Weissella paramesenteroides NRIC1542 inhibits dextran sodium sulfate-induced colitis in mice through regulating gut microbiota and SIRT1/NF-κB signaling pathway.

Inflammatory bowel disease (IBD) is a kind of recurrent inflammatory disorder of the intestinal tract. The purpose of this study was to investigate the effects of Weissella paramesenteroides NRIC1542 on colitis in mice. A colitis model was induced by adding 1.5% DSS to sterile distilled water for seven consecutive days. During this process, mice were administered different concentrations of W. paramesenteroides NRIC1542. Colitis was assessed by DAI, colon length and hematoxylin-eosin staining of colon sections. The expressions of NF-κB signaling proteins and the tight junction proteins ZO-1 and occludin were detected by western blotting, and the gut microbiota was analyzed by 16S rDNA. The results showed that W. paramesenteroides NRIC1542 significantly reduced the degree of pathological tissue damage and the levels of TNF-α and IL-1ß in colonic tissue, inhibiting the NF-κB signaling pathway and increasing the expression of SIRT1, ZO-1 and occludin. In addition, W. paramesenteroides NRIC1542 can modulate the structure of the gut microbiota, characterized by increased relative abundance of Muribaculaceae_unclassified, Paraprevotella, Prevotellaceae_UCG_001 and Roseburia, and decrease the relative abundance of Akkermansia and Alloprevotella induced by DSS. The above results suggested that W. paramesenteroides NRIC1542 can protect against DSS-induced colitis in mice through anti-inflammatory, intestinal barrier maintenance and flora modulation.

Nanoscale myelinogenesis image in developing brain via super-resolution nanoscopy by near-infrared emissive curcumin-BODIPY derivatives.

Understanding the intricate nanoscale architecture of neuronal myelin during central nervous system development is of utmost importance. However, current visualization methods heavily rely on electron microscopy or indirect fluorescent method, lacking direct and real-time imaging capabilities. Here, we introduce a breakthrough near-infrared emissive curcumin-BODIPY derivative (MyL-1) that enables direct visualization of myelin structure in brain tissues. The remarkable compatibility of MyL-1 with stimulated emission depletion nanoscopy allows for unprecedented super-resolution imaging of myelin ultrastructure. Through this innovative approach, we comprehensively characterize the nanoscale myelinogenesis in three dimensions over the course of brain development, spanning from infancy to adulthood in mouse models. Moreover, we investigate the correlation between myelin substances and Myelin Basic Protein (MBP), shedding light on the essential role of MBP in facilitating myelinogenesis during vertebral development. This novel material, MyL-1, opens up new avenues for studying and understanding the intricate process of myelinogenesis in a direct and non-invasive manner, paving the way for further advancements in the field of nanoscale neuroimaging.

Sensory nerves, but not sympathetic nerves, promote reparative dentine formation after dentine injury via CGRP-mediated angiogenesis: An in vivo study.

AIM: Dental pulp is richly innervated by nerve fibres, which are mainly involved in the sensation of pain. Aside from pain sensation, little is known regarding the role of dental innervation in reparative dentine formation. We herein generated a mouse model of experimental dentine injury to examine nerve sprouting within the odontoblast and subodontoblastic layers and investigated the potential effects of this innervation in reparative dentinogenesis. METHODOLOGY: Mouse tooth cavity model (bur preparation + etching) was established, and then nerve sprouting, angiogenesis and reparative dentinogenesis were determined by histological and immunofluorescent staining at 1, 3, 7, 14 and 28 days postoperatively. We also established the mouse-denervated molar models to determine the role of sensory and sympathetic nerves in reparative dentinogenesis, respectively. Finally, we applied calcitonin gene-related peptide (CGRP) receptor antagonist to analyse the changes in angiogenesis and reparative dentinogenesis. RESULTS: Sequential histological results from dentine-exposed teeth revealed a significant increase in innervation directly beneath the injured area on the first day after dentine exposure, followed by vascularisation and reparative dentine production at 3 and 7 days, respectively. Intriguingly, abundant type H vessels (CD31+ Endomucin+ ) were present in the innervated area, and their formation precedes the onset of reparative dentine formation. Additionally, we found that sensory denervation led to blunted angiogenesis and impaired dentinogenesis, while sympathetic denervation did not affect dentinogenesis. Moreover, a marked increase in the density of CGRP+ nerve fibres was seen on day 3, which was reduced but remained elevated over the baseline level on day 14, whereas the density of substance P-positive nerve fibres did not change significantly. CGRP receptor antagonist-treated mice showed similar results as those with sensory denervation, including impairments in type H angiogenesis, which confirms the importance of CGRP in the formation of type H vessels. CONCLUSIONS: Dental pulp sensory nerves act as an essential upstream mediator to promote angiogenesis, including the formation of type H vessels, and reparative dentinogenesis. CGRP signalling governs the nerve-vessel-reparative dentine network, which is mostly produced by newly dense sensory nerve fibres within the dental pulp.

Geniposidic acid attenuates DSS-induced colitis through inhibiting inflammation and regulating gut microbiota.

Geniposidic acid (GPA) is a bioactive compound isolated from Gardenia jasminoides Ellis (Rubiaceae) that has long been used to treat arthritis, jaundice, and hypertension. However, the therapeutic effects of GPA against colitis remain underexplored. This study aimed to investigate the effect of GPA on the remission of colitis and the underlying mechanisms. A DSS-induced colitis mouse model was used to evaluate the influence of GPA on the modulation of gut microbiota and intestinal epithelial barrier function. Our results indicated that GPA improved DSS-induced mouse colitis, including loss of body weight, disease activity index (DAI), colon length, and colonic pathological damage. DSS-induced destruction of the intestinal barrier was also significantly repaired by GPA treatment. In addition, the relative levels of pro-inflammatory cytokines, such as IL-1ß and TNF-α, were markedly alleviated by GPA. Furthermore, western blot analysis revealed that GPA downregulated the protein expression of the nuclear transcription factor NF-κB. Finally, we first demonstrated that GPA could alleviate gut microbiota dysbiosis in mice with colitis by bacterial 16S rRNA sequencing. In conclusion, our study demonstrates the therapeutic and protective effects of GPA on IBD and provides novel insights into the prevention of colitis by targeting gut microbiota metabolism using natural products.

Synthesis of the Key Intermediate of SM-406 (Xevinapant) and Its Analogues.

Efficient methods for the synthesis of three dipeptide mimetics with diazabicycloalkanone amino acid scaffolds were developed. Among them, compound 3, which contains a 1,5-diazabicyclo[6,3,0]dodecanone amino acid core structure, was used as the key intermediate of a clinical staged IAP inhibitor SM-406 (Xevinapant). Compared with the reported methods for the synthesis of compound 3 and its derivatives, our method is more efficient and more suitable for large scale preparation.

A ratiometric fluorescence method based on nitrogen-doped carbon quantum dots for the determination of the activity of alkaline phosphatase.

Herein, a simple and sensitive ratiometric fluorescence sensing platform to detect alkaline phosphatase (ALP) activity is developed on the basis of yellow fluorescent nitrogen-doped carbon quantum dots (YNCDs). The hydrolysis of ascorbic acid 2-phosphate (AAP) into ascorbic acid (AA) is catalyzed by ALP. Then, AA will react with o-phenylenediamine (OPD) to form 3-(1,2-dihydroxyethyl)furo[3,4b]-quinoxaline (QXD) which is a blue fluorescent quinoxaline derivative with emission at 435 nm in the presence of Cu2+. YNCDs have yellow fluorescence emission at 555 nm, and can maintain stable in QXD reaction system. Therefore, by utilizing the fluorescence of YNCDs at 555 nm as reference signal and the fluorescence of QXD at 435 nm as report signal, we can detect the ALP activity by monitoring the fluorescence ratio (F435/F555). The linear range is 0.5-5 U/L, and the limit of detection is 0.14 U/L. An application of this method for the analysis of ALP in human serum has given satisfactory results. A ratiometric fluorescent nanoprobe for ascorbic acid and alkaline phosphatase detection with excellent biocompatible and high sensitivity was successfully constructed based on YNCDs and QXD.

Heparin-enhanced peroxidase-like activity of iron-cobalt oxide nanosheets for sensitive colorimetric detection of trypsin.

Iron-cobalt oxide nanosheets (FeCo-ONSs) were proved to have intrinsic peroxidase-like activity. Additionally, the peroxidase-like activity of FeCo-ONSs toward the oxidation of 3,3,5,5-tetramethylbenzidine (TMB) was dramatically enhanced after heparin addition due to the stronger affinity toward TMB. Protamine combines with heparin, so the promotion of peroxidase-like activity of FeCo-ONSs with heparin was suppressed. With the addition of trypsin, protamine was hydrolyzed and the enhancement effect of catalytic activity of FeCo-ONSs was recovered. Based on above process, a sensitive colorimetric platform for trypsin activity determination was constructed through measuring the absorbance of produced oxTMB at 652 nm, providing a linear detection range of 5 to 500 ng/mL and a low detection limit of 2.8 ng/mL. The method was applied to trypsin determination in real samples (human urine sample and multienzyme tablet sample) with satisfactory results, illustrating the potential application of this biosensor.

Fe-N-C single-atom nanozymes with peroxidase-like activity for the detection of alkaline phosphatase.

Single-atom nanozymes have drawn wide attention in bio-sensing for their remarkable merits such as low cost, high stability, and maximum atom utilization. Herein, a colorimetric strategy based on Fe-N-C single-atom nanozymes (Fe/NC-SAs) was established for the detection of alkaline phosphatase (ALP) activity. The Fe/NC-SAs prepared by pyrolysis have excellent peroxidase-like activity and can oxidize 3,3',5,5'-tetramethylbenzidine (TMB) to a blue color product in the presence of hydrogen peroxide (H2O2). When ascorbic acid (AA) is added to the system, the blue color fades, and the absorbance has a linear relationship with the concentration of AA. Alkaline phosphatase (ALP) can catalyze the hydrolysis of ascorbic acid 2-phosphate (AAP) to produce AA. Thus, a strategy based on Fe/NC-SAs for the detection of ALP activity was established, which provided a linear range of 0.1-1.5 U L-1 and a limit of detection as low as 0.05 U L-1. Besides, Fe/NC-SAs showed high stability under harsh conditions. Moreover, an Fe/NC-SA-based assay was successfully validated using human serum samples for ALP determination with satisfactory results, and has broad prospects in the field of biosensing.

Magnetic Order-Induced Polarization Anomaly of Raman Scattering in 2D Magnet CrI3.

The recent discovery of 2D magnets has revealed various intriguing phenomena due to the coupling between spin and other degrees of freedoms (such as helical photoluminescence, nonreciprocal SHG). Previous research on the spin-phonon coupling effect mainly focuses on the renormalization of phonon frequency. Here we demonstrate that the Raman polarization selection rules of optical phonons can be greatly modified by the magnetic ordering in 2D magnet CrI3. For monolayer samples, the dominant A1g peak shows an abnormally high intensity in the cross-polarization channel at low temperatures, which is forbidden by the selection rule based on the lattice symmetry. For the bilayer, this peak is absent in the cross-polarization channel for the layered antiferromagnetic (AFM) state and reappears when it is tuned to the ferromagnetic (FM) state by an external magnetic field. Our findings shed light on exploring the emergent magneto-optical effects in 2D magnets.

Observation of High Spin-to-Charge Conversion by Sputtered Bismuth Selenide Thin Films at Room Temperature.

We investigated spin-to-charge conversion in sputtered Bi43Se57/Co20Fe60B20 heterostructures with in-plane magnetization at room temperature. High spin-to-charge conversion voltage signals have been observed at room temperature. The transmission electron microscope images show that the sputtered bismuth selenide thin films are nanogranular in structure. The spin-pumping voltage decreases with an increase in the size of the grains. The inverse Edelstein effect length (λIEE) is estimated to be as large as 0.32 nm. The large λIEE is due to the spin-momentum locking and is further enhanced by quantum confinement in the nanosized grains of the sputtered bismuth selenide films. We also investigated the effect on spin-pumping voltage due to the insertion of layers of MgO and Ag. The MgO insertion layer has almost completely suppressed the spin-pumping voltage, whereas the Ag insertion layer has enhanced the λIEE by 43%.

Immunoglobulin-Like Transcript 5 Inhibits Macrophage-Mediated Bacterial Killing and Antigen Presentation During Sepsis.

BACKGROUND: Immunosuppression contributes to the mortality of sepsis. However, the underlying mechanism remains unclear. METHODS: In the present study, we investigated the role of inhibitory receptor immunoglobulin-like transcript 5 (ILT5) in sepsis. We first screened the expression of ILT family members, and we found that ILT5 was dramatically up-regulated in the peripheral blood mononuclear cells from sepsis patients versus healthy donors. RESULTS: Knockdown of ILT5 by small interfering ribonucleic acid increased bacterial killing and reactive oxygen species production in THP-1 and RAW264.7 cells. Moreover, ILT5-expressing monocytes/macrophages exhibited lower expression of antigen-presenting molecules including major histocompatibility complex-II and CD80. In the in vitro coculture system with monocytes/macrophages, blockage of ILT5 facilitated Th1 proliferation and differentiation of CD4+ T cells. Furthermore, in vivo experiments demonstrated that pretreatment with ILT5 blocking peptide improved the survival and pulmonary pathology of septic mice. CONCLUSIONS: Together, our study identified ILT5 as an immunosuppressive regulator during sepsis, which may provide potential therapeutic strategy for sepsis.

Room-temperature high spin-orbit torque due to quantum confinement in sputtered BixSe(1-x) films.

The spin-orbit torque (SOT) that arises from materials with large spin-orbit coupling promises a path for ultralow power and fast magnetic-based storage and computational devices. We investigated the SOT from magnetron-sputtered BixSe(1-x) thin films in BixSe(1-x)/Co20Fe60B20 heterostructures by using d.c. planar Hall and spin-torque ferromagnetic resonance (ST-FMR) methods. Remarkably, the spin torque efficiency (θS) was determined to be as large as 18.62 ± 0.13 and 8.67 ± 1.08 using the d.c. planar Hall and ST-FMR methods, respectively. Moreover, switching of the perpendicular CoFeB multilayers using the SOT from the BixSe(1-x) was observed at room temperature with a low critical magnetization switching current density of 4.3 × 105 A cm-2. Quantum transport simulations using a realistic sp3 tight-binding model suggests that the high SOT in sputtered BixSe(1-x) is due to the quantum confinement effect with a charge-to-spin conversion efficiency that enhances with reduced size and dimensionality. The demonstrated θS, ease of growth of the films on a silicon substrate and successful growth and switching of perpendicular CoFeB multilayers on BixSe(1-x) films provide an avenue for the use of BixSe(1-x) as a spin density generator in SOT-based memory and logic devices.

Gasotransmitter nitric oxide imaging in Alzheimer's disease and glioblastoma with diamino-cyclic-metalloiridium phosphorescence probes.

Nitric Oxide (NO), a significant gasotransmitter in biological systems, plays a crucial role in neurological diseases and cancer. Currently, there is a lack of effective methods for rapidly and sensitively identifying NO and elucidating its relationship with neurological diseases. Novel diamino-cyclic-metalloiridium phosphorescence probes, Ir-CDA and Ir-BDA, have been designed to visualize the gasotransmitter NO in Alzheimer's disease (AD) and glioblastoma (GBM). Ir-CDA and Ir-BDA utilize iridium (III) as the central ion and incorporate a diamino group as a ligand. The interaction between the diamino structure and NO leads to the formation of a three-nitrogen five-membered ring structure, which opens up phosphorescence. The two probes can selectively bind to NO and offer low detection limits. Additionally, Ir-BDA/Ir-CDA can image NO in brain cancer cell models, neuroinflammatory models, and AD cell models. Furthermore, the NO content in fresh brain sections from AD mice was considerably higher than that in wild-type (WT) mice. Consequently, it is plausible that NO is generated in significant quantities around cells hosting larger Aß deposits, gradually diffusing throughout the entire brain region. Furthermore, we posit that this phenomenon is a key factor contributing to the higher brain NO content in AD mice compared to that in WT mice. This discovery offers novel insights into the diagnosis and treatment of AD.

Loss of SIL1 Affects Actin Dynamics and Leads to Abnormal Neural Migration.

SIL1 is a nucleotide exchange factor for the molecular chaperone protein Bip in the endoplasmic reticulum that plays a crucial role in protein folding. The Sil1 gene is currently the only known causative gene of Marinesco-Sjögren syndrome (MSS). Intellectual developmental disability is the main symptom of MSS, and its mechanism has not been fully elucidated. Studies have shown that mutations in the Sil1 gene can delay neuronal migration during cortical development, but the underlying molecular mechanisms remain unclear. To further identify potential molecules involved in the regulation of central nervous system development by SIL1, we established a cortical neuron model with SIL1 protein deficiency and used proteomic analysis to screen for differentially expressed proteins after Sil1 silencing, followed by GO functional enrichment and protein‒protein interaction (PPI) network analysis. We identified 68 upregulated and 137 downregulated proteins in total, and among them, 10 upregulated and 3 downregulated proteins were mainly related to actin cytoskeleton dynamics. We further validated the differential changes in actin-related molecules using qRT‒PCR and Western blotting of a Sil1 gene knockout (Sil1-/-) mouse model. The results showed that the protein levels of ACTN1 and VIM decreased, while their mRNA levels increased as a compensatory response to protein deficiency. The mRNA and protein levels of IQGAP1 both showed a secondary increase. In conclusion, we identified ACTN1 and VIM as the key molecules regulated by SIL1 that are involved in neuronal migration during cortical development.

GluN2B-containing NMDA receptor attenuated neuronal apoptosis in the mouse model of HIBD through inhibiting endoplasmic reticulum stress-activated PERK/eIF2α signaling pathway.

Introduction: Neonatal hypoxic-ischemic brain damage (HIBD) refers to brain damage in newborns caused by hypoxia and reduced or even stopped cerebral blood flow during the perinatal period. Currently, there are no targeted treatments for neonatal ischemic hypoxic brain damage, primarily due to the incomplete understanding of its pathophysiological mechanisms. Especially, the role of NMDA receptors is less studied in HIBD. Therefore, this study explored the molecular mechanism of endogenous protection mediated by GluN2B-NMDAR in HIBD. Method: Hypoxic ischemia was induced in mice aged 9-11 days. The brain damage was examined by Nissl staining and HE staining, while neuronal apoptosis was examined by Hoechst staining and TTC staining. And cognitive deficiency of mice was examined by various behavior tests including Barnes Maze, Three Chamber Social Interaction Test and Elevated Plus Maze. The activation of ER stress signaling pathways were evaluated by Western blot. Results: We found that after HIBD induction, the activation of GluN2B-NMDAR attenuated neuronal apoptosis and brain damage. Meanwhile, the ER stress PERK/eIF2α signaling pathway was activated in a time-dependent manner after HIBE. Furthermore, after selective inhibiting GluN2B-NMDAR in HIBD mice with ifenprodil, the PERK/eIF2α signaling pathway remains continuously activated, leading to neuronal apoptosis, morphological brain damage. and aggravating deficits in spatial memory, cognition, and social abilities in adult mice. Discussion: The results of this study indicate that, unlike its role in adult brain damage, GluN2B in early development plays a neuroprotective role in HIBD by inhibiting excessive activation of the PERK/eIF2α signaling pathway. This study provides theoretical support for the clinical development of targeted drugs or treatment methods for HIBD.

Quaternion Cross-Modality Spatial Learning for Multi-Modal Medical Image Segmentation.

Recently, the Deep Neural Networks (DNNs) have had a large impact on imaging process including medical image segmentation, and the real-valued convolution of DNN has been extensively utilized in multi-modal medical image segmentation to accurately segment lesions via learning data information. However, the weighted summation operation in such convolution limits the ability to maintain spatial dependence that is crucial for identifying different lesion distributions. In this paper, we propose a novel Quaternion Cross-modality Spatial Learning (Q-CSL) which explores the spatial information while considering the linkage between multi-modal images. Specifically, we introduce to quaternion to represent data and coordinates that contain spatial information. Additionally, we propose Quaternion Spatial-association Convolution to learn the spatial information. Subsequently, the proposed De-level Quaternion Cross-modality Fusion (De-QCF) module excavates inner space features and fuses cross-modality spatial dependency. Our experimental results demonstrate that our approach compared to the competitive methods perform well with only 0.01061 M parameters and 9.95G FLOPs.

Metal-Phenolic Nanocapsules with Photothermal Antibacterial and Ros Scavenging Ability for Diabetic Wound Healing.

The presence of bacteria in diabetic wounds not only leads to the formation of biofilms but also triggers oxidative stress and inflammatory responses, which hinder the wound-healing process. Therefore, it is imperative to formulate a comprehensive strategy that can proficiently eliminate bacteria and enhance the wound microenvironment. Herein, this work develops multifunctional metal-phenolic nanozymes (TA-Fe/Cu nanocapsules), wherein the one-pot coordination of tannic acid (TA)and Fe3+/Cu2+ using a self-sacrificial template afforded hollow nanoparticles (NPs) with exceptional photothermal and reactive oxygen species scavenging capabilities. After photothermal disruption of the biofilms, TA-Fe/Cu NPs autonomously capture bacteria through hydrogen bonding interactions with peptidoglycans (the bacterial cell wall component), ultimately bolstering the bactericidal efficacy. Furthermore, these NPs exhibit peroxidase-like enzymatic activity, efficiently eliminating surplus hydrogen peroxide in the vicinity of the wound and mitigating inflammatory responses. As the wound transitions into the remodeling phase, the presence of Cu2+ stimulates vascular migration and regeneration, expediting the wound-healing process. This study innovatively devises a minimalist approach to synthesize multifunctional metal-phenolic nanozymes integrating potent photothermal antibacterial activity, bacterial capture, anti-inflammatory, and angiogenesis properties, showcasing their great potential for diabetic wound treatment.

DNA nanoassembly based turn-on amplification probe for sensitive colorimetric CRISPR/Cas12a-mediated detection of pathogen DNA.

Clustered regularly interspaced short palindromic repeat (CRISPR) system has been explored as an efficient tool for nucleic acid diagnostics. However, it normally needs instrumentation or produces turn-off signals. Herein, a bulged Y-shape DNA (Y-DNA) nanoassembly was designed and synthesized as a novel turn-on probe. A CRISPR/Cas12a and Y-DNA probe mediated colorimetric assay (named as CYMCOA) strategy was developed for visual detection of pathogen DNA. Upon activating Cas12a with pathogen DNA, the Y-DNA bulge is catalytically trans-cleaved, releasing the G-quadruplex sequence embedded in the Y-DNA nanoassembly as a peroxidase-like DNAzyme. Visible signals with chromogen substrates are thus produced. The CYMCOA strategy was combined with recombinase polymerase amplification (RPA), an isothermal amplification technique, in detecting Helicobacter pylori (Hp) bacteria and SARS-CoV-2 N plasmids as two model pathogens. The bioassay has very excellent detection sensitivity and specificity, owing to the triple cascade amplification reactions and the very low mismatch tolerance. The lower limit of detection values were 0.16 cfu⋅mL-1, 1.5 copies⋅µL-1, and 0.17 copies⋅µL-1 for Hp bacteria, Hp plasmids, and SARS-CoV-2 N plasmids respectively. The detection is fast and accurate. The colorimetric bioassay strategy provides to be a simple, accurate, fast and instrumentation-free platform for nucleic acids detections in various settings, including crude and emergent situations.

Optimization and mechanisms of proteolytic enzyme immobilization onto large-pore mesoporous silica nanoparticles: Enhanced tumor penetration.

Immobilization of proteolytic enzymes onto nanocarriers is effective to improve drug diffusion in tumors through degrading the dense extracellular matrix (ECM). Herein, immobilization and release behaviors of hyaluronidase, bromelain, and collagenase (Coll) on mesoporous silica nanoparticles (MSNs) were explored. A series of cationic MSNs (CMSNs) with large and adjustable pore sizes were synthesized, and investigated together with two anionic MSNs of different pore sizes. CMSNs4.0 exhibited the highest enzyme loading capacity for hyaluronidase and bromelain, and CMSNs4.5 was the best for Coll. High electrostatic interaction, matched pore size, and large pore volume and surface area favor the immobilization. Changes of the enzyme conformations and surface charges with pH, existence of a space around the immobilized enzymes, and the depth of the pore structures, affect the release ratio and tunability. The optimal CMSNs-enzyme complexes exhibited deep and homogeneous penetration into pancreatic tumors, a tumor model with the densest ECM, with CMSNs4.5-Coll as the best. Upon loading with doxorubicin (DOX), the CMSNs-enzyme complexes induced high anti-tumor efficiencies. Conceivably, the DOX/CMSNs4.5-NH2-Coll nanodrug exhibited the most effective tumor therapy, with a tumor growth inhibition ratio of 86.1 %. The study provides excellent nanocarrier-enzyme complexes, and offers instructive theories for enhanced tumor penetration and therapy.

Painless and accurate medical image analysis using deep reinforcement learning with task-oriented homogenized automatic pre-processing.

Pre-processing is widely applied in medical image analysis to remove the interference information. However, the existing pre-processing solutions mainly encounter two problems: (i) it is heavily relied on the assistance of clinical experts, making it hard for intelligent CAD systems to deploy quickly; (ii) due to the personnel and information barriers, it is difficult for medical institutions to conduct the same pre-processing operations, making a deep model that performs well on a specific medical institution difficult to achieve similar performances on the same task in other medical institutions. To overcome these problems, we propose a deep-reinforcement-learning-based task-oriented homogenized automatic pre-processing (DRL-HAPre) framework to overcome these two problems. This framework utilizes deep reinforcement learning techniques to learn a policy network to automatically and adaptively select the optimal pre-processing operations for the input medical images according to different analysis tasks, thus helping the intelligent CAD system to achieve a rapid deployment (i.e., painless) and maintain a satisfactory performance (i.e., accurate) among different medical institutes. To verify the effectiveness and advantages of the proposed DRL-HAPre framework, we further develop a homogenized automatic pre-processing model based on the DRL-HAPre framework to realize the automatic pre-processing of key region selection (called HAPre-KRS) in the pneumonia image classification task. Extensive experimental studies are conducted on three pediatric pneumonia classification datasets with different image qualities, and the results show that: (i) There does exist a hard-to-reproduce problem in clinical practices and the fact that having different medical image qualities in different medical institutes is an important reason for the existing of hard-to-reproduce problem, so it is compelling to propose homogenized automatic pre-processing method. (ii) The proposed HAPre-KRS model and DRL-HAPre framework greatly outperform three kinds of state-of-the-art baselines (i.e., pre-processing, attention and pneumonia baseline), and the lower the medical image quality, the greater the improvements of using our HAPre-KRS model and DRL-HAPre framework. (iii) With the help of homogenized pre-processing, HAPre-KRS (and DRL-HAPre framework) can greatly avoid performance degradation in real-world cross-source applications (i.e., thus overcoming the hard-to-reproduce problem).