PEGylation Can Effectively Strike a Balance in siRNA Delivery Performances of Guanidinylated Linear Synthetic Polypeptides with Potential Use for Transcriptional Gene Silencing.

The prevailing design philosophy for polymeric vectors delivering siRNA is rooted in the post-transcriptional gene silencing (PTGS) mechanism. Yet, the transcriptional gene silencing (TGS) mechanism offers a potentially more durable silencing effect, which necessitates efficient siRNA delivery into the nucleus. However, it remains a challenge for the polymeric vectors to efficiently deliver siRNA into the nucleus. We have explored guanidinylated cyclic synthetic polypeptides (GCSPs) to enhance the nuclear delivery of siRNA, but an increased cytotoxicity and difficulty in producing the GCSPs on a large scale limit their utility. Herein, we simply prepare PEGylated guanidinylated linear synthetic polypeptides (PGLSPs) exhibiting improved membrane penetration, direct siRNA transport to the nucleus, reduced toxicity, high cellular uptake, and mitigation of protein corona formation. The PEGylation can effectively balance the vector's nuclear delivery capacity with other critical aspects of performances for siRNA delivery. Therefore, the PGLSPs hold promise as TGS-based delivery vectors, offering potential for future therapeutic applications.

Density functional theory guide for copolymerization mechanism between allyl radical with radicalophile: photo-driven radical mediated [3 + 2] cyclization.

CONTEXT: The challenge of activating inert allyl monomers for polymerization has persisted, prompting our proposal of the photo-driven radical mediated [3 + 2] cyclization reaction (PRMC). This innovative approach significantly expedites the homopolymerization of multi-allyl monomers, enabling the synthesis of embolic microspheres for hepatocellular carcinoma interventions. PRMC involves allyl monomers to form allylic radicals and then radicals participating in a cycloaddition reaction with unsaturated olefins as radicalophiles to form cyclopentane-based radical products. While extensively studied in the theoretical and experimental homopolymerization, PRMC's application in copolymerization remains unexplored. To address this knowledge gap, we explored the elementary reaction, selecting allyl methyl ether radicals (AMER) and α,ß-unsaturated ketones as radicalophiles for copolymerization investigations by density functional theory (DFT) analysis. We quantified energy differences between ground and excited states of reactants, elucidated frontier molecular orbitals, and assessed thermodynamic data for copolymerization feasibility. We also evaluated the electronic properties of reactants, predicting the reactivity of radicalophiles and the interactions of intermolecular reactions. Additionally, we applied transition state theory and interaction/deformation models and conducted a local orbital analysis to comprehensively study excess electron distribution and gyration radius of cyclic radical product. Our findings offer vital insights into PRMC's potential in copolymerization. This research provides a robust theoretical foundation for practical application, enhancing the polymerization field. METHODS: Based on density functional theory (DFT), the calculations were performed at the M06-2X/6-311 + + G(d,p) level in/by Gaussian 16 package. Subsequently, our analytical results apply time-dependent density-functional theory (TD-DFT) and solvent modeling (SMD). Single-point energy calculations determine the driving force behind the radicals' reaction with radicalophiles. Furthermore, we assessed the electrostatic potential (ESP) of the reactants. The results of the calculations were visualized by the Multiwfn 3.6 and VMD 1.9 programs.

Study of andrographolide bioactivity against Pseudomonas aeruginosa based on computational methodology and biochemical analysis.

Andrographolide is one of the main biologically active molecules isolated from Andrographis paniculata (A. paniculata), which is a traditional Chinese herb used extensively throughout Eastern Asia, India, and China. Pseudomonas aeruginosa, often known as P. aeruginosa, is a common clinical opportunistic pathogen with remarkable adaptability to harsh settings and resistance to antibiotics. P. aeruginosa possesses a wide array of virulence traits, one of which is biofilm formation, which contributes to its pathogenicity. One of the main modulators of the P. aeruginosa-controlled intramembrane proteolysis pathway is AlgW, a membrane-bound periplasmic serine protease. In this work, we have used a set of density functional theory (DFT) calculations to understand the variety of chemical parameters in detail between andrographolide and levofloxacin, which show strong bactericidal activity against P. aeruginosa. Additionally, the stability and interaction of andrographolide and levofloxacin with the protein AlgW have been investigated by molecular docking and molecular dynamics (MD) simulations . Moreover, the growth and inhibition of biofilm production by P. aeruginosa experiments were also investigated, providing insight that andrographolide could be a potential natural product to inhibit P. aeruginosa.

Synthesis and characterization of 3-in-1 multifunctional lipiodol-doped Fe3O4@Poly (diallyl isophthalate) microspheres for arterial embolization, chemotherapy, and imaging.

Transcatheter arterial embolization plays a pivotal role in treating various diseases. However, the efficacy of embolization therapy in cancer treatment can be limited by several factors, such as inevitable incomplete or non-target embolization, and the tumor recurrence and metastasis caused by the hypoxic microenvironment. Moreover, it is essential to explore simpler, more economical, and efficient methods for microsphere synthesis. Herein, we achieved one-step photocatalytic synthesis of lipiodol-doped Fe3O4@Poly (diallyliso-phthalate) multifunctional microspheres (IFeD MS) for arterial embolization, chemotherapy, and imaging. The prepared microspheres are in the shape of dried plums, with a particle size of 100-300 µm. Lipiodol demonstrates a certain degree of chemotherapeutic activity, and the incorporation of Fe3O4enables the microspheres to exhibit magnetothermal response and magnetic resonance imaging capabilities. Furthermore, the radiopaque characteristics of both agents provide the microspheres with promising potential for computed tomography and digital radiography imaging. The renal embolization experiment in rabbits demonstrated that IFeD MS achieved significant embolization and chemotherapeutic effects. Biocompatibility experiments revealed that this embolic agent did not induce tissue damage or inflammation beyond the treatment area. Additionally, IFeD MS exhibited promising imaging potential. The results of this study imply that the developed multifunctional embolic agent IFeD MS may have significant potential in transforming tumors previously only suitable for palliative cares into resectable radical treatments.

Texture Analysis of Chinese Dried Noodles during Drying Based on Acoustic-Mechanical Detection Methods.

To better understand the textural transformation of Chinese dried noodles during the drying process, a convenient acoustic-force detection method was established. By comparing the breaking point, it was possible to determine the time-scale correlation between the force-displacement curves and acoustic spectrograms. The acoustic eigenvalues showed a consistent upward trend with the mechanical parameters during the drying process. With a wave crest reaching 152.8 dB and a signal maximum reaching 0.072, the structural stability of the dried noodles hardly induces a higher acoustic response. This suggests that the mechanical strength and rigidity of the dried noodles undergo minimal changes during this period. In comparison to the mechanical parameters, the acoustic eigenvalues accurately describe the changes in texture of dried noodles under various drying conditions, moreover, the sound threshold also provides a more effective response to the dried noodles' structural strength threshold. Therefore, the acoustic detection method can be applied to assist the conventional mechanical measurement in the field of the texture evaluation of dried food.

Effects of oat ß-glucan on the retrogradation behavior of rice starch and its potential mechanism.

In this study, to minimize the quality deterioration caused by the retrogradation of starch-based food, the effect and mechanism of oat ß-glucan (OG) on the retrogradation of rice starch was investigated. OG effectively decreased storage modulus (G'), syneresis, and retrogradation enthalpy, indicating the inhibition of short-term and long-term retrogradation of rice starch. The competition for water molecules between the OG and rice starch resulted in partial swelling of the starch granules, consequently reducing particle size, lowering amylose leaching, and decreasing the proportion of short-amylose chains. The microstructure characterization showed that the OG-treated rice starch group (ST-OG) exhibited a smoother and denser surface. Particularly, no notable alterations were observed in the structure of the ST-OG sample during storage, owing to the improved water-holding capacity of starch gel and reduced proportion of free water caused by OG. Furthermore, the ordered structure results confirmed the occurrence of hydrogen bonding between OG and rice starch, which hindered the rearrangement of starch molecules. Therefore, OG is an effective natural additive for controlling the retrogradation of starch-based foods.

DFT studies of solvent effect in hydrogen abstraction reactions from different allyl-type monomers with benzoyl radical.

Inert allyl-type monomers have been widely documented due to reduce degradation chain transfer. Recently, we and others discovered that the [3 + 2] cyclization reaction process by a photo-driven radical reaction, which can accelerate the polymerization. It was discovered that allyl ether monomers had much higher reactivity than other allyl monomers in the suspension photopolymerization initiated by Type I photoinitiator. Since the hydrogen abstraction reaction (HAR) is the initial step of cyclization, and in order to clarify the influence of solvents effect, three allyl-type monomers were employed, containing "O", "N" and "S" atom as hydrogen donors. The benzoyl radical obtained from cleavage of photoinitiator was chosen as hydrogen acceptors. We explored the hydrogen abstraction reaction in different solvents (methanol, water and DMSO) by quantum chemistry for geometry and energy. An investigation was undertaken regarding the structural orbital by electrostatic potential (ESP) and topological analysis (ELF and LOL). The findings were also combined with the distortion model and transition state theory. We obtained the molecular interactions used independent gradient method in the Hirshfeld molecular density partition (IGMH). The Eckart's correction allowed to examine the driving factors of the hydrogen abstraction reaction tunnels and these reactions constant rates are determined in the range of 500-2500 K depending on the modified Arrhenius form in different solvents effect. Our results can provide an answer for the different reactivities.

Design of an imaging magnetic microsphere based on photopolymerization for magnetic hyperthermia in tumor therapy.

Magnetic hyperthermia therapy has been widely used in the nonsurgical treatment of patients with advanced stage cancers that cannot be treated by surgery. It is minimally invasive, precise, and highly efficient and has a good curative effect. In this paper, a magnetic microsphere with Fe3O4 was prepared for thermal therapy and imaging based on a photoinitiated suspension polymerization method from biallelic monomers. The preparation method clearly minimized the degradative chain transfer of allyl polymerization reactions. The microspheres were characterized by microscope observation, spectral analysis, thermal analysis, and magnetic testing. The magnetothermal effect was detected by an infrared thermal imager in vitro and in vivo under a high-frequency alternating magnetic field (AMF). The antitumor effect was verified by testing the viability of H22 cells and observing a tumor-bearing mouse model under high-frequency AMF. Biocompatibility was evaluated by cell viability assay, tissue section observation, and blood biochemical analysis. The imaging capacity was tested by X-ray, MRI, and CT imaging experiments. The results show that the product has good dispersibility, thermal stability, superparamagnetism, and biocompatibility. Under the action of an AMF, the magnetic hyperthermia effect in tumor-bearing mice was better, and an antitumor effect could be achieved.

Apatinib remodels the immunosuppressive tumor ecosystem of gastric cancer enhancing anti-PD-1 immunotherapy.

Apatinib has been shown to clinically enhance anti-PD-1 immunotherapy for advanced gastric cancer (GC). However, the complexity of GC immunosuppression remains a challenge for precision immunotherapy. Here, we profile the transcriptomes of 34,182 single cells from GC patient-derived xenografts of humanized mouse models treated with vehicle, nivolumab, or nivolumab plus apatinib. Notably, excessive expression of CXCL5 in the CellCycle malignant epithelium, induced by anti-PD-1 immunotherapy and blocked by combined apatinib treatment, is found to be a key driver of tumor-associated neutrophil (TAN) recruitment in the tumor microenvironment through the CXCL5/CXCR2 axis. We further show that the protumor TAN signature is associated with anti-PD-1 immunotherapy-related progressive disease and poor cancer prognosis. Molecular and functional analyses in cell-derived xenograft models confirm the positive in vivo therapeutic effect of targeting the CXCL5/CXCR2 axis during anti-PD-1 immunotherapy. Altogether, our study elucidates the GC immunosuppressive landscape in anti-PD-1 immunotherapy and highlights potential targets for overcoming checkpoint immunotherapy resistance.

One-step photocatalytic synthesis of Fe3O4@polydiallyl isophthalate magnetic microspheres for magnetocaloric tumor ablation and its potential for tracing on MRI and CT.

Allyl monomers that were previously considered to be difficult to polymerize are applied, and Fe3O4@polydiallyl isophthalate (Fe3O4@PDAIP) magnetic were synthesized by one-step photopolymerization. The skeleton of the microspheres is made of diallyl isophthalate (DAIP). We obtained the microspheres using the photo-click technique in a soft template with Nano-Fe3O4 evenly disseminated in hydrophobic DAIP by cation-π and polar interaction. The obtained Fe3O4@PDAIP magnetic microspheres can achieve tumor cell necrosis temperatures (41-52 °C) in an alternating magnetic field due to their inherent magnetic response. The results of in vitro CT and MR imaging indicate that the microspheres might be monitored accurately in vivo. Then the structural characteristics of the microspheres were confirmed by morphological analysis and physicochemical property analysis. Experiments in vitro and in vivo revealed that the microspheres had an anti-tumor effect and their biocompatibility satisfies the standards. The stability experiment proves that the microspheres have the potential for long-term effectiveness in vivo. It demonstrates the promise of Fe3O4@PDAIP magnetic microspheres in clinical applications.

Prediction of Potential Biomarkers in Early-Stage Nasopharyngeal Carcinoma Based on Platelet RNA Sequencing.

Early diagnosis is essential for the treatment and prevention of nasopharyngeal cancer. However, there is a lack of effective biological indicators for nasopharyngeal carcinoma (NPC). Therefore, we explored the potential biomarkers in tumour-educated blood platelet (TEP) RNA in early NPC. Platelets were isolated from blood plasma and their RNA was extracted. High-throughput sequenced data from a total of 33 plasma samples were analysed using DESeq2 to identify the differentially expressed genes (DEGs). Subsequently, the DEGs were subjected to principal component analysis (PCA), gene ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis; and Cytoscape, TargetScan, and miRanda software were used for inferring the competing endogenous RNA network. We identified 19 long non-coding (lnc) RNAs (DElncRNAs) and 248 mRNAs (DEmRNAs) that were differentially expressed in the TEP RNA. In addition, SELP gene mRNA and lncRNAs AC092135.3, AC012358.2, AL021807.1, AP001972.5, and GPX1 were found to be down-regulated DEmRNA and DElncRNAs in the early stage of NPC. Bioinformatic analysis showed that these DEmRNAs and DElncRNAs may be involved in regulating the pathogenesis of NPC. Our research may provide new insights for exploring the biological mechanisms of NPC and early diagnosis using potential biomarkers.

A comparison of hydrogen abstraction reaction between allyl-type monomers with thioxanthone-based photoinitiators without amine synergists.

The photodriven radical-mediated [3 + 2] cyclization reaction was found to yield polymers efficiently without being hindered by degradative chain transfer. The first reaction is a hydrogen abstraction process in which one hydrogen atom migrates from the α-methylene group of an allyl monomer to the triplet state (or fragments) of the photoinitiator, thus yielding primary allyl radicals as primary radicals and then begins chain propagation via a 3 + 2 cyclization reaction. Allyl ether monomers were found to be significantly higher than other allyl monomers even with the absence of amine-like synergists. In order to clarify the procedure of the hydrogen abstraction mechanism, we used four allyl-type monomers as hydrogen donors and three thioxanthone photoinitiators as hydrogen acceptors by the quantum chemistry method in terms of geometry and energy. The results were interpreted with transition-state theory and the interaction/deformation model. Then, the tunneling factors of hydrogen abstraction reactions were also investigated by Eckart's correction. The results show allyl ether systems are more reactive than other allyl systems, and it would provide us with new insights into these hydrogen abstractions.

Coassembling functionalized glycopolypeptides to prepare pH-responsive self-indicating nanocomplexes to manipulate self-assembly/drug delivery and visualize intracellular drug release.

The pH-responsive polymeric micelles (PMs) have been widely used as smart nano drug delivery systems to treat tumors. However, synchronously manipulating these PMs' self-assembly properties, drug release dynamics and tracing their pH-dependent intracellular fate remain challenges. Herein, we have first synthesized hyaluronic acid (HA) based glycopolypeptides modified by tetraphenylethylene (TPE) and a pH-sensitive doxorubicin (DOX) prodrug through Diels-Alder reaction, respectively. Then, the pH-responsive nanocomplexes (NCs) were prepared by coassembling the two obtained glycopolypeptides with different formulations. Controllable size within the range of 60-125 nm and morphologies like spherical, vesicular and oblate micelles can be easily accomplished by using this method; High drug encapsulating and loading efficiency can be easily realized and adjusted within a range of 86-97% and 7-25%, respectively; Acid sensitive drug release dynamics of these NCs are also tunable by using this way. Additionally, the programmed drug release induced by subtle pH variations can be extracellularly self-indicated by detecting the blue AIE changes of the TPE units through fluorescence resonance energy transfer (FRET) effect between DOX and TPE. More importantly, the dynamic pH-triggered DOX release can be easily traced inside the tumor cells by visualizing blue emission changes of the TPE through the FRET effect. In addition, both the size and the shape can affect the endocytic routes of the NCs; The HA coated NCs targeting the tumor cells can effectively inhibit the proliferation of the HeLa cells. This work can provide a new route to acquire the stimuli-responsive self-indicating PMs with the ability to adjust their self-assembly properties and their pH-triggered drug release dynamics, and even to simultaneously visualize the PMs' intracellular fate in a real-time.

Asymmetric image encryption scheme based on the Quantum logistic map and cyclic modulo diffusion.

In this study, a novel asymmetric image encryption scheme based on the Rivest-Shamir-Adleman (RSA) algorithm and Arnold transformation is proposed. First, the asymmetric public key RSA algorithm is used to generate the initial values for a quantum logistic map. Second, the parameters of the Arnold map are calculated. Then, Arnold scrambling operation is performed on the plain image to achieve the rough hiding of image information. Third, each row and each column of the image are taken as different units respectively and then exclusive-OR (XOR) diffusion is applied. Finally, the generated keystream is used to perform an end-to-start cyclic modulo diffusion operation for all rows and columns to produce the final cipher image. In addition, the keystream is related to the plain image, which can enhance the ability to resist chosen plaintext attack and known plaintext attack. The test results also show that the proposed encryption algorithm has strong plain sensitivity and key sensitivity.

A new DNA coding and hyperchaotic system based asymmetric image encryption algorithm.

In this paper, an asymmetric image encryption algorithm based on DNA coding and hyperchaotic system is designed. Unlike other image encryption schemes, for example, sharing of same private keys between sender and receiver, and fixed rules with simple operation, three stages are studied as follows to deal with these problems. Firstly, to eliminate the possible risk of key transmission and management, the initial values of the hyperchaotic system are generated for ahead by the RSA (Rivest-Shamir-Adleman) algorithm and the plain image, in which the sum of odd rows, even rows, odd columns, and even columns are computed respectively to extra the plain message from the plain image as input of RSA algorithm. Then, a mathematical map is established to transform all of them into initial values of the hyperchaotic system. Secondly, the pixel level permutation is performed to confuse the image according to the chaotic sequences generated. Finally, to solve the problem of fixed rules with simple operations in current DNA based image encryption algorithms, dynamical DNA encryption is designed to diffuse the permuted image. The process of DNA encryption includes DNA coding, DNA operation and DNA decoding. In particular, DNA rules are selected according to chaotic sequences dynamically, rather than fixed rules with simple operation. Theoretical analysis and numerical simulations show that the proposed algorithm is secure and reliable for image encryption.

Density Functional Theory Guide for an Allyl Monomer Polymerization Mechanism: Photoinduced Radical-Mediated [3 + 2] Cyclization.

Polymerization of allyl ether monomers has previously been considered a free-radical addition polymerization mechanism, but it is difficult to achieve because of the high electron density of their double bond. To interpret the mechanism of photopolymerization, we therefore proposed a radical-mediated cyclization (RMC) reaction, which has been validated by results from quantum chemistry calculations and real-time infrared observation. Our RMC reaction begins with the radical abstracting one allylic hydrogen atom from the methylene group of allyl ether to generate an allyl ether radical with a delocalized π3 3 bond. Then, the radical reacts with the double bond of a second allyl ether molecule to form a five-membered cyclopentane-like ring (CP) radical. The CP radical abstracts a hydrogen atom from a third ether molecule. At last, a new allyl ether radical is generated and the next circulation as chain propagation begins. The distortion/interaction model was employed to explore the transient state of reaction, and real-time infrared was chosen to clarify the RMC reaction mechanism initiated by different photoinitiators. These results demonstrated that the RMC mechanism can give new insights into these fundamental processes.

One-step preparation of photoclick method for embolic microsphere synthesis and assessment for transcatheter arterial embolization.

Vascular embolization is a well-known therapeutic treatment against hepatocellular carcinoma. However, existing embolic agents require complex synthesis, toxic organic solvents and sometimes produce only low yields. In this study, a novel photopolymerization technique, which addresses these issues, was used to prepare embolic microspheres successfully from the sucrose multi-allyl ether monomer in one step. Compared to the preparation of such microspheres always involved in multiple steps or complicated conditions, we obtained the microspheres used photoclick method in a soft template with simple, economic and feasible procedure. This work focuses on the synthesis of new materials by conducting a photopolymerzation in the presence of the sucrose monomer and the photoinitiator. Then, the embolic microspheres obtained were characterized by morphology assay, degradation, and swelling test. Cell experiments showed that the microspheres had good biocompatibility. Rabbit embolizations showed that the microspheres had long-term embolic effects. It is manifested that one-step preparation of photoclick method hold great potential and competitiveness of being used in preparation embolic microspheres in clinic.