The biological behavior and clinical outcome of pituitary adenoma are affected by the microenvironment.

BACKGROUND: Pituitary adenoma is one of the most common brain tumors. Most pituitary adenomas are benign and can be cured by surgery and/or medication. However, some pituitary adenomas show aggressive growth with a fast growth rate and are resistant to conventional treatments such as surgery, drug therapy, and radiation therapy. These tumors, referred to as refractory pituitary adenomas, often relapse or regrow in the early postoperative period. The tumor microenvironment (TME) has recently been identified as an important factor affecting the biological manifestations of tumors and acts as the main battlefield between the tumor and the host immune system. MAIN BODY: In this review, we focus on describing TME in pituitary adenomas and refractory pituitary adenomas. Research on the immune microenvironment of pituitary adenomas is currently focused on immune cells such as macrophages and lymphocytes, and extensive research and experimental verifications are still required regarding other components of the TME. In particular, studies are needed to determine the role of the TME in the specific biological behaviors of refractory pituitary adenomas, such as high invasion, fast recurrence rate, and high tolerance to traditional treatments and to identify the mechanisms involved. CONCLUSION: Overall, we summarize the similarities and differences between the TME of pituitary adenomas and refractory pituitary adenomas as well as the changes in the biological behavior of pituitary adenomas that may be caused by the microenvironment. These changes greatly affect the outcome of patients.

Validated enhancement and temperature modulated absorbance of a WS2 monolayer based on a planar structure.

Transition-metal dichalcogenides (TMDCs), as emerging optoelectronic materials, necessitate the establishment of an experimentally viable system to study their interaction with light. In this study, we propose and analyze a WS2/PMMA/Ag planar Fabry-Perot (F-P) cavity, enabling the direct experimental measurement of WS2 absorbance. By optimizing the structure, the absorbance of A exciton of WS2 up to 0.546 can be experimentally achieved, which matches well with the theoretical calculations. Through temperature and thermal expansion strain induced by temperature, the absorbance of the A exciton can be tuned in situ. Furthermore, temperature-dependent photocurrent measurements confirmed the consistent absorbance of the A exciton under varying temperatures. This WS2/PMMA/Ag planar structure provides a straightforward and practical platform for investigating light interaction in TMDCs, laying a solid foundation for future developments of TMDC-based optoelectronic devices.

Adaptive water oxidation catalysis on a carboxylate-sulfonate ligand with low onset potential.

A water oxidation catalyst Ru-bcs (bcs = 2,2'-bipyridine-6'-carboxylate-6-sulfonate) with a hybrid ligand was reported. Ru-bcs utilizes the electron-donating properties of carboxylate ligands and the on-demand coordination feature of sulfonate ligands to enable a low onset potential of 1.21 V vs. NHE and a high TOF over 1000 s-1 at pH 7. The adaptive chemistry uncovered in this work provides new perspectives for developing molecular catalysts with high efficiency under low driving forces.

Substrate and functional characterization of the lysine acetyltransferase MsKat and deacetylase MsCobB in Mycobacterium smegmatis.

Tuberculosis (TB) is a serious cause of infectious death worldwide. Recent studies have reported that about 30% of the Mtb proteome was modified post-translationally, indicating that their functions are essential for drug resistance, mycobacterial survival, and pathogenicity. Among them, lysine acetylation, reversibly regulated by acetyltransferase and deacetylase, has important roles involved in energy metabolism, cellular adaptation, and protein interactions. However, the substrate and biological functions of these two important regulatory enzymes remain unclear. Herein, we utilized the non-pathogenic M. smegmatis strain as a model and systematically investigated the dynamic proteome changes in response to the overexpressing of MsKat/MsCobB in mycobacteria. A total of 4179 proteins and 1236 acetylated sites were identified in our data. Further analysis of the dynamic changes involved in proteome and acetylome showed that MsKat/MsCobB played a regulatory role in various metabolic pathways and nucleic acid processes. After that, the quantitative mass spectrometric method was utilized and proved that the AMP-dependent synthetase, Citrate synthase, ATP-dependent specificity component of the Clp protease, and ATP-dependent DNA/RNA helicases were identified to be the substrates of MsKat. Overall, our study provided an important resource underlying the substrates and functions of the acetylation regulatory enzymes in mycobacteria. SIGNIFICANCE: In this study, we systematically analyzed the dynamic molecular changes in response to the MsKat/MsCobB overexpression in mycobacteria at proteome and lysine acetylation level by using a TMT-based quantitative proteomic approach. Pathways related with glycolysis, degradation of branched chain amino acids, phosphotransferase system were affected after disturbance of the two regulates enzymes involved in lysine acetylation. We also proved that AMP-dependent synthetase Clp protease, ATP-dependent DNA/RNA helicases and citrate synthase was the substrate of MsKat according to our proteomic data and biological validation. Together, our study underlined the substrates and functions of the acetylation regulatory enzymes in mycobacteria.

Polygonatum kingianum Polysaccharides Enhance the Preventive Efficacy of Heat-Inactivated Limosilactobacillus reuteri WX-94 against High-Fat-High-Sucrose-Induced Liver Injury and Gut Dysbacteriosis.

Limosilactobacillus reuteri (L. reuteri) is an efficacious probiotic that could reduce inflammation and prevent metabolic disorders. Here, we innovatively found that Polygonatum kingianum polysaccharides (PKP) promoted proliferation and increased stability of L. reuteri WX-94 (a probiotic strain showing anti-inflammation potentials) in simulated digestive fluids in vitro. PKP was composed of galactose, glucose, mannose, and arabinose. The cell-free supernatant extracted from L. reuteri cultured with PKP increased ABTS•+, DPPH•, and FRAP scavenging capacities compared with the supernatant of the medium without PKP and increased metabolites with health-promoting activities, e.g., 3-phenyllactic acid, indole-3-lactic acid, indole-3-carbinol, and propionic acid. Moreover, PKP enhanced alleviating effects of heat-inactivated L. reuteri on high-fat-high-sucrose-induced liver injury in rats via reducing inflammation and regulating expressions of protein and genes involved in fatty acid metabolism (such as HIF1-α, FAßO, CPT1, and AMPK) and fatty acid profiles in liver. Such benefits correlated with its prominent effects on enriching Lactobacillus and short-chain fatty acids while reducing Dubosiella, Fusicatenilacter, Helicobacter, and Oscillospira. Our work provides novel insights into the probiotic property of PKP and emphasizes the great potential of the inactivated L. reuteri cultured with PKP in contracting unhealthy diet-induced liver dysfunctions and gut dysbacteriosis.

Integration of metformin-loaded MIL-100(Fe) into hydrogel microneedles for prolonged regulation of blood glucose levels.

The transdermal drug delivery based on microneedles (MNs) provides a suitable and painless self-administration for diabetic patients. In this work, the hydrogel-forming MNs were firstly fabricated using poly(vinyl alcohol) (PVA) and chitosan (CS) as matrix. A hypoglycemic drug, metformin (Met), had been loaded into MIL-100(Fe). Then, both of free Met and Met-loaded MIL-100(Fe) were integrated into hydrogel-forming MNs for regulation of blood glucose levels (BGLs) on diabetic rats. After penetrated into the skin, the free Met could be firstly released from MNs. Due to the absorption of interstitial fluid and subsequent release of loaded Met from MIL-100(Fe), leading to a sustainable and long-term drug release behaviors. A notable hypoglycemic effect and low risk of hypoglycemia could be obtained on diabetic rat modelsin vivo. The as-fabricated hydrogel-forming MNs expected to become a new type of transdermal drug delivery platform for transdermal delivery of high-dose drugs to form a long-term hypoglycemic effect.

Intermittent fasting, exercise, and dietary modification induce unique transcriptomic signatures of multiple tissues governing metabolic homeostasis during weight loss and rebound weight gain.

Obesity and its related metabolic diseases bring great challenges to public health. In-depth understanding on the efficacy of weight-loss interventions is critical for long-term weight control. Our study demonstrated the comparable efficacy of exercise (EX), intermittent fasting (IF), or the change of daily diet from an unhealthy to a normal chow (DR) for weight reduction, but largely divergently affected metabolic status and transcriptome of subcutaneous fat, scapular brown fat, skeletal muscles and liver in high-fat-high-fructose diet (HFHF) induced obese mice. EX and IF reduced systematic inflammation, improved glucose and lipid metabolism in liver and muscle, and amino acid metabolism and thermogenesis in adipose tissues. EX exhibited broad regulatory effects on TCA cycle, carbon metabolism, thermogenesis, propanoate-, fatty acid and amino acid metabolism across multiple tissues. IF prominently affected genes involved in mitophagy and autophagy in adipose tissues and core genes involved in butanoate metabolism in liver. DR, however, failed to improve metabolic homeostasis and biological dysfunctions in obese mice. Notably, by exploring potential inter-organ communication, we identified an obesity-resistant-like gene profile that were strongly correlated with HFHF induced metabolic derangements and could predict the degree of weight regain induced by the follow-up HFHF diet. Among them, 12 genes (e.g., Gdf15, Tfrc, Cdv3, Map2k4, and Nqo1) were causally associated with human metabolic traits, i.e., BMI, body fat mass, HbA1C, fasting glucose, and cholesterol. Our findings provide critical groundwork for improved understanding of the impacts of weight-loss interventions on host metabolism. The identified genes predicting weight regain may be considered regulatory targets for improving long-term weight control.

A multimodal physiological dataset for driving behaviour analysis.

Physiological signal monitoring and driver behavior analysis have gained increasing attention in both fundamental research and applied research. This study involved the analysis of driving behavior using multimodal physiological data collected from 35 participants. The data included 59-channel EEG, single-channel ECG, 4-channel EMG, single-channel GSR, and eye movement data obtained via a six-degree-of-freedom driving simulator. We categorized driving behavior into five groups: smooth driving, acceleration, deceleration, lane changing, and turning. Through extensive experiments, we confirmed that both physiological and vehicle data met the requirements. Subsequently, we developed classification models, including linear discriminant analysis (LDA), MMPNet, and EEGNet, to demonstrate the correlation between physiological data and driving behaviors. Notably, we propose a multimodal physiological dataset for analyzing driving behavior(MPDB). The MPDB dataset's scale, accuracy, and multimodality provide unprecedented opportunities for researchers in the autonomous driving field and beyond. With this dataset, we will contribute to the field of traffic psychology and behavior.

Research on inhibitory effect of mixed suppressants CaCO3, KCl, and K2CO3 on coal dust explosion pressure.

To discuss the inhibitory effect of micrometer scale coal dust explosion pressure, three types of explosion suppressants are selected for mixed explosion suppression. The results indicate that the coal dust explosion process includes three stages: accelerated and decelerated energy release, as well as energy dissipation. When using explosive suppressants, K2CO3 has the greatest inhibitory effect on coal dust explosion, followed by KCl, and CaCO3 has the smallest effect. The K2O, K2O2, and KOH generated by the thermal decomposition of K2CO3 can also block the heat transfer of coal dust, playing a good role in suppressing explosions. The explosion suppression effect of mixing CaCO3 and K2CO3 is better than that of mixing CaCO3 and KCl, and is worse than the explosion suppression effect of using K2CO3 alone. The synergistic effect of KCl and K2CO3 mixed explosion suppression makes the suppression effect better than using K2CO3 alone. This is because KCl generates K2O during pyrolysis, promoting the dynamic equilibrium of K2CO3 explosion suppression process. This makes mixed explosion suppression more worthy of attention and adoption when considering purchase costs.

Start-up of pilot-scale ANAMMOX reactor for low-carbon nitrogen removal from anaerobic digestion effluent of kitchen waste.

The pilot-scale simultaneous denitrification and methanation (SDM)-partial nitrification (PN)-anaerobic ammonia oxidation (Anammox) system was designed to treat anaerobic digestion effluent of kitchen waste (ADE-KW). The SDM-PN was first started to avoid the inhibition of high-concentration pollutants. Subsequently, Anammox was coupled to realize autotrophic nitrogen removal. Shortcut nitrification-denitrification achieved by the SDM-PN. The NO2--N accumulation (92 %) and NH4+-N conversion (60 %) were achieved by PN, and the removal of TN and COD from the SDM-PN was 70 % and 73 %, respectively. After coupling Anammox, the TN (95 %) was removed with a TN removal rate of 0.51 kg·m-3·d-1. Microbiological analyses showed a shift from dominance by Methanothermobacter to co-dominance by Methanothermobacter, Thermomonas, and Flavobacterium in SDM during the SDM-PN. While after coupling Anammox, Candidatus kuenenia was enriched in the Anammox zone, the SDM zone shifted back to being dominated by Methanothermobacter. Overall, this study provides new ideas for the treatment of ADE-KW.

Rizatriptan benzoate-loaded dissolving microneedle patch for management of acute migraine therapy.

In this study, dissolving microneedles (MNs) using polyvinyl alcohol (PVA) and poly (1-vinylpyrrolidone-co-vinyl acetate) (P(VP-co-VA)) as matrix materials were developed for transdermal delivery of rizatriptan benzoate (RB) for acute migraine treatment. In-vitro permeation studies were conducted to assess the feasibility of the as-fabricated dissolving MNs to release RB. Drug skin penetration were tested by Franz diffusion cells, showing an increase of the transdermal flux compared to passive diffusion due to the as-fabricated dissolving MNs having a sufficient mechanical strength to penetrate the skin and form microchannels. The pharmacological study in vivo showed that RB-loaded dissolving MNs significantly alleviated migraine-related response by up-regulating the level of 5-hydroxytryptamine (5-HT) and down-regulating the levels of calcitonin gene-related peptide (CGRP) and substance P (SP). In conclusion, the RB-loaded dissolving MNs have advantages of safety, convenience, and high efficacy over conventional administrations, laying a foundation for the transdermal drug delivery system treatment for acute migraine.

De Novo Screening and Mirror Image Isomerization of Linear Peptides Targeting α7 Nicotinic Acetylcholine Receptor.

As ligand-gated ion channels, nicotinic acetylcholine receptors (nAChRs) are widely distributed in the central and peripheral nervous systems and are associated with the pathogenesis of various degenerative neurological diseases. Here, we report the results of phage display-based de novo screening of an 11-residue linear peptide (named LKP1794) that targets the α7 nAChR, which is among the most abundant nAChR subtypes in the brain. Moreover, two d-peptides were generated through mirror image and/or primary sequence inverso isomerization (termed DRKP1794 and DKP1794) and displayed improved inhibitory effects (IC50 = 0.86 and 0.35 µM, respectively) on α7 nAChR compared with the parent l-peptide LKP1794 (IC50 = 2.48 µM), which markedly enhanced serum stability. A peptide-based fluorescence probe was developed using proteolytically resistant DKP1794 to specifically image the α7 nAChR in living cells. This work provides a new peptide tool to achieve inhibitory modulation and specifically image the α7 nAChR.

Genome-Wide Analysis of the Oat (Avena sativa) HSP90 Gene Family Reveals Its Identification, Evolution, and Response to Abiotic Stress.

Oats (Avena sativa) are an important cereal crop and cool-season forage worldwide. Heat shock protein 90 (HSP90) is a protein ubiquitously expressed in response to heat stress in almost all plants. To date, the HSP90 gene family has not been comprehensively reported in oats. Herein, we have identified twenty HSP90 genes in oats and elucidated their evolutionary pathways and responses to five abiotic stresses. The gene structure and motif analyses demonstrated consistency across the phylogenetic tree branches, and the groups exhibited relative structural conservation. Additionally, we identified ten pairs of segmentally duplicated genes in oats. Interspecies synteny analysis and orthologous gene identification indicated that oats share a significant number of orthologous genes with their ancestral species; this implies that the expansion of the oat HSP90 gene family may have occurred through oat polyploidization and large fragment duplication. The analysis of cis-acting elements revealed their influential role in the expression pattern of HSP90 genes under abiotic stresses. Analysis of oat gene expression under high-temperature, salt, cadmium (Cd), polyethylene glycol (PEG), and abscisic acid (ABA) stresses demonstrated that most AsHSP90 genes were significantly up-regulated by heat stress, particularly AsHSP90-7, AsHSP90-8, and AsHSP90-9. This study offers new insights into the amplification and evolutionary processes of the AsHSP90 protein, as well as its potential role in response to abiotic stresses. Furthermore, it lays the groundwork for understanding oat adaptation to abiotic stress, contributing to research and applications in plant breeding.

Electrochemical Doping and Structural Modulation of Conductive Metal-Organic Frameworks.

In this study, we introduce an electrochemical doping strategy aimed at manipulating the structure and composition of electrically conductive metal-organic frameworks (c-MOFs). Our methodology is exemplified through a representative c-MOF, Ni3(HITP)2 (HITP=2, 3, 6, 7, 10, 11-hexaiminotriphenylene), synthesized into porous thin films supported by nanocellulose. While the c-MOF exhibits characteristic capacitive behavior in neutral electrolyte; it manifests redox behaviors in both acidic and alkaline electrolytes. Evidence indicates that the organic ligands within c-MOF undergo oxidation (p-doping) and reduction (n-doping) when exposed to specific electrochemical potentials in acidic and alkaline electrolyte, respectively. Interestingly, the p-doping process proves reversible, with the c-MOF structure remaining stable across cyclic p-doping/de-doping. In contrast, the n-doping is irreversible, leading to the gradual decomposition of the framework into inorganic species over a few cycles. Drawing on these findings, we showcase the versatile electrochemical applications of c-MOFs and their derived composites, encompassing electrochemical energy storage, electrocatalysis, and ultrafast actuation. This study provides profound insights into the doping of c-MOFs, offering a new avenue for modulating their chemical and electronic structure, thereby broadening their potential for diverse electrochemical applications.

Core-shell structured microneedles with programmed drug release functions for prolonged hyperuricemia management.

An appropriate non-oral platform via transdermal delivery of drugs is highly recommended for the treatment of hyperuricemia. Herein, a core-shell structured microneedle patch with programmed drug release functions was designed to regulate serum uric acid (SUA) levels for prolonged hyperuricemia management. The patch was fabricated using a three-step casting method. Allopurinol (AP), an anti-hyperuricemic drug, was encapsulated within the carboxymethyl cellulose (CMC) layer, forming the "shell" of the MNs. The MN's inner core was composed of polyvinylpyrrolidone (PVP) loaded with urate oxidase-calcium peroxide nanoparticles (UOx-CaO2 NPs). When the as-fabricated core-shell structured microneedles were inserted into the skin, the loaded AP was first released immediately to effectively inhibit the production of SUA due to the water solubility of CMC. Subsequently, the internal SUA was further metabolized by UOx, leading to exposure of CaO2 NPs. The sustained release of UOx accompanied by the decomposition of CaO2 NPs contributed to maintaining a state of normal uric acid levels over an extended period. More attractively, uric acid could be oxidized due to the strong oxidant of CaO2, which was beneficial to the continuous consumption of uric acid. In vivo results showed that the as-fabricated MNs exhibited an excellent anti-hyperuricemia effect to reduce SUA levels to the normal state within 3 h and maintain the normouricemia state for 12 h. In addition, the levels of creatinine (Cr) and blood urea nitrogen (BUN) in the serum remained within the normal range, and the activities of adenosine deaminase (ADA) and xanthine oxidase (XOD) in the liver were effectively inhabited, mitigating the risk of liver and kidney damage for clinical anti-hyperuricemia management.

'Nine Steaming Nine Sun-drying' processing enhanced properties of Polygonatum kingianum against inflammation, oxidative stress and hyperglycemia.

BACKGROUND: Polygonatum kingianum Coll. & Hemsl (PK), a prominent medicine and food homology plant, has been consumed as a decoction from boiling water for thousands of years. 'Nine Steaming Nine Sun-drying' processing has been considered an effective method for enriching tonic properties, but studies investigating such impacts on PK and underlying mechanisms are extremely rare. RESULTS: We first demonstrated substantial improvements in the anti-oxidative, anti-inflammatory and anti-hyperglycemia effects of the Nine Steaming Nine Sun-drying processed PK water extracts compared with crude PK in cell models (i.e., HepG2 and Raw 264.7 cells). We then integrated foodomics and network pharmacology analysis to uncover the key compounds responsible for the improved benefits. A total of 551 metabolites of PK extracts were identified, including polyphenols, flavonoids, alkaloids, and organic acids. During processing, 204 metabolites were enhanced, and 32 metabolites were recognized as key constituents of processed PK responsible for the improved health-promoting activities, which may affect PI3K-Akt-, MAPK-, and HIF-1 pathways. We further confirmed the high affinity between identified key constituents of processed PK and their predicted acting targets using molecular docking. CONCLUSION: Our results provide novel insights into bioactive compounds of processed PK, elaborating the rationality of processing from the perspective of tonic effects. Consuming processed PK could be an efficacious strategy to combat the high prevalence of metabolic diseases that currently affect millions of people worldwide. © 2023 Society of Chemical Industry.

Ultrahigh-printing-speed photoresists for additive manufacturing.

Printing technology for precise additive manufacturing at the nanoscale currently relies on two-photon lithography. Although this methodology can overcome the Rayleigh limit to achieve nanoscale structures, it still operates at too slow of a speed for large-scale practical applications. Here we show an extremely sensitive zirconium oxide hybrid-(2,4-bis(trichloromethyl)-6-(4-methoxystyryl)-1,3,5-triazine) (ZrO2-BTMST) photoresist system that can achieve a printing speed of 7.77 m s-1, which is between three and five orders of magnitude faster than conventional polymer-based photoresists. We build a polygon laser scanner-based two-photon lithography machine with a linear stepping speed approaching 10 m s-1. Using the ZrO2-BTMST photoresist, we fabricate a square raster with an area of 1 cm2 in ~33 min. Furthermore, the extremely small chemical components of the ZrO2-BTMST photoresist enable high-precision patterning, leading to a line width as small as 38 nm. Calculations assisted by characterizations reveal that the unusual sensitivity arises from an efficient light-induced polarity change of the ZrO2 hybrid. We envisage that the exceptional sensitivity of our organic-inorganic hybrid photoresist may lead to a viable large-scale additive manufacturing nanofabrication technology.

Tetracycline inhibits the nitrogen fixation ability of soybean (Glycine max (L.) Merr.) nodules in black soil by altering the root and rhizosphere bacterial communities.

Tetracycline is a widely used antibiotic and may thus also be an environmental contaminant with an influence on plant growth. The aim of this study was to investigate the inhibition mechanisms of tetracycline in relation to soybean growth and ecological networks in the roots and rhizosphere. To this end, we conducted a pot experiment in which soybean seedlings were grown in soil treated with 0, 10, or 25 mg/kg tetracycline. The effects of tetracycline pollution on growth, productivity, oxidative stress, and nitrogenase activity were evaluated. We further identified the changes in microbial taxa composition and structure at the genus and species levels by sequencing the 16S rRNA gene region. The results showed that tetracycline activates the antioxidant defense system in soybeans, which reduces the abundance of Bradyrhizobiaceae, inhibits the nitrogen-fixing ability, and decreases the nitrogen content in the root system. Tetracycline was also found to suppress the formation of the rhizospheric environment and decrease the complexity and stability of bacterial networks. Beta diversity analysis showed that the community structure of the root was markedly changed by the addition of tetracycline, which predominantly affected stochastic processes. These findings demonstrate that the influence of tetracycline on soybean roots could be attributed to the decreased stability of the bacterial community structure, which limits the number of rhizobium nodules and inhibits the nitrogen-fixing capacity. This exploration of the inhibitory mechanisms of tetracycline in relation to soybean root development emphasises the potential risks of tetracycline pollution to plant growth in an agricultural setting. Furthermore, this study provides a theoretical foundation from which to improve our understanding of the physiological toxicity of antibiotics in farmland.

Oat-based postbiotics ameliorate high-sucrose induced liver injury and colitis susceptibility by modulating fatty acids metabolism and gut microbiota.

High-sucrose (HS) consumption leads to metabolic disorders and increases susceptibility to colitis. Postbiotics hold great potentials in combating metabolic diseases and offer advantages in safety and processability, compared with living probiotics. We developed innovative oat-based postbiotics and extensively explored how they could benefit in rats with long-term high-sucrose consumption. The postbiotics fermented with Lactiplantibacillus plantarum (OF-1) and OF-5, the one fermented with the optimal selection of five probiotics (i.e., L. plantarum, Limosilactobacillus reuteri, Lacticaseibacillus rhamnosus, Lactobacillus acidophilus, and Bifidobacterium lactis) alleviated HS induced liver injury, impaired fatty acid metabolism and inflammation through activating AMPK/SREBP-1c pathways. Moreover, oat-based postbiotics restored detrimental effects of HS on fatty acid profiles in liver, as evidenced by the increases in polyunsaturated fatty acids and decreases in saturated fatty acids, with OF-5 showing most pronounced effects. Furthermore, oat-based postbiotics prevented HS exacerbated susceptibility to dextran sodium sulfate caused colitis and reconstructed epithelial tight junction proteins in colons. Oat-based postbiotics, in particular OF-5 notably remodeled gut microbiota composition, e.g., enriching the relative abundances of Akkermansia, Bifidobacterium, Alloprevotella and Prevotella, which may play an important role in the liver-colon axis responsible for improvements of liver functions and reduction of colitis susceptibility. The heat-inactivated probiotics protected against HS-induced liver and colon damage, but such effects were less pronounced compared with oat-based postbiotics. Our findings emphasize the great value of oat-based postbiotics as nutritional therapeutics to combat unhealthy diet induced metabolic dysfunctions.

Tumor microenvironment remodeling plus immunotherapy could be used in mesenchymal-like tumor with high tumor residual and drug resistant rate.

Epithelial-mesenchymal transition (EMT) is a common process during tumor progression and is always related to residual tumor, drug resistance and immune suppression. However, considering the heterogeneity in EMT process, there is still a need to establish robust EMT classification system with reasonable molecular, biological and clinical implications to investigate whether these unfavorable survival factors are common or unique in different individuals. In our work, we classify tumors with four EMT status, that is, EMTlow, EMTmid, EMThigh-NOS (Not Otherwise Specified), and EMThigh-AKT (AKT pathway overactivation) subtypes. We find that EMThigh-NOS subtype is driven by intrinsic somatic alterations. While, EMThigh-AKT subtype is maintained by extrinsic cellular interplay between tumor cells and macrophages in an AKT-dependent manner. EMThigh-AKT subtype is both unresectable and drug resistant while EMThigh-NOS subtype can be treated with cell cycle related drugs. Importantly, AKT activation in EMThigh-AKT not only enhances EMT process, but also contributes to the immunosuppressive microenvironment. By remodeling tumor immune-microenvironment by AKT inhibition, EMThigh-AKT can be treated by immune checkpoint blockade therapies. Meanwhile, we develop TumorMT website ( http://tumormt.neuroscience.org.cn/ ) to apply this EMT classification and provide reasonable therapeutic guidance.