Double-layered microneedle patch loaded with bioinspired nano-vaccine for melanoma treatment and wound healing.

Malignant melanoma is a challenging problem worldwide, because the remaining tumor cells and extensive skin defects following surgical resection are difficult to treat. Biomaterial-mediated immunotherapy has emerged as a superior strategy for anti-tumor applications in recent years. Herein, a unique double-layer MNP was developed to address the problem of malignant melanoma. Hydroxyapatite (HAP) and short-chain peptides from tumor cells were self-assembled to prepare the bioinspired nano-vaccine, and then they were loaded onto the microneedle tips of methacrylated gelatin (GelMA)-based MNP. The products (dubbed HVMN) demonstrated relatively good biocompatibility and immune activity, inhibiting the proliferation and inducing apoptosis of malignant melanoma in a B16 cell-bearing model of C57BL/6 mice, and promoting skin tissue regeneration in a full thickness skin defect model of SD rats in 15 days. The putative molecular pathways were examined preliminarily. In conclusion, this research will develop a competitive microneedle patch with dual anti-tumor and pro-regenerative properties for the postoperative treatment of malignant melanoma.

Pre-training and ensembling based Alzheimer's disease detection.

BACKGROUND: Alzheimer's disease (AD) endangers the physical and mental health of the elderly, constituting one of the most crucial social challenges. Due to lack of effective AD intervention drugs, it is very important to diagnose AD in the early stage, especially in the Mild Cognitive Impairment (MCI) phase. OBJECTIVE: At present, an automatic classification technology is urgently needed to assist doctors in analyzing the status of the candidate patient. The artificial intelligence enhanced Alzheimer's disease detection can reduce costs to detect Alzheimer's disease. METHODS: In this paper, a novel pre-trained ensemble-based AD detection (PEADD) framework with three base learners (i.e., ResNet, VGG, and EfficientNet) for both the audio-based and PET (Positron Emission Tomography)-based AD detection is proposed under a unified image modality. Specifically, the effectiveness of context-enriched image modalities instead of the traditional speech modality (i.e., context-free audio matrix) for the audio-based AD detection, along with simple and efficient image denoising strategy has been inspected comprehensively. Meanwhile, the PET-based AD detection based on the denoised PET image has been described. Furthermore, different voting methods for applying an ensemble strategy (i.e., hard voting and soft voting) has been investigated in detail. RESULTS: The results showed that the classification accuracy was 92% and 99% on the audio-based and PET-based AD datasets, respectively. Our extensive experimental results demonstrate that our PEADD outperforms the state-of-the-art methods on both audio-based and PET-based AD datasets simultaneously. CONCLUSIONS: The network model can provide an objective basis for doctors to detect Alzheimer's Disease.

Interactions of soy protein isolate with common and waxy corn starches and their effects on acid-induced cold gelation properties of complexes.

Soy protein isolate (SPI) was mixed with different concentrations of common starch (CS) and waxy starch (WS) from corn. The interactions of SPI with CS or WS and their effects on the acid-induced cold gelation properties of complexes were investigated. Compared with WS, SPI could bind to CS more strongly and formed a tighter SPI-CS non-covalent complex, which resulted in the increased ß-sheet and a more ordered secondary structure. The gel strength, water holding capacity (WHC), viscoelasticity, hydrophobic interactions and thermal stability of SPI-CS complex gels were enhanced as increasing CS concentration, and the complex with 2% of CS had the best gelation properties. Although adding WS reduced the gel strength, rheological properties and hydrophobic interactions of SPI-WS complex gels, it improved the WHC and thermal stability of the complex gels. Therefore, CS had a broader effect on improving acid-induced cold gelation properties of SPI than WS.

Citrobacter sp. Y3 harbouring novel gene HBCD-hd-1 mineralizes hexabromocyclododecane via new metabolic pathways according to multi-omics characterization.

Hexabromocyclododecane (HBCD) is a typical persistent organic pollutant that is widely detected in the environment. Despite the significant efforts put into its mineralisation, there is still a lack of microorganism resources that can completely mineralise HBCD. Stable isotope analysis revealed that the Citrobacter sp. Y3 can use [13C]HBCD as its sole carbon source and degrade or even mineralise it into 13CO2, with a maximum conversion rate of 100% in approximately 14 days. Strain Y3 could completely mineralise HBCD, which it used as its only carbon source, and six debromination enzymes related to HBCD degradation were found in Y3, including haloalkane dehalogenase (DhaA), haloacid dehalogenase (HAD), etc. A functional gene named HBCD-hd-1, encoding a HAD, was found to be upregulated during HBCD degradation and heterologously expressed in Escherichia coli. Recombinant E. coli with the HBCD-hd-1 gene transformed the typical intermediate 4-bromobutyric acid to 4-hydroxybutanoic acid and showed excellent degradation performance on HBCD, accompanied by nearly 100% bromine (Br) ion generation. The expression of HBCD-hd-1 in Y3 rapidly accelerated the biodegradation of HBCD. With HBCD as its sole carbon source, strain Y3 could potentially degrade HBCD, especially in a low-nutrient environment.

Effects of Different Amounts of Corn Silk Polysaccharide on the Structure and Function of Peanut Protein Isolate Glycosylation Products.

Covalent complexes of peanut protein isolate (PPI) and corn silk polysaccharide (CSP) (PPI-CSP) were prepared using an ultrasonic-assisted moist heat method to improve the functional properties of peanut protein isolate. The properties of the complexes were affected by the level of corn silk polysaccharide. By increasing the polysaccharide addition, the grafting degree first increased, and then tended to be flat (the highest was 38.85%); the foaming, foam stability, and solubility were also significantly improved. In a neutral buffer, the solubility of the sample with a protein/polysaccharide ratio of 2:1 was 73.69%, which was 1.61 times higher than that of PPI. As compared with PPI, the complexes had higher thermal stability and lower surface hydrophobicity. High addition of CSP could made the secondary structure of PPI change from ordered α-helix to disordered ß-sheet, ß-turn, and random coil structure, and the complex conformation become more flexible and loose. The results of multiple light scattering showed that the composite solution exhibited high stability, which could be beneficial to industrial processing, storage, and transportation. Therefore, the functional properties of peanut protein isolate glycosylation products could be regulated by controlling the amount of polysaccharide added.

Candida tropicalis prompted effectively simultaneous removal of carbon, nitrogen and phosphorus in activated sludge reactor: Microbial community succession and functional characteristics.

A new Candida tropicalis that simultaneously remove nitrogen and phosphorus, and degrade organic matters was isolated. Three continuous stirred tank reactors inoculated with C. tropicalis, activated sludge, and their co-existing system in aerobic condition were operated for 150 days. Results demonstrated that the inoculation of C. tropicalis in the co-existing system remarkably improved the carbon, nitrogen, and phosphorus removal efficiencies. The co-existing system had increased carbon, nitrogen, and phosphorus removal efficiencies (92%, 73%, and 63%, respectively); decreased biomass (reduced from 1200 mg/L to 500 mg/L); and C. tropicalis as the dominant strain. The relative abundance of traditional nitrogen- and phosphorus-removing microorganisms, such as Mycobacterium, Flavonifactor, and Devsia, increased in the co-existing system. Metagenomic analysis showed that the presence of the PCYT2, EPT1, and phnPP genes and more complexed metabolism pathways in the co-existing system might be responsible for the more activated metabolism process.

Efficient biodegradation of tetrabromobisphenol A by the novel strain Enterobacter sp. T2 with good environmental adaptation: Kinetics, pathways and genomic characteristics.

T2, a gram-positive bacterium capable of rapidly degrading tetrabromobisphenol A (TBBPA), and affiliated with the genus Enterobacter, was isolated for the first time from sludge that had been contaminated for several years. The TBBPA degradation data fitted the first-order model well. Under optimal conditions (pH of 7, temperature of 31 °C, TBBPA concentration of 5 mg L-1, and inoculum size of 5%), 99.4% of the initially added TBBPA was degraded after 48 h. TBBPA degradation fitted the first-order model with the half-life of 3.3 h. These results illustrated that the TBBPA degradation capability of strain T2 was significantly better than that of previously reported bacteria. A total of 17 intermediates were detected, among which five were reported for the first time. Whole-genome sequencing revealed that strain T2 had a chromosome with the total length of 4 854 376 bp and a plasmid with the total length of 21 444 bp. It harbored essential genes responsible for debromination, such as cyp450, gstB, gstA, and HADH, and genes responsible for subsequent complete mineralization, such as bioC, yrrM, Tam, and Ubil. A key protein of haloacid dehalogenases responsible for the biodegradation of TBBPA may also be involved in the regulation of TBBPA degradation in natural environment. In soil bioremediation experiments, strain T2 showed excellent environmental adaptation. It was able to biodegrade TBBPA and its typical intermediate bisphenol A efficiently. Therefore, it could potentially be applied to treat TBBPA-contaminated sites.