Machine Learning-Assisted Optimization of Mixed Carbon Source Compositions for High-Performance Denitrification.

Appropriate mixed carbon sources have great potential to enhance denitrification efficiency and reduce operational costs in municipal wastewater treatment plants (WWTPs). However, traditional methods struggle to efficiently select the optimal mixture due to the variety of compositions. Herein, we developed a machine learning-assisted high-throughput method enabling WWTPs to rapidly identify and optimize mixed carbon sources. Taking a local WWTP as an example, a mixed carbon source denitrification data set was established via a high-throughput method and employed to train a machine learning model. The composition of carbon sources and the types of inoculated sludge served as input variables. The XGBoost algorithm was employed to predict the total nitrogen removal rate and microbial growth, thereby aiding in the assessment of the denitrification potential. The predicted carbon sources exhibited an enhanced denitrification potential over single carbon sources in both kinetic experiments and long-term reactor operations. Model feature analysis shows that the cumulative effect and interaction among individual carbon sources in a mixture significantly enhance the overall denitrification potential. Metagenomic analysis reveals that the mixed carbon sources increased the diversity and complexity of denitrifying bacterial ecological networks in WWTPs. This work offers an efficient method for WWTPs to optimize mixed carbon source compositions and provides new insights into the mechanism behind enhanced denitrification under a supply of multiple carbon sources.

iEnhancer-MRBF: Identifying enhancers and their strength with a multiple Laplacian-regularized radial basis function network.

An enhancer is a short DNA sequence containing many binding sites of transcription factors that plays a crucial role in the gene expression of major eukaryotes. It is difficult to avoid the time consumption and high cost of experimental methods. Therefore, with the continuous development of genomics, it is an urgent task to identify enhancers and their intensities by computational methods. In this paper, we propose a two-layer model called iEnhancer-MRBF, wherein the first layer is used to identify enhancers, and the identified enhancers are divided into strong enhancers and weak enhancers according to their strength in the second layer. In iEnhancer-MRBF, a new classifier multiple Laplacian-regularized radial basis function network (MLR-RBFN) is proposed, and three feature representation methods, namely, kmer, nucleotide binary profiles (NBP) and ac-cumulated nucleotide frequency (ANF), as well as feature selection, are used to process DNA sequences. The experimental results show that the model is significantly better than the previous prediction models, and the test accuracy rates of the first and second layers of independent datasets are 79.75% and 83.50%, respectively.

Animal by-products collagen and derived peptide, as important components of innovative sustainable food systems-a comprehensive review.

In 2020, the world's food crisis and health industry ushered into a real outbreak. On one side, there were natural disasters such as the novel coronavirus (2019-nCoV), desert locusts, floods, and droughts exacerbating the world food crisis, while on the other side, the social development and changes in lifestyles prompted the health industry to gradually shift from a traditional medical model to a new pattern of prevention, treatment, and nourishment. Therefore, this article reviews animal by-products collagen and derived peptide, as important components of innovative sustainable food systems. The review also considered the preparation, identification, and characterization of animal by-product collagen and collagen peptides as well as their impacts on the food system (including food processing, packaging, preservation, and functional foods). Finally, the application and research progress of animal by-product collagen and peptide in the food system along with the future development trend were discussed. This knowledge would be of great significance for a comprehensive understanding of animal by-product collagen and collagen peptides and would encourage the use of collagen in food processing, preservation, and functional foods.

The experience of treating patients with acute myocardial infarction under the COVID-19 epidemic.

Worldwide Coronavirus Disease 2019 (COVID-19) epidemic makes the management of acute myocardial infarction (AMI) more complicated, effective treatment without further dissemination is thus quite challenging. Recently, we successfully treated three representative AMI cases, by sharing these detailed procedures, we summarized some important issues including patient screening, reperfusion strategy selecting, personnel/catheter lab protection principle, as well as operation tactics, which may lend precious experience on AMI treating during the ongoing COVID-19 pandemic situation.

Reduced expression of cardiac ryanodine receptor protects against stress-induced ventricular tachyarrhythmia, but increases the susceptibility to cardiac alternans.

Reduced protein expression of the cardiac ryanodine receptor type 2 (RyR2) is thought to affect the susceptibility to stress-induced ventricular tachyarrhythmia (VT) and cardiac alternans, but direct evidence for the role of RyR2 protein expression in VT and cardiac alternans is lacking. Here, we used a mouse model (crrm1) that expresses a reduced level of the RyR2 protein to determine the impact of reduced RyR2 protein expression on the susceptibility to VT, cardiac alternans, cardiac hypertrophy, and sudden death. Electrocardiographic analysis revealed that after the injection of relatively high doses of caffeine and epinephrine (agents commonly used for stress test), wild-type (WT) mice displayed long-lasting VTs, whereas the crrm1 mutant mice exhibited no VTs at all, indicating that the crrm1 mutant mice are resistant to stress-induced VTs. Intact heart Ca2+ imaging and action potential (AP) recordings showed that the crrm1 mutant mice are more susceptible to fast-pacing induced Ca2+ alternans and AP duration alternans compared with WT mice. The crrm1 mutant mice also showed an increased heart-to-body-weight ratio and incidence of sudden death at young ages. Furthermore, the crrm1 mutant hearts displayed altered Ca2+ transients with increased time-to-peak and decay time (T50), increased ventricular wall thickness and ventricular cell area compared with WT hearts. These results indicate that reduced RyR2 protein expression suppresses stress-induced VTs, but enhances the susceptibility to cardiac alternans, hypertrophy, and sudden death.

1 H-NMR-based water-soluble low molecular weight compound characterization and fatty acid composition of boiled Wuding chicken during processing.

BACKGROUND: Boiled Wuding chicken was produced using whole chicken by washing, boiling 1 h with salt, deep frying, and boiling 2 h. The effect of the process on the water-soluble low molecular weight (WLOM) compound profiles of products was characterized using proton nuclear magnetic resonance spectroscopy, and the fatty acid composition of products was analyzed using gas chromatography-mass spectrometry. RESULTS: The metabolome was dominated by 49 WLOM compounds, and 22 fatty acid compounds were detected. Principal component (PC)1 and PC2 explained a total of 93.4% and 3% of variance respectively. Compared with the control group, the total WLOM compound and fatty acid contents of the chicken breast were significantly decreased in the other three processing stages (P < 0.05). Comprehensive multivariate data analysis showed significant differences about precursor substance between the different processing including creatine, lactate, creatinine, glucose, taurine, anserine, and acetate (P < 0.05). CONCLUSION: These results contribute to a more accurate understanding of precursor substance changes of flavor in chicken meat during processing. Boiled, treated chicken had significant effects on fatty acid and WLOM compounds. © 2018 Society of Chemical Industry.

The EF-hand Ca2+ Binding Domain Is Not Required for Cytosolic Ca2+ Activation of the Cardiac Ryanodine Receptor.

Activation of the cardiac ryanodine receptor (RyR2) by elevating cytosolic Ca(2+) is a central step in the process of Ca(2+)-induced Ca(2+) release, but the molecular basis of RyR2 activation by cytosolic Ca(2+) is poorly defined. It has been proposed recently that the putative Ca(2+) binding domain encompassing a pair of EF-hand motifs (EF1 and EF2) in the skeletal muscle ryanodine receptor (RyR1) functions as a Ca(2+) sensor that regulates the gating of RyR1. Although the role of the EF-hand domain in RyR1 function has been studied extensively, little is known about the functional significance of the corresponding EF-hand domain in RyR2. Here we investigate the effect of mutations in the EF-hand motifs on the Ca(2+) activation of RyR2. We found that mutations in the EF-hand motifs or deletion of the entire EF-hand domain did not affect the Ca(2+)-dependent activation of [(3)H]ryanodine binding or the cytosolic Ca(2+) activation of RyR2. On the other hand, deletion of the EF-hand domain markedly suppressed the luminal Ca(2+) activation of RyR2 and spontaneous Ca(2+) release in HEK293 cells during store Ca(2+) overload or store overload-induced Ca(2+) release (SOICR). Furthermore, mutations in the EF2 motif, but not EF1 motif, of RyR2 raised the threshold for SOICR termination, whereas deletion of the EF-hand domain of RyR2 increased both the activation and termination thresholds for SOICR. These results indicate that, although the EF-hand domain is not required for RyR2 activation by cytosolic Ca(2+), it plays an important role in luminal Ca(2+) activation and SOICR.

Enhanced Cytosolic Ca2+ Activation Underlies a Common Defect of Central Domain Cardiac Ryanodine Receptor Mutations Linked to Arrhythmias.

Recent three-dimensional structural studies reveal that the central domain of ryanodine receptor (RyR) serves as a transducer that converts long-range conformational changes into the gating of the channel pore. Interestingly, the central domain encompasses one of the mutation hotspots (corresponding to amino acid residues 3778-4201) that contains a number of cardiac RyR (RyR2) mutations associated with catecholaminergic polymorphic ventricular tachycardia (CPVT) and atrial fibrillation (AF). However, the functional consequences of these central domain RyR2 mutations are not well understood. To gain insights into the impact of the mutation and the role of the central domain in channel function, we generated and characterized eight disease-associated RyR2 mutations in the central domain. We found that all eight central domain RyR2 mutations enhanced the Ca2+-dependent activation of [3H]ryanodine binding, increased cytosolic Ca2+-induced fractional Ca2+ release, and reduced the activation and termination thresholds for spontaneous Ca2+ release in HEK293 cells. We also showed that racemic carvedilol and the non-beta-blocking carvedilol enantiomer, (R)-carvedilol, suppressed spontaneous Ca2+ oscillations in HEK293 cells expressing the central domain RyR2 mutations associated with CPVT and AF. These data indicate that the central domain is an important determinant of cytosolic Ca2+ activation of RyR2. These results also suggest that altered cytosolic Ca2+ activation of RyR2 represents a common defect of RyR2 mutations associated with CPVT and AF, which could potentially be suppressed by carvedilol or (R)-carvedilol.

Nebivolol suppresses cardiac ryanodine receptor-mediated spontaneous Ca2+ release and catecholaminergic polymorphic ventricular tachycardia.

ß-Blockers are a standard treatment for heart failure and cardiac arrhythmias. There are ∼30 commonly used ß-blockers, representing a diverse class of drugs with different receptor affinities and pleiotropic properties. We reported that among 14 ß-blockers tested previously, only carvedilol effectively suppressed cardiac ryanodine receptor (RyR2)-mediated spontaneous Ca2+ waves during store Ca2+ overload, also known as store overload-induced Ca2+ release (SOICR). Given the critical role of SOICR in arrhythmogenesis, it is of importance to determine whether there are other ß-blockers that suppress SOICR. Here, we assessed the effect of other commonly used ß-blockers on RyR2-mediated SOICR in HEK293 cells, using single-cell Ca2+ imaging. Of the 13 ß-blockers tested, only nebivolol, a ß-1-selective ß-blocker with nitric oxide synthase (NOS)-stimulating action, effectively suppressed SOICR. The NOS inhibitor (N-nitro-l-arginine methyl ester) had no effect on nebivolol's SOICR inhibition, and the NOS activator (histamine or prostaglandin E2) alone did not inhibit SOICR. Hence, nebivolol's SOICR inhibition was independent of NOS stimulation. Like carvedilol, nebivolol reduced the opening of single RyR2 channels and suppressed spontaneous Ca2+ waves in intact hearts and catecholaminergic polymorphic ventricular tachycardia (CPVT) in the mice harboring a RyR2 mutation (R4496C). Interestingly, a non-ß-blocking nebivolol enantiomer, (l)-nebivolol, also suppressed SOICR and CPVT without lowering heart rate. These data indicate that nebivolol, like carvedilol, possesses a RyR2-targeted action that suppresses SOICR and SOICR-evoked VTs. Thus, nebivolol represents a promising agent for Ca2+-triggered arrhythmias.

Roles of the NH2-terminal domains of cardiac ryanodine receptor in Ca2+ release activation and termination.

The NH2-terminal region (residues 1-543) of the cardiac ryanodine receptor (RyR2) harbors a large number of mutations associated with cardiac arrhythmias and cardiomyopathies. Functional studies have revealed that the NH2-terminal region is involved in the activation and termination of Ca(2+) release. The three-dimensional structure of the NH2-terminal region has recently been solved. It is composed of three domains (A, B, and C). However, the roles of these individual domains in Ca(2+) release activation and termination are largely unknown. To understand the functional significance of each of these NH2-terminal domains, we systematically deleted these domains and assessed their impact on caffeine- or Ca(2+)-induced Ca(2+) release and store overload-induced Ca(2+) release (SOICR) in HEK293 cells. We found that all deletion mutants were capable of forming caffeine- and ryanodine-sensitive functional channels, indicating that the NH2-terminal region is not essential for channel gating. Ca(2+) release measurements revealed that deleting domain A markedly reduced the threshold for SOICR termination but had no effect on caffeine or Ca(2+) activation or the threshold for SOICR activation, whereas deleting domain B substantially enhanced caffeine and Ca(2+) activation and lowered the threshold for SOICR activation and termination. Conversely, deleting domain C suppressed caffeine activation, abolished Ca(2+) activation and SOICR, and diminished protein expression. These results suggest that domain A is involved in channel termination, domain B is involved in channel suppression, and domain C is critical for channel activation and expression. Our data shed new insights into the structure-function relationship of the NH2-terminal domains of RyR2 and the action of NH2-terminal disease mutations.

Suppression of store overload-induced calcium release by hydroxylated metabolites of carvedilol.

Carvedilol is a drug widely used in the treatment of heart failure and associated cardiac arrhythmias. A unique action of carvedilol is its suppression of store overload-induced calcium release (SOICR) through the cardiac ryanodine receptor (RyR2), which can trigger ventricular arrhythmias. Since the effects of carvedilol metabolites on SOICR have not yet been investigated, three carvedilol metabolites hydroxylated at the 3-, 4' and 5'-positions were synthesized and assayed for SOICR inhibition in mutant HEK 293 cells expressing the RyR2 mutant R4496C. This cell line is especially prone to SOICR and calcium release through the defective RyR2 channel was measured with a calcium-sensitive fluorescent dye. These results revealed that the 3- and 4'-hydroxy derivatives are slightly more effective than carvedilol in suppressing SOICR, while the 5'-analog proved slightly less active. Metabolic deactivation of carvedilol via these hydroxylation pathways is therefore insignificant.

Role of Cys³6°² in the function and regulation of the cardiac ryanodine receptor.

The cardiac Ca²âº release channel [ryanodine receptor type 2 (RyR2)] is modulated by thiol reactive agents, but the molecular basis of RyR2 modulation by thiol reagents is poorly understood. Cys³6³5 in the skeletal muscle RyR1 is one of the most hyper-reactive thiols and is important for the redox and calmodulin (CaM) regulation of the RyR1 channel. However, little is known about the role of the corresponding cysteine residue in RyR2 (Cys³6°²) in the function and regulation of the RyR2 channel. In the present study, we assessed the impact of mutating Cys³6°² (C³6°²A) on store overload-induced Ca²âº release (SOICR) and the regulation of RyR2 by thiol reagents and CaM. We found that the C³6°²A mutation suppressed SOICR by raising the activation threshold and delayed the termination of Ca²âº release by reducing the termination threshold. As a result, C³6°²A markedly increased the fractional Ca²âº release. Furthermore, the C³6°²A mutation diminished the inhibitory effect of N-ethylmaleimide on Ca²âº release, but it had no effect on the stimulatory action of 4,4'-dithiodipyridine (DTDP) on Ca²âº release. In addition, Cys³6°² mutations (C³6°²A or C³6°²R) did not abolish the effect of CaM on Ca²âº-release termination. Therefore, RyR2-Cys³6°² is a major site mediating the action of thiol alkylating agent N-ethylmaleimide, but not the action of the oxidant DTDP. Our data also indicate that residue Cys³6°² plays an important role in the activation and termination of Ca²âº release, but it is not essential for CaM regulation of RyR2.

Based on proteomics probing into the deterioration mechanism of pork batter gel caused by different cooking temperatures.

The purpose of this experiment was to explore the influence of different cooking temperatures on the deterioration characteristics of pork batter gel by using proteomics, gel electrophoresis, size and chemical bond of aggregates. The results showed that the protein molecules of the pork batter gel was degraded during heating cooking and the protein aggregates were composed of many degraded protein fragments; compared with the control group 75 °C (0 min), the significant degradation of cytoskeleton showed at 110 °C (30 min) and 121 °C (30 min) and the significant degradation of myosin complexonly appeared at 121 °C (30 min). As the heating temperature points increased, compared with the control group 75 °C (0 min), the different temperatures could promote the separation of metal ions with proteins especially at 110 °C (30 min) and 121 °C (30 min), which could ultimately influence quality of pork batter gel by the size of particle. As the increase of heating temperature points, the recombination of aggregates composed of different proteins was not conducive to the retention of capillary water, which reduced the texture of pork batter gel. This research provided theoretical support for improving the process property of the meat products.

Analysis of nearly 3000 archaeal genomes from terrestrial geothermal springs sheds light on interconnected biogeochemical processes.

Terrestrial geothermal springs are physicochemically diverse and host abundant populations of Archaea. However, the diversity, functionality, and geological influences of these Archaea are not well understood. Here we explore the genomic diversity of Archaea in 152 metagenomes from 48 geothermal springs in Tengchong, China, collected from 2016 to 2021. Our dataset is comprised of 2949 archaeal metagenome-assembled genomes spanning 12 phyla and 392 newly identified species, which increases the known species diversity of Archaea by ~48.6%. The structures and potential functions of the archaeal communities are strongly influenced by temperature and pH, with high-temperature acidic and alkaline springs favoring archaeal abundance over Bacteria. Genome-resolved metagenomics and metatranscriptomics provide insights into the potential ecological niches of these Archaea and their potential roles in carbon, sulfur, nitrogen, and hydrogen metabolism. Furthermore, our findings illustrate the interplay of competition and cooperation among Archaea in biogeochemical cycles, possibly arising from overlapping functional niches and metabolic handoffs. Taken together, our study expands the genomic diversity of Archaea inhabiting geothermal springs and provides a foundation for more incisive study of biogeochemical processes mediated by Archaea in geothermal ecosystems.

Combination of Nicorandil and Beta-Adrenergic Receptor Blockers in Patients with Coronary Artery Disease: A Real-World Observational Study.

BACKGROUND: The effect of combined nicorandil and beta-adrenergic receptor blockers (BBs) compared with that of BBs alone on long-term clinical outcomes in patients with coronary artery disease (CAD) remains undetermined. METHODS: A multicenter retrospective cohort study was performed. Adult patients who had been hospitalized for CAD and treated for angina with a combination of nicorandil and BBs or BBs alone were included. The effect of different treatments on the cumulative incidence of major adverse cardiovascular event (MACE) and their components within a follow-up duration of 2.5 years were analyzed using Kaplan-Meier survival curves. An inverse probability of treatment weighting (IPTW) method was used to adjust for the possible effect of confounding factors. RESULTS: A total of 137,714 patients were screened, of whom 16,912 individuals (mean age: 61.5 years, men: 67.1%) were successfully enrolled. Among the enrolled participants, 4669 received the combined treatment of nicorandil and BBs, while 12,243 received BBs alone. After IPTW, the results demonstrated that the combined treatment was associated with a significantly reduced incidence of MACE (hazard ratio [HR] 0.79, 95% conidence interval [CI] 0.72-0.87) and stroke (HR 0.48, 95% CI 0.42-0.54) but not of MI (HR 1.03, 95% CI 0.92-1.15) or all-cause mortality (HR 0.93, 95% CI 0.64-1.37). Sensitivity analyses revealed similar results. CONCLUSIONS: A combined antiangina treatment of nicorandil and BBs may be more effective than treatment of BBs alone in reducing the long-term incidence of MACE in patients with CAD.

LINC00668 promoted non-small lung cancer progression by miR-518c-3p/TRIP4 axis.

BACKGROUND: Non-small lung cancer ranks first in the cancer-related death of all malignant tumors. Exploring novel biological targets is of great significance for diagnosis and therapy of NSCLC. OBJECTIVE: In this study, we aimed to explore the effect of LINC00668 on the biological functions of NSCLC cells and the underlying mechanism. METHODS: RT-qPCR assays and western blot assays were utilized to estimate the relative gene expression at mRNA and protein levels, respectively. CCK8, colony formation, wound healing, transwell, and cell apoptosis assays were employed to assess cell function. IHC and FISH assays were used to determine the gene expression in NSCLC tissues. RIP and dual-luciferase assays were conducted to validate the combination between LINC00668 and miR-518c-3p. The correlation of expression between miR-518c-3p and LINC00668 or TRIP4 was determined by Pearson correlation analysis. RESULTS: LINC00668 was aberrantly upregulated in NSCLC tumor tissues and cell lines. Inhibition of LINC00668 significantly suppressed tumor proliferation, migration, invasion and promoted cell apoptosis. Mechanistically, LINC00668 could bind to miR-518c-3p, thus targeting the 3'UTR of TRIP4. TRIP4 overexpression rescued the weakened cell function mediated by LINC00668 silencing. CONCLUSIONS: LINC00668 acted as an oncogene in NSCLC progression through miR-518c-3p/TRIP4 axis. Our study disclosed a new mechanism of LINC00668 functioned in NSCLC and may give a deeper insight of the targeted therapy of NSCLC in the future.

Regulation mechanism of curcumin-loaded oil on the emulsification and gelation properties of myofibrillar protein: Emphasizing the dose-response of curcumin.

The regulation mechanism of curcumin (CUR) in the oil phase on the emulsification and gelation properties of myofibrillar protein (MP) was investigated. CUR enhanced the emulsifying activity index (EAI) of MP but decreased its turbiscan stability index (TSI) and surface hydrophobicity, which exacerbated oil droplet aggregation. Medium amounts (200 mg/L) of CUR changed the 3D network architectures of emulsion gels from lamellar to reticular, improving the gels' water-holding capacity (WHC), storage modulus, springiness, and cohesiveness. Besides, the LF-NMR revealed that CUR had limited effects on the mobility of immobilized and free water. The α-helix of MP in gels with medium amounts of CUR decreased from 51% to 45%, but the ß-sheet increased from 23% to 27% compared to those without CUR. Overall, CUR has the potential to become a novel structural modifier in emulsified meat products due to its dose-response.

Re-evaluation and modification of dehydrogenase activity tests in assessing microbial activity for wastewater treatment plant operation.

Reliable and cost-effective methods for monitoring microbial activity are critical for process control in wastewater treatment plants. The dehydrogenase activity (DHA) test has been recognized as an efficient measure of biological activity due to its simplicity and broad applicability. Nevertheless, the existing DHA test methods suffer from imperfections and are difficult to implement as routine monitoring techniques. In this work, an accurate and cost-effective modified DHA approach was developed and the procedure for the DHA test was critically evaluated with respect to the standard construction, sample pretreatment, incubation and extraction conditions. The feasibility of the modified DHA test was demonstrated by comparison with the oxygen uptake rate and adenosine triphosphate in a sequencing batch reactor. The sensitivities of the two typical tetrazolium salts to toxicant inhibition by heavy metals and antibiotics were compared, revealing that 2,3,5-triphenyltetrazolium chloride (TTC) exhibited a higher sensitivity. Furthermore, the sensitivity mechanism of the two DHA tests was elucidated through electrochemical experiments, theoretical analysis and molecular simulations. Both tetrazolium salts were found to be effective artificial electron acceptors due to their low redox potentials. Molecular docking simulations revealed that TTC could outperform other tetrazolium salts in accepting electrons and hydrogens from dehydrogenase. Overall, the modified DHA approach presents an accurate and cost-effective way to measure microbial activity, making it a practical tool for wastewater treatment plants.

miR-30e-5p-mediated FOXD1 promotes cell proliferation by blocking cellular senescence and apoptosis through p21/CDK2/Rb signaling in head and neck carcinoma.

Forkhead box D1 (FOXD1) belongs to the FOX protein family, which has been found to function as a oncogene in multiple cancer types, but its role in head and neck squamous cell carcinoma (HNSCC) requires further investigation. Our research aimed to investigate the function of FOXD1 in HNSCC. Bioinformatics analysis indicated that mRNA level of FOXD1 was highly expressed in HNSCC tissues, and over-expressed FOXD1 was related to poor prognosis. Moreover, FOXD1 knockdown increased the ratio of senescent cells but decreased the proliferation ability, while FOXD1 overexpression obtained the opposite results. In vitro experiments revealed that FOXD1 bound to the p21 promoter and inhibited its transcription, which blocked the cyclin dependent kinase 2 (CDK2)/retinoblastoma (Rb) signaling pathway, thus preventing senescence and accelerating proliferation of tumor cells. CDK2 inhibitor could reverse the process to some extent. Further research has shown that miR-3oe-5p serves as a tumor suppressant by repressing the translation of FOXD1 through combining with the 3'-untranslated region (UTR). Thus, FOXD1 resists cellular senescence and facilitates HNSCC cell proliferation by affecting the expression of p21/CDK2/Rb signaling, suggesting that FOXD1 may be a potential curative target for HNSCC.

Oral Intake of Chicken Bone Collagen Peptides Anti-Skin Aging in Mice by Regulating Collagen Degradation and Synthesis, Inhibiting Inflammation and Activating Lysosomes.

The effect of diet on skin aging has become an interesting research topic. Previous studies have mostly focused on the beneficial effects of collagen peptides derived from marine organisms on the aging skin when administered orally, while the beneficial effects of collagen peptides derived from poultry on aging skin have been rarely reported. In this study, collagen peptides were prepared from chicken bone by enzymatic hydrolysis, and the effect and mechanism of action of orally administered collagen peptides on alleviating skin aging induced by UV combined with D-galactose were investigated. The results showed that the chicken bone collagen had typical characteristics of collagen, and the chicken bone collagen peptides (CPs) were mainly small molecular peptides with a molecular weight of <3000 Da. In vivo experiments showed that CPs had a significant relieving effect on aging skin, indicated by the changes in the compostion and structure of the aging skin, improvement of skin antioxidant level, and inhibition of inflammation; the relieving effect was positively correlated with the dose of CPs. Further investigation showed that CPs first reduce the level of skin oxidation, inhibit the expression of the key transcription factor AP-1 (c-Jun and c-Fos), then activate the TGF-ß/Smad signaling pathway to promote collagen synthesis, inhibit the expression of MMP-1/3 to inhibit collagen degradation, and inhibit skin inflammation to alleviate skin aging in mice. Moreover, the skin transcriptome found that lysosomes activated after oral administration of CPs may be an important pathway for CPs in anti-skin aging, and is worthy of further research. These results suggested that CPs might be used as a functional anti-aging nutritional component.