Development of antifibrotic therapy for stricturing Crohn's disease: lessons from randomized trials in other fibrotic diseases.

Intestinal fibrosis is considered an inevitable complication of Crohn's disease (CD) that results in symptoms of obstruction and stricture formation. Endoscopic or surgical treatment is required to treat the majority of patients. Progress in the management of stricturing CD is hampered by the lack of effective antifibrotic therapy; however, this situation is likely to change because of recent advances in other fibrotic diseases of the lung, liver, and skin. In this review, we summarize data from randomized controlled trials (RCTs) of antifibrotic therapies in these conditions. Multiple compounds have been tested for antifibrotic effects in other organs. According to their mechanisms, they were categorized into growth factor modulators, inflammation modulators, 5-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, intracellular enzymes and kinases, renin-angiotensin system (RAS) modulators, and others. From our review of the results from the clinical trials and discussion of their implications in the gastrointestinal tract, we have identified several molecular candidates that could serve as potential therapies for intestinal fibrosis in CD.

Self-Healing B ← N-Based Hydrogen-Bonded Organic Framework for Exclusive Recognition and Separation of Toluene from Methyl-Cyclohexane.

The effective separation of aromatic and aliphatic hydrocarbons remains a notable challenge in the petrochemical industry. Herein, we report a self-healing three-dimensional B ← N-based hydrogen-bonded organic framework (HOF), BN-HOF-1, constructed from discrete B ← N inclusive dimers through weak C-H···F and C-H···N hydrogen-bonding interactions. To make use of the specific recognition of the B ← N inclusive dimers for the toluene molecules and the reversible ad/desorption nature of this novel HOF, BN-HOF-1 can exclusively recognize and separate toluene from the mixtures of toluene-methylcyclohexane, thus generating 99.6% pure toluene from its mixtures after gentle heating, the recorded value among any reported materials for toluene purification. After the toluene molecules were released from the framework, it becomes the condensed BN-HOF-1a, which can be further reused for the highly selective recognition and purification of toluene from its binary mixtures, through the reversible structural recovery back to BN-HOF-1. Single-crystal X-ray diffraction and molecular modeling studies reveal that the high specific toluene recognition is attributed to the complementary electrostatic potential between the host B ← N inclusive dimers and the guest toluene, while the self-healing and recovery nature of this HOF is attributed to weak intermolecular hydrogen-bonding interactions.

IFIT1 + neutrophil is a causative factor of immunosuppressive features of poorly cohesive carcinoma (PCC).

The importance of the immune microenvironment in poorly cohesive carcinoma (PCC) has been highlighted due to its limited response rate to conventional therapy and emerging treatment resistance. A combination of clinical cohorts, bioinformatics analyses, and functional/molecular experiments revealed that high infiltration of Interferon Induced Protein with Tetratricopeptide Repeats 1 (IFIT1) + tumor-associated neutrophils (TANs) is a distinguishing feature of PCC patients. Upregulation of IFIT1 + TANs promote migration and invasion of gastric cancer (GC) cell lines (MKN45 and MKN74) and stimulates the growth of cell-derived xenograft models. Besides, by promoting macrophage secreted phosphoprotein 1 (SPP1) expression and facilitating cancer-associated fibroblast and endothelial cell recruitment and activation through TANs, IFIT1 promotes a mesenchymal phenotype, which is associated with a poor prognosis. Importantly, compared to non-PCC (NPCC), PCC tumors is more immunosuppressive. Mechanistically, IFIT1 can be stimulated by IFN-γ and contributes to the expression of Programmed Cell Death 1 Ligand (PDL1) in TANs. We demonstrated in mouse models that IFIT1 + PDL1 + TANs can induce acquired resistance to anti-PD-1 immunotherapy, which may be responsible for the difficulty of PCC patients to benefit from immunotherapy. This work highlights the role of IFIT1 + TANs in mediating the remodeling of the tumor immune microenvironment and immunotherapeutic resistance and introduces IFIT1 + TANs as a promising target for precision therapy of PCC.

Trained quantity discrimination in invasive red-eared slider and a comparison with the native stripe-necked turtle.

Little is known about the behavioral and cognitive traits that best predict invasion success. Evidence is mounting that cognitive performance correlates with survival and fecundity, two pivotal factors for the successful establishment of invasive populations. We assessed the quantity discrimination ability of the globally invasive red-eared slider (Trachemys scripta elegans). We further compared it to that of the native stripe-necked turtle (Mauremys sinensis), which has been previously evaluated for its superior quantity discrimination ability. Specifically, our experimental designs aimed to quantify the learning ability as numerosity pairs increased in difficulty (termed fixed numerosity tests), and the immediate response when turtles were presented with varied challenges concurrently in the same tests (termed mixed numerosity tests). Our findings reaffirm the remarkable ability of freshwater turtles to discern numerical differences as close as 9 vs 10 (ratio = 0.9), which was comparable to the stripe-necked turtle's performance. However, the red-eared slider exhibited a moderate decrease in performance in high ratio tests, indicating a potentially enhanced cognitive capacity to adapt to novel challenges. Our experimental design is repeatable and is adaptable to a range of freshwater turtles. These findings emphasize the potential importance of cognitive research to the underlying mechanisms of successful species invasions.

Methylomonas defluvii sp. nov., a type I methane-oxidizing bacterium from a secondary sedimentation tank of a wastewater treatment plant.

An aerobic methanotroph was isolated from a secondary sedimentation tank of a wastewater treatment plant and designated strain OY6T. Cells of OY6T were Gram-stain-negative, pink-pigmented, motile rods and contained an intracytoplasmic membrane structure typical of type I methanotrophs. OY6T could grow at a pH range of 4.5-7.5 (optimum pH 6.5) and at temperatures ranging from 20 °C to 37 °C (optimum 30 °C). The major cellular fatty acids were C14 : 0, C16 : 1ω7c/C16 : 1ω6c and C16 : 1ω5c; the predominant respiratory quinone was MQ-8. The genome size was 5.41 Mbp with a DNA G+C content of 51.7 mol%. OY6T represents a member of the family Methylococcaceae of the class Gammaproteobacteria and displayed 95.74-99.64 % 16S rRNA gene sequence similarity to the type strains of species of the genus Methylomonas. Whole-genome comparisons based on average nucleotide identity (ANI) and digital DNA-DNA hybridisation (dDDH) confirmed that OY6T should be classified as representing a novel species. The most closely related type strain was Methylomonas fluvii EbBT, with 16S rRNA gene sequence similarity, ANI by blast (ANIb), ANI by MUMmer (ANIm) and dDDH values of 99.64, 90.46, 91.92 and 44.5 %, respectively. OY6T possessed genes encoding both the particulate methane monooxygenase enzyme and the soluble methane monooxygenase enzyme. It grew only on methane or methanol as carbon sources. On the basis of phenotypic, genetic and phylogenetic data, strain OY6T represents a novel species within the genus Methylomonas for which the name Methylomonas defluvii sp. nov. is proposed, with strain OY6T (=GDMCC 1.4114T=KCTC 8159T=LMG 33371T) as the type strain.

Functional role of P2X7 purinergic receptor in cancer and cancer-related pain.

Numerous studies have revealed that the ATP-gated ion channel purinergic 2X7 receptor (P2X7R) plays an important role in tumor progression and the pathogenesis of cancer pain. P2X7R requires activation by extracellular ATP to perform its regulatory role functions. During tumor development or cancer-induced pain, ATP is released from tumor cells or other cells in the tumor microenvironment (such as tumor-associated immune cells), which activates P2X7R, opens ion channels on the cell membrane, affects intracellular molecular metabolism, and regulates the activity of tumor cells. Furthermore, peripheral organs and receptors can be damaged during tumor progression, and P2X7R expression in nerve cells (such as microglia) is significantly upregulated, enhancing sensory afferent information, sensitizing the central nervous system, and inducing or exacerbating pain. These findings reveal that the ATP-P2X7R signaling axis plays a key regulatory role in the pathogenesis of tumors and cancer pain and also has a therapeutic role. Accordingly, in this study, we explored the role of P2X7R in tumors and cancer pain, discussed the pharmacological properties of inhibiting P2X7R activity (such as the use of antagonists) or blocking its expression in the treatment of tumor and cancer pain, and provided an important evidence for the treatment of both in the future.

Astrocytic P2X7 receptor in retrosplenial cortex drives electroacupuncture analgesia.

P2X7 receptor (P2X7R) has been found to contribute to the peripheral mechanism of acupuncture analgesia (AA). However, whether it plays an important role in central mechanism remains unknown. In this study, we aimed to reveal the role of astrocytic P2X7R in retrosplenial cortex (RSC) in AA and provide new evidence for underlying the central mechanism of AA. We applied the chemogenetic receptors hM3Dq to stimulate or hM4Di to inhibit astrocytes ligand clozapine-N-oxide (CNO) following injection of adeno-associated virus (AAV) into the bilateral RSC, or pharmacologically intervened in the activity of the purinergic receptor P2X7R. Current data indicated that chemogenetic inhibition of astrocytes or injection of P2X7R agonist Bz-ATP in the bilateral RSC significantly reverses the analgesic effect of electroacupuncture (EA) in formalin tests while the bilateral injection of the P2X7R antagonist A438079 alleviated formalin-induced nociceptive behavior. Additionally, chemogenetic suppression of astrocytic P2X7R by injection of AAV in the bilateral RSC decreased hind paw flinches induced by formalin in the mice. These findings indicate the participation of both astrocytes and P2X7R in the RSC in EA analgesic. Moreover, P2X7R on astrocytes in the RSC appears to play a critical role in the ability of EA to attenuate formalin-induced pain responses in mice.

ABBV-744 alleviates LPS-induced neuroinflammation via regulation of BATF2-IRF4-STAT1/3/5 axis.

Suppression of neuroinflammation using small molecule compounds targeting the key pathways in microglial inflammation has attracted great interest. Recently, increasing attention has been gained to the role of the second bromodomain (BD2) of the bromodomain and extra-terminal (BET) proteins, while its effect and molecular mechanism on microglial inflammation has not yet been explored. In this study, we evaluated the therapeutic effects of ABBV-744, a BD2 high selective BET inhibitor, on lipopolysaccharide (LPS)-induced microglial inflammation in vitro and in vivo, and explored the key pathways by which ABBV-744 regulated microglia-mediated neuroinflammation. We found that pretreatment of ABBV-744 concentration-dependently inhibited the expression of LPS-induced inflammatory mediators/enzymes including NO, TNF-α, IL-1ß, IL-6, iNOS, and COX-2 in BV-2 microglial cells. These effects were validated in LPS-treated primary microglial cells. Furthermore, we observed that administration of ABBV-744 significantly alleviated LPS-induced activation of microglia and transcriptional levels of pro-inflammatory factors TNF-α and IL-1ß in mouse hippocampus and cortex. RNA-Sequencing (RNA-seq) analysis revealed that ABBV-744 induced 508 differentially expressed genes (DEGs) in LPS-stimulated BV-2 cells, and gene enrichment and gene expression network analysis verified its regulation on activated microglial genes and inflammatory pathways. We demonstrated that pretreatment of ABBV-744 significantly reduced the expression levels of basic leucine zipper ATF-like transcription factor 2 (BATF2) and interferon regulatory factor 4 (IRF4), and suppressed JAK-STAT signaling pathway in LPS-stimulated BV-2 cells and mice, suggesting that the anti-neuroinflammatory effect of ABBV-744 might be associated with regulation of BATF2-IRF4-STAT1/3/5 pathway, which was confirmed by gene knockdown experiments. This study demonstrates the effect of a BD2 high selective BET inhibitor, ABBV-744, against microglial inflammation, and reveals a BATF2-IRF4-STAT1/3/5 pathway in regulation of microglial inflammation, which might provide new clues for discovery of effective therapeutic strategy against neuroinflammation.

Detailed analysis of learning phases and outcomes in robotic and endoscopic thyroidectomy.

BACKGROUND: Thyroid surgery has undergone significant transformation with the introduction of minimally invasive techniques, particularly robotic and endoscopic thyroidectomy. These advancements offer improved precision and faster recovery but also present unique challenges. This study aims to compare the learning curves, operational efficiencies, and patient outcomes of robotic versus endoscopic thyroidectomy. METHODS: A retrospective cohort study was conducted, analyzing 258 robotic (da Vinci) and 214 endoscopic thyroidectomy cases. Key metrics such as operation duration, drainage volume, lymph node dissection outcomes, and hypoparathyroidism incidence were assessed to understand surgical learning curves and efficiency. RESULTS: Robotic thyroidectomy showed a longer learning curve with initially longer operation times and higher drainage volumes but superior lymph node dissection outcomes. Both techniques were safe, with no permanent hypoparathyroidism or recurrent laryngeal nerve damage reported. The study delineated four distinct stages in the robotic and endoscopic surgery learning curve, each marked by specific improvements in proficiency. Endoscopic thyroidectomy displayed a shorter learning curve, leading to quicker operational efficiency gains. CONCLUSION: Robotic and endoscopic thyroidectomies are viable minimally invasive approaches, each with its learning curves and efficiency metrics. Despite initial challenges and a longer learning period for robotic surgery, its benefits in complex dissections may justify specialized training. Structured training programs tailored to each technique are crucial for improving outcomes and efficiency. Future research should focus on optimizing training protocols and increasing accessibility to these technologies, enhancing patient care in thyroid surgery.

Prevalence and risk factors for dementia and mild cognitive impairment among older people in Southeast China: a community-based study.

BACKGROUND: With the aging population, the number of individuals with dementia in China is increasing rapidly. This community-based study aimed to investigate the prevalence and risk factors for dementia and mild cognitive impairment (MCI) among older adults in China. METHODS: In this study, 20,070 individuals aged ≥ 65 were recruited between January 1, 2022, and February 1, 2023, from ten communities in Xiamen City, China. We collected data on age, sex, level of education, and medical history, as well as global cognition and functional status. The prevalence of dementia and MCI was examined, and the risk factors for different groups were assessed. RESULTS: The overall prevalence of dementia and MCI was approximately 5.4% (95% confidence interval [CI], 5.1-5.7) and 7.7% (95% CI, 7.4-8.1), respectively. The results also indicated that dementia and MCI share similar risk factors, including older age, female sex, hypertension, and diabetes mellitus. Compared with individuals with no formal education, those with > 6 years of education had an odds ratio for MCI of 1.83 (95% CI, 1.49-2.25). We also found that only 5.5% of the positive participants chose to be referred to the hospital for further diagnosis and treatment during follow-up visits. CONCLUSIONS: This study estimated the prevalence and risk factors for dementia and MCI among individuals aged ≥ 65 years in Southeast China. These findings are crucial for preventing and managing dementia and MCI in China.

Progress on SOX9 and its enhancers in mammalian sex determination.

The sex determination in mammals refers to the development of an initial bipotential organ, termed the bipotential gonad/genital ridge, into either a testis or an ovary at the early stages of embryonic development, under the precise regulation of transcription factors. SOX9 (SRY-box transcription factor 9) is a multifunctional transcription factor in mammalian development and plays a critical role in sex determination and subsequent male reproductive organs development. Recent studies have shown that several enhancers upstream of SOX9 also play an important role in the process of sex determination. In this review, we summarize the progress on the role of SOX9 and its gonadal enhancers in sex determination. This review will facilitate to understand the regulatory mechanism of sex determination of SOX9 and provides a theoretical basis for the further development of animal sex manipulation technologies.

Enantioselective Synthesis of Chiral Cyclobutenes Enabled by Brønsted Acid-Catalyzed Isomerization of BCBs.

Chiral cyclobutene units are commonly found in natural products and biologically active molecules. Transition-metal-catalysis has been extensively used in asymmetric synthesis of such structures, while organocatalytic approaches remain elusive. In this study, bicyclo[1.1.0]butanes are involved in enantioselective transformation for the first time to offer a highly efficient route toward cyclobutenes with good regio- and enantiocontrol. The utilization of N-triflyl phosphoramide as a chiral Brønsted acid promoter enables this isomerization process to proceed under mild conditions with low catalyst loading as well as good functional group compatibility. The resulting chiral cyclobutenes could serve as platform molecules for downstream manipulations with excellent reservation of stereochemical integrity, demonstrating the synthetic practicality of the developed method. Control experiments have also been performed to verify the formation of a key carbocation intermediate at the benzylic position.

Fully Integrated Microfluidic Device for Magnetic Bead Manipulation to Assist Rapid Reaction and Cleaning.

Methods to manipulate magnetic beads are essential factors to determine the efficiency and dimension of an in vitro diagnostic system. Currently, using movable permanent magnets and planar electromagnets is still the major approach to achieve magnetic bead control, causing significant constraint in the miniaturization of in vitro diagnostic systems. Here, we propose techniques to construct a fully integrated microfluidic device that can conduct automatic magnetic bead manipulation as well as rapid chemical reaction and cleaning in a minimized dimension similar to a USB disk. The device combines the precision control of multiple electromagnetic coils with the compactness of microfluidic channels, leading to one of the smallest automatic magnetic bead manipulation systems that can complete several major magnetic bead-based operation steps such as sample injection, reaction, cleaning, and collection. The influencing factors such as coil driving parameters, surface treatment of the microchannels, and properties of magnetic particles have also been investigated to optimize the device performance. The device can drive mixtures of Fe3O4 microparticles and polymer magnetic beads (PMBs) with a weight ratio of 1:1 at a maximum speed of 0.5 cm·s-1 and reduce the time for DNA binding and dissociation reactions from 20 min to only 48 s. This device has significantly advanced the conventional manipulation methods of magnetic beads and has demonstrated the possibility to construct an automatic and ultraminiaturized in vitro diagnostic system that may facilitate portable or even wearable chemical analysis.

MACC1 and Gasdermin-E (GSDME) regulate the resistance of colorectal cancer cells to irinotecan.

Metastasis-associated in colon cancer 1 (MACC1) is an oncogene associated with the progression and metastasis of many solid cancer entities. High expression of MACC1 is found in colorectal cancer (CRC) tissues. So far, the role of MACC1 in CRC cell pyroptosis and resistance to irinotecan is unclear. The cleavage of Gasdermin-E (GSDME) is the main executors of activated pyroptosis. We found that GSDME enhanced CRC cell pyroptosis and reduced their resistance to irinotecan, while MACC1 inhibited the cleavage of GSDME and CRC cell pyroptosis, promoted CRC cell proliferation, and enhanced the resistance of CRC cells to irinotecan. Therefore, CRC cells with high MACC1 expression and low GSDME expression had higher resistance to irinotecan, while CRC cells with low MACC1 expression and high GSDME expression had lower resistance to irinotecan. Consistently, by analyzing CRC patients who received FOLFIRI (Fluorouracil + Irinotecan + Leucovorin) in combination with chemotherapy in the GEO database, we found that CRC patients with low MACC1 expression and high GSDME expression had higher survival rate. Our study suggests that the expression of MACC1 and GSDME can be used as detection markers to divide CRC patients into irinotecan resistant and sensitive groups, helping to determine the treatment strategy of patients.

Three-Dimensional Coffee-Ring Effect Induced Deposition on Foam Surface for Enhanced Photothermal Conversion.

Uniformly depositing a thin layer of functional constituents on porous foam is attractive to realize their concentrated interfacial application. Here, a simple but robust polyvinyl alcohol (PVA)-mediated evaporation drying strategy to achieve uniform surface deposition on melamine foam (MF) is introduced. Solutes can be accumulated homogeneously to the surface periphery of MF due to the enhanced coffee-ring effect of PVA and its stabilizing effect on various functional constituents, including molecules and colloidal particles. The deposition thickness is positively correlated with the feeding amounts of PVA but seems to be independent of drying temperature. 3D outward capillary flow driven by the combination of contact surface pinning and continual interfacial evaporation induces the forming of core-shell foams. The enhanced interfacial photothermal effect and solar desalination performance using PVA/polypyrrole-coated MF as a Janus solar evaporator are demonstrated.

Mo2 N-ZrO2 Heterostructure Engineering in Freestanding Carbon Nanofibers for Upgrading Cycling Stability and Energy Efficiency of Li-CO2 Batteries.

Li-CO2 batteries have attracted considerable attention for their advantages of CO2 fixation and high energy density. However, the sluggish dynamics of CO2 reduction/evolution reactions restrict the practical application of Li-CO2 batteries. Herein, a dual-functional Mo2 N-ZrO2 heterostructure engineering in conductive freestanding carbon nanofibers (Mo2 N-ZrO2 @NCNF) is reported. The integration of Mo2 N-ZrO2 heterostructure in porous carbons provides the opportunity to simultaneously accelerate electron transport, boost CO2 conversion, and stabilize intermediate discharge product Li2 C2 O4 . Benefiting from the synchronous advantages, the Mo2 N-ZrO2 @NCNF catalyst endows the Li-CO2 batteries with excellent cycle stability, good rate capability, and high energy efficiency even under high current densities. The designed cathodes exhibit an ultrahigh energy efficiency of 89.8% and a low charging voltage below 3.3 V with a potential gap of 0.32 V. Remarkably, stable operation over 400 cycles can be achieved even at high current densities of 50 µA cm-2 . This work provides valuable guidance for developing multifunctional heterostructured catalysts to upgrade longevity and energy efficiency of Li-CO2 batteries.

Simultaneous sensing of strain and temperature based on the inline-MZI embedded point-shaped taper structure with low crosstalk.

An embedded spherical dot taper structure (EDT) based on the MZI principle is proposed in this paper, which is mainly fabricated by using two special arc discharges in the preparation process. The proposed structure involves two specialized arc discharge techniques. First, an oversaturated discharge fusion process creates a micro-arc spherical area on the fiber end face to form the first link type. Second, an unsaturated discharge-pulling taper fusion joint creates a local micro-extrusion operation on this micro-arc fiber end face to form the second link. The thermal stress from instantaneous discharge causes a reverse spherical expansion zone to form in the end face structure, similar to the micromachining of long-period fiber gratings that use local CO2 laser etching to create modulated zones. The study involves a mathematical and theoretical analysis of how geometric parameters in the spherical modulation zone impact the structure's characteristic spectrum. The research demonstrates the potential for this structure to function as a light-intensity modulated strain sensor device through both theoretical and experimental means. As per the experimental findings, the optimized structure displays a high level of strain sensing sensitivity at 0.03 dB/µÎµ and temperature sensing sensitivity of 73 pm/°C (20°C-75°C) and 169 pm/°C (75°C-120°C). Additionally, it possesses excellent cross-sensitivity at only ∼0.0015 µÎµ/°C. Therefore, this sensor presents a favorable option for strain and temperature synchronization sensing and monitoring components, and exhibits notable application prospects in precision engineering, which encompasses mechanical manufacturing, the power and electrical industry, healthcare domain, and certain specialized areas of small-scale precision engineering.

Major pathological remissions in a patient with stage IIIA nonsmall cell lung cancer after neoadjuvant tislelizumab combined with chemotherapy: a case report and literature review.

INTRODUCTION: Currently, there are few reports of patients with locally advanced lung cancer achieving a clinical complete response by medical treatment. Preoperative neoadjuvant immunotherapy combined with chemotherapy is an option for patients with unresectable, locally advanced nonsmall cell lung cancer (NSCLC) which is of great potential, and may change traditional treatment paradigms. There are relatively few large-scale, high-quality randomized-controlled trials yet, and limitations such as short postoperative follow-up period and immature disease-free survival and overall survival data still persist. Thus, evidence-based medical evidence is urgently needed. It is worthy to explore the further treatment of patients who achieved complete response after initial treatment, though lacking of evidence by now. CASE PRESENTATION: We report a stage IIIA lung squamous cell carcinoma case who achieved a major pathologic remission after neoadjuvant treatment with tislelizumab and chemotherapy. CONCLUSION: Our case study contributes to the existing evidence on the feasibility, efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced unresectable NSCLC.

Machine learning on MRI radiomic features: identification of molecular subtype alteration in breast cancer after neoadjuvant therapy.

OBJECTIVES: Recent studies have revealed the change of molecular subtypes in breast cancer (BC) after neoadjuvant therapy (NAT). This study aims to construct a non-invasive model for predicting molecular subtype alteration in breast cancer after NAT. METHODS: Eighty-two estrogen receptor (ER)-negative/ human epidermal growth factor receptor 2 (HER2)-negative or ER-low-positive/HER2-negative breast cancer patients who underwent NAT and completed baseline MRI were retrospectively recruited between July 2010 and November 2020. Subtype alteration was observed in 21 cases after NAT. A 2D-DenseUNet machine-learning model was built to perform automatic segmentation of breast cancer. 851 radiomic features were extracted from each MRI sequence (T2-weighted imaging, ADC, DCE, and contrast-enhanced T1-weighted imaging), both in the manual and auto-segmentation masks. All samples were divided into a training set (n = 66) and a test set (n = 16). XGBoost model with 5-fold cross-validation was performed to predict molecular subtype alterations in breast cancer patients after NAT. The predictive ability of these models was subsequently evaluated by the AUC of the ROC curve, sensitivity, and specificity. RESULTS: A model consisting of three radiomics features from the manual segmentation of multi-sequence MRI achieved favorable predictive efficacy in identifying molecular subtype alteration in BC after NAT (cross-validation set: AUC = 0.908, independent test set: AUC = 0.864); whereas an automatic segmentation approach of BC lesions on the DCE sequence produced good segmentation results (Dice similarity coefficient = 0.720). CONCLUSIONS: A machine learning model based on baseline MRI is proven useful for predicting molecular subtype alterations in breast cancer after NAT. KEY POINTS: • Machine learning models using MRI-based radiomics signature have the ability to predict molecular subtype alterations in breast cancer after neoadjuvant therapy, which subsequently affect treatment protocols. • The application of deep learning in the automatic segmentation of breast cancer lesions from MRI images shows the potential to replace manual segmentation..

P2 purinergic receptors regulate the progression of colorectal cancer.

More and more studies have revealed that P2 purinergic receptors play a key role in the progression of colorectal cancer (CRC). P2X and P2Y purinergic receptors can be used as promoters and regulators of CRC and play a dual role in the progression of CRC. CRC microenvironment is rich in ATP and its cleavage products (ADP, AMP, Ado), which act as activators of P2X and P2Y purinergic receptors. The activation of P2X and P2Y purinergic receptors regulates the progression of CRC mainly by regulating the function of immune cells and mediating different signal pathways. In this paper, we focus on the specific mechanisms and functional roles of P2X7, P2Y12, and P2Y2 receptors in the growth and progression of CRC. The antagonistic effects of these selective antagonists of P2X purinergic receptors on the growth, invasion, and metastasis of CRC were further discussed. Moreover, different studies have reported that P2X7 receptor can be used as an effective predictor of patients with CRC. All these indicate that P2 purinergic receptors are a key regulator of CRC. Therefore, antagonizing P2 purinergic receptors may be an innovative treatment for CRC.