Bacteriocins: Curial guardians of gastrointestinal tract.

The human gastrointestinal (GI) tract microbiome secretes various metabolites that play pivotal roles in maintaining host physiological balance and influencing disease progression. Among these metabolites, bacteriocins-small, heat-stable peptides synthesized by ribosomes-are notably prevalent in the GI region. Their multifaceted benefits have garnered significant interest in the scientific community. This review comprehensively explores the methods for mining bacteriocins (traditional separation and purification, bioinformatics, and artificial intelligence), their effects on the stomach and intestines, and their complex bioactive mechanisms. These mechanisms include flora regulation, biological barrier restoration, and intervention in epithelial cell pathways. By detailing each well-documented bacteriocin, we reveal the diverse ways in which bacteriocins interact with the GI environment. Moreover, the future research direction is prospected. By further studying the function and interaction of intestinal bacteriocins, we can discover new pharmacological targets and develop drugs targeting intestinal bacteriocins to regulate and improve human health. It provides innovative ideas and infinite possibilities for further exploration, development, and utilization of bacteriocins. The inevitable fact is that the continuously exploration of bacteriocins is sure to bring the promising future for demic GI health understanding and interference strategy.

HAKE: A Knowledge Engine Foundation for Human Activity Understanding.

Human activity understanding is of widespread interest in artificial intelligence and spans diverse applications like health care and behavior analysis. Although there have been advances with deep learning, it remains challenging. The object recognition-like solutions usually try to map pixels to semantics directly, but activity patterns are much different from object patterns, thus hindering another success. In this article, we propose a novel paradigm to reformulate this task in two-stage: first mapping pixels to an intermediate space spanned by atomic activity primitives, then programming detected primitives with interpretable logic rules to infer semantics. To afford a representative primitive space, we build a knowledge base including 26+ M primitive labels and logic rules from human priors or automatic discovering. Our framework, Human Activity Knowledge Engine (HAKE), exhibits superior generalization ability and performance upon canonical methods on challenging benchmarks. Code and data are available at http://hake-mvig.cn/.

AlphaTracker: a multi-animal tracking and behavioral analysis tool.

Computer vision has emerged as a powerful tool to elevate behavioral research. This protocol describes a computer vision machine learning pipeline called AlphaTracker, which has minimal hardware requirements and produces reliable tracking of multiple unmarked animals, as well as behavioral clustering. AlphaTracker pairs a top-down pose-estimation software combined with unsupervised clustering to facilitate behavioral motif discovery that will accelerate behavioral research. All steps of the protocol are provided as open-source software with graphic user interfaces or implementable with command-line prompts. Users with a graphical processing unit (GPU) can model and analyze animal behaviors of interest in less than a day. AlphaTracker greatly facilitates the analysis of the mechanism of individual/social behavior and group dynamics.

AlphaPose: Whole-Body Regional Multi-Person Pose Estimation and Tracking in Real-Time.

Accurate whole-body multi-person pose estimation and tracking is an important yet challenging topic in computer vision. To capture the subtle actions of humans for complex behavior analysis, whole-body pose estimation including the face, body, hand and foot is essential over conventional body-only pose estimation. In this article, we present AlphaPose, a system that can perform accurate whole-body pose estimation and tracking jointly while running in realtime. To this end, we propose several new techniques: Symmetric Integral Keypoint Regression (SIKR) for fast and fine localization, Parametric Pose Non-Maximum-Suppression (P-NMS) for eliminating redundant human detections and Pose Aware Identity Embedding for jointly pose estimation and tracking. During training, we resort to Part-Guided Proposal Generator (PGPG) and multi-domain knowledge distillation to further improve the accuracy. Our method is able to localize whole-body keypoints accurately and tracks humans simultaneously given inaccurate bounding boxes and redundant detections. We show a significant improvement over current state-of-the-art methods in both speed and accuracy on COCO-wholebody, COCO, PoseTrack, and our proposed Halpe-FullBody pose estimation dataset. Our model, source codes and dataset are made publicly available at https://github.com/MVIG-SJTU/AlphaPose.

Exploitation of In Vivo-Emulated In Vitro System in Advanced Food Science.

Reasonable model construction contributes to the accuracy of experimental results. Multiple in vivo models offer reliable choices for effective evaluation, whereas their applications are hampered due to adverse features including high time-consumption, high cost and ethical contradictions. In vivo-emulated in vitro systems (IVE systems) have experienced rapid development and have been brought into food science for about two decades. IVE systems' flexibly gathers the strengths of in vitro and in vivo models into one, reflecting the results in an efficient, systematic and interacted manner. In this review, we comprehensively reviewed the current research progress of IVE systems based on the literature published in the recent two decades. By categorizing the IVE systems into 2D coculture models, spheroids and organoids, their applications were systematically summarized and typically exemplified. The pros and cons of IVE systems were also thoroughly discussed, drawing attention to present challenges and inspiring potential orientation and future perspectives. The wide applicability and multiple possibilities suggest IVE systems as an effective and persuasive platform in the future of advanced food science.

Radix Tetrastigma Inhibits the Non-Small Cell Lung Cancer via Bax/Bcl-2/Caspase-9/Caspase-3 Pathway.

Lung cancer with high mortality is regarded as a challenging global problem with unsatisfied curative effects. Clinically, the chemotherapy drugs are often faced with side-effects and tumor resistance. Radix Tetrastigma (RT) is a traditional Chinese herb and now regarded as a kind of functional food. In this study, A549-bearing nude mice control was adopted to evaluate the anti-tumor capacity of RT. Results demonstrated that RT showed excellent anti-tumor ability with no side-effect on mice compared to chemotherapy drug (5-Fu).Further studies proved that RT down-regulated the proliferation-related proteins (PCNA, Ki67) and vascular endothelial growth factor (VEGF). Additionally, RT up-regulated the ratio of Bax/Bcl-2, which caused the over-expression of Caspase-9, leading to the activation of downstream protein caspase-3, eventually resulting in apoptosis of A549 in solid tumor. These results together suggest that RT inhibits the non-small cell lung cancer (NSCLC) via Bax/Bcl2/Caspase-9/Caspase-3 pathway. Furthermore, the anti-A549 abilities of the main flavonoid components from RT were compared, and kaempferol-3-O-rutinoside would play a role in RT's outstanding anti-NSCLC ability.

Transferable Interactiveness Knowledge for Human-Object Interaction Detection.

Human-object interaction (HOI) Detection is an important problem to understand how humans interact with objects. In this paper, we explore Interactiveness Knowledge which indicates whether human and object interact with each other or not. We found that interactiveness knowledge can be learned across HOI datasets and alleviate the gap between diverse HOI category settings. Our core idea is to exploit an Interactiveness Network to learn the general interactiveness knowledge from multiple HOI datasets and perform Non-Interaction Suppression before HOI classification in inference. On account of the generalization of interactiveness, interactiveness network is a transferable knowledge learner and can be cooperated with any HOI detection models to achieve desirable results. We utilize the human instance and body part features together to learn the interactiveness in hierarchical paradigm, i.e., instance-level and body part-level interactivenesses. Thereafter, a consistency task is proposed to guide the learning and extract deeper interactive visual clues. We extensively evaluate the proposed method on HICO-DET, V-COCO, and a newly constructed HAKE-HOI dataset. With the learned interactiveness, our method outperforms state-of-the-art HOI detection methods, verifying its efficacy and flexibility. Code is available at https://github.com/DirtyHarryLYL/Transferable-Interactiveness-Network.

Neochlorogenic acid anchors MCU-based calcium overload for cancer therapy.

Cancer is a major threat to human health worldwide, yet the clinical therapies remain unsatisfactory. In this study, we found that a Tetrastigma hemsleyanum leaves flavone (TLF) intervention could achieve tumor inhibition. Besides, neochlorogenic acid (NA), which had the highest absorbance peak in the HPLC profile of TLF, showed superior anti-proliferation ability over TLF, and could effectively trigger apoptosis, restrain migration, and facilitate cytoskeleton collapse, suggesting its key role in TLF's anticancer property. Molecular docking analysis suggested that NA was capable of binding with mitochondrial Ca2+ uniporter (MCU), and further experiments confirmed that NA upregulated the MCU level to permit excess calcium ion influx, leading to mitochondrial calcium imbalance, dysfunction, structure alteration, and ROS elevation. Moreover, tumor-bearing mice were applied to further confirm the excellent tumor inhibition ability of NA under Ca2+-abundant conditions. Therefore, this study uncovered that NA could effectively trigger robust MCU-mediated calcium overload cancer therapy, which could be utilized in novel strategies for future cancer treatment.

Learning Single/Multi-Attribute of Object with Symmetry and Group.

Attributes and objects can compose diverse compositions. To model the compositional nature of these concepts, it is a good choice to learn them as transformations, e.g., coupling and decoupling. However, complex transformations need to satisfy specific principles to guarantee rationality. Here, we first propose a previously ignored principle of attribute-object transformation: Symmetry. For example, coupling peeled-apple with attribute peeled should result in peeled-apple, and decoupling peeled from apple should still output apple. Incorporating the symmetry, we propose a transformation framework inspired by group theory, i.e., SymNet. It consists of two modules: Coupling Network and Decoupling Network. We adopt deep neural networks to implement SymNet and train it in an end-to-end paradigm with the group axioms and symmetry as objectives. Then, we propose a Relative Moving Distance (RMD) based method to utilize the attribute change instead of the attribute pattern itself to classify attributes. Besides the compositions of single-attribute and object, our RMD is also suitable for complex compositions of multiple attributes and objects when incorporating attribute correlations. SymNet can be utilized for attribute learning, compositional zero-shot learning and outperforms the state-of-the-art on four widely-used benchmarks. Code is at https://github.com/DirtyHarryLYL/SymNet.

Food-derived cyanidin-3-O-glucoside alleviates oxidative stress: evidence from the islet cell line and diabetic db/db mice.

Type 2 diabetes mellitus is a disease associated with an oxidative milieu that often leads to adverse health outcomes. Multiple anthocyanins have been reported to possess outstanding antioxidant activity, however, their effects on hyperglycemia-related oxidative stress remain elusive. In the present study, cyanidin-3-O-glucoside (C3G), a typical anthocyanin with various widely accepted health benefits, was applied to alleviate oxidative stress in pancreas islets under the conditions of hyperglycemia. Firstly, significantly decreased mitochondrial membrane potential (MMP) and antioxidant enzymes, as well as increased reactive oxygen species (ROS) and O2- levels, were detected after exposure to a series of concentrations of high glucose (HG) and palmitic acid (PA), which manifested oxidative stress triggered by mitochondrial damage. To evaluate the antioxidant effect of C3G in vitro, the islet cell line NIT-1 was used, and results proved that C3G could effectively relieve cellular oxidative stress induced by HG and PA. Furthermore, we found that the antioxidant effect of C3G was achieved by activating mitophagy via the PINK1-PARKIN signaling pathway. More importantly, an autophagy inhibitor chloroquine (CQ) was added to verify our findings at the protein level, and we observed the co-localization of mitochondria and lysosomes, which may form autophagolysosomes to clean damaged mitochondria. Immediately afterwards, more studies were conducted on pancreatic islets of diabetic db/db mice to verify the antioxidant effect of C3G discovered in islet cells. Along with the decline in fasting blood glucose, the oxidative stress in pancreas islets was successfully alleviated in diabetic db/db mice after supplementation with C3G. This was demonstrated by increased levels of ROS, and the impaired activities of anti-oxidative enzymes superoxide dismutase (SOD) and catalase (CAT) were partly reversed by C3G intervention. Our study has provided evidence for the alleviation effect of C3G against oxidative stress in pancreas islets, which may provide enlightenment for improving the health situation of diabetic patients in the future.

CaCO3 nanoparticles incorporated with KAE to enable amplified calcium overload cancer therapy.

Calcium overload therapy has attracted widespread attention in oncological field, whereas its efficacy has been limited due to insufficient calcium ions in tumor site and poor efficiency of calcium entering tumor, resulting in dissatisfied therapeutic effect. Kaempferol-3-O-rutinoside (KAE), a biosafe flavone with excellent anti-cancer ability, can effectively disrupt calcium homeostasis regulation and facilitate calcium influx, while calcium carbonate (CaCO3) serves as an ideal calcium ions supplier. Inspired by these concepts, KAE loaded into CaCO3 nanoparticles and incorporated with the cancer cell membrane (M) for synergistic tumor therapy. In this therapeutic platform (M@CaCO3@KAE), membrane coating ensures targeted delivery of CaCO3@KAE. Upon reaching tumor, CaCO3@KAE specifically responds to tumor microenvironment, consequently releases KAE and calcium ions. KAE effectively breaks the calcium balance, while calcium ions remarkably aggravate and magnify KAE-mediated calcium overload. Accordingly, mitochondrial structure and functions are destructed, causing cytoskeleton collapse and oxidative stress, leading to cancerous cellular apoptosis. With the combined and cascaded efficacy, considerable in vitro and in vivo tumor inhibition was achieved by M@CaCO3@KAE. This study provides an alternative nano-system, acting as a biomimetic calcium bomb, to ensure targeted, synergistic, efficient and biosafe calcium overload tumor therapy.

Kaempferol-3-O-rutinoside, a flavone derived from Tetrastigma hemsleyanum, suppresses lung adenocarcinoma via the calcium signaling pathway.

Lung cancer has been threatening human health worldwide for a long time. However, the clinic therapies remain unsatisfactory. In this study, the anti-adenocarcinoma lung cancer A549 cell line abilities of Tetrastigma hemsleyanum tuber flavonoids (THTF) were evaluated in vivo, and isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic analysis was conducted to detect the protein alterations in THTF-treated solid tumors. The differentially expressed proteins were related to the cytoskeleton and mostly accumulated in the calcium signaling pathway. The in vitro study illustrated that 80 µg mL-1 THTF significantly suppressed cellular viability to approximately 75% of the control. Further results suggested that kaempferol-3-O-rutinoside (K3R), the major component of THTF, effectively triggered cytoskeleton collapse, mitochondrial dysfunction and consequent calcium overload to achieve apoptosis, which remained consistent with proteomic results. This study uncovers a new mechanism for THTF anti-tumor ability, and suggests THTF and K3R as promising anti-cancer agents, providing new ideas and possible strategies for future anti-lung cancer prevention and therapy.

Canidin-3-glucoside prevents nano-plastics induced toxicity via activating autophagy and promoting discharge.

Increasing attention has been brought to microplastics pollution recently, while emerging evidences indicate that nano-plastics degraded from microplastics are more of research significance owing to stronger toxicity. However, there is little study focused on the prevention of nano-plastics induced toxicity until now. Canidin-3-glucoside (C3G), a natural anthocyanin proved to possess multiple functions like antioxidant and intestinal tissue protection. Thus, we proposed whether C3G could act as a molecular weapon against nano-plastics induced toxicity. In Caco2 cell and Caenorhabditis elegans (C. elegans) models, we found that polystyrene (PS) nano-plastics exposure resulted in physiological toxicity and oxidative damage, which could be restored by C3G. More significantly in Caco2 cells, we observed that autophagy was activated via Sirt1-Foxo1 signaling pathway to attenuate PS induced toxicity after C3G intervention and further verified by adding autophagy inhibitor 3-Methyladenine (3-MA). Meanwhile, PS co-localization with lysosomes was observed, indicating the encapsulation and degradation of PS. In C. elegans, by detecting LGG-1/LC3 expression in GFP-targeted LGG-1 report gene (LGG-1:GFP) labeled transgenic DA2123 strain, the co-localization of LGG-1:GFP with PS was found as well, means that autophagy is involved in C3G's beneficial effects. Furthermore, we were surprised to find that C3G could promote the discharge of PS from N2 nematodes, which reduces PS toxicity more directly.

Dietary flavone from the Tetrastigma hemsleyanum vine triggers human lung adenocarcinoma apoptosis via autophagy.

Among all types of cancers, lung cancer ranks first in morbidity and mortality, and non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancer cases. Chemotherapy has shown promising results, but the accompanying side-effects cannot be neglected. Herein, we introduce novel flavones (TVF), which were characterized as 3-caffeoylquinic acid, 5-caffeoylquinic acid, quercetin-3-O-rutinoside, and kaempferol-3-O-rutinoside by UPLC-MS/MS, derived from the vine of Tetrastigma hemsleyanum (TV), a traditional Chinese herb and food. TVF exhibited outstanding anti-cancer abilities at the in vitro and in vivo level, and markedly triggered apoptosis via the Bax/Bcl-2/caspase-9/caspase-3 pathway. The intrinsic mechanism study illustrated that TVF might induce apoptosis by activating autophagy by inhibiting the Akt-mTOR pathway, and the main component of TVF, quercetin-3-O-rutinoside, enabled THR308 site binding to block the phosphorylation of Akt, which was further evidenced by molecular docking computation. Our study reveals the excellent anti-cancer ability and inner mechanism of TVF, suggesting TVF as a potential candidate for clinical drug exploitation or dietary supplementation in cancer medication and prevention, providing a promising strategy for cancer chemotherapy.

Tetrastigma hemsleyanum Vine Flavone Ameliorates Glutamic Acid-Induced Neurotoxicity via MAPK Pathways.

Glutamic acid (Glu) is a worldwide flavor enhancer with various positive effects. However, Glu-induced neurotoxicity has been reported less. Tetrastigma hemsleyanum (TH), a rare herbal plant in China, possesses high medicinal value. More studies paid attention to tuber of TH whereas vine part (THV) attracts fewer focus. In this study, we extracted and purified flavones from THV (THVF), and UPLC-TOF/MS showed THVF was consisted of 3-caffeoylquinic acid, 5-caffeoylquinic acid, quercetin-3-O-rutinoside, and kaempferol-3-O-rutinoside. In vitro, Glu caused severe cytotoxicity, genotoxicity, mitochondrial dysfunction, and oxidative damage to rat phaeochromocytoma (PC12) cells. Conversely, THVF attenuated Glu-induced toxicity via MAPK pathways. In vivo, the neurotoxicity triggered by Glu restrained the athletic ability in Caenorhabditis elegans (C. elegans). The treatment of THVF reversed the situation induced by Glu. In a word, Glu could cause neurotoxicity and THVF owns potential neuroprotective effects both in vitro and in vivo via MAPK pathways.

Radix Tetrastigma extract from different origins protect RAW264.7 macrophages against LPS-induced inflammation.

Radix Tetrastigma (RT) is a medicinal plant and functional food in China, distributed in various places in the south of China. Radix Tetrastigma extract (RTE) from different origins were collected and analyzed for their anti-inflammatory effects. Different RTEs showed different abilities to suppress shape deformation, decrease the nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in RAW 264.7 cells. Subsequently, their bioactive components were compared, and results showed RTEs are rich in flavonoid (85.25-436.70 mg RE/g DW), polysaccharides (100.45-349.26 mg glucose/g DW), phenolic (12.92-225.40 mg GAE/g DW) and protein contents (4.429-7.719 mg/g DW). Principal component analysis (PCA) and correlation studies indicated that anti-inflammatory capacity could be more associated with total flavonoid contents. High-performance liquid chromatography (HPLC) and Ultraperformance liquid chromatography-time-of flight mass spectrometry (UPLC-TOF/MS) analysis were conducted, and results showed that rutin, isoquercitrin, kaempferol-3-O-rutinoside and astragalin were main flavonoid compounds, among them astragalin exhibited a prior protective effect, suggesting it might be responsible for RTE's excellent anti-inflammatory capacity.

Tetrastigma hemsleyanum leaves extract against acrylamide-induced toxicity in HepG2 cells and Caenorhabditis elegans.

Acrylamide (ACR), as a raw material of polyacrylamide that used in water purification, was verified to possess various toxicity. Tetrastigma hemsleyanum (TH) is a medicinal plant widely used to anti-inflammation and anti-tumor in Chinese folks. However, more researches focused on the biological activities in tubers and the leaves were ignored. Thus, the protective effect of Tetrastigma hemsleyanum leaves extract (THLE) against ACR-induced toxicity in HepG2 cells and Caenorhabditis elegans (C. elegans) was explored in this study. In vitro, we observed that THLE attenuated ACR-induced toxicity in HepG2 cell via regulating Akt/mTOR/FOXO1/MAPK signaling pathway. Further research proved that 5-caffeoylquinic acid (5-CA) plays a major role in THLE's amelioration effect of ACR toxicity. In vivo, it was found that THLE possesses the same protective effect in ACR-treated wild-type N2 C. elegans and daf-2 (-) (deficit in DAF-2) mutants. However, the anti-ACR toxicity effect of THLE in daf-16 (-) mutants (deficit in DAF-16 that homologous to FOXO family in human) was weakened. Our results indicated that THLE exhibited protective effects against ACR-induced toxicity both in HepG2 cells and C. elegans, while DAF-16/FOXO gene is involved in THLE' protective effect via regulating the expression levels of downstream antioxidant genes.

Apios americana Medik flowers polysaccharide (AFP) alleviate Cyclophosphamide-induced immunosuppression in ICR mice.

Immunosuppression refers to the suppression of the immune response. The immune function of immunocompromised people is not enough to resist bacterial, viral, fungal and other infections, leading to a series of diseases. A large number of experimental data show that polysaccharide compounds are immune modulators, which can enhance the body immunity with little toxic. Meanwhile, it can reduce the side effects of commonly used immunosuppressants, such as cytotoxicity, decreased ability of the body to fight infection, and inhibition of the reproduction of bone marrow hematopoietic cells. It can be used as oral or injectable drugs. In this study, a purified polysaccharide was primarily extracted from the flowers of Apios americana Medik (AAM), which can improve the immunosuppression induced by cyclophosphamide (CTX). The immunoenhancement effect of AFP was evaluated by measuring the body weight, immune organ index, cytokine secretion and antibody generated levels of CTX-induced mice. Our results showed that AFP could significantly improve the above immune indexes, which indicated AFP could alleviate immunosuppression induced by CTX. The study provided a theoretical basis for the promotion, development and application of AAM as a newly introduced food material.

Russula alutacea Fr. polysaccharide ameliorates inflammation in both RAW264.7 and zebrafish (Danio rerio) larvae.

Russula alutacea Fr. (RaF) is a tasty mushroom with high nutritional value and have been regarded as food by local people for a long time. However, few researches have focused on the polysaccharide in RaF. In this study, a purified polysaccharide (Rap-1) was isolated with an average molecular weight of 1029.7 kDa. In vitro, Rap-1 significantly suppressed cell morphological changes and inhibited the production of nitric oxide (NO) in LPS-induced RAW 264.7 cells extracellularly and intracellularly. Besides, Rap-1 also down-regulated the expression of nuclear factor kappa-B (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) contents. Rap-1 ameliorated the oxidative stress and mitochondrial dysfunction caused by LPS via MAPKs signaling pathways in macrophages. In vivo, Rap-1 decreased the ROS and O2- levels and recovered the heart in zebrafish (Danio rerio) larvae induced by LPS, These results together suggested that Rap-1 could be a potential functional resource to protect against inflammatory and oxidative damage.

Purified Tetrastigma hemsleyanum vines polysaccharide attenuates EC-induced toxicity in Caco-2 cells and Caenorhabditis elegans via DAF-16/FOXO pathway.

Ethyl Carbamate (EC), as a carcinogen widely found in fermented foods, was verified that its cytotoxicity was associated with oxidative stress. Polysaccharides from natural sources due to their antioxidative capacity have attracted great attention in the past time. In this study, purified polysaccharide from Tetrastigma hemsleyanum vines (TVP) with 64.89 kDA was extracted and conducted multiple analysis to identify its structural information. It could be discovered that TVP was composed of mannose, rhamnose, glucuronic acid, glucose, galactose, and arabinose. In vitro, TVP could inhibit cytotoxicity and genotoxicity, attenuate oxidative damage and mitochondrial dysfunction induced by EC in Caco-2 cells. Meanwhile, TVP could suppress apoptosis by mTOR and Bcl-2 signaling pathways, ameliorate oxidative via Sirt1-FoxO1 and Nrf2-Keap1 signaling pathways. In vivo, EC as well triggered the decline of survival and athletic ability in Caenorhabditis elegans (C. elegans) and TVP could reverse the decline. In the meantime, TVP could ameliorate oxidative damage in N2 and daf-2 (-) mutant but fail in daf-16 (-) mutant, which suggested that DAF-16 (FOXO) might affect the antioxidative protection of TVP in C. elegans. In brief, our results manifested that TVP could attenuate EC-induced cytotoxicity both in vitro and in vivo.