PDGFRß-Antagonistic Affibody-Mediated Tumor-Targeted Tumor Necrosis Factor-Alpha for Enhanced Radiotherapy in Lung Cancer.

The morbidity and mortality of lung cancer are still the highest among all malignant tumors. Radiotherapy plays an important role in clinical treatment of lung cancer. However, the effect of radiotherapy is not ideal due to the radiation resistance of tumor tissues. Abnormalities in tumor vascular structure and function affect blood perfusion, and oxygen transport is impeded, making tumor microenvironment hypoxic. Tumor hypoxia is the major cause of radiotherapy resistance. By promoting tumor vessel normalization and enhancing vascular transport function, tumor hypoxia can be relieved to reduce radiotherapy resistance and increase tumor radiotherapy sensitivity. In our previous study, a pericytes-targeted tumor necrosis factor alpha (named Z-TNFα) was first constructed and produced by genetically fusing the platelet-derived growth factor receptor ß (PDGFRß)-antagonistic affibody (ZPDGFRß) to the TNFα, and the Z-TNFα induced normalization of tumor vessels and improved the delivery of doxorubicin, enhancing tumor chemotherapy. In this study, the tumor vessel normalization effect of Z-TNFα in lung cancer was further clarified. Moreover, the tumor hypoxia improvement and radiosensitizing effect of Z-TNFα were emphatically explored in vivo. Inspiringly, Z-TNFα specifically accumulated in Lewis lung carcinoma (LLC) tumor graft and relieved tumor hypoxia as well as inhibited HIF-1α expression. As expected, Z-TNFα significantly increased the effect of radiotherapy in mice bearing LLC tumor graft. In conclusion, these results demonstrated that Z-TNFα is also a promising radiosensitizer for lung cancer radiotherapy.

ICG-Dimeric Her2-Specific Affibody Conjugates for Tumor Imaging and Photothermal Therapy for Her2-Positive Tumors.

Human epidermal growth factor receptor 2 (Her2) is abundantly expressed in various solid tumors. The Her2-specific Affibody (ZHer2:2891) has been clinically tested in patients with Her2-positive breast cancer and is regarded as an ideal drug carrier for tumor diagnosis and targeted treatment. Indocyanine green (ICG) can be used as a photosensitizer for photothermal therapy (PTT), in addition to fluorescent dyes for tumor imaging. In this study, a dimeric Her2-specific Affibody (ZHer2) based on ZHer2:2891 was prepared using the E. coli expression system and then coupled to ICG through an N-hydroxysuccinimide (NHS) ester reactive group to construct a novel bifunctional protein drug (named ICG-ZHer2) for tumor diagnosis and PTT. In vitro, ICG-ZHer2-mediated PTT selectively and efficiently killed Her2-positive BT-474 and SKOV-3 tumor cells rather than Her2-negative HeLa tumor cells. In vivo, ICG-ZHer2 specifically accumulated in Her2-positive SKOV-3 tumor grafts rather than Her2-negative HeLa tumor grafts; high-contrast tumor optical images were obtained. However, Her2-negative HeLa tumor grafts were not detected. More importantly, ICG-ZHer2-mediated PTT exhibited a significantly enhanced antitumor effect in mice bearing SKOV-3 tumor grafts owing to the good photothermal properties of ICG-ZHer2. Of note, ICG-ZHer2 did not exhibit acute toxicity in mice during short-term treatment. Overall, our findings indicate that ICG-ZHer2 is a promising bifunctional drug for Her2-positive tumor diagnosis and PTT.

Confirming the association between low serum 25OHD levels in girls with central precocious puberty and its severity.

BACKGROUND: To assess the differences in vitamin D levels in girls with rapidly progressive (RP) or slowly progressive (SP) central precocious puberty (CPP) and to compare whether the factors related to RP-CPP influenced the vitamin D status. A cross-sectional study was performed among girls with CPP classified as RP-CPP or SP-CPP. METHODS: The baseline data, gonadotropin-releasing hormone (GnRH) stimulation test results, serum 25-hydroxyvitamin D (25OHD) levels, and season of sample collection were analyzed. RESULTS: The mean 25OHD level in 340 girls was 15.89 ± 6.87 ng/mL, of whom only 10 (2.9%) had normal levels (≥ 30 ng/mL). A total of 114 girls in the SP-CPP group and 226 in the RP-CPP group had similar chronological age, disease course, height SDS, bone mineral density, baseline follicle-stimulating hormone (FSH), peak FSH, and 25OHD levels. Developmental age, body mass index (BMI), BMI SDS, peak luteinizing hormone (LH)/FSH, insulin-like growth factor 1 (IGF-1), and IGF-1 SDS were independent risk factors for RP-CPP. Significant differences were observed among the different serum 25OHD levels in terms of season, disease course, IGF1 level, and BMI SDS (P < 0.05). Moreover, the sampling season was strongly correlated with serum 25OHD levels (r = 0.402, P < 0.001). CONCLUSION: The vitamin D levels were generally deficient or insufficient in girls with CPP, but were not related to the different types of CPP. High BMI levels, IGF1 levels, or peak LH/FSH ratio, but not vitamin D levels, could promote the progression of RP-CPP. Seasonal factors mainly influenced the vitamin D levels.

Self-Aligned Plasmonic Lithography for Maskless Fabrication of Large-Area Long-Range Ordered 2D Nanostructures.

This paper proposes a one-step maskless 2D nanopatterning approach named self-aligned plasmonic lithography (SPL) by line-shaped ultrafast laser ablation under atmospheric conditions for the first time. Through a theoretical calculation of electric field and experimental verification, we proved that homogeneous interference of laser-excited surface plasmon polaritons (SPPs) can be achieved and used to generate long-range ordered 2D nanostructures in a self-aligned way over a wafer-sized area within several minutes. Moreover, the self-aligned nanostructures can be freely transferred between embossed nanopillars and engraved nanoholes by modulating the excitation intensity of SPPs interference through altering the incident laser energy. The SPL technique exhibits further controllability in the shape, orientation, and period of achievable nanopatterns on a wide range of semiconductors and metals by tuning processing parameters. Nanopatterned films can further act as masks to transfer structures into other bulk materials, as demonstrated in silica.

Dimeric Her2-specific affibody mediated cisplatin-loaded nanoparticles for tumor enhanced chemo-radiotherapy.

BACKGROUND: Solid tumor hypoxic conditions prevent the generation of reactive oxygen species (ROS) and the formation of DNA double-strand breaks (DSBs) induced by ionizing radiation, which ultimately contributes to radiotherapy (RT) resistance. Recently, there have been significant technical advances in nanomedicine to reduce hypoxia by facilitating in situ O2 production, which in turn serves as a "radiosensitizer" to increase the sensitivity of tumor cells to ionizing radiation. However, off-target damage to the tumor-surrounding healthy tissue by high-energy radiation is often unavoidable, and tumor cells that are further away from the focal point of ionizing radiation may avoid damage. Therefore, there is an urgent need to develop an intelligent targeted nanoplatform to enable precise enhanced RT-induced DNA damage and combined therapy. RESULTS: Human epidermal growth factor receptor 2 (Her2)-specific dimeric affibody (ZHer2) mediated cisplatin-loaded mesoporous polydopamine/MnO2/polydopamine nanoparticles (Pt@mPDA/MnO2/PDA-ZHer2 NPs) for MRI and enhanced chemo-radiotherapy of Her2-positive ovarian tumors is reported. These NPs are biodegradable under a simulated tumor microenvironment, resulting in accelerated cisplatin release, as well as localized production of O2. ZHer2, produced using the E. coli expression system, endowed NPs with Her2-dependent binding ability in Her2-positive SKOV-3 cells. An in vivo MRI revealed obvious T1 contrast enhancement at the tumor site. Moreover, these NPs achieved efficient tumor homing and penetration via the efficient internalization and penetrability of ZHer2. These NPs exhibited excellent inhibition of tumor growth with X-ray irradiation. An immunofluorescence assay showed that these NPs significantly reduced the expression of HIF-1α and improved ROS levels, resulting in radiosensitization. CONCLUSIONS: The nanocarriers described in the present study integrated Her2 targeting, diagnosis and RT sensitization into a single platform, thus providing a novel approach for translational tumor theranostics.

Synergistic inhibition of metastatic breast cancer by dual-chemotherapy with excipient-free rhein/DOX nanodispersions.

BACKGROUND: The management of metastatic cancer remains a major challenge in cancer therapy worldwide. The targeted delivery of chemotherapeutic drugs through rationally designed formulations is one potential therapeutic option. Notably, excipient-free nanodispersions that are entirely composed of pharmaceutically active molecules have been evaluated as promising candidates for the next generation of drug formulations. Formulated from the self-assembly of drug molecules, these nanodispersions enable the safe and effective delivery of therapeutic drugs to local disease lesions. Here, we developed a novel and green approach for preparing nanoparticles via the self-assembly of rhein (RHE) and doxorubicin (DOX) molecules, named RHE/DOX nanoparticles (RD NPs); this assembly was associated with the interaction force and did not involve any organic solvents. RESULTS: According to molecular dynamics (MD) simulations, DOX molecules tend to assemble around RHE molecules through intermolecular forces. This intermolecular retention of DOX was further improved by the nanosizing effect of RD NPs. Compared to free DOX, RD NPs exerted a slightly stronger inhibitory effect on 4T1 cells in the scratch healing assay. As a dual drug-loaded nanoformulation, the efficacy of RD NPs against tumor cells in vitro was synergistically enhanced. Compared to free DOX, the combination of DOX and RHE in nanoparticles exerted a synergistic effect with a combination index (CI) value of 0.51 and showed a stronger ability to induce cell apoptosis. Furthermore, the RD NP treatment not only effectively suppressed primary tumor growth but also significantly inhibited tumor metastasis both in vitro and in vivo, with a better safety profile. CONCLUSIONS: The generation of pure nanodrugs via a self-assembly approach might hold promise for the development of more efficient and novel excipient-free nanodispersions, particularly for two small molecular antitumor drugs that potentially exert synergistic antiproliferative effects on metastatic breast cancer.

Cooperative Au/Ag Dual-Catalyzed Cross-Dehydrogenative Biaryl Coupling: Reaction Development and Mechanistic Insight.

An operationally simple and highly selective Au/Ag bimetallic-catalyzed cross-dehydrogenative biaryl coupling between pyrazoles and fluoroarenes has been developed. With this reaction, a wide range of biheteroaryl products can be obtained in moderate to good yields with excellent functional group compatibility. The exact role of silver salts, previously overlooked in most gold-catalyzed transformations, has been carefully investigated in this biaryl coupling. Insightful experimental and theoretical studies indicate that silver acetate is the actual catalyst for C-H activation of electron-poor arenes, rather than the previously reported gold(I)-catalyzed process. An unprecedented Au/Ag dual catalysis is proposed, in which silver(I) is responsible for the activation of electron-poor fluoroarenes via a concerted metalation-deprotonation pathway, and gold(III) is responsible for the activation of electron-rich pyrazoles via an electrophilic aromatic substitution process. Kinetic studies reveal that ArFnAu(III)-mediated C-H activation of pyrazoles is most likely the rate-limiting step.

Kruppel-like factor 2 mediated anti-proliferative and anti-metastasis effects of simvastatin in p53 mutant colon cancer.

The changes in cellular metabolism play an important role in promoting tumor progression. Recent findings suggested that the mutation of tumor suppressor gene p53 promoted lipids synthesis and mutant p53 (mutp53) was essential for regulating mevalonate pathway for cholesterol synthesis. Simvastatin, a 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor, was found to exhibit therapeutic effects against many types of cancers including breast cancer, colon cancer, lung cancer, etc. However, the underlying mechanism of the antitumor effect of simvastatin still needs to be further investigated. Our data demonstrated that suppression of mevalonate pathway by simvastatin significantly upregulated Kruppel-like factor 2 (KLF2) and p21WAF1/CIP1 expression in mutp53 colon cancer cells SW1116 but not in p53 wild type cells HCT116. Meanwhile, we found that overexpression of KLF2 could significantly induce p21WAF1/CIP1 expression, inhibit Wnt signaling and suppress epithelial-mesenchymal transition, indicating that KL2 might mediate antitumor effect of simvastatin in SW1116 cells. Moreover, bioinformatic analysis from The Cancer Genome Atlas (TCGA) database indicated that KLF2 were positively correlated with CDKN1A (encoding p21WAF1/CIP1), both of which were downregulated in colon cancer tissue, especially in p53 mutant colon cancer tissue. The results showed that KLF2 might be a tumor suppressor gene in colon cancer, which was in accordance with our experimental data. We also found that CDKN1A expression in mutant p53 colon cancer tissue was significant decreased when compared with p53 wild type colon cancer tissue, while Wnt ligand Wnt5a exhibited the highest level in p53 mutant colon cancer tissue. These data provide strong evidences for clinical application of simvastatin in treatment of colon cancer with p53 mutation.

Droplet digital PCR for quantification of PML-RARα in acute promyelocytic leukemia: a comprehensive comparison with real-time PCR.

Real-time quantitative PCR (qPCR) has been widely implemented for molecular testing, but there are still some inherent limitations that hamper its usefulness. Droplet digital PCR (ddPCR), which can provide direct, standards-free quantification, has recently received increasing attention. In our study, a comprehensive comparison of ddPCR with qPCR in relation to the quantification of PML-RARα was performed to evaluate the diagnostic potential of ddPCR. Results showed that ddPCR displayed significant concordance with qPCR in the detection of PML-RARα in clinical samples, but showed advantages over qPCR in terms of precision, limit of detection (LOD), and other basic performance parameters. A study of the feasibility of duplexing also indicated that ddPCR could simultaneously quantify the target PML-RARα and the clinical common reference gene ABL in a reaction, in contrast to qPCR. Moreover, ddPCR was more tolerant than qPCR of inhibition, and was shown to be able to quantify inhibition-prone samples. Another advantage of using ddPCR in clinical applications is that it will yield accurate results for patients with PML-RARα levels that fluctuate around the LOD of qPCR. Therefore, ddPCR is considered to have the potential to become a reliable alternative technique for quantifying PML-RARα. Graphical abstract ᅟ.

Structures and properties of large supramolecular coordination complexes predicted with the generalized energy-based fragmentation method.

The generalized energy-based fragmentation (GEBF) method has been extended to facilitate ab initio calculations of large supramolecular coordination complexes. For metal-containing coordination complexes, a special fragmentation scheme is proposed for GEBF calculations, in which coordinate bonds between metal ions and ligands are kept intact, and only single covalent bonds in organic ligands are cut into fragments. A simple strategy is exploited for the determination of the ground-state spin multiplicity of each metal ion so that the total spin of all metal-containing subsystems is assigned automatically. With this fragmentation scheme, the GEBF method is demonstrated to provide reliable energies, optimized geometry, nuclear magnetic resonance (NMR) properties and the infrared spectrum for a medium-sized supramolecular coordination complex, which are very consistent with those from the full-system quantum chemistry calculations. The GEBF method is then applied to two large supramolecular coordination complexes to illustrate its capability. For the trimetallic coordination complex Fe2Zn2(RuL2)2 (with 618 atoms), the calculated 1H chemical shifts from GEBF calculations with the B97-2 functional can account well for the experimental NMR spectrum. For the cage-guest complex Pd4L8(BF4-)3, the computed infrared spectrum obtained with the GEBF-M06-2X method can help assign the experimental peaks to the corresponding vibrational motions. The GEBF method combining with advanced electronic structure methods is expected to be a useful tool to understand and interpret structural and spectroscopic information of various supramolecular coordination complexes.

Accurate prediction of the structure and vibrational spectra of ionic liquid clusters with the generalized energy-based fragmentation approach: critical role of ion-pair-based fragmentation.

A generalized energy-based fragmentation (GEBF) approach has been developed to facilitate ab initio calculations of the ground-state energies, structures and vibrational spectra of general ionic liquid (IL) clusters. For the selected IL clusters, the accuracy of the GEBF approach with two different fragmentation schemes (ion-pair-based fragmentation and ion-based fragmentation) is evaluated with the conventional quantum chemistry calculations. Our results demonstrate that for the selected IL clusters, the GEBF approach with the ion-pair-based fragmentation scheme can provide much more accurate descriptions than that with the ion-based fragmentation scheme. The main reason for these results is that the non-integer charge behavior of each ion (cation or anion) in IL systems may induce significant errors for the GEBF approach with the ion-based fragmentation scheme, in which every ion is assumed to have an integer charge. However, this problem can be avoided by the ion-pair-based fragmentation scheme, in which each ion pair is assumed to be electrically neutral. Our illustrative results show that the GEBF approach with a dynamic ion-pair-based fragmentation scheme, in which ion pair fragments are updated for every structure, can provide satisfactory descriptions on the ground-state energies, optimized structures, and vibrational spectra of general IL clusters. The performance of the GEBF approach is found to be almost independent of the basis sets or theoretical methods, and the computational cost of the GEBF approach scales linearly with the system size at density functional theory (DFT) and second-order Møller-Plesset perturbation theory (MP2) levels. Due to its excellent parallel efficiency, the GEBF approach is expected to be a cost-effective tool for investigating the structure, vibrational spectra, as well as other properties of large IL clusters.

DNA nanopore functionalized with aptamer and cell-penetrating peptide for tumor cell recognition.

In the present work, DNA nanopore was composed of a bundle of six DNA duplexes folded from six DNA strands and functionalized with Ramos cell aptamer and cell-penetrating peptide (CPP). Herein, we present a unique dually conjugated molecule with an aptamer and cell-penetrating peptide for targeting and recognition of Ramos cells. The aptamer sequence was specific bound to Ramos cell, at the meanwhile the nanopore assembly was taken onto the surface of cell membrane and then got into the cells with the help of CPP. Specific targeting and increased intracellular uptake of nanostructures by Ramos cells were aimed. The intracellular uptake of the structure was determined using confocal microscopy. This study is the first to describe the recognition of tumor cells with functional DNA nanopores, establishing the foundation for the tumor cell detection with low cytotoxic agents. Graphical abstract DNA nanopore was composed of a bundle of six DNA duplexes folded from six DNA strands and functionalized with Ramos cell aptamer and cell-penetrating peptide. The dually conjugated molecule was found to show both improved cellular uptake and effective Ramos cell targeting.

Are fragment-based quantum chemistry methods applicable to medium-sized water clusters?

Fragment-based quantum chemistry methods are either based on the many-body expansion or the inclusion-exclusion principle. To compare the applicability of these two categories of methods, we have systematically evaluated the performance of the generalized energy based fragmentation (GEBF) method (J. Phys. Chem. A, 2007, 111, 2193) and the electrostatically embedded many-body (EE-MB) method (J. Chem. Theory Comput., 2007, 3, 46) for medium-sized water clusters (H2O)n (n = 10, 20, 30). Our calculations demonstrate that the GEBF method provides uniformly accurate ground-state energies for 10 low-energy isomers of three water clusters under study at a series of theory levels, while the EE-MB method (with one water molecule as a fragment and without using the cutoff distance) shows a poor convergence for (H2O)20 and (H2O)30 when the basis set contains diffuse functions. Our analysis shows that the neglect of the basis set superposition error for each subsystem has little effect on the accuracy of the GEBF method, but leads to much less accurate results for the EE-MB method. The accuracy of the EE-MB method can be dramatically improved by using an appropriate cutoff distance and using two water molecules as a fragment. For (H2O)30, the average deviation of the EE-MB method truncated up to the three-body level calculated using this strategy (relative to the conventional energies) is about 0.003 hartree at the M06-2X/6-311++G** level, while the deviation of the GEBF method with a similar computational cost is less than 0.001 hartree. The GEBF method is demonstrated to be applicable for electronic structure calculations of water clusters at any basis set.

A Quinoline-Based Ratiometric and Reversible Fluorescent Probe for Cadmium Imaging in Living Cells.

We report a novel ratiometric and reversible fluorescent probe for Cd(2+) detection utilizing a 6-(dimethylamino)quinaldine derivative as the fluorophore and a 2-hydrazinopyridine derivative as Cd(2+) chelator. This ratiometric fluorescent probe possesses favorable photophysical properties. It shows a large (55 nm) red-shift from 515 nm to 570 nm in the emission spectrum. Moreover, this probe also exhibits an excellent linear relationship of fluorescence intensity ratio (F570/F515) (R(2)=0.989) vs. Cd(2+) concentration in the range of 0-10 µM at physiological pH, which can serve as a "quantitative detecting" probe for Cd(2+). Utilizing this sensitive and selective probe, we have successfully detected Cd(2+) in living cells.

Evaluation of the correlation of wall elasticity between different sections of radial artery by velocity vector imaging.

AIM: This study aimed to evaluate the correlation between the elasticity of the anterior and posterior walls of the radial artery in different sections using velocity vector imaging. MATERIAL AND METHODS: In this retrospective analysis, 30 healthy people who underwent physical examination in our hospital from January 2022 to January 2023 were analyzed offline by velocity vector imaging technology. The following parameters were assessed: peak systolic strain (Ss; %), peak diastolic strain (Sd; %), peak systolic strain rate (SRs; 1/s), and peak diastolic strain rate (SRd; 1/s). Elastic function was evaluated by analyzing the systolic and diastolic motion of the arterial walls. RESULT: In the long-axis sections, there was a significant positive correlation between Ss, SRs, and SRd of both the anterior and posterior walls (r=0.531, r=0.803, and r=0.898, all p<0.01). Additionally, Sd showed a positive correlation (r=0.402, p<0.05). In the short-axis sections, there was a significant and positive correlation between SRs and SRd of both walls (r=0.762, r=0.667, both p<0.01). Furthermore, a positive correlation was found between SRd in the long-axis and short-axis sections of the anterior wall (r=0.382, p<0.05). CONCLUSIONS: Velocity vector imaging is a valuable tool for assessing the elasticity of the radial artery in different sections, and the longitudinal SRd in the long-axis section may serve as a highly sensitive and accurate parameter for assessing changes in wall elastic function during the occurrence of radial artery lesions.

Significant Differences in Intestinal Bacterial Communities of Sympatric Bean Goose, Hooded Crane, and Domestic Goose.

The host's physiological well-being is intricately associated with the gut microbiota. However, previous studies regarding the intestinal microbiota have focused on domesticated or captive birds. This study used high-throughput sequencing technology to identify the gut bacterial communities of sympatric bean geese, hooded cranes, and domestic geese. The results indicated that the gut bacterial diversity in domestic geese and hooded cranes showed considerably higher diversity than bean geese. The gut bacterial community compositions varied significantly among the three hosts (p < 0.05). Compared to the hooded crane, the bean goose and domestic goose were more similar in their genotype and evolutionary history, with less difference in the bacterial community composition and assembly processes between the two species. Thus, the results might support the crucial role of host genotypes on their gut microbiota. The gut bacteria of wild hooded cranes and bean geese had a greater capacity for energy metabolism compared to domestic geese, suggesting that wild birds may rely more on their gut microbiota to survive in cold conditions. Moreover, the intestines of the three hosts were identified as harboring potential pathogens. The relative abundance of pathogens was higher in the hooded crane compared to the other two species. The hooded crane gut bacterial community assemblage revealed the least deterministic process with the lowest filtering/selection on the gut microbiota, which might have been a reason for the highest number of pathogens result. Compared to the hooded crane, the sympatric bean goose showed the least diversity and relative abundance of pathogens. The intestinal bacterial co-occurrence network showed the highest stability in the bean goose, potentially enhancing host resistance to adverse environments and reducing the susceptibility to pathogen invasion. In this study, the pathogens were also discovered to overlap among the three hosts, reminding us to monitor the potential for pathogen transmission between poultry and wild birds. Overall, the current findings have the potential to enhance the understanding of gut bacterial and pathogenic community structures in poultry and wild birds.

Clinical-Molecular characteristics and Post-Translational modifications of colorectal cancer in north China: Implications for future targeted therapies.

This study delineated the elucidate molecular changes and their post-translational modifications (PTMs) in heterogenetic colorectal cancer (CRC) for a deeper understanding of the CRC pathophysiology and identifying potential therapeutic targets. In this retrospective study, the profiles of 13 hot spot gene mutations were analyzed and the microsatellite instability (MSI) status was determined.Employing the Circulating Single-Molecule Amplification and Resequencing Technology (cSMART) assay, the clinical-pathological features of CRC were characterized in 249 Chinese patients. PTMs were quantified online.Among the patients with CRC, the mutation frequencies of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC genes were 47.8%, 3.6%, 4.8%, 13.7%, 55.8%, and 36.9%, respectively. The proportion of MSI-high (MSI-H) was 7.8%.Subsequent multiple logistic regression analysis showed significant associations including a link between lung metastasis and KRAS mutation, between liver metastasis and lymph node metastasis, between MSI-H and early-onset CRC (EOCRC) and KRAS mutation, between right-sided colon cancer and peritoneal metastasis, and between PIK3CA mutation and PTEN mutation. Patients with KRAS mutation presented with MSI-H, lung metastasis, and PIK3CA mutation. MSI-H, BRAF mutation, and PTEN mutation were more frequent in EOCRC. Phosphorylation and ubiquitylation were found in KRAS, BRAF, PTEN, and SMAD4; SUMOylation and ubiquitylation were observed in HRAS and NRAS; while phosphorylation was obvious in APC, P53, and MLH1. Notably, Phosphorylation and ubiquitylation were the two most common PTMs. The biological characteristics of CRC in Chinese patients have some unique clinical features, which can be explained by the genetic mutation profile, correlations among gene mutations and clinical characteristics. These distinctions set the Chinese patient population apart from their Western counterparts.

Responsive Liquid Crystal Network Microstructures with Customized Shapes and Predetermined Morphing for Adaptive Soft Micro-Optics.

Stimuli-responsive materials have garnered substantial interest in recent years, particularly liquid crystal networks (LCNs) with sophisticatedly designed structures and morphing capabilities. Extensive efforts have been devoted to LCN structural designs spanning from two-dimensional (2D) to three-dimensional (3D) configurations and their intricate morphing behaviors through designed alignment. However, achieving microscale structures and large-area preparation necessitates the development of novel techniques capable of facilely fabricating LCN microstructures with precise control over both overall shape and alignment, enabling a 3D-to-3D shape change. Herein, a simple and cost-effective in-cell soft lithography (ICSL) technique is proposed to create LCN microstructures with customized shapes and predesigned morphing. The ICSL technique involves two sequential steps: fabricating the desired microstructure as the template by using the photopolymerization-induced phase separation (PIPS) method and reproducing the LCN microstructures through templating. Meanwhile, surface anchoring is employed to design and achieve molecular alignment, accommodating different deformation modes. With the proposed ICSL technique, cylindrical and spherical microlens arrays (CMLAs and SMLAs) have been successfully fabricated with stimulus-driven polarization-dependent focusing effects. This technique offers distinct advantages including high customizability, large-area production, and cost-effectiveness, which pave a new avenue for extensive applications in different fields, exemplified by adaptive soft micro-optics and photonics.

ICG-labeled PD-L1-antagonistic affibody dimer for tumor imaging and enhancement of tumor photothermal-immunotherapy.

In clinical practice, tumor-targeting diagnosis and immunotherapy against programmed death ligand 1 (PD-L1) have a significant impact. In this research, a PD-L1-antagonistic affibody dimer (ZPD-L1) was successfully prepared through Escherichia coli expression system, and conjugated with the photosensitizer of ICG via N-hydroxysuccinimide (NHS) ester to develop a novel tumor-targeting agent (ICG-ZPD-L1) for both tumor imaging diagnosis and photothermal-immunotherapy simultaneously. In vitro, ZPD-L1 could specifically bind to PD-L1-positive LLC and MC38 tumor cells, and ICG-ZPD-L1-mediated photothermal therapy (PTT) also showed excellent phototoxicity to these tumor cells. In vivo, ICG-ZPD-L1 selectively enriched into the PD-L1-positive MC38 tumor tissues, and the high-contrast optical imaging of tumors was obtained. ICG-ZPD-L1-mediated PTT exhibited a potent anti-tumor effect in vivo due to its remarkable photothermal properties. Furthermore, ICG-ZPD-L1-mediated PTT significantly induced the immunogenic cell death (ICD) of primary tumors, promoted maturation of dendritic cells (DCs), up-regulated anti-tumor immune response, enhanced immunotherapy, and superiorly inhibited the growth of metastatic tumors. In addition, ICG-ZPD-L1 showed favorable biosafety throughout the brief duration of treatment. In summary, these results suggest that ICG-ZPD-L1 is a multifunctional tumor-targeting drug integrating tumor imaging diagnosis and photothermal-immunotherapy, and has great guiding significance for the diagnosis and treatment of clinical PD-L1-positive tumor patients.

[The effect of eukaryotic expression plasmid ARHI on gastric cancer].

OBJECTIVE: To study the effect of expressed aplasia ras homolog member I (ARHI) on the malignant biological behaviors of gastric cancer including the proliferation, migration and invasion of the cell. METHODS: The eukaryotic expression plasmid of ARHI was constructed and transfected into MKN-28 cell with lipofectamine 2000 as pEGFP-ARHI group, transfected with pEGFP-N1 as pEGFP-N1 group, and untreated MKN-28 as control group. The expression of ARHI was detected by Western blotting and fluorescence microscope. CCK-8 assay was used to analyze the cell proliferation, the wound-healing assay and transwell assay were performed to investigate the effects on migration and invasion. RESULTS: Compared with the pEGFP-N1 group and control group, proliferation, invasion and migration of the pEGFP-ARHI group were depressed (P < 0.05). CONCLUSION: Recombination eukaryotic expression pEGFP-ARHI could partially reverse the malignant phenotypes of gastric cancer cell MKN-28.