Antigen processing and presentation-related signature-derived BNIP3 is a novel oncogene and immunotherapy determinant in osteosarcoma based on machine learning and in vitro validation.

BACKGROUND: In recent decades, osteosarcoma has remained the most prevalent kind of malignant tumor. An important and crucial factor in immunotherapy is antigen processing and presentation (APP). The specific functions and pathogenic processes of APP in osteosarcoma have not, however, been studied. METHODS: Patients with osteosarcoma were divided into groups using APP-related genes. Machine learning was used to further build the APP-related score. Investigated in-depth were the prognostic relevance of the score, mutation features, immunological aspects, and pharmacological prediction performance. Investigations of the prognostic utility, immunological traits, drug prediction effectiveness and immunotherapy prediction of BNIP3 were performed in-depth. RESULTS: Investigations by cell counting kit-8, Transwell and 5-ethynyl-2-deoxyuridine (EdU) demonstrated that BNIP3 is an osteosarcoma tumor accelerator. The osteosarcoma gene BNIP3 may promote macrophage migration. The APP-related score shows potential for clinical use. CONCLUSIONS: It was anticipated that more in vitro and in vivo studies would confirm BNIP3's tumorigenic and immunogenic processes in osteosarcoma.

Quaternary pulse width modulation based ultra-high frame rate scene projector used for hard-ware-in-the-loop testing.

The scene projector (SP) can provide simulated scene images with same optical characteristics as the real scenes to evaluate imaging systems in hard-ware-in-the-loop (HWIL) simulation testing. The single scene generation device (SGD) based SP typically projects 8-bit images at 220 fps, which is insufficient to fulfill the requirements of ultra-high frame rate imaging systems, such as star trackers and space debris detectors. In this paper, an innovative quaternary pulse width modulation (PWM) based SP is developed and implemented to realize the ultra-high frame rate projection. By optically overlapping modulation layers of two digital micro-mirror devices (DMDs) in parallel, and illuminating them with light intensities, a quaternary SGD is built up to modulate quaternary digit-planes (QDs) with four grayscale levels. And the quaternary digit-plane de-composition (QDD) is adopted to decompose an 8-bit image into 4 QDs. In addition, the exposure time of each QD is controlled by quaternary PWM, and the base time is optimized to 8 µs. The experimental results prove that the total exposure time of all QDs sequentially modulated by quaternary PWM is approximately 760 µs, namely projecting 8-bit images at 1300 fps. The quaternary PWM using two DMDs in parallel dramatically improves the grayscale modulation efficiency compared to the existing projection technologies, which provides a new approach for the SP design with ultra-high frame rate.

Peripheral 5-HT Mediates Gonadotropin-Inhibitory Hormone-Induced Feeding Behavior and Energy Metabolism Disorder in Chickens via the 5-HT2C Receptor.

INTRODUCTION: Since the discovery of gonadotropin-inhibitory hormone (GnIH), it has been found to play a critical role in reproduction in vertebrates. Recently, a regulatory role of GnIH in appetite and energy metabolism has emerged, although its precise physiological mechanisms remain unknown. METHODS: Thus, the present study evaluated the effects of a single or long-term intraperitoneal GnIH treatment on the food intake, weight, and glucolipid metabolism of chickens, as well as investigating the possible neuroendocrinology factors and mechanisms involved in GnIH-induced obesity and glucolipid metabolism disorder. RESULTS: Our results show that the intraperitoneal administration of GnIH to chickens resulted in a marked body mass increase, hyperlipidemia, hyperglycemia, and glucose intolerance. Subsequently, the results of metabolomics studies and the pharmacological inhibition of the 5-HT2C receptor revealed that blocking the 5-HT2C receptor reinforced the effects of GnIH on food intake, body weight, and blood glucose and lipid levels, resulting in even worse cases of GnIH-induced hyperglycemia, hyperlipidemia, and hepatic lipid deposition. This suggests that, via the 5-HT2C receptor, peripheral 5-HT may act as a negative feedback regulator to interplay with GnIH and jointly control energy balance homeostasis in chickens. DISCUSSION: Our present study provides evidence of cross-talk between GnIH and 5-HT in food intake and energy metabolism at the in vivo pharmacological level, and it proposes a molecular basis for these interactions, suggesting that functional interactions between GnIH and 5-HT may open new avenues for understanding the mechanism of the neuroendocrine network involved in appetite and energy metabolism, as well as providing a new therapeutic strategy to prevent obesity, diabetes, and metabolic disorders.

Injectable Hydrogels Based on Hyaluronic Acid and Gelatin Combined with Salvianolic Acid B and Vascular Endothelial Growth Factor for Treatment of Traumatic Brain Injury in Mice.

Traumatic brain injury (TBI) leads to structural damage in the brain, and is one of the major causes of disability and death in the world. Herein, we developed a composite injectable hydrogel (HA/Gel) composed of hyaluronic acid (HA) and gelatin (Gel), loaded with vascular endothelial growth factor (VEGF) and salvianolic acid B (SAB) for treatment of TBI. The HA/Gel hydrogels were formed by the coupling of phenol-rich tyramine-modified HA (HA-TA) and tyramine-modified Gel (Gel-TA) catalyzed by horseradish peroxidase (HRP) in the presence of hydrogen peroxide (H2O2). SEM results showed that HA/Gel hydrogel had a porous structure. Rheological test results showed that the hydrogel possessed appropriate rheological properties, and UV spectrophotometry results showed that the hydrogel exhibited excellent SAB release performance. The results of LIVE/DEAD staining, CCK-8 and Phalloidin/DAPI fluorescence staining showed that the HA/Gel hydrogel possessed good cell biocompatibility. Moreover, the hydrogels loaded with SAB and VEGF (HA/Gel/SAB/VEGF) could effectively promote the proliferation of bone marrow mesenchymal stem cells (BMSCs). In addition, the results of H&E staining, CD31 and α-SMA immunofluorescence staining showed that the HA/Gel/SAB/VEGF hydrogel possessed good in vivo biocompatibility and pro-angiogenic ability. Furthermore, immunohistochemical results showed that the injection of HA/Gel/SAB/VEGF hydrogel to the injury site could effectively reduce the volume of defective tissues in traumatic brain injured mice. Our results suggest that the injection of HA/Gel hydrogel loaded with SAB and VEGF might provide a new approach for therapeutic brain tissue repair after traumatic brain injury.

Biological characteristics and genomic analysis of a novel Escherichia phage Kayfunavirus CY1.

As the problem of bacterial resistance becomes serious day by day, bacteriophage as a potential antibiotic substitute attracts more and more researchers' interest. In this study, Escherichia phage Kayfunavirus CY1 was isolated from sewage samples of swine farms and identified by biological characteristics and genomic analysis. One-step growth curve showed that the latent period of phage CY1 was about 10 min, the outbreak period was about 40 min and the burst size was 35 PFU/cell. Analysis of the electron microscopy and whole-genome sequence showed that the phage should be classified as a member of the Autographiviridae family, Studiervirinae subfamily. Genomic analysis of phage CY1 (GenBank accession no. OM937123) revealed a genome size of 39,173 bp with an average GC content of 50.51% and 46 coding domain sequences (CDSs). Eight CDSs encoding proteins involved in the replication and regulation of phage DNA, 2 CDSs encoded lysis proteins, 14 CDSs encoded packing and morphogenesis proteins. Genomic and proteomic analysis identified no sequence that encoded for virulence factor, integration-related proteins or antibiotic resistance genes. In summary, morphological and genomics suggest that phage CY1 is more likely a novel Escherichia phage.

Characterization and genome analysis of a novel phage Kayfunavirus TM1.

Escherichia coli is a common conditional pathogen, for which antibiotic therapy is considered an effective treatment. The imprudent use of antibiotics has led to the increase of multiple-antibiotic-resistant E. coli species. With the incidence of antibiotic resistance reaching a crisis point, it is imperative to find alternative treatments for multidrug-resistant infections. Using phage for pathogen control is a promising treatment option to combat bacterial resistance. In this study, a novel virulent Podoviridae phage Kayfunavirus TM1 infecting Escherichia coli was isolated from pig farm sewage in Guangxi, China. The one-step growth curve with the optimal multiplicity of infection of 0.01 revealed a latent period of 10 min and a burst size of 50 plaque-forming units per cell. The stability test reveals that it is stable from 4 to 60 °C and pH from 3 to 11. The double-stranded DNA genome of phage Kayfunavirus TM1 is composed of 39,948 base pairs with a GC content of 50.03%.

Oral phage therapy with microencapsulated phage A221 against Escherichia coli infections in weaned piglets.

BACKGROUND: Escherichia coli (E. coli) is a common pathogen that often causes diarrhea in piglets. Since bacteria are becoming more and more resistant to antibiotics, phages have become a promising alternative therapy. However, the therapy of oral phage often fails to achieve the desired effect. A novel phage named A221 was isolated by using E. coli GXXW-1103 as host strain, characterized by electron microscopy, genomic sequencing and analyzed by measuring lysis ability in vitro. RESULTS: Phage A221 was identified as a member of Ackermannviridae, Aglimvirinae, Agtrevirus with 153297 bp genome and effectively inhibited bacterial growth in vitro for 16 h. This study was conducted to evaluate the therapeutic effect of oral microencapsulated phage A221 on E. coli GXXW-1103 infections in weaned piglets. The protective effect of phage was evaluated by body weight analysis, bacterial load and histopathological changes. The results showed that with the treatment of phage A221, the body weight of piglets increased, the percentage of Enterobacteriaceae in duodenum decreased to 0.64%, the lesions in cecum and duodenum were alleviated, and the bacterial load in the jejunal lymph nodes, cecum and spleen were also significantly different with infected group (P < 0.001). CONCLUSIONS: The results showed that phage A221 significantly increased the daily weight gain of piglets, reduced the bacterial load of tissues and the intestinal lesions, achieved the same therapeutic effect as antibiotic Florfenicol. Taken together, oral microencapsulated phage A221 has a good therapeutic effect on bacterial diarrhea of weaned piglets, which provides guidance for the clinical application of phage therapy in the future.

Isolation and characterization of a novel Escherichia coli phage Kayfunavirus ZH4.

Escherichia coli, a gram-negative bacterium, was generally considered conditional pathogenic bacteria and the proportion of bacteria resistant to commonly used specified antibacterial drugs exceeded 50%. Phage therapeutic application has been revitalized since antibiotic resistance in bacteria was increasing. Compared with antibiotics, phage is the virus specific to bacterial hosts. However, further understanding of phage-host interactions is required. In this study, a novel phage specific to a E. coli strain, named as phage Kayfunavirus ZH4, was isolated and characterized. Transmission electron microscopy showed that phage ZH4 belongs to the family Autographiviridae. The whole-genome analysis showed that the length of phage ZH4 genome was 39,496 bp with 49 coding domain sequence (CDS) and no tRNA was detected. Comparative genome and phylogenetic analysis demonstrated that phage ZH4 was highly similar to phages belonging to the genus Kayfunavirus. Moreover, the highest average nucleotide identity (ANI) values of phage ZH4 with all the known phages was 0.86, suggesting that ZH4 was a relatively novel phage. Temperature and pH stability tests showed that phage ZH4 was stable from 4° to 50 °C and pH range from 3 to 11. Host range of phage ZH4 showed that there were only 2 out of 17 strains lysed by phage ZH4. Taken together, phage ZH4 was considered as a novel phage with the potential for applications in the food and pharmaceutical industries.

Ammonia-nitrogen removal from water with gC3N4-rGO-TiO2 Z-scheme system via photocatalytic nitrification-denitrification process.

Photocatalytic removal of NH3-N is expected to be an alternative to the biological method that accompanied with high energy consumption and secondary pollution. However, NH3-N is always oxidized into nitrate and nitrite during the photocatalytic processes, which also need to be removed from the water. Herein, the g-C3N4/rGO/TiO2 Z-scheme photocatalytic system was prepared and used for the NH3-N removal. The results showed the rate constant of NH3-N conversion on it was 0.705 h-1, 1.7 times as high as that on g-C3N4/TiO2, and most of the NH3-N were converted into gaseous products. And the experiment result indicated NH3-N and NO3- in water could enhance the removal of each other. According to the results, the main reaction mechanism is speculated as: ·OH radicals and ·O2- radicals were generated on TiO2 and oxidized the NH3-N into NO3-, and the latter was reduced into non-toxic N2 on the conduction band of g-C3N4. Finally, NH3-N removal performance for actual coking wastewater was investigated, and the stability of the photocatalyst was tested. This work provides some theoretical basis for the two-step degradation of pollutants by Z-scheme photocatalytic system.

Peripheral Gonadotropin-Inhibitory Hormone (GnIH) Acting as a Novel Modulator Involved in Hyperphagia-Induced Obesity and Associated Disorders of Metabolism in an In Vivo Female Piglet Model.

Apart from the well-established role of the gonadotropin-inhibitory hormone (GnIH) in the regulation of the reproductive functions, much less is known about the peripheral role of the GnIH and its receptor in the metabolic processes. On account of pig being an excellent model for studies of food intake and obesity in humans, we investigated the peripheral effects of the GnIH on food intake and energy homeostasis and revealed the underlying mechanism(s) in female piglets in vivo. Compared to the vehicle-treated group, intraperitoneally injected GnIH significantly increased the food intake and altered the meal microstructure both in the fasting and ad libitum female piglet. GnIH-triggered hyperphagia induced female piglet obesity and altered islet hormone secretion in the pancreas, accompanied with dyslipidemia and hyperglycemia. Interestingly, GnIH decreased the glucose transport capacity and glycogen synthesis, whereas it increased the gluconeogenesis in the liver, while it also induced an insulin resistance in white adipose tissue (WAT) via inhibiting the activity of AKT-GSK3-ß signaling. In terms of the lipid metabolism, GnIH reduced the oxidation of fatty acids, whereas the elevated fat synthesis ability in the liver and WAT was developed though the inhibited AMPK phosphorylation. Our findings demonstrate that peripheral GnIH could trigger hyperphagia-induced obesity and an associated glycolipid metabolism disorder in female piglets, suggesting that GnIH may act as a potential therapeutic agent for metabolic syndrome, obesity and diabetes.