Glutenin-chitosan 3D porous scaffolds with tunable stiffness and systematized microstructure for cultured meat model.

A glutenin (G)-chitosan (CS) complex (G-CS) was cross-linked by water annealing with aim to prepare structured 3D porous cultured meat scaffolds (CMS) here. The CMS has pore diameters ranging from 18 to 67 µm and compressive moduli from 16.09 to 60.35 kPa, along with the mixing ratio of G/CS. SEM showed the porous organized structure of CMS. FTIR and CD showed the increscent content of α-helix and ß-sheet of G and strengthened hydrogen-bondings among G-CS molecules, which strengthened the stiffness of G-CS. Raman spectra exhibited an increase of G concentration resulted in higher crosslinking of disulfide-bonds in G-CS, which aggrandized the bridging effect of G-CS and maintained its three-dimensional network. Cell viability assay and immuno-fluorescence staining showed that G-CS effectively facilitated the growth and myogenic differentiation of porcine skeletal muscle satellite cells (PSCs). CLSM displayed that cells first occupied the angular space of hexagon and then ring-growth circle of PSCs were orderly formed on G-CS. The texture and color of CMS which loaded proliferated PSCs were fresh-meat like. These results showed that physical cross-linked G-CS scaffolds are the biocompatible and stable adaptable extracellular matrix with appropriate architectural cues and natural micro-environment for structured CM models.

An oocyte-specific Cas9-expressing mouse for germline CRISPR/Cas9-mediated genome editing.

Cas9 transgenes can be employed for genome editing in mouse zygotes. However, using transgenic instead of exogenous Cas9 to produce gene-edited animals creates unique issues including ill-defined transgene integration sites, the potential for prolonged Cas9 expression in transgenic embryos, and increased genotyping burden. To overcome these issues, we generated mice harboring an oocyte-specific, Gdf9 promoter driven, Cas9 transgene (Gdf9-Cas9) targeted as a single copy into the Hprt1 locus. The X-linked Hprt1 locus was selected because it is a defined integration site that does not influence transgene expression, and breeding of transgenic males generates obligate transgenic females to serve as embryo donors. Using microinjections and electroporation to introduce sgRNAs into zygotes derived from transgenic dams, we demonstrate that Gdf9-Cas9 mediates genome editing as efficiently as exogenous Cas9 at several loci. We show that genome editing efficiency is independent of transgene inheritance, verifying that maternally derived Cas9 facilitates genome editing. We also show that paternal inheritance of Gdf9-Cas9 does not mediate genome editing, confirming that Gdf9-Cas9 is not expressed in embryos. Finally, we demonstrate that off-target mutagenesis is equally rare when using transgenic or exogenous Cas9. Together, these results show that the Gdf9-Cas9 transgene is a viable alternative to exogenous Cas9.

Oxoaporphine Pr(III) complex inhibits hepatocellular carcinoma progression and metastasis by disrupting tumor cell-macrophage crosstalk.

Tumor cells and macrophages communicate through the secretion of various cytokines to jointly promote the malignant development of cancers. We synthesized and characterized an oxoaporphine Pr(III) complex (PrL3(NO3)3) and found that it inhibits hepatocellular carcinoma (HCC) progression and metastasis by disrupting HCC cell-macrophage crosstalk. PrL3(NO3)3 treatment upregulated CD86, TNF-α, and IL-1ß and downregulated CD163, CD206, CCL2, and VEGFA in macrophages. Our mRNA-Seq results demonstrated that PrL3(NO3)3 inhibited macrophage M2-like polarization by inhibiting the AMPK pathway and activating the NF-κB pathway by upregulating RelA/p65 Ser536 phosphorylation. This kind of macrophage polarization significantly inhibited HCC cell proliferation, migration, and invasion. In addition, PrL3(NO3)3 inhibited the migration, invasion, and chemotaxis of HCC cells by downregulating the expression of EMT-related markers and CCL2. hTFtarget database analysis revealed that PrL3(NO3)3 inhibited NF-κB nuclear translocation by upregulating RelA/p65 Ser536 phosphorylation in HCC cells, thereby downregulating the expression of Snail and CCL2. HCC tissue microarray analysis revealed that downregulation of RelA/p65 Ser536 phosphorylation is a driving event in HCC malignant progression. In conclusion, PrL3(NO3)3 effectively inhibits HCC cell-macrophage crosstalk by upregulating RelA/p65 Ser536 phosphorylation. This is the first report of a lanthanide complex exerting regulatory effects on both tumors and tumor-associated macrophages, providing a new strategy for the development of effective antitumor drugs.

The Role of Gluten in Food Products and Dietary Restriction: Exploring the Potential for Restoring Immune Tolerance.

Wheat is extensively utilized in various processed foods due to unique proteins forming from the gluten network. The gluten network in food undergoes morphological and molecular structural changes during food processing, affecting the final quality and digestibility of the food. The present review introduces the formation of the gluten network and the role of gluten in the key steps of the production of several typical food products such as bread, pasta, and beer. Also, it summarizes the factors that affect the digestibility of gluten, considering that different processing conditions probably affect its structure and properties, contributing to an in-depth understanding of the digestion of gluten by the human body under various circumstances. Nevertheless, consumption of gluten protein may lead to the development of celiac disease (CD). The best way is theoretically proposed to prevent and treat CD by the inducement of oral tolerance, an immune non-response system formed by the interaction of oral food antigens with the intestinal immune system. This review proposes the restoration of oral tolerance in CD patients through adjunctive dietary therapy via gluten-encapsulated/modified dietary polyphenols. It will reduce the dietary restriction of gluten and help patients achieve a comprehensive dietary intake by better understanding the interactions between gluten and food-derived active products like polyphenols.

Regional odontodysplasia diagnosed and treated via multidisciplinary approach: a case report.

Regional odontodysplasia (RO) is a rare non-hereditary dental anomaly associated with dysplasia. Its etiology remains unclear but is known to affect both the mesodermal and ectodermal dental components, as well as deciduous and permanent dentitions. Its young age of onset and complexity has great physical and psychological impact on the affected patients. However, the clinical management of RO remains unified without standardized treatment guidelines. Thus, this study aimed to report an RO case, the first from Jiangxi Province, China, and discuss its clinical diagnosis and treatment to provide a reference to treat similar cases more effectively in the future.

The preliminary in vitro study and application of deep learning algorithm in cone beam computed tomography image implant recognition.

To properly repair and maintain implants, which are bone tissue implants that replace natural tooth roots, it is crucial to accurately identify their brand and specification. Deep learning has demonstrated outstanding capabilities in analysis, such as image identification and classification, by learning the inherent rules and degrees of representation of data models. The purpose of this study is to evaluate deep learning algorithms and their supporting application software for their ability to recognize and categorize three dimensional (3D) Cone Beam Computed Tomography (CBCT) images of dental implants. By using CBCT technology, the 3D imaging data of 27 implants of various sizes and brands were obtained. Following manual processing, the data were transformed into a data set that had 13,500 two-dimensional data. Nine deep learning algorithms including GoogleNet, InceptionResNetV2, InceptionV3, ResNet50, ResNet50V2, ResNet101, ResNet101V2, ResNet152 and ResNet152V2 were used to perform the data. Accuracy rates, confusion matrix, ROC curve, AUC, number of model parameters and training times were used to assess the efficacy of these algorithms. These 9 deep learning algorithms achieved training accuracy rates of 100%, 99.3%, 89.3%, 99.2%, 99.1%, 99.5%, 99.4%, 99.5%, 98.9%, test accuracy rates of 98.3%, 97.5%, 94.8%, 85.4%, 92.5%, 80.7%, 93.6%, 93.2%, 99.3%, area under the curve (AUC) values of 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00. When used to identify implants, all nine algorithms perform satisfactorily, with ResNet152V2 achieving the highest test accuracy, classification accuracy, confusion matrix area under the curve, and receiver operating characteristic curve area under the curve area. The results showed that the ResNet152V2 has the best classification effect on identifying implants. The artificial intelligence identification system and application software based on this algorithm can efficiently and accurately identify the brands and specifications of 27 classified implants through processed 3D CBCT images in vitro, with high stability and low recognition cost.

Innovative date syrup processing with ohmic heating technology: Physiochemical characteristics, yield optimization, and sensory attributes.

The present study aimed to investigate the application of the ohmic heating (OH) technique in the production of date syrup from the date fruit of the Sukkary variety at different electric field strengths (EFS) (9, 10, and 11 V/cm). The results were compared to the conventional heating method (CH). The response surface methodology was used to optimize yield. The results showed that the time to reach the boiling point of dates and water mixture using OH was less than the CH by 80% for extracting and 900% for evaporation. In addition, the productivity of date syrup using OH at EFS of 11 V/cm was higher than the CH by 86.11%. There is no significant effect between OH at EFS of 11 V/cm and CH in moisture content, refractive index, density, TSS, and viscosity. The optimum level of EFS was 11.5 V/cm, which gave a higher yield (64.93%). OH, save consumed power and cost. The OH gave the highest scores of sensory characteristics compared to CH. Total sugars, monosaccharides, and ketone monosaccharides were detected in the date syrup, and the result was positive, while the quintuple sugars and multiple sugars were negative for all treatments. The OH reduced the cost by 85.78% compared with CH.

Molecular mechanisms of TWIST1-regulated transcription in EMT and cancer metastasis.

TWIST1 induces epithelial-to-mesenchymal transition (EMT) to drive cancer metastasis. It is yet unclear what determines TWIST1 functions to activate or repress transcription. We found that the TWIST1 N-terminus antagonizes TWIST1-regulated gene expression, cancer growth and metastasis. TWIST1 interacts with both the NuRD complex and the NuA4/TIP60 complex (TIP60-Com) via its N-terminus. Non-acetylated TWIST1-K73/76 selectively interacts with and recruits NuRD to repress epithelial target gene transcription. Diacetylated TWIST1-acK73/76 binds BRD8, a component of TIP60-Com that also binds histone H4-acK5/8, to recruit TIP60-Com to activate mesenchymal target genes and MYC. Knockdown of BRD8 abolishes TWIST1 and TIP60-Com interaction and TIP60-Com recruitment to TWIST1-activated genes, resulting in decreasing TWIST1-activated target gene expression and cancer metastasis. Both TWIST1/NuRD and TWIST1/TIP60-Com complexes are required for TWIST1 to promote EMT, proliferation, and metastasis at full capacity. Therefore, the diacetylation status of TWIST1-K73/76 dictates whether TWIST1 interacts either with NuRD to repress epithelial genes, or with TIP60-Com to activate mesenchymal genes and MYC. Since BRD8 is essential for TWIST1-acK73/76 and TIP60-Com interaction, targeting BRD8 could be a means to inhibit TWIST1-activated gene expression.

Microenvironment-Responsive Metal-Phenolic Nanozyme Release Platform with Antibacterial, ROS Scavenging, and Osteogenesis for Periodontitis.

Periodontitis is a chronic inflammatory disease deriving from dental plaque, characterized by the excessive accumulation of reactive oxygen species (ROS), matrix metalloproteinase (MMP) and other substances, resulting in the destruction of periodontal tissues. At present, the main therapeutic modalities, such as local mechanical debridement and antibiotic delivery, are not only difficult to solve the intractable bacterial biofilm effectively but also tricky to ameliorate the excessive inflammatory response as well as regenerate the impaired periodontal tissues. Herein, we have proposed the TM/BHT/CuTA hydrogel system formed by the self-assembly of the copper-based nanozyme (copper tannic acid coordination nanosheets, CuTA NSs) and the triglycerol monostearate/2,6-di-tert-butyl-4-methylphenol (TM/BHT) hydrogel. The negatively charged TM/BHT/CuTA can retain at the inflammation sites with a positive charge through electrostatic adsorption and hydrolyze in response to the increasing MMP of periodontitis, realizing the on-demand release of the CuTA nanozyme. The released CuTA nanozyme has antibacterial and antiplaque properties. Meanwhile, as a metal-phenolic nanozyme, it can scavenge multiple ROS by simulating the cascade process of superoxide dismutase (SOD) and catalase (CAT). Further, the CuTA nanozyme can modulate the macrophage polarization from M1 phenotype to M2 phenotype through the Nrf2/NF-κB pathway, which reduces the pro-inflammatory cytokines, increases the anti-inflammatory cytokines, and promotes the expression of osteogenetic genes successively, thus relieving the inflammation and accelerating the tissue regeneration of periodontitis. Altogether, this multifunctional nanozyme on-demand release platform (TM/BHT/CuTA) provides a desirable strategy for the treatment of periodontitis.

Identification of an endoplasmic reticulum stress-related prognostic risk model with excellent prognostic and clinical value in oral squamous cell carcinoma.

BACKGROUND: Recently, endoplasmic reticulum stress related gene (ERS) markers have performed very well in predicting the prognosis of tumor patients. METHODS: The differentially expressed genes in Oral squamous cell carcinoma (OSCC) were obtained from TCGA and GTEx database. Three prognosis-related and differentially expressed ERSs were screened out by Least Absolute Selection and Shrinkage Operator (Lasso) regression to construct a prognostic risk model. Receiver Operating Characteristic Curve (ROC), riskplots and survival curves were used to verify the model's accuracy in predicting prognosis. Multi-omics analysis of immune infiltration, gene mutation, and stem cell characteristics were performed to explore the possible mechanism of OSCC. Finally, we discussed the model's clinical application value from the perspective of drug sensitivity. RESULTS: Three genes used in the model (IBSP, RDM1, RBP4) were identified as prognostic risk factors. Bioinformatics analysis, tissue and cell experiments have fully verified the abnormal expression of these three genes in OSCC. Multiple validation methods and internal and external datasets confirmed the model's excellent performance in predicting and discriminating prognosis. Cox regression analysis identified risk score as an independent predictor of prognosis. Multi-omics analysis found strong correlations between risk scores and immune cells, cell stemness index, and tumor mutational burden (TMB). It was also observed that the risk score was closely related to the half maximal inhibitory concentration of docetaxel, gefitinib and erlotinib. The excellent performance of the nomogram has been verified by various means. CONCLUSION: A prognostic model with high clinical application value was constructed. Immune cells, cellular stemness, and TMB may be involved in the progression of OSCC.

Multifunctional magnesium organic framework-based photothermal and pH dual-responsive mouthguard for caries prevention and tooth self-healing promotion.

Caries is considered to be the most prevalent non-communicable disease in humans, mainly deriving from acidogenic bacterial biofilm and resulting in the demineralization and decomposition of hard dental tissue. Herein, a composite responsive foam brace loaded with magnesium organic framework (MPC) is designed for caries prevention and tooth remineralization. MPC can intelligently release organic antibacterial molecules (gallic acid) and mineralized ions (Mg2+, Ca2+ and PO43-) under acidic conditions (pH < 5.5) of biofilm infection, regulating pH and killing bacteria. Additionally, due to the excellent photothermal conversion efficiency, MPC can further enhance the destruction of bacterial biofilm by inhibiting virulence genes and destroying bacterial adhesion under near-infrared light irradiation (808 nm). More importantly, MPC can not only reverse the cariogenic environment at both pH and microbial levels, but also promote self-healing of demineralized teeth in terms of both the micro-structure and mechanical properties.

Potent Zinc(II)-Based Immunogenic Cell Death Inducer Triggered by ROS-Mediated ERS and Mitochondrial Ca2+ Overload.

Zn1 and Zn2 are Zn-based complexes that activate the immunogenic cell death (ICD) effect by Ca2+-mediated endoplasmic reticulum stress (ERS) and mitochondrial dysfunction. Compared with Zn1, Zn2 effectively caused reactive oxidative species (ROS) overproduction in the early phase, leading to ERS response. Severe ERS caused the release of Ca2+ from ER to cytoplasm and further to mitochondria. Excessive Ca2+ in mitochondria triggered mitochondrial dysfunction. The damage-associated molecular patterns (DAMPs) of CRT, HMGB1, and ATP occurred in T-24 cells exposed to Zn1 and Zn2. The vaccination assay demonstrated that Zn1 and Zn2 efficiently suppressed the growth of distant tumors. The elevated CD8+ cytotoxic T cells and decreased Foxp3+ cells in vaccinated mice supported our conclusion. Moreover, Zn1 and Zn2 improved the survival rate of mice compared with oxaliplatin. Collectively, our findings provided a new design strategy for a zinc-based ICD inducer via ROS-induced ERS and mitochondrial Ca2+ overload.

Anoctamin 4 channel currents activate glucose-inhibited neurons in the mouse ventromedial hypothalamus during hypoglycemia.

Glucose is the basic fuel essential for maintenance of viability and functionality of all cells. However, some neurons - namely, glucose-inhibited (GI) neurons - paradoxically increase their firing activity in low-glucose conditions and decrease that activity in high-glucose conditions. The ionic mechanisms mediating electric responses of GI neurons to glucose fluctuations remain unclear. Here, we showed that currents mediated by the anoctamin 4 (Ano4) channel are only detected in GI neurons in the ventromedial hypothalamic nucleus (VMH) and are functionally required for their activation in response to low glucose. Genetic disruption of the Ano4 gene in VMH neurons reduced blood glucose and impaired counterregulatory responses during hypoglycemia in mice. Activation of VMHAno4 neurons increased food intake and blood glucose, while chronic inhibition of VMHAno4 neurons ameliorated hyperglycemia in a type 1 diabetic mouse model. Finally, we showed that VMHAno4 neurons represent a unique orexigenic VMH population and transmit a positive valence, while stimulation of neurons that do not express Ano4 in the VMH (VMHnon-Ano4) suppress feeding and transmit a negative valence. Together, our results indicate that the Ano4 channel and VMHAno4 neurons are potential therapeutic targets for human diseases with abnormal feeding behavior or glucose imbalance.

Dual-light defined in situ oral mucosal lesion therapy through a mode switchable anti-bacterial and anti-inflammatory mucoadhesive hydrogel.

Oral mucosal ulcer is the most prevalent oral mucosal lesion, affecting the quality of life. Due to the moist and highly dynamic oral lining, the existing oral mucoadhesives are unable to serially address the challenges of residency, hemorrhage, bacterial infection and inflammatory reaction. Herein, a dual-light defined oral mucoadhesive (ZPTA-G/HMA) was proposed, with a methacrylate gelatin-methacrylate hyaluronic acid (GelMA-HAMA, G/HMA) double network hydrogel as a matrix, tannic acid (TA) as a high content anchor moiety provider for the moist oral mucosa, and polydopamine modified zinc oxide (ZnO@PDA, ZP) as a photocatalytic antibacterial substance. This platform had good adhesive and hemostatic properties both in vitro and in vivo. Under 520 nm green light (GL) irradiation, ZPTA-G/HMA would anchor to the wet mucosa surface by crosslinking and exert broad-spectrum antibacterial ability (even including Candida albicans) by in situ producing reactive oxygen species (ROS). Moreover, under 808 nm near-infrared (NIR) irradiation, the increased release of TA combined with the photothermal effect of ZP endowed ZPTA-G/HMA with enhanced anti-inflammatory and pro-healing performance. Collectively, ZPTA-G/HMA could be switched by light sources to achieve the dual-mode real-time adjustment of in situ anti-bacterial function and controlled anti-inflammation, combined with ideal mucosal residence, thus promising in developing personalized sequential strategies for varied oral mucosal lesions.

A ferroptosis-related prognostic model with excellent clinical performance based on the exploration of the mechanism of oral squamous cell carcinoma progression.

As a hot topic today, ferroptosis is closely involved in the progression and treatment of cancer. Accordingly, we built a prognostic model around ferroptosis to predict the overall survival of OSCC patients. We used up to 6 datasets from 3 different databases to ensure the credibility of the model. Then, through differentially expressed, Univariate Cox, and Lasso regression analyses, a model composed of nine prognostic-related differently expressed ferroptosis-related genes (CISD2, DDIT4, CA9, ALOX15, ATG5, BECN1, BNIP3, PRDX5 and MAP1LC3A) were constructed. Moreover, Kaplan-Meier curves, Receiver Operating Characteristic curves and principal component analysis used to verify the model's predictive ability showed the model's superiority. To deeply understand the mechanism of ferroptosis affecting the occurrence, development and prognosis of OSCC, we performed enrichment analysis in different risk groups identified by the model. The results showed that numerous TP53-related, immune-related and ferroptosis-related functions and pathways were enriched. Further immune microenvironment analysis and mutation analysis have once again revealed the correlation between risk score and immunity and TP53 mutation. Finally, the correlation between risk score and OSCC clinical treatment, as well as Nomogram show the brilliant clinical application prospects of the prognostic model.

Human loss-of-function variants in the serotonin 2C receptor associated with obesity and maladaptive behavior.

Serotonin reuptake inhibitors and receptor agonists are used to treat obesity, anxiety and depression. Here we studied the role of the serotonin 2C receptor (5-HT2CR) in weight regulation and behavior. Using exome sequencing of 2,548 people with severe obesity and 1,117 control individuals without obesity, we identified 13 rare variants in the gene encoding 5-HT2CR (HTR2C) in 19 unrelated people (3 males and 16 females). Eleven variants caused a loss of function in HEK293 cells. All people who carried variants had hyperphagia and some degree of maladaptive behavior. Knock-in male mice harboring a human loss-of-function HTR2C variant developed obesity and reduced social exploratory behavior; female mice heterozygous for the same variant showed similar deficits with reduced severity. Using the 5-HT2CR agonist lorcaserin, we found that depolarization of appetite-suppressing proopiomelanocortin neurons was impaired in knock-in mice. In conclusion, we demonstrate that 5-HT2CR is involved in the regulation of human appetite, weight and behavior. Our findings suggest that melanocortin receptor agonists might be effective in treating severe obesity in individuals carrying HTR2C variants. We suggest that HTR2C should be included in diagnostic gene panels for severe childhood-onset obesity.

Efficacy of indocyanine green fluorescence imaging-guided lymphadenectomy in radical gastrectomy for gastric cancer: A systematic review and meta-analysis.

Background: Indocyanine green (ICG) imaging-guided lymphadenectomy has been introduced in gastric cancer (GC) surgery and its clinical value remains controversial. The aim of this study is to evaluate the efficacy of ICG fluorescence imaging-guided lymphadenectomy in radical gastrectomy for GC. Methods: Studies comparing lymphadenectomy in radical gastrectomy between use and non-use of ICG fluorescence imaging up to July 2022 were systematically searched from PubMed, Web of Science, Embase and Cochrane Library. A pooled analysis was performed for the available data regarding the baseline features, the number of retrieved lymph nodes (LNs), the number of metastatic LNs and surgical outcomes as well as oncological outcomes. RevMan 5.3 software was used to perform the statistical analysis. Quality evaluation and publication bias were also conducted. Results: 17 studies with a total of 2274 patients (1186 in the ICG group and 1088 in the control group) undergoing radical gastrectomy and lymphadenectomy were included. In the pooled analysis, the baseline features were basically comparable. However, the number of retrieved LNs in the ICG group was significantly more than that in the control group (MD = 7.41, 95% CI = 5.44 to 9.37, P < 0.00001). No significant difference was found between the ICG and control groups in terms of metastatic LNs (MD = -0.05, 95% CI = -0.25 to 0.16, P = 0.65). In addition, the use of ICG could reduce intraoperative blood loss (MD = -17.96, 95% CI = -27.89 to -8.04, P = 0.0004) without increasing operative time (P = 0.14) and overall complications (P = 0.10). In terms of oncological outcomes, the use of ICG could reduce the overall recurrence rate (OR = 0.50; 95% CI 0.28-0.89; P = 0.02) but could not increase the 2-year overall survival rate (OR = 1.25; 95% CI 0.72-2.18; P = 0.43). Conclusions: ICG imaging-guided lymphadenectomy is valuable for complete LNs dissection in radical gastrectomy for GC. However, more high-quality randomized controlled trials are needed to confirm this benefit.

Gold Nanoparticle-Incorporated Chitosan Nanogels as a Theranostic Nanoplatform for CT Imaging and Tumour Chemotherapy.

Purpose: The translation of nanocarrier-based theranostics into cancer treatment is limited by their poor cellular uptake, low drug-loading capacity, uncontrolled drug release, and insufficient imaging ability. Methods: In this study, novel hybrid nanogels were fabricated as theranostic nanocarriers by modifying chitosan (CTS)/tripolyphosphate (TPP) nanoparticles (NPs) with polyacrylic acid (PAA) and further conjugating cysteine-functionalized gold nanoparticles (AuNPs). Results: The resultant nanogels, referred to as CTS/TPP/PAA@AuNPs (CTPA), exhibited excellent colloidal stability and a high encapsulation rate of 87% for the cationic drug doxorubicin (DOX). In the tumour microenvironment, the acidic pH and overexpression of lysozyme triggered CTPA@DOX to degrade and emit smaller nanoblocks (30-40 nm), which sequentially released the drug in a tumour-responsive manner. Cellular uptake experiments demonstrated that CTPA facilitates the entry of DOX into the cytoplasm. Furthermore, as visualised through AuNP-mediated computed tomography (CT) imaging, CTPA@DOX enabled favourable accumulation in the tumour. Our in vitro and in vivo data demonstrated that CTPA enabled advanced tumour cell-targeting delivery of DOX, which showed greater anti-tumour activity and biosafety than free DOX. Conclusion: The natural polymer CTS was developed for degradable nanogels, which can precisely track drugs with high antitumour activity. Additionally, the surface adjustment strategy can be assembled to achieve cationic drug loading and high drug-loading capacity, controlled drug release, and sufficient imaging ability. Therefore, multifunctional CTPA enables efficient drug delivery and CT imaging, which is expected to provide a valuable strategy for designing advanced theranostic systems.

[Mechanism of HOG-MAPK pathway in regulating mycotoxins formation under environmental stresses].

In order to adapt to different environmental stresses including heat stress, oxidative stress, osmotic pressure stress and ultraviolet stress in the process of growing and infecting agricultural products, fungi have developed a set of high osmolarity glycerol mitogen-activated protein kinase (HOG-MAPK) pathway to alleviate the environmental stresses. This pathway plays an important role in the growth, development, mycotoxin production and pathogenicity of fungi. There are two branches in the HOG-MAPK pathway, among which the SLN1 branch is more sensitive to osmotic stress than another branch (SHO1 branch), and is able to respond to high osmotic pressure and high salt concentration. The SHO1 branch is involved in a variety of signal transduction in response to oxidative stress and thermal stress. This paper reviews the functions of key genes sln1, sho1, ste11, ssk2, pbs2 and hog1 in the HOG-MAPK pathway of phytopathogenic fungi in responses to different environmental stresses such as osmotic stress and oxidative stress. We show that the HOG-MAPK pathway can respond to a variety of environmental signals and is involved in regulating the growth of phytopathogenic fungi such as Aspergillus flavus and Aspergillus ochraceus, and the production of mycotoxins such as aflatoxins and ochratoxins. Understanding the mechanism of how HOG-MAPK pathway regulates mycotoxins' formation under different environmental stresses that provides a theoretical basis and guidance for the prevention and control of mycotoxins in agricultural products such as food and feed.

Fast Cross-Linked Hydrogel as a Green Light-Activated Photocatalyst for Localized Biofilm Disruption and Brush-Free Tooth Whitening.

Biofilm-driven caries and tooth discoloration are two major problems in oral health care. The current methods have the disadvantages of insufficient biofilm targeting and irreversible enamel damage. Herein, an injectable sodium alginate hydrogel membrane doped with bismuth oxychloride (Bi12O17Cl2) and cubic cuprous oxide (Cu2O) nanoparticles was designed to simultaneously achieve local tooth whitening and biofilm removal through a photodynamic dental therapy process. This fast cross-linked hydrogel could form a biofilm removal coating on the target tooth surface precisely. Afterward, reactive oxygen species was effectively released on demand under green light, which could not only eradicate the biofilm but also whiten the tooth non-destructively in a facile manner without significant damage to both the enamel and biological cells. After the usage, the removal of this hydrogel can also enhance the effect of biofilm destruction and caries prevention.