Catalytic Dual-Mode Immunotherapy: Anisotropic AuPt Heterostructure Decorated with Starry Pt Nanoclusters for Robust Cancer Photometalloimmunotherapy.

To overcome current limitations in photoimmunotherapy, such as insufficient tumor antigen generation and a subdued immune response, a novel photo-/metallo dual-mode immunotherapeutic agent (PMIA) is introduced for potent near-infrared (NIR) light-triggered cancer therapy. PMIA features a dumbbell-like AuPt heterostructure decorated with starry Pt nanoclusters, meticulously engineered for enhancing plasmonic catalysis through multi-dimensional regulation of Pt growth on Au nanorods. Under NIR laser exposure, end-tipped Pt nanoclusters induce efficient electron-hole spatial separation along the longitudinal axis, resulting in radial and axial electron distribution polarization, conferring unique anisotropic properties to PMIA. Additionally, starry Pt nanoclusters on the sides of Au nanorods augment the local electron enrichment field. Validated through finite-difference time-domain analysis and Raman scattering, this configuration fosters local electron enrichment, facilitating robust reactive oxygen species generation for potent photoimmunotherapy. Moreover, Pt nanoclusters facilitate Pt2+ ion release, instigating intranuclear DNA damage and inducing synergistic immunogenic cell death (ICD) for metalloimmunotherapy. Consequently, PMIA elicits abundant danger-associated molecular patterns, promotes T cell infiltration, and triggers systemic immune responses, effectively treating primary and distant tumors, inhibiting metastasis in vivo. This study unveils a pioneering dual-mode ICD amplification strategy driven by NIR light, synergistically integrating photoimmunotherapy and metalloimmunotherapy, culminating in potent cancer photometalloimmunotherapy.

A combination influenza mRNA vaccine candidate provided broad protection against diverse influenza virus challenge.

Influenza viruses present a significant threat to global health. The production of a universal vaccine is considered essential due to the ineffectiveness of current seasonal influenza vaccines against mutant strains. mRNA technology offers new prospects in vaccinology, with various candidates for different infectious diseases currently in development and testing phases. In this study, we encapsulated a universal influenza mRNA vaccine. The vaccine encoded influenza hemagglutinin (HA), nucleoprotein (NP), and three tandem repeats of matrix protein 2 (3M2e). Twice-vaccinated mice exhibited strong humoral and cell-mediated immune responses in vivo. Notably, these immune responses led to a significant reduction in viral load of the lungs in challenged mice, and also conferred protection against future wild-type H1N1, H3N2, or H5N1 influenza virus challenges. Our findings suggest that this mRNA-universal vaccine strategy for influenza virus may be instrumental in mitigating the impact of future influenza pandemics.

Colorectal cancer with low SLC35A3 is associated with immune infiltrates and poor prognosis.

The expression level of SLC35A3 is associated with the prognosis of many cancers, but its role in colorectal cancer (CRC) is unclear. The purpose of our study was to elucidate the role of SLC35A3 in CRC. The expression levels of SLC35A3 in CRC were evaluated through tumor immune resource assessment (TIMER), The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), International Cancer Genome Consortium (ICGC), Human Protein Atlas (HPA), qRT-PCR, and immunohistochemical evaluation. TCGA, GEO, and ICGC databases were used to analyze the diagnostic and prognostic value of SLC35A3 in CRC. A overall survival (OS) model was constructed and validated based on the expression level of SLC35A3 and multivariable analysis results. The cBioPortal tool was used to analyze SLC35A3 mutation in CRC. The UALCAN tool was used to analyze the promoter methylation level of SLC35A3 in colorectal cancer. In addition, the role of SLC35A3 in CRC was determined through GO analysis, KEGG analysis, gene set enrichment analysis (GSEA), immune infiltration analysis, and immune checkpoint correlation analysis. In vitro experiments validated the function of SLC35A3 in colorectal cancer cells. Compared with adjacent normal tissues and colonic epithelial cells, the expression of SLC35A3 was decreased in CRC tissues and CRC cell lines. Low expression of SLC35A3 was associated with N stage, pathological stage, and lymphatic infiltration, and it was unfavorable for OS, disease-specific survival (DSS), recurrence-free survival (RFS), and post-progression survival (PPS). According to the Receiver Operating Characteristic (ROC) analysis, SLC35A3 is a potential important diagnostic biomarker for CRC patients. The nomograph based on the expression level of SLC35A3 showed a better predictive model for OS than single prognostic factors and TNM staging. SLC35A3 has multiple types of mutations in CRC, and its promoter methylation level is significantly decreased. GO and KEGG analysis indicated that SLC35A3 may be involved in transmembrane transport protein activity, cell communication, and interaction with neurotransmitter receptors. GSEA revealed that SLC35A3 may be involved in energy metabolism, DNA repair, and cancer pathways. In addition, SLC35A3 was closely related to immune cell infiltration and immune checkpoint expression. Immunohistochemistry confirmed the positive correlation between SLC35A3 and helper T cell infiltration. In vitro experiments showed that overexpression of SLC35A3 inhibited the proliferation and invasion capability of colorectal cancer cells and promoted apoptosis. The results of this study indicate that decreased expression of SLC35A3 is closely associated with poor prognosis and immune cell infiltration in colorectal cancer, and it can serve as a promising independent prognostic biomarker and potential therapeutic target.

A Recombinant Oncolytic Influenza Virus Carrying GV1001 Triggers an Antitumor Immune Response.

Oncolytic viruses are able to lyse tumor cells selectively in the liver without killing normal hepatocytes, in addition to activating the immune response. Oncolytic virus therapy is expected to revolutionize the treatment of liver cancer, including hepatocellular carcinoma (HCC), one of the most frequent and fatal malignancies. In this study, reverse genetics techniques were exploited to load NA fragments of the A/PuertoRico/8/34 virus (PR8) with GV1001 peptides derived from human telomerase reverse transcriptase. An in vitro assessment of the therapeutic effect of the recombinant oncolytic virus was followed by an in vivo study in mice with HCC. The recombinant virus was verified by sequencing of the recombinant viral gene sequence, and viral virulence was detected by hemagglutination assays and based on the 50% tissue culture infectious dose (TCID50). The morphological structure of the virus was observed by electron microscopy, and GV1001 peptide was localized by cellular immunofluorescence. The selective cytotoxicity of the recombinant oncolytic virus in vitro was demonstrated in cultured HCC cells and normal hepatocytes, as only the tumor cells were killed; the normal cells were not significantly altered. Consistent with the in vitro results, the recombinant oncolytic influenza virus significantly inhibited liver tumor growth in mice in vivo, in addition to inducing an antitumor immune response, including an increase in the number of CD4+ and CD8+ T lymphocytes and, in turn, improving survival. Our results suggest that oncolytic influenza virus carrying GV1001 is a promising immunotherapy in patients with HCC.

Mechanism of Bazhen decoction in the treatment of colorectal cancer based on network pharmacology, molecular docking, and experimental validation.

Objective: Bazhen Decoction (BZD) is a common adjuvant therapy drug for colorectal cancer (CRC), although its anti-tumor mechanism is unknown. This study aims to explore the core components, key targets, and potential mechanisms of BZD treatment for CRC. Methods: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) was employed to acquire the BZD's active ingredient and targets. Meanwhile, the Drugbank, Therapeutic Target Database (TTD), DisGeNET, and GeneCards databases were used to retrieve pertinent targets for CRC. The Venn plot was used to obtain intersection targets. Cytoscape software was used to construct an "herb-ingredient-target" network and identify core targets. GO and KEGG pathway enrichment analyses were conducted using R language software. Molecular docking of key ingredients and core targets of drugs was accomplished using PyMol and Autodock Vina software. Cell and animal research confirmed Bazhen Decoction efficacy and mechanism in treating colorectal cancer. Results: BZD comprises 173 effective active ingredients. Using four databases, 761 targets related to CRC were identified. The intersection of BZD and CRC yielded 98 targets, which were utilized to construct the "herb-ingredient-target" network. The four key effector components with the most targets were quercetin, kaempferol, licochalcone A, and naringenin. Protein-protein interaction (PPI) analysis revealed that the core targets of BZD in treating CRC were AKT1, MYC, CASP3, ESR1, EGFR, HIF-1A, VEGFR, JUN, INS, and STAT3. The findings from molecular docking suggest that the core ingredient exhibits favorable binding potential with the core target. Furthermore, the GO and KEGG enrichment analysis demonstrates that BZD can modulate multiple signaling pathways related to CRC, like the T cell receptor, PI3K-Akt, apoptosis, P53, and VEGF signaling pathway. In vitro, studies have shown that BZD dose-dependently inhibits colon cancer cell growth and invasion and promotes apoptosis. Animal experiments have shown that BZD treatment can reverse abnormal expression of PI3K, AKT, MYC, EGFR, HIF-1A, VEGFR, JUN, STAT3, CASP3, and TP53 genes. BZD also increases the ratio of CD4+ T cells to CD8+ T cells in the spleen and tumor tissues, boosting IFN-γ expression, essential for anti-tumor immunity. Furthermore, BZD has the potential to downregulate the PD-1 expression on T cell surfaces, indicating its ability to effectively restore T cell function by inhibiting immune checkpoints. The results of HE staining suggest that BZD exhibits favorable safety profiles. Conclusion: BZD treats CRC through multiple components, targets, and metabolic pathways. BZD can reverse the abnormal expression of genes such as PI3K, AKT, MYC, EGFR, HIF-1A, VEGFR, JUN, STAT3, CASP3, and TP53, and suppresses the progression of colorectal cancer by regulating signaling pathways such as PI3K-AKT, P53, and VEGF. Furthermore, BZD can increase the number of T cells and promote T cell activation in tumor-bearing mice, enhancing the immune function against colorectal cancer. Among them, quercetin, kaempferol, licochalcone A, naringenin, and formaronetin are more highly predictive components related to the T cell activation in colorectal cancer mice. This study is of great significance for the development of novel anti-cancer drugs. It highlights the importance of network pharmacology-based approaches in studying complex traditional Chinese medicine formulations.

Gold-semiconductor nanohybrids as advanced phototherapeutics.

Phototherapeutics is gaining momentum as a mainstream treatment for cancer, with gold-semiconductor nanocomposites showing promise as potent phototherapeutic agents due to their structural tunability, biocompatibility and functional diversity. Such nanohybrids possess plasmonic characteristics in the presence of gold and the catalytic nature of semiconductor units, as well as the unexpected physicochemical properties arising from the contact interface. This perspective provides an overview of the latest research on gold-semiconductor nanocomposites for photodynamic, photothermal and photocatalytic therapy. The relationship between the spatial configuration of these nanohybrids and their practical performance was explored to deliver comprehensive insights and guidance for the design and fabrication of novel composite nanoplatforms to enhance the efficiency of phototherapeutics, promoting the development of nanotechnology-based advanced biomedical applications.

Osmotic stress-induced localisation switch of CBR1 from mitochondria to the endoplasmic reticulum triggers ATP production via ß-oxidation to respond to osmotic shock.

Drought and high salinity are major environmental factors that reduce plant growth and development, leading to loss of plant productivity in agriculture. Under these stress conditions, photosynthesis is greatly suppressed despite the high cellular energy cost of stress response processes. Currently, the process that allows plants to secure the energy required for osmotic stress responses remains elusive. Here, we provide evidence that cytochrome b5 reductase 1 (CBR1), a cytochrome b5 reductase, plays an important role in ATP production in response to NaCl and dehydration stresses. Overexpression and loss of function of CBR1 led to enhanced resistance and sensitivity, respectively, to osmotic stress. Upon exposure to osmotic stress, CBR1 was localised to the endoplasmic reticulum (ER) instead of to mitochondria, where it was localised under normal conditions. Transgenic plants overexpressing ER-targeted CBR1 showed enhanced resistance to osmotic stress. Moreover, CBR1-ER and CBR1-OX plants, had higher levels of ATP and unsaturated fatty acids under osmotic stress. However, these effects were abrogated by thioridazine and 2-deoxy glucose, inhibitors of ß-oxidation and glycolysis, respectively. Based on these results, we propose that ER-localised CBR1 triggers ATP production via the production and ß-oxidation of polyunsaturated fatty acids under osmotic stress.

Circular RNA hsa_circ_0064559 affects tumor cell growth and progression of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally. It is essential to identify new CRC-associated therapeutic targets and diagnostic biomarkers. Previous studies have demonstrated that a series of circular RNAs (circRNAs) play a crucial role in CRC pathogenesis. This study assessed the potential of hsa_circ_0064559 in tumor cell growth and progression of CRC. METHODS: Six pairs of matched CRC and normal colorectal tissue samples were sequenced using the Affymetrix Clariom D array. Using RNA interference, the expression of thirteen circRNAs was knocked down in CRC cells. The proliferation of CRC cell lines (RKO and SW620 cells) was detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Apoptosis and cell cycle were determined by flow-cytometric analysis. An in vivo study uses nude mice to establish a CRC mouse model. The differentially expressed genes were analyzed using Affymetrix primeview human GeneChip array and verified by polymerase chain reaction. RESULTS: Affymetrix Clariom D array analysis revealed that thirteen circRNAs were upregulated in CRC. The proliferation of CRC cell lines was decreased, while the proportion of apoptotic and G1 phase cells was higher after hsa_circ_0064559 knockdown. In vivo xenograft nude mice model revealed that the volume and weight of the tumor were reduced by hsa_circ_0064559 knockdown. In Affymetrix primeview human GeneChip array, we found six upregulated genes (STAT1, ATF2, TNFRSF10B, TGFBR2, BAX, and SQSTM1) and two downregulated genes (SLC4A7 and CD274) related to apoptosis and proliferation of colorectal cancer cells after hsa_circ_0064559 knockdown. CONCLUSIONS: The hsa_circ_0064559 knockdown could inhibit the proliferation, promote apoptosis in CRC cell lines in vitro, and inhibit the development of CRC tumors in vivo. The mechanism may be related to activating a wide range of signaling pathways. The hsa_circ_0064559 may be a potential biomarker for early diagnosis or prognosis of CRC and a novel drug target for CRC therapy.

Strong Ligand Control for Noble Metal Nanostructures.

ConspectusNanosynthesis is the art of creating nanostructures, with on-demand synthesis as the ultimate goal. Noble metal nanoparticles have wide applications, but the available synthetic methods are still limited, often giving nanospheres and symmetrical nanocrystals. The fundamental reason is that the conventional weak ligands are too labile to influence the materials deposition, so the equivalent facets always grow equivalently. Considering that the ligands are the main synthetic handles in colloidal synthesis, our group has been exploring strong ligands for new growth modes, giving a variety of sophisticated nanostructures. The model studies often involve metal deposition on seeds functionalized with a certain strong ligand, so that the uneven distribution of the surface ligands could guide the subsequent deposition.In this Account, we focus on the design principles underlying the new growth modes, summarizing our efforts in this area along with relevant literature works. The basics of ligand control are first revisited. Then, the four major growth modes are summarized as follows: (1) The curvature effects would divert the materials deposition away from the high-curvature tips when the ligands are insufficient. With ligands fully covering the seeds, the sparser ligand packing at the tips would then promote the initial nucleation thereon. (2) The strong ligands may get trapped under the incoming metal layer, thus modulating the interfacial energy of the core-shell interface. The evidence for embedded ligands is discussed, along with examples of Janus nanostructures arising from the synthetic control, including metal-metal, metal-semiconductor, and metal-C60 systems using a variety of ligands. (3) Active surface growth is an unusual mode with divergent growth rates, so that part of the emerging surface is inhibited, and the growth is focused onto a few active sites. With seeds attached to oxide substrates, the selective deposition at the metal-substrate interface produces ultrathin nanowires. The synthesis can be generally applied to grow Au, Ag, Pd, Pt, and hybrid nanowires, with straight, spiral, or helical structures, and even rapid alteration of segments via electrochemical methods. In contrast, active surface growth for colloidal nanoparticles has to be more carefully controlled. The rich growth phenomena are discussed, highlighting the role of strong ligands, the control of deposition rates, the chiral induction, and the evidence for the active sites. (4) An active site with sparse ligands could also be exploited in etching, where the freshly exposed surface would promote further etching. The result is an unusual sharpening etching mode, in contrast to the conventional rounding mode for minimized surface energy.Colloidal nanosynthesis holds great promise for scalable on-demand synthesis, providing the crucial nanomaterials for future explorations. The strong ligands have delivered powerful synthetic controls, which could be further enhanced with in-depth studies on growth mechanisms and synthetic strategies, as well as functions and properties.

Engineering the Au-Cu2 O Crystalline Interfaces for Structural and Catalytic Integration.

Precise structural control has attracted tremendous interest in pursuit of the tailoring of physical properties. Here, this work shows that through strong ligand-mediated interfacial energy control, Au-Cu2 O dumbbell structures where both the Au nanorod (AuNR) and the partially encapsulating Cu2 O domains are highly crystalline. The synthetic advance allows physical separation of the Au and Cu2 O domains, in addition to the use of long nanorods with tunable absorption wavelength, and the crystalline Cu2 O domain with well-defined facets. The interplay of plasmon and Schottky effects boosts the photocatalytic performance in the model photodegradation of methyl orange, showing superior catalytic efficiency than the AuNR@Cu2 O core-shell structures. In addition, compared to the typical core-shell structures, the AuNR-Cu2 O dumbbells can effectively electrochemically catalyze the CO2 to C2+ products (ethanol and ethylene) via a cascade reaction pathway. The excellent dual function of both photo- and electrocatalysis can be attributed to the fine physical separation of the crystalline Au and Cu2 O domains.

Modulating the Charge Transfer Plasmon in Bridged Au Core-Satellite Homometallic Nanostructures.

The localized surface plasmon resonance (LSPR) is one of the important properties for noble metal nanoparticles. Tuning the LSPR on demand thus has attracted tremendous interest. Beyond the size and shape control, manipulating intraparticle coupling is an effective way to tailor their LSPR. The charge transfer plasmon (CTP) is the most important mode of conductive coupling between subunits linked by conductive bridges that are well studied for structures prepared on substrates by lithography method. However, the colloidal synthesis of CTP structure remains a great challenge. This work reports the colloidal synthesis of extraordinary bridged Au core-satellite structures by exploiting the buffer effect of polydopamine shell on Au core for Au atom diffusion, in which the Au bridge is well controlled in terms of width and length. Benefiting from the tunable Au bridges, the resonance energy of the CTP can be readily controlled. As a result, the LSPR absorptions of the core-satellite structures are continuously tuned within the NIR spectral range (from 900 to >1300 nm), demonstrating their great potentials for ultrafast nano-optics and biomedical applications.

Immobilization of ZnIn2S4 on sodium alginate foam for efficient hexavalent chromium removal.

Photocatalytic technology has been extensively studied in the removal of toxic Cr(VI) from wastewater. However, common powdery photocatalysts suffer from poor recyclability and secondly pollution. Herein, the zinc indium sulfide (ZnIn2S4) particles were integrated onto the sodium alginate foam(SA) matrix through a facile way to obtain foam-shape catalyst. Diverse characterization techniques including X-ray diffraction(XRD), Fourier transform infrared(FT-IR), scanning electron microscope(SEM) and X-ray photoelectron spectroscopy(XPS) were employed to reveal the composite compositions, organic-inorganic interface interactions, mechanical property, and pore morphology of the foams. Results demonstrated that the ZnIn2S4 crystals wrapped on SA skeleton tightly and constructed a flower-like structure. As-prepared hybrid foam with lamellar structure showed great potential in Cr(VI) treatment due to the presence of macropores and highly available active sites. A maximum Cr(VI) photoreduction efficiency of 93 % were observed over the optimal sample of ZS-1 (with a ZnIn2S4:SA mass ratio of 1:1) under visible irradiation. When tested with mixed pollutants (Cr(VI)/dyes), the ZS-1 sample displayed an enhanced removal efficiency of 98 % for Cr(VI) and 100 % for Rhodamine B(RhB). Moreover, the composite maintained prominent photocatalytic performance and a relatively integral 3D structure scaffold after continuous six runs, revealing its superior reusability and durability.

Diffusion-controlled bridging of the Au Island and Au core in Au@Rh(OH)3 core-shell structure.

Hybrid nanostructures have garnered considerable interest because of their fascinating properties owing to the hybridization of materials and their structural varieties. In this study, we report the synthesis of [Au@Rh(OH)3]-Au island heterostructures using a seed-mediated sequential growth method. Through the thiol ligand-mediated interfacial energy, Au@Rh(OH)3 core-shell structures with varying shell thicknesses were successfully obtained. On these Au@Rh(OH)3 core-shell seeds, by modulating the diffusion of HAuCl4 in the porous Rh(OH)3 shell, site-specific growth of Au islands on the inner Au core or on the surface of the outer Rh(OH)3 shell was successfully achieved. Consequently, two types of distinct structures, the Au island-on-[Au@Rh(OH)3] dimer and Au island-Au bridge-[Au@Rh(OH)3] dumbbell structures with thin necks were obtained. Further modulations of the growth kinetics led to the formation of Au plate-Au bridge-[Au@Rh(OH)3] heterostructures with larger structural anisotropy. The flexible structural variations were demonstrated to be an effective means of modulating the plasmonic properties; the Au-Au heterostructures exhibited tunable localized surface plasmon resonance in the visible-near-infrared spectral region and can be used as surface-enhanced Raman scattering (SERS) substrates capable of emitting strong SERS signals. This diffusion-controlled growth of Au bridges in the Rh(OH)3 shells (penetrating growth) is an interesting new approach for structural control, which enriches the tool box for colloidal nanosynthesis. This advancement in structural control is expected to create new approaches for colloidal synthesis of sophisticated nanomaterials, and eventually enable their extensive applications in various fields.

Fatty acid desaturases (FADs) modulate multiple lipid metabolism pathways to improve plant resistance.

BACKGROUND: Biological and abiotic stresses such as salt, extreme temperatures, and pests and diseases place major constraints on plant growth and crop yields. Fatty acids (FAs) and FA- derivatives are unique biologically active substance that show a wide range of functions in biological systems. They are not only participated in the regulation of energy storage substances and cell membrane plasm composition, but also extensively participate in the regulation of plant basic immunity, effector induced resistance and systemic resistance and other defense pathways, thereby improving plant resistance to adversity stress. Fatty acid desaturases (FADs) is involved in the desaturation of fatty acids, where desaturated fatty acids can be used as substrates for FA-derivatives. OBJECTIVE: In this paper, the role of omega-FADs (ω-3 FADs and ω-6 FADs) in the prokaryotic and eukaryotic pathways of fatty acid biosynthesis in plant defense against stress (biological and abiotic stress) and the latest research progress were summarized. Moreover' the existing problems in related research and future research directions were also discussed. RESULTS: Fatty acid desaturases are involved in various responses of plants during biotic and abiotic stress. For example, it is involved in regulating the stability and fluidity of cell membranes, reactive oxygen species signaling pathways, etc. In this review, we have collected several experimental studies to represent the differential effects of fatty acid desaturases on biotic and abiotic species. CONCLUSION: Fatty acid desaturases play an important role in regulating biotic and abiotic stresses.

Metachronous small bowel adenocarcinoma after rectal adenocarcinoma: A case report.

RATIONALE: Small bowel adenocarcinoma (SBA), an uncommon gastrointestinal malignant tumor, is difficult to diagnose at an early stage because of its non-specific disease presentation. Metachronous SBA is a special type of SBA that is rarely reported. We herein report a case of metachronous primary SBA following resection of rectal adenocarcinoma. PATIENT CONCERNS: A 65-year-old man presented to our hospital after having experienced recurrent bowel obstruction for 6 months. He had undergone a Dixon operation 30 months previously followed by adjuvant chemotherapy with capecitabine plus oxaliplatin. DIAGNOSIS: Abdominal computed tomography showed thickened bowel walls in the right lower abdomen, and the patient was initially misdiagnosed with intestinal adhesion. After the operation, he was diagnosed with primary SBA (T3N0M0, stage IIA). INTERVENTIONS: Treatment with a transnasal ileus tube was ineffective. Therefore, we performed small intestinal segmental resection and side-to-side anastomosis through open surgery. OUTCOMES: The patient completed all postoperative adjuvant chemotherapy, and posttreatment surveillance revealed no further abnormalities. LESSONS: This case suggests that patients with colorectal adenocarcinoma may have an increased risk of metachronous SBA. Corresponding symptoms in high-risk patients should raise clinicians' suspicion for SBA, and further detailed examinations are imperative. Early screening for SBA may help to improve the patients' prognosis.

MYB Transcription Factors and Its Regulation in Secondary Cell Wall Formation and Lignin Biosynthesis during Xylem Development.

The secondary wall is the main part of wood and is composed of cellulose, xylan, lignin, and small amounts of structural proteins and enzymes. Lignin molecules can interact directly or indirectly with cellulose, xylan and other polysaccharide molecules in the cell wall, increasing the mechanical strength and hydrophobicity of plant cells and tissues and facilitating the long-distance transportation of water in plants. MYBs (v-myb avian myeloblastosis viral oncogene homolog) belong to one of the largest superfamilies of transcription factors, the members of which regulate secondary cell-wall formation by promoting/inhibiting the biosynthesis of lignin, cellulose, and xylan. Among them, MYB46 and MYB83, which comprise the second layer of the main switch of secondary cell-wall biosynthesis, coordinate upstream and downstream secondary wall synthesis-related transcription factors. In addition, MYB transcription factors other than MYB46/83, as well as noncoding RNAs, hormones, and other factors, interact with one another to regulate the biosynthesis of the secondary wall. Here, we discuss the biosynthesis of secondary wall, classification and functions of MYB transcription factors and their regulation of lignin polymerization and secondary cell-wall formation during wood formation.

Monoamine Oxidase A is a Major Mediator of Mitochondrial Homeostasis and Glycolysis in Gastric Cancer Progression.

OBJECTIVE: Monoamine oxidase A (MAO-A) is a mitochondrial protein involved in tumourigenesis in different types of cancer. However, the biological function of MAO-A in gastric cancer development remains unknown. METHODS: We examined MAO-A expression in gastric cancer tissues and in gastric cancer cell lines by immunohistochemistry and Western blot analyses. CCK8, FACS and bromodeoxyuridine incorporation assays were performed to assess the effects of MAO-A on gastric cancer cell proliferation. The role of MAO-A in mitochondrial function was determined through MitoSOX Red staining, ATP generation and glycolysis assays. RESULTS: In the present study, we observed that MAO-A was significantly upregulated in gastric cancer tissues and in AGS and MGC803 cells. The observed MAO-A inhibition indicated decreased cell cycle progression and proliferation. Silencing MAO-A expression was associated with suppressed migration and invasion of gastric cancer cells in vitro. Moreover, alleviated mitochondrial damage in these cells was demonstrated by decreased levels of mitochondrial reactive oxygen species and increased ATP generation. MAO-A knockdown also regulated the expression of the glycolysis rate-limiting enzymes hexokinase 2 and pyruvate dehydrogenase. Finally, we observed that the glycolysis-mediated effect was weakened in AGS and MGC803 cells when MAO-A was blocked. CONCLUSION: The findings of the present study indicate that MAO-A is responsible for mitochondrial dysfunction and aerobic glycolysis, which in turn leads to the proliferation and metastasis of human gastric tumour cells.

A non-synonymous polymorphism in NBS1 is associated with progression from chronic hepatitis B virus infection to hepatocellular carcinoma in a Chinese population.

PURPOSE: Nijmegen breakage syndrome 1 (NBS1) has a vital role in DNA double-strand break (DSB) repair, functioning as a sensor to identify and repair DNA damage and maintaining genomic stability by participating in the intra-S-phase checkpoint. Polymorphisms of NBS1 have been investigated in multiple cancers with variable results. To our best knowledge, no previous study has focused on the association between NBS1 single-nucleotide polymorphisms (SNPs) and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Five NBS1 SNPs were selected based on their potential functional impact. A hospital-based cohort, comprising 481 patients with HBV-related HCC, 508 patients with chronic hepatitis B virus infection (CHB), and 581 healthy controls, was recruited for genotyping analysis. RESULTS: After quality control, four SNPs were successfully genotyped (rs10464867, rs1063053, rs1805794, and rs709816), none of which were significantly associated with HCC or CHB compared with those of healthy controls. Similarly, the combined HBV-infected group (including the HCC and CHB groups) exhibited no significant associations with these SNPs compared with healthy controls. In contrast, comparison of the frequency of rs1805794 between patients with CHB and those with HCC identified a significant association (P=2.99E-03, odds ratio =1.31, 95% confidence interval =1.10-1.56). CONCLUSION: These findings suggest that, as a non-synonymous SNP, the rs1805794 C/G polymorphism may play a role in the progression from CHB to HCC.

MicroRNA­499 rs3746444 A/G polymorphism functions as a biomarker to predict recurrence following endoscopic submucosal dissection in primary early gastric cancer.

The aim of the present study was to investigate the molecular mechanism, including the potential regulatory and signaling pathways, of platelet­derived growth factor receptor ß (PDGFRB), which underlies the recurrence of early gastric cancer (EGC) following endoscopic submucosal dissection (ESD). Online microRNA (miRNA) target prediction tools were used, which identified PDGFRB as the candidate target gene of miR­499a in gastric cancer cells, and PFGRBR was then confirmed as the direct gene using a luciferase reporter assay system. The Kaplan­Meier method was used to plot recurrence­free curves, which were compared between genotype groups. A negative regulatory association between miR­499a and PDGFRB was established by investigating the relative luciferase activity at different concentrations of miR­499a mimics. Furthermore, as the rs3746444 polymorphism has been previously reported to interfere with the expression of miR­499a, the present study investigated the expression levels of different genotypes, including TT (n=20), TC (n=9) and CC (n=3), the results of which supported the hypothesis that the presence of the minor allele (C) of the rs3746444 polymorphism compromised the expression of miR­499a. The present study also performed polymerase chain reaction and western blot analyses to examine the mRNA and protein expression levels of PFGRBR among different genotypes or cells treated with different concentrations of miR­499a mimics/inhibitors, which indicated the negative regulatory association between miR­499a and PDGFRB. The present study also investigated the relative viabilities of EGC cells transfected with miR­499a mimics (50 and 100 nM) and miR­499a inhibitors (100 nM), and confirmed that miR­499a negatively interfered with the viability of the EGC cells. The miR­499a rs3746444 polymorphism was also recognized as a biomarker to predict recurrence following ESD in patients with EGC via analyzing the recurrence­free rates among patients with EGC with different genotypes. The results showed that PDGFRB was validated as a target of miR­499a, and rs3746444 was identified as a potential biomarker to predict the recurrence of EGC following ESD.

Antitumor effects of oncolytic herpes simplex virus type 2 against colorectal cancer in vitro and in vivo.

BACKGROUND: The incidence of colorectal cancer (CRC) is on the rise. Furthermore, late-stage diagnoses and limited efficacious treatment options make CRC a complex clinical challenge. Therefore, a new therapeutic regimen with a completely novel therapeutic mechanism is necessary for CRC. In the present study, the therapeutic efficacy of oncolytic herpes simplex virus type 2 (oHSV2) in CRC was assessed in vitro and in vivo. oHSV2 is an oncolytic agent derived from herpes simplex virus type 2 that encodes granulocyte-macrophage colony-stimulating factor. MATERIALS AND METHODS: We investigated the cytopathic effects of oHSV2 in CRC cell lines using the MTT assay. Then, cell cycle progression and apoptosis of oHSV2 were examined by flow cytometry. We generated a model of CRC with mouse CRC cell CT26 in BALB/c mice. The antitumor effects and adaptive immune response of oHSV2 were assessed in tumor-bearing mice. The therapeutic efficacy of oHSV2 was compared with the traditional chemotherapeutic agent, 5-fluorouracil. RESULTS: The in vitro data showed that oHSV2 infected the CRC cell lines successfully and that the tumor cells formed a significant number of syncytiae postinfection. The oHSV2 killed cancer cells independent of the cell cycle and mainly caused tumor cells necrosis. The in vivo results showed that oHSV2 significantly inhibited tumor growth and prolonged survival of tumor-bearing mice without weight loss. With virus replication, oHSV2 not only resulted in a reduction of myeloid-derived suppressor cells and regulatory T cells in the spleen, but also increased the number of mature dendritic cells in tumor-draining lymph nodes and the effective CD4+T and CD8+T-cells in the tumor microenvironment. CONCLUSION: Our study provides the first evidence that oHSV2 induces cell death in CRC in vitro and in vivo. These findings indicate that oHSV2 is an effective therapeutic cancer candidate that causes an oncolytic effect and recruits adaptive immune responses for an enhanced therapeutic impact, thus providing a potential therapeutic tool for treatment of CRC.