effectively reduce nonspecific adsorption of proteins and cells, demonstrating remarkable antifouling properties. Given the outstanding antifouling behavior of the sulfoxide polymers and versatility of surface-initiated PET-RAFT technology, this work presents a useful and general approach to engineering various material surfaces with antifouling properties, for potential biomedical applications in areas such as tissue engineering, medical implants, and regenerative medicine.

Isolation and Identification of Pseudomonas sp. Strain DY-1 from Agricultural Soil and Its Degradation Effect on Prometryne.

Prometryne is a widely used herbicide in China to control annual grasses and broadleaf weeds. However, the stability of prometryne makes it difficult to be degraded, which poses a threat to human health. This study presents a bacterial strain isolated from soil samples with a prometryne application history, designated strain DY-1. Strain DY-1, identified as Pseudomonas sp., is capable of utilizing prometryne as a sole carbon source for growth and degrading 100% of prometryne within 48 h from an initial concentration of 50 mg L-1. To further optimize the degradation of prometryne, the prometryne concentration, temperature, pH, and salt concentration were examined. The optimal conditions for degradation of prometryne by strain DY-1 were an initial prometryne concentration of 50 mg L-1, 30 °C, pH 7-8, and NaCl concentration of 200 mg L-1. The same strain also degraded other s-triazine herbicides, including simetryne, ametryne, desmetryne, and metribuzin, under the same conditions. The biodegradation pathway of prometryne was established by isolating sulfoxide prometryne as the first metabolite and by the identification of sulfone prometryne and 2-hydroxy prometryne by liquid chromatography-mass spectrometry (LC-MS/MS). The results illustrated that strain DY-1 achieved the removal of prometryne by gradually oxidizing and hydrolyzing the methylthio groups. A bioremediation trial with contaminated soil and pot experiments showed that after treating the prometryne-contaminated soil with strain DY-1, the content of prometryne was significantly reduced (P < 0.05). This study provides an efficient bacterial strain and approach that could be potentially useful for detoxification and bioremediation of prometryne analogs.

In situ surface-enhanced Raman scattering spectroscopy exploring molecular changes of drug-treated cancer cell nucleus.

Investigating the molecular changes of cancer cell nucleus with drugs treatment is crucial for the design of new anticancer drugs, the development of novel diagnostic strategies, and the advancement of cancer therapy efficiency. In order to better understand the action effects of drugs, accurate location and in situ acquisition of the molecular information of the cell nuclei are necessary. In this work, we report a microspectroscopic technique called dark-field and fluorescence coimaging assisted surface-enhanced Raman scattering (SERS) spectroscopy, combined with nuclear targeting nanoprobes, to in situ study Soma Gastric Cancer (SGC-7901) cell nuclei treated with two model drugs, e.g., DNA binder (Hoechst33342) and anticancer drug (doxorubicin, Dox) via spectral analysis at the molecular level. Nuclear targeting nanoprobes with an assembly structure of thiol-modified polyethylene glycol polymers (PEG) and nuclear localizing signal peptides (NLS) around gold nanorods (AuNRs) were prepared to achieve the amplified SERS signals of biomolecules in the cell nuclei. With the assistance of dark field/fluorescence imaging with simultaneous location, in situ SERS spectra in one cell nucleus were measured and analyzed to disclose the effects of Hoechst33342 and Dox on main biomolecules in the cell nuclei. The experimental results show that this method possesses great potential to investigate the targets of new anticancer drugs and the real-time monitoring of the dynamic changes of cells caused by exogenous molecules.

The improvement effects of Lentinus edodes powder marination on sous vide cooked chicken patties: Physicochemical attributes, oxidative properties and flavor characteristics.

The improvement effects of Lentinus edodes powder (LEP) marination with different concentrations (0, 6-14 %) on physicochemical, oxidative and flavor quality of chicken patties were evaluated. Greater pH, redness, yellowness, water holding capacity and their strong correlations were observed in LEP-marinated samples. Changed water distribution, inhibited lipid oxidation and enhanced protein oxidation occurred through LEP marination. The highest gel strength and resilience and the lowest hardness and chewiness were obtained in 10 % LEP-marinated sample. Meanwhile, taste activity values of amino acids and saltiness peaked and umami rose in this sample. 124 volatiles were detected and 16 compounds were simultaneously detected by gas chromatography-ion mobility spectrometry and gas chromatography-mass spectrometry. Hexanal, 1,2,4-trithiolane and 1-hexanol were considered as the key differential aroma-active compounds according to odor activity values and chemometric analysis. This study confirmed LEP as a prospective ingredient to improve the quality of meat products.

Decitabine priming increases anti-PD-1 antitumor efficacy by promoting CD8+ progenitor exhausted T cell expansion in tumor models.

CD8+ exhausted T cells (Tex) are heterogeneous. PD-1 inhibitors reinvigorate progenitor Tex, which subsequently differentiate into irresponsive terminal Tex. The ability to maintain a capacity for durable proliferation of progenitor Tex is important, but the mechanism remains unclear. Here, we showed CD8+ progenitor Tex pretreated with decitabine, a low-dose DNA demethylating agent, had enhanced proliferation and effector function against tumors after anti-PD-1 treatment in vitro. Treatment with decitabine plus anti-PD-1 promoted the activation and expansion of tumor-infiltrated CD8+ progenitor Tex and efficiently suppressed tumor growth in multiple tumor models. Transcriptional and epigenetic profiling of tumor-infiltrated T cells demonstrated that the combination of decitabine plus anti-PD-1 markedly elevated the clonal expansion and cytolytic activity of progenitor Tex compared with anti-PD-1 monotherapy and restrained CD8+ T cell terminal differentiation. Strikingly, decitabine plus anti-PD-1 sustained the expression and activity of the AP-1 transcription factor JunD, which was reduced following PD-1 blockade therapy. Downregulation of JunD repressed T cell proliferation, and activation of JNK/AP-1 signaling in CD8+ T cells enhanced the antitumor capacity of PD-1 inhibitors. Together, epigenetic agents remodel CD8+ progenitor Tex populations and improve responsiveness to anti-PD-1 therapy.

CRTAC1 enhances the chemosensitivity of non-small cell lung cancer to cisplatin by eliciting RyR-mediated calcium release and inhibiting Akt1 expression.

Sensitivity to platinum-based combination chemotherapy is associated with a favorable prognosis in patients with non-small cell lung cancer (NSCLC). Here, our results obtained from analyses of the Gene Expression Omnibus database of NSCLC patients showed that cartilage acidic protein 1 (CRTAC1) plays a role in the response to platinum-based chemotherapy. Overexpression of CRTAC1 increased sensitivity to cisplatin in vitro, whereas knockdown of CRTAC1 decreased chemosensitivity of NSCLC cells. In vivo mouse experiments showed that CRTAC1 overexpression increased the antitumor effects of cisplatin. CRTAC1 overexpression promoted NFAT transcriptional activation by increasing intracellular Ca2+ levels, thereby inducing its regulated STUB1 mRNA transcription and protein expression, accelerating Akt1 protein degradation and, in turn, enhancing cisplatin-induced apoptosis. Taken together, the present results indicate that CRTAC1 overexpression increases the chemosensitivity of NSCLC to cisplatin treatment by inducing Ca2+-dependent Akt1 degradation and apoptosis, suggesting the potential of CRTAC1 as a biomarker for predicting cisplatin chemosensitivity. Our results further reveal that modulating the expression of CRTAC1 could be a new strategy for increasing the efficacy of cisplatin in chemotherapy of NSCLC patients.

Fluoropolymer-MOF Hybrids with Switchable Hydrophilicity for 19F MRI-Monitored Cancer Therapy.

Cancer theranostics that combines cancer diagnosis and therapy is a promising approach for personalized cancer treatment. However, current theranostic strategies suffer from low imaging sensitivity for visualization and an inability to target the diseased tissue site with high specificity, thus hindering their translation to the clinic. In this study, we have developed a tumor microenvironment-responsive hybrid theranostic agent by grafting water-soluble, low-fouling fluoropolymers to pH-responsive zeolitic imidazolate framework-8 (ZIF-8) nanoparticles by surface-initiated RAFT polymerization. The conjugation of the fluoropolymers to ZIF-8 nanoparticles not only allows sensitive in vivo visualization of the nanoparticles by 19F MRI but also significantly prolongs their circulation time in the bloodstream, resulting in improved delivery efficiency to tumor tissue. The ZIF-8-fluoropolymer nanoparticles can respond to the acidic tumor microenvironment, leading to progressive degradation of the nanoparticles and release of zinc ions as well as encapsulated anticancer drugs. The zinc ions released from the ZIF-8 can further coordinate to the fluoropolymers to switch the hydrophilicity and reverse the surface charge of the nanoparticles. This transition in hydrophilicity and surface charge of the polymeric coating can reduce the "stealth-like" nature of the agent and enhance specific uptake by cancer cells. Hence, these hybrid nanoparticles represent intelligent theranostics with highly sensitive imaging capability, significantly prolonged blood circulation time, greatly improved accumulation within the tumor tissue, and enhanced anticancer therapeutic efficiency.

Antifouling and Antibacterial Surfaces Grafted with Sulfur-Containing Copolymers.

Antifouling and antibacterial surfaces that can prevent nonspecific biological adhesion are important to support a myriad of biomedical applications. In this study, we have used an innovative photopolymerization technology to develop sulfur-containing polymer-grafted antifouling and antibacterial surfaces. The relationship between the hydrophilic property and the capability to resist protein and macrophage adsorption of the surface copolymer brushes was investigated. The sulfide monomer incorporated into the surface copolymer brushes can be further ionized to carry positive charges and impart antibacterial activity, leading to surfaces with dual antifouling and antibacterial functions. We believe that the reported sulfur-containing polymer brushes can be considered an emerging and important polymer for antifouling and antibacterial applications.

Lnc00892 competes with c-Jun to block NCL transcription, reducing the stability of RhoA/RhoC mRNA and impairing bladder cancer invasion.

Metastasis of bladder cancer is a complex process and has been associated with poor clinical outcomes. However, the mechanisms of bladder cancer metastasis remain largely unknown. The present study found that the long noncoding RNA lnc00892 was significantly downregulated in bladder cancer tissues, with low lnc00892 expression associated with poor prognosis of bladder cancer patients. Lnc00892 significantly inhibited the migration, invasion, and metastasis of bladder cancer cells in vitro and in vivo. In-depth analysis showed that RhoA/C acted downstream of lnc00892 to inhibit bladder cancer metastasis. Mechanistically, lnc00892 reduces nucleolin gene transcription by competitively binding the promoter of nucleolin with c-Jun, thereby inhibiting nucleolin-mediated stabilization of RhoA/RhoC mRNA. Taken together, these findings provide novel insights into understanding the mechanisms of bladder cancer metastasis and suggest that lnc00892 can serve as a potential therapeutic target in patients with invasive bladder cancer.

Downregulation of microRNA-6125 promotes colorectal cancer growth through YTHDF2-dependent recognition of N6-methyladenosine-modified GSK3ß.

BACKGROUND: MicroRNAs (miRNAs), the key regulator of gene expression, and N6-methyladenosine (m6A) RNA modification play a significant role in tumour progression. However, regulation of m6A-modified mRNAs by miRNAs in colorectal cancer (CRC), and its effect on progression of CRC, remains to be investigated. METHODS: Expression of miR-6125 and YTH Domain-Containing Family Protein 2 (YTHDF2) was detected by western blotting and immunohistochemistry. The effects of miR-6125 and YTHDF2 on proliferative capacity of CRC cells were analysed using soft agar, ATP, CCK8 and EdU assays, and in animal experiments. RESULTS: MiR-6125 expression was downregulated markedly in CRC, and expression correlated negatively with tumour size and prognosis. MiR-6125 targeted the 3'-UTR of YTHDF2 and downregulated the YTHDF2 protein, thereby increasing the stability of m6A-modified glycogen synthase kinase 3 beta (GSK3ß) mRNA. Increased GSK3ß protein levels inhibited the expression of Wnt/ß-catenin/Cyclin D1 pathway-related proteins, leading to G0-G1 phase arrest and ultimately inhibiting the proliferation of CRC cells. CONCLUSIONS: MiR-6125 regulates YTHDF2 and thus plays a critical role in regulating the Wnt/ß-catenin pathway, thereby affecting the growth of CRC. Collectively, these results suggest that miR-6125 and YTHDF2 are potential targets for treatment of CRC.

uc.77- Downregulation Promotes Colorectal Cancer Cell Proliferation by Inhibiting FBXW8-Mediated CDK4 Protein Degradation.

Transcribed ultraconserved regions (T-UCRs) are a new type of long non-coding RNA, and the UCR has 481 segments longer than 200 base pairs that are 100% conserved between humans, rats, and mice. T-UCRs involved in colorectal cancer (CRC) have not been studied in detail. We performed T-UCR microarray analysis and found that uc.77- was significantly downregulated in CRC tissues and cell lines. Ectopic expression of uc.77- significantly inhibited the proliferation of CRC cells in vitro and the growth of xenograft tumors in nude mice in vivo. Mechanistic studies showed that uc.77- competed with FBXW8 mRNA for binding to microRNA (miR)-4676-5p through a competing endogenous RNA mechanism and inhibited the proliferation of CRC cells by negatively regulating CDK4. The present findings highlight the role of the uc.77-/miR-4676-5p/FBXW8 axis in CRC and identify uc.77- as a potential novel target for the treatment of CRC.

Physiological response in the leaf and stolon of white clover under acid precipitation and freeze-thaw stress.

Freeze-thaw (FT) in northern China is a common event in spring and autumn, and the release of sulfur dioxide from coal-burning in winter is apt to trigger acid precipitation. Both these stresses can aggravate the wintering ability of white clover (Trifolium repens L.). Acid precipitation and FT simulation experiments were carried out in the field and an indoor alternation refrigerator, respectively. The contents of soluble protein, soluble sugar, malondialdehyde (MDA), proline and antioxidant activity were tested under acid precipitation and FT stress. The results showed that under acid precipitation stress, the content of MDA, peroxidase and superoxide dismutase increased in both leaves and stolons, whereas soluble protein and soluble sugar content declined compared with the control groups. During the freezing period, the content of antioxidant enzyme activity, soluble protein and proline increased at first and then dropped, whereas MDA and soluble sugar content both increased. As a conclusion, the stolon of white clover is more sensitive than the leaf to short-term stress, either as the single FT stress or the combined stress of FT and acid precipitation, suggesting that maintaining more leaves can contribute to the resistance of white clover to these stresses.

Gold Nanotetrapods with Unique Topological Structure and Ultranarrow Plasmonic Band as Multifunctional Therapeutic Agents.

Owing to their excellent surface plasmonic properties, Au nanobranches have drawn increasing attention in various bioapplications, such as contrast agents for photoacoustic imaging, nanomedicines for photothermal therapy, and carriers for drug delivery. The monodispersity and plasmonic bandwidth of Au nanobranches are of great importance for the efficacy of those bioapplications. However, it is still a challenge to accurately synthesize size- and shape-controlled Au nanobranches. Here we report a facile seed-mediated growth method to synthesize monodisperse Au nanotetrapods (NTPs) with tunable and ultranarrow plasmonic bands. The NTPs have a novel D2d symmetry with four arms elongated in four ⟨110⟩ directions. The growth mechanism of NTPs relies on the delicate kinetic control of deposition and diffusion rates of adatoms. Upon laser irradiation, the PEGylated NTPs possess remarkable photothermal conversion efficiencies and photoacoustic imaging properties. The NTPs can be applied as a multifunctional theranostic agent for both photoacoustic imaging and image-guided photothermal therapy.

Synergistic Reducing Effect for Synthesis of Well-Defined Au Nanooctopods With Ultra-Narrow Plasmon Band Width and High Photothermal Conversion Efficiency.

Branched Au nanoparticles have attracted intense interest owing to their remarkable properties and a wide variety of potential applications in surface-enhanced Raman spectroscopy (SERS), photothermal therapy, photoacoustic imaging, and biomedicines. The morphology and spatial arrangement of branches play the most crucial role in the determination of their properties and applications. However, it is still a synthetic challenge to control the exact arm numbers of branches with specific spatial arrangements. Here we report a facile method for the kinetically controlled growth of Au nanooctopods (NOPs) with a high yield (81%), monodispersity, and reproducibility by using the synergistic reducing effect of ascorbic acid and 1-methylpyrrolidine. The NOPs have eight arms elongated along <111> directions with uniform arm lengths. Due to their well-defined size and shape, NOPs show ultra-narrow surface plasmon band width with a full width at half maximum of only 76 nm (0.20 eV). Upon irradiation with laser, the NOPs possessed excellent photothermal conversion efficiencies up to 83.0% and photoacoustic imaging properties. This work highlights the future prospects of using NOPs with desired physicochemical properties for biomedical applications.

A Dy4 single-molecule magnet and its Gd(iii), Tb(iii), Ho(iii), and Er(iii) analogues encapsulated by an 8-hydroxyquinoline Schiff base derivative and ß-diketonate coligand.

Five new tetranuclear complexes based on an 8-hydroxyquinoline Schiff base derivative and the ß-diketone coligand, [Ln4(acac)4L6(µ3-OH)2]·CH3CN·0.5CH2Cl2 (Ln = Gd (1), Tb (2), Dy (3), Ho (4) and Er (5); HL = 5-(benzylidene)amino-8-hydroxyquinoline; acac = acetylacetonate) have been synthesized, and structurally and magnetically characterized. Complexes 1-5 have similar tetranuclear structures. Each LnIII ion is eight coordinated and its coordination polyhedra can be described as being in a distorted square-antiprismatic geometry. The magnetic studies reveal that 1 features the magnetocaloric effect (MCE) with the magnetic entropy change of -ΔSm(T) = 25.08 J kg-1 K-1 at 2 K for ΔH = 7 T, and 3 displays the slow magnetic relaxation behavior of Single Molecule Magnets (SMMs) with the anisotropic barrier of 86.20 K and the pre-exponential factor τ0 = 2.99 × 10-8 s.

Chiral Plasmonic Nanochains via the Self-Assembly of Gold Nanorods and Helical Glutathione Oligomers Facilitated by Cetyltrimethylammonium Bromide Micelles.

Gold nanorods are excellent anisotropic building blocks for plasmonic chiral nanostructures. The near-infrared plasmonic band of nanorods makes them highly desirable for biomedical applications such as chiral bioimaging and sensing, in which a strong circular dichroism (CD) signal is required. Chiral assemblies of gold nanorods induced by self-associating peptides are especially attractive for this purpose as they exhibit plasmonic-enhanced chiroptical activity. Here, we showed that the presence of cetyltrimethylammonium bromide (CTAB) micelles in a gold nanorod solution promoted the self-association of l-/d-glutathione (GSH) and significantly enhanced the chirality of the resulting plasmonic nanochains. Chiroptical signals for the ensemble in the presence of CTAB micelles were 20 times greater than those obtained below the critical micelle concentration of CTAB. The strong optical activity was attributed to the formation of helical GSH oligomers in the hydrophobic core of the CTAB micelles. The helical GSH oligomers led the nanorods to assemble in a chiral, end-to-end crossed fashion. The CD signal intensities were also proportional to the fraction of nanorods in the nanochains. In addition, finite-difference time-domain simulations agreed well with the experimental extinction and CD spectra. Our work demonstrated a substantial effect from the CTAB micelles on gold nanoparticle assemblies induced by biomolecules and showed the importance of size matching between the inorganic nanobuilding blocks and the chiral molecular templates (i.e., the GSH oligomers in the present case) in order to attain strong chiroptical activities.

Modulation of the relaxation dynamics of linear-shaped tetranuclear rare-earth clusters through utilizing different solvents.

Nine new tetranuclear centrosymmetric linear complexes, [RE4(dbm)8L2(DMF)2]·nCH2Cl2·mC2H3N (RE = Y (1), Tb (2), Dy (3), Ho (4), Er (5), Lu (6)) and [RE4(dbm)8L2(C2H5OH)2]·nCH3CN (RE = Tb (7), Dy (8), Ho (9)) (HL = 2-[(2-(hydroxyimino)propanehydrazide)methyl]-8-hydroxyquinoline and dbm = 1,3-diphenyl-1,3-propanedione) have been synthesized. Complexes 1-9 are tetranuclear complexes. Magnetic studies reveal that both DyIII-based complexes (3 and 8) exhibit single-molecule magnet (SMM) behavior under a zero dc field. Furthermore, complex 3 presents one relaxation process under a zero dc field, while application of an external dc field (1500 Oe) induces multi-relaxation signals of the ac magnetic susceptibility.