Organoids in gastrointestinal diseases: from bench to clinic.

The etiology of gastrointestinal (GI) diseases is intricate and multifactorial, encompassing complex interactions between genetic predisposition and gut microbiota. The cell fate change, immune function regulation, and microenvironment composition in diseased tissues are governed by microorganisms and mutated genes either independently or through synergistic interactions. A comprehensive understanding of GI disease etiology is imperative for developing precise prevention and treatment strategies. However, the existing models used for studying the microenvironment in GI diseases-whether cancer cell lines or mouse models-exhibit significant limitations, which leads to the prosperity of organoids models. This review first describes the development history of organoids models, followed by a detailed demonstration of organoids application from bench to clinic. As for bench utilization, we present a layer-by-layer elucidation of organoid simulation on host-microbial interactions, as well as the application in molecular mechanism analysis. As for clinical adhibition, we provide a generalized interpretation of organoid application in GI disease simulation from inflammatory disorders to malignancy diseases, as well as in GI disease treatment including drug screening, immunotherapy, and microbial-targeting and screening treatment. This review draws a comprehensive and systematical depiction of organoids models, providing a novel insight into the utilization of organoids models from bench to clinic.

Characteristics of Gut Microbiota and Fecal Metabolites in Patients with Colorectal Cancer-Associated Iron Deficiency Anemia.

Patients with colorectal cancer (CRC) have a high prevalence of iron deficiency anemia (IDA), and the gut microbiota is closely related to iron metabolism. We performed metagenomic and metabolomic analyses of stool samples from 558 eligible samples, including IDA CRC patients (IDA, n = 69), non-anemia CRC patients (Non-Anemia, n = 245), and healthy controls (CTRL, n = 244), to explore the dynamically altered gut microbes and their metabolites. Compared with the CTRL group, fecal bacteria in both the IDA group and the Non-Anemia group showed a decrease in alpha diversity and changes in microbial communities. Flavonifractor plautii (F. plautii) increases progressively from CTRL to Non-Anemia to IDA, accompanied by decreased trimethoxyflavanone and a downregulated KO gene, megDIII. In the Non-Anemia group, Parabacteroides showed a specifically elevated abundance positively correlated with enriched 1,25-dihydroxyvitamin D3. The intricate correlations among gut microbiota, metabolites, and KO genes were uncovered and highlighted, implicating an aberrant iron metabolism vulnerable to chronic inflammation during the deterioration of the anemic condition. Furthermore, the amount of F. plautii in feces achieved independent and effective prediction performance for the poor outcome of CRC. Perturbed host-microbe interplays represent a novel prospect for explaining the pathogenesis of CRC-associated IDA. The fecal microbial features also reflect the associations between IDA and elevated CRC recurrence risk.

Low-light image enhancement via adaptive frequency decomposition network.

Images captured in low light conditions suffer from low visibility, blurred details and strong noise, resulting in unpleasant visual appearance and poor performance of high level visual tasks. To address these problems, existing approaches have attempted to enhance the visibility of low-light images using convolutional neural networks (CNN). However, due to the insufficient consideration of the characteristics of the information of different frequency layers in the image, most of them yield blurry details and amplified noise. In this work, to fully extract and utilize these information, we proposed a novel Adaptive Frequency Decomposition Network (AFDNet) for low-light image enhancement. An Adaptive Frequency Decomposition (AFD) module is designed to adaptively extract low and high frequency information of different granularities. Specifically, the low-frequency information is employed for contrast enhancement and noise suppression in low-scale space and high-frequency information is for detail restoration in high-scale space. Meanwhile, a new frequency loss function are proposed to guarantee AFDNet's recovery capability for different frequency information. Extensive experiments on various publicly available datasets show that AFDNet outperforms the existing state-of-the-art methods both quantitatively and visually. In addition, our results showed that the performance of the face detection can be effectively improved by using AFDNet as pre-processing.

Applications of human organoids in the personalized treatment for digestive diseases.

Digestive system diseases arise primarily through the interplay of genetic and environmental influences; there is an urgent need in elucidating the pathogenic mechanisms of these diseases and deploy personalized treatments. Traditional and long-established model systems rarely reproduce either tissue complexity or human physiology faithfully; these shortcomings underscore the need for better models. Organoids represent a promising research model, helping us gain a more profound understanding of the digestive organs; this model can also be used to provide patients with precise and individualized treatment and to build rapid in vitro test models for drug screening or gene/cell therapy, linking basic research with clinical treatment. Over the past few decades, the use of organoids has led to an advanced understanding of the composition of each digestive organ and has facilitated disease modeling, chemotherapy dose prediction, CRISPR-Cas9 genetic intervention, high-throughput drug screening, and identification of SARS-CoV-2 targets, pathogenic infection. However, the existing organoids of the digestive system mainly include the epithelial system. In order to reveal the pathogenic mechanism of digestive diseases, it is necessary to establish a completer and more physiological organoid model. Combining organoids and advanced techniques to test individualized treatments of different formulations is a promising approach that requires further exploration. This review highlights the advancements in the field of organoid technology from the perspectives of disease modeling and personalized therapy.

circ-Ncam2 (mmu_circ_0006413) Participates in LPS-Induced Microglia Activation and Neuronal Apoptosis via the TLR4/NF-κB Pathway.

Spinal cord injury (SCI) can cause permanent neurological deficits. Circular RNA Ncam2 (circ-Ncam2 also termed mmu_circ_0006413) has been reported to be overexpressed in SCI mouse models. However, the function of circ-Ncam2 in SCI has not been validated. Lipopolysaccharide (LPS) was used to activate mouse microglia (BV2 cells). Expression levels of circ-Ncam2 were determined by RT-qPCR. Relative protein levels were evaluated by western blotting. Cytokines were determined by ELISA. The regulatory mechanism of circ-Ncam2 was validated by dual-luciferase reporter and RNA pull-down assays. Effects of LPS-induced BV2 cells on mouse neuronal (HT22 cells) viability, proliferation, and apoptosis were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry assays. LPS stimulation promoted circ-Ncam2 expression in BV2 cells. Inhibition of circ-Ncam2 mitigated LPS-induced BV2 cell activation and inflammation. Mechanically, circ-Ncam2 adsorbed miR-544-3p to regulate TLR4 expression. Also, either miR-544-3p inhibition or TLR4 overexpression weakened circ-Ncam2 silencing-mediated effects on LPS-induced BV2 cell activation and inflammation. Furthermore, LPS-induced BV2 cells suppressed HT22 cell proliferation and promoted HT22 cell apoptosis through the circ-Ncam2/miR-544-3p axis. Importantly, circ-Ncam2 activated the NF-κB signaling via the miR-544-3p/TLR4axis. circ-Ncam2 silencing lowered LPS-induced microglia activation and neuronal apoptosis via blocking the TLR4/NF-κB pathway through acting as a miR-544-3p sponge, suggesting that circ-Ncam2 may be involved in secondary SCI.

Organic-Inorganic Artificial Ion Channel Polyvinylidene Fluoride Membranes for Controllable Selectivity Transport of Alkali Metal Cations.

In this article, organic-inorganic hybrid materials with different functional groups were used to form organic-inorganic hybrid dense membranes for selective separation of mono/divalent ions by blending these materials and polyvinylidene fluoride (PVDF) in dimethylacetamide with HCl as the catalyst. The membranes prepared by 3-(ureido benzene) propyltriethoxysilane (H1), 3-(ureido-4-methoxyphenyl) propyltriethoxysilane (H2), 3-(ureido-3-chloro-4-methoxyphenyl) propyltriethoxysilane (H3), 3-(ureidoindazolyl) propyltrieth-oxysilane (H4), or 3-(ureidopentanol) propyltriethoxysilane (H5) were labeled as HM1-HM5, respectively. The transport properties of different chlorides were tested. The effects of different anions on sodium cation transport were also tested. The results showed that HM1-HM4 could transport monovalent Li+, Na+, and K+ except Ca2+ and Mg2+, and the permeability of Li+, Na+, and K+ through the hybrid membranes followed the order of PNa+ > PK+ > PLi+. Moreover, membranes with different H2 content were also prepared due to HM2 having the best ion transport performance. The ion transport performance increased accordingly with the mass ratio of H2 to PVDF, and the permeability of Na+ was twice that of Li+ and K+ when the mass ratio was 15/10. Under this condition, it was also proved that NH4+ could not transport through the hybrid membrane with various selectivity for different anions as Cl- > NO3- > HCO3- > SO42-.

Phenanthroline-Based Polyarylate Porous Membranes with Rapid Water Transport for Metal Cation Separation.

The selective separation of ions in terms of extremely similar size and properties remains an important challenge in water purification. We innovated a kind of porous nanofilm via interfacial polymerization using rigid heterocyclic ligands to achieve high valent cation selectivity and rapid water/ion transport. The interconnected microporosity and uniformly distributed cation-affinitive sites of the ultrathin membranes enabled water permeation (7.5 L m-2 h-1 bar-1), ion permeance of Na+ (1.5 mol m-2 h-1 bar-1), and Mg2+/Na+ permselectivity (2.1) during nanofiltration. The forward osmosis exhibited a prominent water flux of 95 LMH at 1 M NaCl draw solution, which expanded various applications. The polyarylate membranes comprising 4,7-diphenyl-1,10-phenanthroline showed a higher water permeation and ion selectivity than the planar monomers, e.g., resorcinol. A distinct fluorescence responsiveness existed between membranes and cations for the interaction characterization. Host-guest nuclear magnetic resonance (NMR) spectroscopy and solid-state nuclear magnetic resonance spectroscopy characterized the preferential affinitive of divalent/high-valent cations in the interconnected microporous powders; an ultraviolet spectrophotometer characterized the light responsiveness of the porous nanofilms. Such an active membrane has potential applications in selective separation and adsorption of cations, photocatalytic materials, photosensors, and other fields.