Tumor-targeted delivery of copper-manganese biomineralized oncolytic adenovirus for colorectal cancer immunotherapy.

Oncolytic viral therapy (OVT) is a novel anti-tumor immunotherapy approach, specifically replicating within tumor cells. Currently, oncolytic viruses are mainly administered by intratumoral injection. However, achieving good results for distant metastatic tumors is challenging. In this study, a multifunctional oncolytic adenovirus, OA@CuMnCs, was developed using bimetallic ions copper and manganese. These metal cations form a biomineralized coating on the virus's surface, reducing immune clearance. It is known that viruses upregulate the expression of PD-L1. Copper ions in OA@CuMnCs can decrease the PD-L1 expression of tumor cells, thereby promoting immune cell-related factor release. This process involves antigen presentation and the combination of immature dendritic cells, transforming them into mature dendritic cells. It changes "cold" tumors into "hot" tumors, further inducing immunogenic cell death. While oncolytic virus replication requires oxygen, manganese ions in OA@CuMnCs can react with endogenous hydrogen peroxide. This reaction produces oxygen, enhancing the virus's replication ability and the tumor lysis effect. Thus, this multifunctionally coated OA@CuMnCs demonstrates potent amplification in immunotherapy efficacy, and shows great potential for further clinical OVT. STATEMENT OF SIGNIFICANCE: Oncolytic virus therapy (OVs) is a new anti-tumor immunotherapy method that can specifically replicate in tumor cells. Although the oncolytic virus can achieve a therapeutic effect on some non-metastatic tumors through direct intratumoral injection, there are still three major defects in the treatment of metastatic tumors: immune response, hypoxia effect, and administration route. Various studies have shown that the immune response in vivo can be overcome by modifying or wrapping the surface protein of the oncolytic virus. In this paper, a multifunctional coating of copper and manganese was prepared by combining the advantages of copper and manganese ions. The coating has a simple preparation method and mild conditions, and can effectively enhance tumor immunotherapy.

Engineered Luminescent Oncolytic Vaccinia Virus Activation of Photodynamic-Immune Combination Therapy for Colorectal Cancer.

Oncolytic virus therapy is currently regarded as a promising approach in cancer immunotherapy. It has greater therapeutic advantages for colorectal cancer that is prone to distant metastasis. However, the therapeutic efficacy and clinical application of viral agents alone for colorectal cancer remain suboptimal. In this study, an engineered oncolytic vaccinia virus (OVV-Luc) that expresses the firefly luciferase gene is developed and loaded Chlorin e6 (Ce6) onto the virus surface through covalent coupling, resulting in OVV-Luc@Ce6 (OV@C). The OV@C infiltrates tumor tissue and induces endogenous luminescence through substrate catalysis, resulting in the production of reactive oxygen species. This unique system eliminates the need for an external light source, making it suitable for photodynamic therapy (PDT) in deep tissues. Moreover, this synergistic effect between PDT and viral immunotherapy enhances dendritic cell maturation, macrophage polarization, and reversal of the immunosuppressive microenvironment. This synergistic effect has the potential to convert a "cold" into a "hot" tumor, it offers valuable insights for clinical translation and application.

Aquincola amnicola sp. nov., isolated from a freshwater river.

Strain TTM-94T, isolated from a water sample taken from the Caohu River in Taiwan, was characterized using a polyphasic taxonomic approach. Cells of strain TTM-94T were Gram-staining-negative, aerobic, poly-ß-hydroxybutyrate-accumulating, motile by a single polar flagellum, short rod-shaped and surrounded by a thick capsule and it formed cream colored colonies. Growth occurred at 20-30 °C (optimum, 30 °C), at pH 6.0-8.0 (optimum, pH 6.0), and in the presence of 0-2% NaCl (optimum 0.5%). Phylogenetic analyses based on 16S rRNA gene sequences showed that strain TTM-94T belonged to the genus Aquincola in the Rubrivivax-Roseateles-Leptothrix-Ideonella-Aquabacterium branch of the class Betaproteobacteria and its most closely related neighbour was Aquincola tertiaricarbonis L10T with sequence similarity of 97.0%. Strain TTM-94T contained summed feature 3 (comprising C16:1ω7c and/or C16:1ω6c), C16:0 and C18:1ω7c as the predominant fatty acids. The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and several uncharacterized lipids. The major respiratory quinone was Q-8. Genomic DNA G + C content of strain TTM-94T was 70.7 mol%. Strain TTM-94T exhibited less than 30% DNA-DNA relatedness with A. tertiaricarbonis L10T. Differential phenotypic properties, together with the phylogenetic inference, demonstrate that strain TTM-94T should be classified as a novel species of the genus Aquincola, for which the name Aquincola amnicola sp. nov. is presented. The type strain is TTM-94T (= BCRC 80890T = LMG 28709T).

Paracoccus mangrovi sp. nov., isolated from a mangrove.

A bacterial strain, designated gyp-1T, was isolated from a mangrove in Taiwan and characterized using the polyphasic taxonomic approach. Cells of gyp-1T were Gram-staining-negative, aerobic, poly-ß-hydroxybutyrate-accumulating, non-motile, coccoid or short-rod-shaped and formed cream-coloured colonies. Growth occurred at 15-37 °C (optimum, 25-30 °C), at pH 5.5-7.0 (optimum, pH 6.0) and with 0-4 % NaCl (optimum, 1-2 %). Phylogenetic analyses based on 16S rRNA gene sequences indicated that gyp-1T represented a member of the genus Paracoccus and showed the highest levels of sequence similarity with respect to Paracoccus lutimaris HDM-25T (97.8 %) and Paracoccus aminovorans DM-82T (97.7 %). The major fatty acids (>10 %) of gyp-1T were C18 : 1ω7c and C16 : 0. The polar lipid profile consisted of phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, diphosphatidylglycerol, an unidentified glycolipid and two unidentified phospholipids. The major isoprenoid quinone was Q-10. The DNA G+C content was 64.6 mol%. The DNA-DNA hybridization value for gyp-1T with P. lutimaris HDM-25T and P. aminovorans DM-82T was less than 50 %. Differential phenotypic properties, together with the phylogenetic inference, demonstrate that gyp-1T should be classified as representing a novel species of the genus Paracoccus, for which the name Paracoccus mangrovi sp. nov. is presented. The type strain is gyp-1T (=BCRC 80920T=LMG 29172T=KCTC 42899T).

Hymenobacter pallidus sp. nov., isolated from a freshwater fish culture pond.

A bacterial strain designated LYH-12T was isolated from a freshwater fish culture pond in Taiwan, ROC and characterized by taking a polyphasic taxonomy approach. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain LYH-12T belonged to the genus Hymenobacter and was most closely related to Hymenobacter xinjiangensis X2-1gT and Hymenobacter rigui WPCB131T with a sequence similarity of 96.6 % and less than 96.5 % with other members of the genus. Cells of strain LYH-12T were Gram-stain-negative, aerobic, non-motile rods that were covered by large capsules and formed light pink-coloured colonies. Growth occurred at 10-37 °C (optimum, 20-30 °C), at pH 6.5-7.5 (optimum, pH 7) and with 0-1 % NaCl (optimum, 0.5 %). Strain LYH-12T contained iso-C15 : 0, C16 : 1ω5c, C16 : 0, iso-C17 : 0 3-OH, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and anteiso-C17 : 1ω9c as the predominant fatty acids. The only isoprenoid quinone detected was MK-7. The polar lipid profile consisted of phosphatidylethanolamine, one uncharacterized aminophospholipid, four uncharacterized aminolipids, two uncharacterized phospholipids and three uncharacterized lipids. The major polyamine was homospermidine. The DNA G+C content of the genomic DNA was 64.3 mol%. On the basis of the phylogenetic inference and phenotypic data, strain LYH-12T should be classified as a novel species, for which the name Hymenobacter pallidus sp. nov. is proposed. The type strain is LYH-12T (=BCRC 80919T=LMG 29171T=KCTC 42898T).

Piscinibacterium candidicorallinum gen. nov., sp. nov., a member of the order Burkholderiales isolated from a fish pond.

A bacterial strain designated LYH-15T was isolated from a freshwater fish pond in Taiwan and characterized using a polyphasic taxonomy approach. Cells of LYH-15T were Gram-staining-negative, aerobic, motile by means of a single polar flagellum, poly-ß-hydroxybutyrate-containing, non-spore forming, straight rods and formed light-coral-colored colonies. Growth occurred at 15-40 °C (optimum, 30 °C), at pH 5.0-9.0 (optimum, pH 7.0) and with 0-0.5 % NaCl (optimum, 0 %). Phylogenetic analyses based on 16S rRNA gene sequences showed that LYH-15T forms a distinct phyletic line within the order Burkholderiales, with less than 94 % sequence similarity to its closest relatives with validly published names. The predominant fatty acids were summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c), C16 : 0 and C18 : 1ω7c. The major isoprenoid quinone was Q-8 and the DNA G+C content was 63.8 mol%. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and several uncharacterized lipids. The major polyamines were 2-hydroxyputrescine and putrescine. On the basis of the genotypic and phenotypic data, LYH-15T represents a novel species of a new genus in the order Burkholderiales, for which the name Piscinibacterium candidicorallinum gen. nov., sp. nov. is proposed. The type strain is LYH-15T (=BCRC 80969T=LMG 29480T=KCTC 52168T).

Sphingomonas piscinae sp. nov., isolated from a fish pond.

A bacterial strain designated LYH-20T was isolated from a fish pond in Taiwan and characterized using a polyphasic taxonomy approach. Cells of strain LYH-20T were aerobic, Gram-stain-negative, non-motile, poly-ß-hydroxybutyrate containing, showing straight and rod shaped that were covered by large capsules and formed yellow-coloured colonies. Growth occurred at 15-40 °C (optimum, 30 °C), with 0-1.0 % NaCl (optimum, 0-0.1 %) and at pH 5.0-9.0 (optimum, pH 8.0-9.0). According to a phylogenetic tree based on 16S rRNA gene sequence analysis, strain LYH-20T belonged to the genus Sphingomonas and clustered with Sphingomonas fonticola TNR-2T, with which it shared the highest 16S rRNA gene sequence similarity (97.5 %). The major fatty acids (>10 %) of strain LYH-20T were C18 : 1ω7c and C16 : 0. The DNA G+C content was 67.5 mol%. The sole isoprenoid quinone was Q-10. The polyamines detected were spermidine, putrescine and homospermidine. The polar lipid profile consisted of a mixture of sphingoglycolipid, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, diphosphatidylglycerol and three uncharacterized phospholipids. The DNA-DNA hybridization value for strain LYH-20T with Sphingomonas fonticola TNR-2T was less than 35 %. Phenotypic characteristics of the novel strain also differed from those of the closest related species of the genus Sphingomonas. On the basis of the genotypic, chemotaxonomic and phenotypic data, strain LYH-20T represents a novel species in the genus Sphingomonas, for which the name Sphingomonas piscinae sp. nov. is proposed. The type strain is LYH-20T (=BCRC 80911T=LMG 29002T=KCTC 42741T).

Uliginosibacterium paludis sp. nov., isolated from a marsh.

A novel bacterial strain, designated KBP-13T, was isolated from a water sample taken from the Banping Lake Wetland Park in Taiwan and characterized using a polyphasic taxonomic approach. Cells of strain KBP-13T were Gram-stain-negative, aerobic, poly-ß-hydroxybutyrate-accumulating, motile rods that formed light yellow colonies. Growth occurred at 15-40 °C (optimum, 30-40 °C), at pH 6.0-8.0 (optimum, pH 6.0) and with 0-2 % (w/v) NaCl (optimum, 0 %). Phylogenetic analyses based on 16S rRNA gene sequences showed that strain KBP-13T belonged to the genus Uliginosibacterium within the family Rhodocyclaceae of the class Betaproteobacteria and its most closely related neighbour was Uliginosibacterium gangwonense 5YN10-9T with sequence similarity of 96.0 %. Strain KBP-13T contained summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c), C16 : 0 and C14 : 0 as predominant fatty acids. The major respiratory quinone was Q-8. The DNA G+C content of the genomic DNA was 65.1 mol%. The polar lipid profile consisted of a mixture of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, one uncharacterized aminophospholipid, one uncharacterized aminolipid, two uncharacterized phospholipids and three uncharacterized glycolipids. On the basis of the genotypic, chemotaxonomic and phenotypic data, strain KBP-13T represents a novel species in the genus Uliginosibacterium, for which the name Uliginosibacterium paludis sp. nov. is proposed. The type strain is KBP-13T (=BCRC 80903T=LMG 28837T=KCTC 42655T).

Chitinibacter fontanus sp. nov., isolated from a spring.

A bacterial strain, designated STM-7T, was isolated from a spring in Taiwan and characterized using a polyphasic taxonomy approach. Cells of strain STM-7T were Gram-staining-negative, aerobic, poly-ß-hydroxybutyrate-accumulating, motile by a single polar flagellum, rod-shaped, surrounded by a thick capsule and formed milky-white colonies. Growth occurred at 15-37 °C (optimum, 25-30 °C), at pH 6-8 (optimum, pH 6-7) and with 0-2 % NaCl (optimum, 0-1 %). Phylogenetic analyses based on 16S rRNA gene sequences showed that strain STM-7T belonged to the genus Chitinibacter and was most closely related to Chitinibacter tainanensis S1T with a sequence similarity of 97.3 %. Strain STM-7T contained summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 0 as the predominant fatty acids. The major hydroxyl fatty acids were C12 : 0 3-OH and C16 : 0 3-OH. The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, an uncharacterized aminophospholipid, an uncharacterized glycolipid and an uncharacterized phospholipid. The major isoprenoid quinone was Q-8. The DNA G+C content of the genomic DNA was 52.4 mol%. The DNA-DNA hybridization value for strain STM-7T with Chitinibacter tainanensis BCRC 17254T was less than 47 %. On the basis of the phylogenetic inference and phenotypic data, strain STM-7T should be classified as a representative of a novel species, for which the name Chitinibacter fontanus sp. nov. is proposed. The type strain is STM-7T (=BCRC 80923T=LMG 29289T=KCTC 42982T).

[An experimental study on the prevention of enteral bacterial translocation in scalded rats by smectite powder].

OBJECTIVE: To explore the preventive and treatment effects of smectite powder on enteral bacterial translocation in scalded rats. METHODS: Fifty-four Sprague-Dawley (SD) rats were randomly divided into three groups, i.e. normal control (A, n = 6), burn control (B, n = 24), and burn treatment (T, n = 24) groups. The rats in B and T groups were fed with tracing bacteria JM109, which was transfected with PUC19 plasmid in advance. The rats were subjected to 30% TBSA scald injury after the plasmid was shown to have colonized in the intestine. Smectite powder (0.6 g/day/kg) was fed to rats of T group immediately after the scalding, while those in B group received no smectite powder. Bacterial translocation in blood and mesenteric lymph nodes in all groups was observed and identified by enzyme digestion at 12 post scald hour (PSH) and on 1, 3 and 5 post-scald days (PSD). The contents of malondialdehyde (MDA) and superoxide dismutase (SOD) were determined in rat intestinal tissue. And the degree of injury to the entire small intestine was observed pathologically. The villus height of intestinal mucosa was measured, and the rate of epithelial nuclear splitting of mucosal crypts was calculated. RESULTS: The number of rats with positive blood bacterial culture in B group was obviously higher than that in A and T groups (P < 0.05) on 1 and 5 PSD. The bacterial quantity in mesenteric lymph nodes (MLN) in T group on 1 PSD (38 +/- 16 CFU/g) and 5 PSD (68 +/- 20 CFU/g) were obviously lower than those in B group (228 +/- 67 vs 183 +/- 29 CFU/g, P < 0.05). There was significant difference in the intestinal contents of MDA and SOD between B and T groups at each time point (P < 0.05). The rat jejunum villus height and the epithelial nuclear splitting in the small intestine mucosa in T group were evidently higher than those in B group (P < 0.05 or 0.01). CONCLUSION: Smectite powder is beneficial to the protection of the intestinal mucosa in scalded rats, and can effectively prevent postburn intestinal bacterial translocation in rats.

[Clinical study on the relationship among the dermis, fat dome and postburn hyperplastic scar formation].

OBJECTIVE: To explore the influence of dermal defect and fat dome structure destruction in burn wounds on the formation of hyperplastic scar. METHODS: Fifty two wounds in 24 burn patients with deep partial thickness burn indicating tangential excision in the extremities were enrolled in the study, and they were divided into three groups according to the extent of exposure of dermal fat granules, i.e. A (without fat exposure), B (with little fat exposure) and C (with much fat exposure) groups. These three groups were subdivided into A1 (without grafting), A2 (grafting with razor thin skin), B1 (without grafting), B2 (with razor thin skin grafting), C1 (without grafting) and C2 (with split-thickness skin grafting) groups, with 9 wounds in each group. The dermal depth and exposure rate of the fat granules in each group were measured and analyzed by KS400 photography analysis apparatus. The follow-up conditions of the scars 6 months after operation were evaluated with Vancouver remark system by Vancouver score assessment. RESULTS: There was obvious difference in the dermal depth and exposure rate of the fat granules among all the groups (P < 0.05 or 0.01). The fat exposure rate was positively correlated with the extent of the dermal defect (gamma = 0.554, P < 0.05). The Vancouver score in group A was lower than that in B and C groups (P < 0.05), while that in B1 group (3.714 +/- 2.498) was evidently higher than that in other groups (P < 0.01). The scar score was lowered when the wounds were grafted with the dermis with its thickness similar to the depth of the defect, The scar score was increased along with the elevation of fat exposure rate (P < 0.05). CONCLUSION: There was a positive correlation between the degree of dermal defect and that of hyperplastic scar after burns. The disruption of fat dome structure might also be an important factor in the scar development.