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Integrin αvβ3 is restrictedly expressed on angiogenic blood vessels and tumour cells. It plays a key role in angiogenesis for tumour growth and metastasis. RGD peptide can specifically recognise the integrin αvβ3, which serves as targeted molecular for anti-angiogenesis strategies. Therefore, the targeted delivery of therapeutics by RGD peptide-based non-viral vectors to tumour vasculature and tumour cells is recognised as a promising approach for treating cancer. In this review, we illustrate the interaction between RGD peptide and integrin αvβ3 from different perspectives. Meanwhile, four types of RGD peptide-based non-viral gene delivery vectors for cancer therapy, including RGD-based cationic polymers, lipids, peptides and hybrid systems, are summarised. The aim is to particularly highlight the enhanced therapeutic effects and specific targeting ability exhibited by these vectors for cancer gene therapy both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Piperidine absorbs CO2 and H2O contents in air to form a molecular complex: piperidium-1-piperidinecarboxylate-H2O. The structure of the complex was characterized by FT-IR and NMR. The complex is stabilized via five hydrogen bonds between the three components, N···O electrostatic interaction and O···O interaction (electron transfer) between1-piperidinecarboxylate and H2O. Through electron transfer from the carbamate ion, the oxygen atom in water molecule is strongly negatively charged and the O—H bond is considerably shorter than that of free water molecule. The formation of the molecular complex is a reversible process and will decompose upon heating. The mechanism of formation and stabilization is further investigated herein. [ABSTRACT FROM AUTHOR]

Piperidine absorbs CO2 and H2O in air to form a molecular complex: piperidium-1-piperidinecarboxylate-H2O. The structure of the complex was characterized by X-ray single crystal diffraction. The crystal structure was determined to be triclinic, space group P $$\bar 1$$ with a=0.648 6(8) nm, b=0.809 2(10) nm, c=1.357 1(16) nm, α=96.967(16)°, β=102.506(15)°,, γ=104.202 (15)°, Z=2. The complex is stabilized via five hydrogen bonds between the three components, N—O electrostatic interaction and O—O interaction (electron transfer) between1-piperidinecarboxylate and H2O. Due to electron transference of carbamate ion, the oxygen atom in water molecule is strongly negatively charged and the O—H bond is considerably shorter than that of the free molecule of water. The formation of the molecular complex is a reversible process and will decompose upon heating. The mechanism of formation and stabilization is further investigated herein. [ABSTRACT FROM AUTHOR]

Deep vein thrombosis is a common complication after orthopedic, gynecological, and obstetric operations. However, instances of this complication after oral and maxillofacial surgeries have been rarely reported. We report a case with odontogenic keratocyst in the jaw that gained left lower extremity venous thrombosis after operation, and discuss the risk factors and prevention of lower extremity venous thrombosis through literature review. [ABSTRACT FROM AUTHOR]

Spur‐type varieties play an important role in facilitating high‐density plantings. However, the underlying mechanisms of internode elongation in spur‐type varieties are poorly understood. In this research, we investigated the morphological phenotype of annual shoots in four spur‐type varieties ('Miyazak', 'Jinfu 18', 'Yanfu No. 6', and 'Liquan spur') and four standard‐type varieties ('Aomorifu', 'Shou Fuji', 'Yanfu No. 10', and 'Yanfu No. 3'). Compared with standard‐type varieties, spur‐type varieties had a shorter shoot length, an average internode length and a smaller xylem size. The content of Jasmonic acid (JA) and Jasmonic acid isoleucine (JA‐Ile) significantly increased in spur‐type varieties, accompanied by an increase in the expression of JA biosynthesis and signal transduction genes. Exogenous methyl jasmonate (MeJA) inhibited plant height, xylem size, and vessel area. Additionally, we identified an IAA‐Leucine Resistant1‐like Hydrolase family member, MdILL6, which was highly expressed in spur‐type varieties and mature stems. MdILL6 was mainly expressed in the shoot tips and stem, and its protein was located on the endoplasmic reticulum. Overexpression of MdILL6 in apple inhibited plant height and average internode length by decreasing xylem size and vessel area. Our results revealed a molecular mechanism of spur‐type variety development affected by the JA pathway and suggest strategies for genetic improvement and regulation of spur‐type varieties. [ABSTRACT FROM AUTHOR]

Liposomes have been extensively applied in gene and drug delivery. It is indicated in many studies that cationic lipids possess a certain degree of cytotoxicity, primarily induced by the lipid head group. In this study, we investigated the cytotoxic mechanisms of peptide headgroup lipid (CDO14) and quaternary ammonium salt headgroup lipid (CDA14) on the NCI-H460 and MRC-5 cell lines. Both lipids were synthesized in our laboratory and with high transfection efficiency. The differences in changes of relevant proteins during the process of inducing cell apoptosis were compared at the cellular level between the two lipids. The results showed that both types of liposomes could lead to an increase in intracellular reactive oxygen species, a decrease in ATP content, a decrease in mitochondrial membrane potential, an increase in cytochrome c content, an increase in the BAX/BCL-2 ratio, and an increase in cleaved caspase-3 content. Among these changes, the variations in CDA14 were more significant than those in CDO14. Additionally, the cellular uptake of CDA14 was significantly higher than that of CDO14. These results suggested that the cytotoxicity of quaternary ammonium salt-based lipids was higher than that of peptide-based lipids. The cytotoxicity of cationic lipids is related to their head group structure, and their cytotoxic effect is mainly achieved by activating caspase-dependent endogenous apoptosis. [ABSTRACT FROM AUTHOR]

This work designed a new delivery system (L-PTX-PSur), which could efficiently co-deliver paclitaxel (PTX) and survivin siRNA (Sur) to overcome the dose-limiting toxicity by effectively accumulating PTX in tumor and obtain enhanced therapy by synergistic effect. In this co-delivery system, protamine was selected to condense siRNA into a compacted 'core', and a carbamate-linked cationic lipid was used to develop PTX-loaded liposome to entrap the core. L-PTX-PSur with protamine could facilitate Sur entry into NCI-H460 cells and exhibited high encapsulation efficiency of PTX. In vitro studies on the NCI-H460 lung cancer cells revealed that L-PTX-PSur offered significant advantages over the control groups, and it had the highest cellular uptake, the lowest cell viability and the strongest apoptosis. Western blot result showed that survivin protein expression could be noticeably suppressed by L-PTX-PSur in NCI-H460 cells. And the down-regulation of survivin protein could lower the apoptotic threshold of cancer cells and render PTX more effective with low doses. Collectively, L-PTX-PSur with a low dose of PTX could induce a synergistic inhibitory effect on cancer cells growth by the collaboration of PTX and Sur. This work provides a promising strategy for the treatment of lung cancer. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) remains a leading life-threatening health challenge worldwide, with pressing needs for novel therapeutic strategies. Sphingosine kinase 1 (SphK1), a well-established pro-cancer enzyme, is aberrantly overexpressed in a multitude of malignancies, including HCC. Our previous research has shown that genetic ablation of Sphk1 mitigates HCC progression in mice. Therefore, the development of PF-543, a highly selective SphK1 inhibitor, opens a new avenue for HCC treatment. However, the anti-cancer efficacy of PF-543 has not yet been investigated in primary cancer models in vivo, thereby limiting its further translation. Methods: Building upon the identification of the active form of SphK1 as a viable therapeutic target in human HCC specimens, we assessed the capacity of PF-543 in suppressing tumor progression using a diethylnitrosamine-induced mouse model of primary HCC. We further delineated its underlying mechanisms in both HCC and endothelial cells. Key findings were validated in Sphk1 knockout mice and lentiviral-mediated SphK1 knockdown cells. Results: SphK1 activity was found to be elevated in human HCC tissues. Administration of PF-543 effectively abrogated hepatic SphK1 activity and significantly suppressed HCC progression in diethylnitrosamine-treated mice. The primary mechanism of action was through the inhibition of tumor neovascularization, as PF-543 disrupted endothelial cell angiogenesis even in a pro-angiogenic milieu. Mechanistically, PF-543 induced proteasomal degradation of the critical glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3, thus restricting the energy supply essential for tumor angiogenesis. These effects of PF-543 could be reversed upon S1P supplementation in an S1P receptor-dependent manner. Conclusions: This study provides the first in vivo evidence supporting the potential of PF-543 as an effective anti-HCC agent. It also uncovers previously undescribed links between the pro-cancer, pro-angiogenic and pro-glycolytic roles of the SphK1/S1P/S1P receptor axis. Importantly, unlike conventional anti-HCC drugs that target individual pro-angiogenic drivers, PF-543 impairs the PFKFB3-dictated glycolytic energy engine that fuels tumor angiogenesis, representing a novel and potentially safer therapeutic strategy for HCC. [ABSTRACT FROM AUTHOR]

[Display omitted] • An FIA method was developed for flavonoid determination during batch adsorption. • The method enables rapid, high-throughput, online and automatic detection. • Precise flavonoid adsorption kinetic and thermodynamic parameters were achieved. • Errors resulted from adsorption volume decrease due to sampling was minimized. • Potential applications of the method in industrial adsorption were realized. Accurate and real-time measurement of flavonoid concentration during the adsorption process is vital for understanding its adsorption mechanism. In this study, a new merging-zone flow injection analysis (FIA) method based on the NaNO 2 -AlCl 3 -NaOH colorimetric reaction was developed for automatic determination of flavonoid concentration in plant extracts and in adsorption solution during batch adsorption process. The method parameters were optimized using a univariate experimental design, and rutin standard solutions in the concentration range of 25–800 mg/L showed good linearity (R2 = 0.9994) with the FIA signal. The sample throughput was 40 h-1and the limit of detection was 4.888 mg/L. The adsorption kinetics, isotherms, and thermodynamics of flavonoids from Dracocephalum Moldavia onto HPD 300 resin were investigated at varying initial concentrations and temperatures. The pseudo-first-order kinetic model was found to be suitable at 25 and 35 ℃, while the pseudo-second-order model exhibited superior performance at 45 ℃. The Freundlich model was found to be appropriate for describing the adsorption isotherm. The thermodynamic parameters ΔG and ΔH were both negative, and ΔS was positive, indicating that the adsorption process of flavonoids onto the HPD 300 resin is spontaneous and exothermic. The FIA method can effectively decrease the errors arising from the big adsorption volume change in conventional method during the batch adsorption. The developed method enables rapid and online determination of total flavonoids, reducing both time and labor costs, suitable for routine measurements as well as online monitoring of adsorption processes. [ABSTRACT FROM AUTHOR]

The efficacy of hydrophobic anticancer drugs is limited by their poor solubility in water, inefficient target delivery, and toxic side effects. In this work, doxorubicin (DOX) was solubilized using OSA-inulins which created micellar aggregates in aqueous solution above a critical concentration. In vitro delivery of OSA-inulin-DOX micelles resulted in strong inhibition of the growth of MCF-7 breast cancer cells as compared to free DOX. They also displayed a faster cellular uptake rate, indicating that the micelles were promptly internalized into the cells through CD44 receptor-mediated endocytosis. During in vivo tumor suppression experiments in tumor-bearing mice, the OSA-inulin-DOX micelles strongly hindered tumor growth and showed substantially lower systemic toxicity compared with free DOX. Our achievements demonstrate that OSA-inulin has great potential for the encapsulating, dissolving, and targeted delivery of hydrophobic drugs, especially antitumor drugs, for nutraceutical, medical, and pharmaceutical applications. • The OSA-inulins formed micellar aggregates in aqueous solution and were able to solubilize doxorubicin. • OSA-inulin micelles efficiently encapsulate and deliver doxorubicin. • OSA-inulin-DOX micelles can strongly hindered tumor growth and metastasis. • OSA-inulin-DOX micelles showed substantially lower systemic toxicity. [ABSTRACT FROM AUTHOR]

Nucleic acid therapy is currently the most promising method for treating tumors and genetic diseases and for preventing infectious diseases. However, the biggest obstacle to this therapy is delivery of the nucleic acids to the target site, which requires overcoming problems such as capture by the immune system, the need to penetrate biofilms, and degradation of nucleic acid performance. Designing suitable delivery vectors is key to solving these problems. Lipids—which consist of a hydrophilic headgroup, a linker, and a hydrophobic tail—are crucial components for the construction of vectors. The headgroup is particularly important because it affects the drug encapsulation rate, the vector cytotoxicity, and the transfection efficiency. Herein, we focus on various headgroup structures (tertiary amines, quaternary ammonium salts, peptides, piperazines, dendrimers, and several others), and we summarize and classify important lipid-based carriers that have been developed in recent years. We also discuss applications of cationic lipids with various headgroups for delivery of nucleic acid drugs, and we analyze how headgroup structure affects transport efficiency and carrier toxicity. Finally, we briefly describe the challenges of developing novel lipid carriers, as well as their prospects. [ABSTRACT FROM AUTHOR]

Although many chemotherapy prodrugs have been developed for tumor therapy, non-targeted delivery, uncontrolled release and tedious construction procedure of prodrugs still limit their clinical application in tumor treatment. In this work, hyaluronic acid (HA) which has tumor-targeting ability was used to conjugate to antitumor drug podophyllotoxin (PPT) to construct a pH-sensitive prodrug named HA-CO-O-PPT just via a one-step esterification reaction. The HA-CO-O-PPT spontaneously assembled into nano spherical micelles in aqueous medium, which had outstanding serum stability and blood compatibility. The obtained prodrug micelles (named HP micelles) exhibited a pH-responsive drug release mode with cumulative release reaching 81.2% due to their dissociation in response to acid stimulus, and had a high cellular uptake efficiency beyond 97% owing to HA receptor-mediated targeting. Furthermore, it was found that the prodrug micelles showed excellent antitumor activities in vivo with the tumor inhibition ratio up to 85% and negligible systemic toxicity. Accordingly, the pH-responsive HP micelles constructed by a simple one-step reaction, could be a promising candidate as a chemotherapeutic agent for cancer therapy. • pH-responsive HA-CO-O-PPT prodrug (HP) micelles were constructed. • HP micelles could selectively accumulate at tumor site via HA-mediated targeting. • HP micelles showed on-demand PPT release with cumulative release of 81.2%. • HP micelles achieved enhanced antitumor effect with inhibition rate of 85%. • HP micelles exhibited negligible systemic toxicity. [ABSTRACT FROM AUTHOR]

Bacterial infections are closely associated with tumor growth and metastasis. Bacteriostasis can not only inhibit the growth and metastasis of tumors during their early diagnosis and treatment but also prevent bacterial infections after recovery. In this study, we synthesized Ag@GQD which consisted of nitrogen-doped graphene quantum dots (N-GQD) wrapped around Ag NPs through the photocatalytic reduction method. Multifunctional nanoprobes (Ag/DOX@GQD) were obtained by doxorubicin (DOX) loading. Ag@GQD exhibited high stability, low cytotoxicity, and good photoacoustic imaging performance. The effective photothermal performance of Ag@GQD enabled us to achieve the controlled release of DOX from probes using near-infrared light and pH response during the treatment of tumors using chemo-photothermal combination therapy. Results from cell-based experiments revealed that combination therapy was superior to single-drug therapy. Besides, Ag@GQD could effectively kill Staphylococcus aureus and Escherichia coli and can be expected to inhibit the growth and metastasis of tumors caused by bacteria and in reducing bacterial infections after recovery. [ABSTRACT FROM AUTHOR]

Nanomaterials with intrinsic enzyme activity (nanozymes) have been widely used as artificial enzymes in biomedicine, especially in tumor diagnosis and treatment. Herein, a kind of water-soluble silver nanozyme (Ag@GQD) was developed with a simple method, which showed two enzymatic activities (peroxidase and oxidase-like activity). Based on the excellent catalytic performance of oxidase-like activity, a simple and highly sensitive colorimetric detection strategy for glutathione (GSH) was established. What's more, after absorbing DOX, Ag/DOX@GQD could realize the combined treatment of reactive oxygen species and chemotherapy. In conclusion, this study provided evidences that Ag@GQD is effective in tumor diagnosis and treatment, which provided new ideas for exploring nanozymes based on the integration of diagnosis and treatment. • Nanozymes (Ag@GQD) exhibiting dual enzyme-like activities were synthesized using a straightforward method. • Based on oxidase-like activity of Ag@GQD, an in vitro method for detecting tumor marker (GSH) was established. • After loading the chemotherapy drug DOX onto Ag@GQD (Ag/DOX@GQD), a synergistic tumor treatment approach combining reactive oxygen species and chemotherapy was achieved. [ABSTRACT FROM AUTHOR]

High-throughput sequencing and multiomics technologies have allowed increasing numbers of biomarkers to be mined and used for disease diagnosis, risk stratification, efficacy assessment, and prognosis prediction. However, the large number and complexity of tumor markers make screening them a substantial challenge. Machine learning (ML) offers new and effective ways to solve the screening problem. ML goes beyond mere data processing and is instrumental in recognizing intricate patterns within data. ML also has a crucial role in modeling dynamic changes associated with diseases. Used together, ML techniques have been included in automatic pipelines for tumor marker screening, thereby enhancing the efficiency and accuracy of the screening process. In this review, we discuss the general processes and common ML algorithms, and highlight recent applications of ML in tumor marker screening of genomic, transcriptomic, proteomic, and metabolomic data of patients with various types of cancers. Finally, the challenges and future prospects of the application of ML in tumor therapy are discussed. Machine learning can be applied to tumor marker screening in genomics, transcriptomics, proteomics and metabolomics. Common tumor markers are derived from circulating tumor cells (CTC), cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), microRNA (miRNA), messenger RNA (mRNA), circular RNA (circRNA), long noncoding RNA (lncRNA), extracellular vesicle (EV), circulating tumor proteins, and metabolites (e.g., glycogen, branched-chain amino acids (BCAA), fatty acids (FA)). Commonly used algorithms in tumor marker screening are least absolute shrinkage and selection operator (LASSO), logistic regression (LR), decision tree (DT), random forest (RF), support vector machine (SVM), gradient boosting (GBoost), extreme gradient boosting (XGBoost), neural network (NN), deep neural network (DNN), hierarchical cluster analysis (HCA), principal component analysis (PCA), and t-distributed stochastic neighbor embedding (t-SNE). [Display omitted] • Tumor markers help in disease diagnosis and prognosis assessment. • Machine leaning can analyze a large amount of tumor-related data. • Machine leaning greatly improves the screening efficiency and accuracy. [ABSTRACT FROM AUTHOR]

The success of skin cancer treatment is severely limited in the route of administration because most genes and drugs cannot break through the excellent stratum corneum (SC) barrier of the skin, leading to their inability to reach the tumor tissues at therapeutic doses. As an excellent minimally invasive delivery method, microneedles (MNs) can bypass the SC and enter the skin microcirculation to achieve drug and gene delivery when used to puncture the skin. Compared with traditional administration approaches, MN-assisted gene and drug delivery have obvious advantages, in that they are simple, safe, painless, easily transport genes (such as DNA and siRNA (small interfering RNA)) and macromolecule drugs (including proteins and antibodies), and have good reproducibility. Besides, other treatment strategies including photothermal therapy (PTT) have been combined with MN arrays containing genes or drugs, which is expected to improve the therapeutic effect of skin cancer. Therefore, this review summarizes the latest developments in MNs for gene and/or drug delivery, with a focus on their performances as effective MNs for skin cancer treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Microneedles (MNs), as an effective minimally invasive delivery route, when used to puncture the skin, can bypass the skin's stratum corneum (SC) to enter the skin microcirculation and achieve systemic administration. Additionally, the MN route has obvious advantages over other routes of administration, including simplicity, non-pain, readily-permitted transport of drugs (including DNA and metformin) and macromolecules (such as antibodies and proteins), good repeatability, and wide range of clinical applications and safety. MNs have been combined with various therapy strategies including photodynamic therapy (PDT) and photothermal therapy (PTT) to treat many diseases, and hold great promise for improving the diagnosis and treatment of diseases. Both MN-assisted PDT and PTT are light-mediated phototherapy methods and have unique advantages, including improved selectivity, and minimal invasiveness and side effects. MN-assisted PDT or PTT has been studied for various applications by many research groups and pharmaceutical companies worldwide. Therefore, this review summarizes recent advances in MNs for PDT or PTT. Unlabelled Image • Microneedle-assisted photodynamic therapy or photothermal therapy is summarized. • Different materials in MNs influence on their photothermal/photodynamic properties. • The nanosystems in MNs bearing targeting ligands can improve its therapeutic effect. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of NLCs were constructed based on SEs and peptide lipids for DNA delivery. • The COL-6 with sucrose laurate exhibits highest transfection efficiency. • SEs increased the interaction of NLC to DNA, it decreased with the increase of SE carbon chain length. • SEs contributed to the formation of ordered membrane structure and enhanced stability. • The addition of SEs enhances lipid aggregation, and DNA molecules twine around the NLCs or are partially compressed within them. Sucrose esters (SEs) have great potential in the field of nucleic acid delivery due to their unique physical and chemical properties and good biosafety. However, the mechanism of the effect of SEs structure on delivery efficiency has not been studied. The liposomes containing peptide lipids and SEs were constructed, and the effects of SEs on the interaction between the liposomes and DNA were studied. The addition of SEs affects the binding rate of liposomes to DNA, and the binding rate gradually decreases with the increase of SEs' carbon chain length. SEs also affect the binding site and affinity of liposomes to DNA, promoting the aggregation of lipids to form liposomes, where DNA wraps around or compresses inside the liposomes, allowing it to compress DNA without damaging the DNA structure. COL-6, which is composed of sucrose laurate, exhibits the optimal affinity for DNA, and SE promotes the formation of ordered membrane structure and enhances membrane stability, so that COL-6 exhibits a balance between rigidity and flexibility, and thus exhibits the highest delivery efficiency of DNA among these formulations. This work provides theoretical foundations for the application of SE in gene delivery and guides for the rational design of delivery systems. [ABSTRACT FROM AUTHOR]