Distinctive Lipid Characteristics of Colorectal Cancer Revealed through Non-targeted Lipidomics Analysis of Tongue Coating.

The metabolites and microbiota in tongue coating display distinct characteristics in certain digestive disorders, yet their relationship with colorectal cancer (CRC) remains unexplored. Here, we employed liquid chromatography coupled with tandem mass spectrometry to analyze the lipid composition of tongue coating using a nontargeted approach in 30 individuals with colorectal adenomas (CRA), 32 with CRC, and 30 healthy controls (HC). We identified 21 tongue coating lipids that effectively distinguished CRC from HC (AUC = 0.89), and 9 lipids that differentiated CRC from CRA (AUC = 0.9). Furthermore, we observed significant alterations in the tongue coating lipid composition in the CRC group compared to HC/CRA groups. As the adenoma-cancer sequence progressed, there was an increase in long-chain unsaturated triglycerides (TG) levels and a decrease in phosphatidylethanolamine plasmalogen (PE-P) levels. Furthermore, we noted a positive correlation between N-acyl ornithine (NAOrn), sphingomyelin (SM), and ceramide phosphoethanolamine (PE-Cer), potentially produced by members of the Bacteroidetes phylum. The levels of inflammatory lipid metabolite 12-HETE showed a decreasing trend with colorectal tumor progression, indicating the potential involvement of tongue coating microbiota and tumor immune regulation in early CRC development. Our findings highlight the potential utility of tongue coating lipid analysis as a noninvasive tool for CRC diagnosis.

Enhanced enterovirus 71 virus-like particle yield from a new baculovirus design.

Enterovirus 71 (EV71) is responsible for the outbreaks of hand-foot-and-mouth disease in the Asia-Pacific region. To produce the virus-like particle (VLP) vaccine, we previously constructed recombinant baculoviruses to co-express EV71 P1 polypeptide and 3CD protease using the Bac-to-Bac(®) vector system. The recombinant baculoviruses resulted in P1 cleavage by 3CD and subsequent VLP assembly in infected insect cells, but caused either low VLP yield or excessive VLP degradation. To tackle the problems, here we explored various expression cassette designs and flashBAC GOLD™ vector system which was deficient in v-cath and chiA genes. We found that the recombinant baculovirus constructed using the flashBAC GOLD™ system was insufficient to improve the EV71 VLP yield. Nonetheless, BacF-P1-C3CD, a recombinant baculovirus constructed using the flashBAC GOLD(TM) system to express P1 under the polh promoter and 3CD under the CMV promoter, dramatically improved the VLP yield while alleviating the VLP degradation. Infection of High Five(TM) cells with BacF-P1-C3CD enhanced the total and extracellular VLP yield to ≈268 and ≈171 mg/L, respectively, which enabled the release of abundant VLP into the supernatant and simplified the downstream purification. Intramuscular immunization of mice with 5 µg purified VLP induced cross-protective humoral responses and conferred protection against lethal virus challenge. Given the significantly improved extracellular VLP yield (≈171 mg/L) and the potent immunogenicity conferred by 5 µg VLP, one liter High Five(TM) culture produced ≈12,000 doses of purified vaccine, thus rendering the EV71 VLP vaccine economically viable and able to compete with inactivated virus vaccines.

Over-expression of miR-125a-5p inhibits proliferation in C2C12 myoblasts by targeting E2F3.

MicroRNAs (miRNAs) are a class of small non-coding RNAs of 20-25 nucleotides in length. It has been shown that miRNAs play important roles in the proliferation of many types of cells, including myoblasts. In this study, we used real-time quantitative polymerase chain reaction, western blotting, EdU, flow cytometry, and CCK-8 assay to explore the role of miR-125a-5p during the proliferation of C2C12 myoblasts. It was found that the expression of miR-125a-5p was decreased during C2C12 myoblast proliferation. Over-expression of miR-125a-5p inhibited C2C12 myoblast proliferation as indicated by EdU staining, flow cytometry, and CCK8 assay. It was also found that miR-125a-5p could negatively regulate E2F3 expression at posttranscriptional level, via a specific target site in the 3' untranslated region. Knockdown of E2F3 showed a similar inhibitory effect on C2C12 myoblast proliferation. Thus, our findings suggest that miR-125a-5p may act as a negative regulator of C2C12 myoblast proliferation by targeting E2F3.

Multifunctional double-network hydrogel with antibacterial and anti-inflammatory synergistic effects contributes to wound healing of bacterial infection.

Wound infection not only hinders the time sequence of tissue repair, but also may lead to serious complications. Multifunctional wound dressings with biocompatibility, excellent mechanical properties and antibacterial properties can promote wound healing during skin infection and reduce the use of antibiotics. In this study, a multifunctional dual-network antibacterial hydrogel was constructed based on the electrostatic interaction of two polyelectrolytes, hydroxypropyl trimethyl ammonium chloride chitosan (HACC) and sodium alginate (SA). Attributing to the suitable physical crosslinking between HACC and SA, the hydrogel not only has good biocompatibility, mechanical property, but also has broad-spectrum antibacterial properties. In vivo results showed that the hydrogel could regulate M2 polarization, promote early vascular regeneration, and create a good microenvironment for wound healing. Therefore, this hydrogel is an effective multifunctional wound dressing. Consequently, we propose a novel hydrogel with combined elements to expedite the intricate repair of wound infection.

The metabolism and transformation of casein-bound lactulosyllysine in vivo: Promoting dicarbonyl stress and the formation of advanced glycation end products accompanied by systemic inflammation.

Lactulosyllysine (LL) widely exists in thermally processed dairy products, while the metabolism and transformation of LL remain poorly understood. We aimed to elucidate the metabolic pathways of LL and its impact on body health by subjecting C57BL/6 mice to a short-term ll-fortified casein diet. Our findings indicated that casein-bound LL might be metabolized and transformed into 3-deoxyglucosone through fructosamine-3-kinase (FN3K) in vivo, which promoted α-dicarbonyl stress, ultimately leading to the formation of advanced glycation end products (AGEs) in various tissues/organs, accompanied by systemic inflammation. The levels of AGEs formation in tissues/organs at various stages of casein-bound LL intake exhibited dynamic changes, correlating with alterations in the expression of FN3K and α-dicarbonyl compounds metabolic detoxification enzymes. The negative effects induced by casein-bound LL cannot be fully reversed by switching to a standard diet for equal periods. Consumption of dairy products rich in LL raises concerns as a potential risk factor for healthy individuals.

2'-Fucosyllactose Promotes Colonization of Akkermansia muciniphila and Prevents Colitis In Vitro and in Mice.

Akkermansia muciniphila is a potential candidate for ulcerative colitis prevention. Considering that it utilizes 2'-fucosyllactose (2'FL) for growth, 2'FL can be used to enrich the abundance of A. muciniphila in feces. However, whether the crosswalk between 2'FL and A. muciniphila can promote the intestinal colonization of A. muciniphila remains unclear. In this study, we explored the effect and the underlying mechanism of 2'FL on the colonization of A. muciniphila in vitro and in vivo as well as its alleviating effect on colitis. Our results revealed that 2'FL can serve as a carbon source of A. muciniphila to support the growth and increase cell-surface hydrophobicity and the expression of the genes coding fibronectin-binding autotransporter adhesin to promote the adhesion to Caco2/HT29 methotrexate (MTX) cells but not of galactooligosaccharides (GOS) and glucose. Moreover, 2'FL could increase the host mucin formation to promote the adhesion of A. muciniphila to Caco2/HT29 MTX cells but not of GOS and glucose. Furthermore, 2'FL could significantly increase the colonization of A. muciniphila in the gut to alleviate colitis in mice. Overall, the interplay between A. muciniphila and 2'FL is expected to provide an advantageous ecological niche for A. muciniphila so as to confer further health benefits against colitis.

Innovative wound management: creating dynamic Alg-Mg/SF hydrogels for controlled Mg2+ release in wound healing.

Antibacterial hydrogels have gained considerable attention for soft tissue repair, particularly in preventing infections associated with wound healing. However, developing an antibacterial hydrogel that simultaneously possesses excellent cell affinity and controlled release of metal ions remains challenging. This study introduces an antibacterial hydrogel based on alginate modified with bisphosphonate, forming a coordination complex with magnesium ions. The hydrogel, through an interpenetrating network with silk fibroin, effectively controls the release of magnesium ions and enhances strain resistance. The Alg-Mg/SF hydrogel not only demonstrates outstanding biocompatibility and broad-spectrum antibacterial properties but also stimulates macrophages to secrete anti-inflammatory factors. This advanced Alg-Mg/SF hydrogel provides a convenient therapeutic approach for chronic wound management, showcasing its potential applications in wound healing and other relevant biomedical fields.

Correction: Innovative wound management: creating dynamic Alg-Mg/SF hydrogels for controlled Mg2+ release in wound healing.

[This corrects the article DOI: 10.1039/D4RA00793J.].

The Interaction between Human Microbes and Advanced Glycation End Products: The Role of Klebsiella X15 on Advanced Glycation End Products' Degradation.

Previous studies have shown that advanced glycation end products (AGEs) are implicated in the occurrence and progression of numerous diseases, with dietary AGEs being particularly associated with intestinal disorders. In this study, methylglyoxal-beta-lactoglobulin AGEs (MGO-ß-LG AGEs) were utilized as the exclusive nitrogen source to investigate the interaction between protein-bound AGEs and human gut microbiota. The high-resolution mass spectrometry analysis of alterations in peptides containing AGEs within metabolites before and after fermentation elucidated the capacity of intestinal microorganisms to enzymatically hydrolyze long-chain AGEs into short-chain counterparts. The 16S rRNA sequencing revealed Klebsiella, Lactobacillus, Escherichia-Shigella, and other genera as dominant microbiota at different fermentation times. A total of 187 potential strains of AGE-metabolizing bacteria were isolated from the fermentation broth at various time points. Notably, one strain of Klebsiella exhibited the most robust growth capacity when AGEs served as the sole nitrogen source. Subsequently, proteomics was employed to compare the changes in protein levels of Klebsiella X15 following cultivation in unmodified proteins and proteins modified with AGEs. This analysis unveiled a remodeled amino acid and energy metabolism pathway in Klebsiella in response to AGEs, indicating that Klebsiella may possess a metabolic pathway specifically tailored to AGEs. This study found that fermenting AGEs in healthy human intestinal microbiota altered the bacterial microbiota structure, especially by increasing Klebsiella proliferation, which could be a key factor in AGEs' role in causing diseases, particularly intestinal inflammation.

WASPSYN: A Challenge for Domain Adaptive Synapse Detection in Microwasp Brain Connectomes.

The size of image volumes in connectomics studies now reaches terabyte and often petabyte scales with a great diversity of appearance due to different sample preparation procedures. However, manual annotation of neuronal structures (e.g., synapses) in these huge image volumes is time-consuming, leading to limited labeled training data often smaller than 0.001% of the large-scale image volumes in application. Methods that can utilize in-domain labeled data and generalize to out-of-domain unlabeled data are in urgent need. Although many domain adaptation approaches are proposed to address such issues in the natural image domain, few of them have been evaluated on connectomics data due to a lack of domain adaptation benchmarks. Therefore, to enable developments of domain adaptive synapse detection methods for large-scale connectomics applications, we annotated 14 image volumes from a biologically diverse set of Megaphragma viggianii brain regions originating from three different whole-brain datasets and organized the WASPSYN challenge at ISBI 2023. The annotations include coordinates of pre-synapses and post-synapses in the 3D space, together with their one-to-many connectivity information. This paper describes the dataset, the tasks, the proposed baseline, the evaluation method, and the results of the challenge. Limitations of the challenge and the impact on neuroscience research are also discussed. The challenge is and will continue to be available at https://codalab.lisn.upsaclay.fr/competitions/9169. Successful algorithms that emerge from our challenge may potentially revolutionize real-world connectomics research and further the cause that aims to unravel the complexity of brain structure and function.

Characterization of tongue coating microbiome from patients with colorectal cancer.

Background: Tongue coating microbiota has aroused particular interest in profiling oral and digestive system cancers. However, little is known on the relationship between tongue coating microbiome and colorectal cancer (CRC). Methods: Metagenomic shotgun sequencing was performed on tongue coating samples collected from 30 patients with CRC, 30 patients with colorectal polyps (CP), and 30 healthy controls (HC). We further validated the potential of the tongue coating microbiota to predict the CRC by a random forest model. Results: We found a greater species diversity in CRC samples, and the nucleoside and nucleotide biosynthesis pathway was more apparent in the CRC group. Importantly, various species across participants jointly shaped three distinguishable fur types.The tongue coating microbiome profiling data gave an area under the receiver operating characteristic curve (AUC) of 0.915 in discriminating CRC patients from control participants; species such as Atopobium rimae, Streptococcus sanguinis, and Prevotella oris aided differentiation of CRC patients from healthy participants. Conclusion: These results elucidate the use of tongue coating microbiome in CRC patients firstly, and the fur-types observed contribute to a better understanding of the microbial community in human. Furthermore, the tongue coating microbiota-based biomarkers provide a valuable reference for CRC prediction and diagnosis.

Discrepancy-Aware Meta-Learning for Zero-Shot Face Manipulation Detection.

In this paper, we propose a discrepancy-aware meta-learning approach for zero-shot face manipulation detection, which aims to learn a discriminative model maximizing the generalization to unseen face manipulation attacks with the guidance of the discrepancy map. Unlike existing face manipulation detection methods that usually present algorithmic solutions to the known face manipulation attacks, where the same types of attacks are used to train and test the models, we define the detection of face manipulation as a zero-shot problem. We formulate the learning of the model as a meta-learning process and generate zero-shot face manipulation tasks for the model to learn the meta-knowledge shared by diversified attacks. We utilize the discrepancy map to keep the model focused on generalized optimization directions during the meta-learning process. We further incorporate a center loss to better guide the model to explore more effective meta-knowledge. Experimental results on the widely used face manipulation datasets demonstrate that our proposed approach achieves very competitive performance under the zero-shot setting.

STAR-FC: Structure-Aware Face Clustering on Ultra-Large-Scale Graphs.

Face clustering is a promising method for annotating unlabeled face images. Recent supervised approaches have boosted the face clustering accuracy greatly, however their performance is still far from satisfactory. These methods can be roughly divided into global-based and local-based ones. Global-based methods suffer from the limitation of training data scale, while local-based ones are inefficient for inference due to the use of numerous overlapped subgraphs. Previous approaches fail to tackle these two challenges simultaneously. To address the dilemma of large-scale training and efficient inference, we propose the STructure-AwaRe Face Clustering (STAR-FC) method. Specifically, we design a structure-preserving subgraph sampling strategy to explore the power of large-scale training data, which can increase the training data scale from 105 to 107. On this basis, a novel hierarchical GCN training paradigm is further proposed for better capturing the dynamic local structure. During inference, the STAR-FC performs efficient full-graph clustering with two steps: graph parsing and graph refinement. And the concept of node intimacy is introduced in the second step to mine the local structural information, where a calibration module is further proposed for fairer edge scores. The STAR-FC gets 93.21 pairwise F-score on standard partial MS1M within 312 seconds, which far surpasses the state-of-the-arts while maintaining high inference efficiency. Furthermore, we are the first to train on an ultra-large-scale graph with 20 M nodes, and achieve superior inference results on 12 M testing data. Overall, as a simple and effective method, the proposed STAR-FC provides a strong baseline for large-scale face clustering.

Gut Microbiota-Derived Indole Derivatives Alleviate Neurodegeneration in Aging through Activating GPR30/AMPK/SIRT1 Pathway.

SCOPE: Tryptophan (Trp) metabolites are closely related to neurological diseases, whereas, the underlying mechanism related to the alleviative effects of Trp metabolites on neurodegeneration in aging remains unclear. This study aims to evaluate the protective effects and mechanisms of Trp metabolites on neurodegeneration in aging process. METHODS AND RESULTS: The neuroprotective properties of Trp metabolites are evaluated in vitro and in vivo experimental model. Trp metabolites such as indole, indole-3-acetic acid (IAA), indole-3-propionic acid (IPA), indole-3-lactic acid (ILA), and indole-3-carboxyaldehyde (Icld) could significantly reduce oxidative stress, inflammation, and neuronal apoptosis induced by H2 O2 in HT-22 cells. Meanwhile, indoles could upregulate the expressions of G protein-coupled receptor 30 (GPR30)/5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK)/silent information regulator 1 (SIRT1) pathway in vitro. Furthermore, the neuroprotective effects of IAA and IPA are unveiled through activation of GPR30/AMPK/SIRT1 pathway in d-galactose induced aging mice. Finally, the regulatory effects of indoles on GPR30/AMPK/SIRT1 pathway are further confirmed by pretreating HT-22 and Neuro-2a with GPR30 antagonist of G15. In that case, indoles are furtherly proved with inhibitory effects on neurodegeneration by activating the GPR30/AMPK/SIRT1 pathway in aging process. CONCLUSIONS: The findings reveal that Trp metabolites significantly improve neurodegeneration via GPR30/AMPK/SIRT1 pathway in aging process. This study provides the potential novel intervention strategy and target to prevent the neurodegeneration.

Establishment of a lysosome-related prognostic signature in breast cancer to predict immune infiltration and therapy response.

Background: Lysosomes are instrumental in intracellular degradation and recycling, with their functional alterations holding significance in tumor growth. Nevertheless, the precise role of lysosome-related genes (LRGs) in breast cancer (BC) remains elucidated. This study aimed to establish a prognostic model for BC based on LRGs. Methods: Employing The Cancer Genome Atlas (TCGA) BC cohort as a training dataset, this study identified differentially expressed lysosome-related genes (DLRGs) through intersecting LRGs with differential expression genes (DEGs) between tumor and normal samples. A prognostic model of BC was subsequently developed using Cox regression analysis and validated within two Gene Expression Omnibus (GEO) external validation sets. Further analyses explored functional pathways, the immune microenvironment, immunotherapeutic responses, and sensitivity to chemotherapeutic drugs in different risk groups. Additionally, the mRNA and protein expression levels of genes within the risk model were examined by utilizing the Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) databases. Clinical tissue specimens obtained from patients were gathered to validate the expression of the model genes via Real-Time Polymerase Chain Reaction (RT-PCR). Results: We developed a risk model of BC based on five specific genes (ATP6AP1, SLC7A5, EPDR1, SDC1, and PIGR). The model was validated for overall survival (OS) in two GEO validation sets (p=0.00034 for GSE20685 and p=0.0095 for GSE58812). In addition, the nomogram incorporating clinical factors showed better predictive performance. Compared to the low-risk group, the high-risk group had a higher level of certain immune cell infiltration, including regulatory T cells (Tregs) and type 2 T helper cells (Th2). The high-risk patients appeared to respond less well to general immunotherapy and chemotherapeutic drugs, according to the Tumor Immune Dysfunction and Exclusion (TIDE), Immunophenotype Score (IPS), and drug sensitivity scores. The RT-PCR results validated the expression trends of some prognostic-related genes in agreement with the previous differential expression analysis. Conclusion: Our innovative lysosome-associated signature can predict the prognosis for BC patients, offering insights for guiding subsequent immunotherapeutic and chemotherapeutic interventions. Furthermore, it has the potential to provide a scientific foundation for identifying prospective therapeutic targets.

A Comparative Study of Three Nucleic Acid Integrity Assay Systems.

Background: The measurement of nucleic acid quality, especially the analysis of integrity, is a key step for many downstream experiments in biomedical research and quality control of biomaterials. General gel electrophoresis is a traditional method for nucleic acid integrity analysis. Currently, more electrophoresis techniques are becoming standardized and automated operations with higher precision. In this study, we have evaluated the comparability and bias of the outcomes from three commercial assay systems. Methods: Seventy-two deoxyribonucleic acid (DNA) and 67 ribonucleic acid (RNA) samples were selected for methodological comparison among different systems. The DNA Quality Number (DQN) and RNA Quality Number (RQN) of BIOptic Qsep400, DNA Quality Score (DQS) and RNA Quality Score (RQS) of PerkinElmer Labchip GX Touch HT were separately compared with the DNA Integrity Number (DIN) and RNA Integrity Number (RINe) of the Agilent 4200 TapeStation according to Clinical and Laboratory Standards Institute (CLSI) guideline (EP09-A3). Results: The biases of the mean estimated between DQN and DIN, DQS and DIN both exceeded the acceptance criteria. The Passing-Bablok regression analysis between DQN and DIN, and the Deming regression analysis between DQS and DIN, showed the biases were both within the acceptance criteria, and the bias between DQN and DIN was smaller. For the comparisons of RQN and RINe, RQS and RINe, the regression analyses revealed the biases were both within the acceptance criteria. The bias of the mean estimated between RQS and RINe was outside of the acceptance criteria. Conclusions: There was a good comparability in nucleic acid integrity detection between BIOptic Qsep400 and PerkinElmer Labchip GX Touch HT with the Agilent 4200 TapeStation. However, the bias and linear correlations require more attention between systems.

Establishment of a Standard Tongue Coating Collection Method for Microbiome Studies.

Objective: Recently, researchers have been focusing on characterizing the tongue coating microbiome from patients with digestive tract disease. However, to the best of our knowledge, the tongue coating collection methods have not been standardized until now. This article focuses on bridging this gap by exploring and validating the conditions suitable for the collection of tongue coating samples. Methods: One hundred forty-one healthy subjects were involved in the standardization of the tongue coating collection method. We conducted our standardization experiment by comparing different sampling tools, different preservation solutions, different scraping times, and different storage days with preservation at room temperature. The tongue coating samples from 59 normal individuals were analyzed using 16S ribosomal RNA (rRNA) gene-sequencing technology. The assessment of the quality of extracted DNA was used to verify our established method. We separated the 59 subjects into two groups (aged and younger), and the sequencing results were used to explore the age-related changes in microbiome. Results: Sterile oral swab B is suitable for the collection of tongue coating samples. To obtain a sufficient amount of DNA from a tongue coating sample, we recommend 30 times of tongue coating scraping. Normal saline, phosphate-buffered saline, and commercial preservation solution are all suitable for short-term sample storage (<1 hour). The commercial long-term preservation solution, which stores samples at room temperature (0 hour to 7 days) and can provide for fast commercial transportation, ensures the integrity of the sample DNA as well as the stability of the DNA quality. By using the established method, extracted DNA from all the 59 normal individuals' tongue coating samples passed an appropriate quality bar for microbiome studies. The average value of OD 260/280 is 1.72 ± 0.10; the average total DNA amount is 334.92 ng (±183.81 ng). The bacterial diversity of the tongue coating is increased and the bacterial community composition changes greatly in the NC group (aged normal subjects). Fusobacteriota is found as the dominant bacteria phyla in aged normal subjects with the 16S rRNA gene-sequencing technology. At the genus level, the relative abundance of Fusobacterium, Haemophilus, and Leptotrichia are significantly higher in aged individuals (all p < 0.05), and Neisseria, Streptococcus, and Porphyromonas are significantly higher in younger individuals (all p < 0.05). Conclusion: A participant-friendly tongue coating collection method for microbiome analyses can be established with good reliability and reproducibility. By taking advantage of our established method and 16S rRNA gene sequencing, significant differences were found in diversity and composition of tongue coating microbiota between aged and younger individuals, which contributes to a better understanding of the age-related composition of tongue coating microbiota.

Autophagy-related gene 7 is downstream of heat shock protein 27 in the regulation of eye morphology, polyglutamine toxicity, and lifespan in Drosophila.

BACKGROUND: Autophagy and molecular chaperones both regulate protein homeostasis and maintain important physiological functions. Atg7 (autophagy-related gene 7) and Hsp27 (heat shock protein 27) are involved in the regulation of neurodegeneration and aging. However, the genetic connection between Atg7 and Hsp27 is not known. METHODS: The appearances of the fly eyes from the different genetic interactions with or without polyglutamine toxicity were examined by light microscopy and scanning electronic microscopy. Immunofluorescence was used to check the effect of Atg7 and Hsp27 knockdown on the formation of autophagosomes. The lifespan of altered expression of Hsp27 or Atg7 and that of the combination of the two different gene expression were measured. RESULTS: We used the Drosophila eye as a model system to examine the epistatic relationship between Hsp27 and Atg7. We found that both genes are involved in normal eye development, and that overexpression of Atg7 could eliminate the need for Hsp27 but Hsp27 could not rescue Atg7 deficient phenotypes. Using a polyglutamine toxicity assay (41Q) to model neurodegeneration, we showed that both Atg7 and Hsp27 can suppress weak, toxic effect by 41Q, and that overexpression of Atg7 improves the worsened mosaic eyes by the knockdown of Hsp27 under 41Q. We also showed that overexpression of Atg7 extends lifespan and the knockdown of Atg7 or Hsp27 by RNAi reduces lifespan. RNAi-knockdown of Atg7 expression can block the extended lifespan phenotype by Hsp27 overexpression, and overexpression of Atg7 can extend lifespan even under Hsp27 knockdown by RNAi. CONCLUSIONS: We propose that Atg7 acts downstream of Hsp27 in the regulation of eye morphology, polyglutamine toxicity, and lifespan in Drosophila.

MetaAge: Meta-Learning Personalized Age Estimators.

Different people age in different ways. Learning a personalized age estimator for each person is a promising direction for age estimation given that it better models the personalization of aging processes. However, most existing personalized methods suffer from the lack of large-scale datasets due to the high-level requirements: identity labels and enough samples for each person to form a long-term aging pattern. In this paper, we aim to learn personalized age estimators without the above requirements and propose a meta-learning method named MetaAge for age estimation. Unlike most existing personalized methods that learn the parameters of a personalized estimator for each person in the training set, our method learns the mapping from identity information to age estimator parameters. Specifically, we introduce a personalized estimator meta-learner, which takes identity features as the input and outputs the parameters of customized estimators. In this way, our method learns the meta knowledge without the above requirements and seamlessly transfers the learned meta knowledge to the test set, which enables us to leverage the existing large-scale age datasets without any additional annotations. Extensive experimental results on three benchmark datasets including MORPH II, ChaLearn LAP 2015 and ChaLearn LAP 2016 databases demonstrate that our MetaAge significantly boosts the performance of existing personalized methods and outperforms the state-of-the-art approaches.

Differential responses on gut microbiota and microbial metabolome of 2'-fucosyllactose and galactooligosaccharide against DSS-induced colitis.

Prebiotics are effective in modulating gut microbiota and may further benefit colitis remission. 2'-fucosyllactose (2'FL) and galactooligosaccharide (GOS) are the main prebiotics in human and animal milk, respectively. This study aimed to investigate the colitis-preventing effects of 2'FL and GOS, and explore the underlying mechanisms involving the gut microbiota. The chronic colitis was induced by 1.5 % dextran sulfate sodium (DSS) for 4 consecutive cycles and manifested as aggravation of colitis symptoms, gut barrier disruption, and colonic inflammation. We found that 2'FL was more effective than GOS against colitis at the same dosage (500 mg/kg bw). 2'FL and GOS have a differential response on gut microbiota, reflecting the inhibition of Romboutsia and the enrichment of Akkermansia, Bifidobacterium, Faecalibaculum, and unclassified_f_Lachnosipiaceae. In addition, the differential response on microbial metabolome was reflected in the elevation of secondary bile acids, which activated Takeda G protein-coupled receptor 5 (TGR5) and further suppressed the nuclear factor-κB (NF-κB) pathway. Furthermore, fecal bacterial transplantation confirmed the critical role of gut microbiota in the prevention of colitis by 2'FL and GOS. Overall, microbiota and microbial metabolites are essential parts of 2'FL and GOS against colitis, and their differential responses may account for different effects in alleviating colitis.