Characterizing the coefficient of friction between a capsule robot and the colon.

OBJECTIVE: A capsule robot (CR) with an onboard active locomotion mechanism, has been developed as a promising alternative to colonoscopy due to its minimally-invasive advantage. Predicting the traction force and locomotion resistance of the CR, which are both the friction force, is significantly important for the CR development and control. However, a comprehensive study concerning the coefficient of friction (COF) in the colon, which is necessary for prediction, is not available in literature. This paper is dedicated to determining a quantitative COF equation in terms of the contact pressure, hoop strain, and sliding velocity. METHODS: The COFs of three commonly-used materials of the CR (i.e., PDMS, white and transparent ABS plastic), are measured under 144 different friction cases (6 contact pressures×4 hoop strains×6 sliding velocities). By analyzing the measurements, the influence law of the three factors on the COFs of the three materials is revealed, and based on which, a general COF equation involving eight fitted constants is determined. RESULTS: The determination coefficients of the COF equation for the three materials are up to 0.9822, 0.9286, and 0.9696, respectively. The COF equation is used to predict the traction force and locomotion resistance of a crawler CR, and the predicting results fit well with the measured ones. CONCLUSION: The COF equation can provide a correct COF for friction force prediction. SIGNIFICANCE: It is promising to enable a better force and locomotion control for the CR in the colon.

Evaluating net primary productivity dynamics and their response to land-use change in the loess plateau after the 'Grain for Green' program.

Assessing net primary productivity (NPP) dynamics and the contribution of land-use change (LUC) to NPP can help guide scientific policy to better restore and control the ecological environment. Since 1999, the "Green for Grain" Program (GGP) has strongly affected the spatial and temporal pattern of NPP on the Loess Plateau (LP); however, the multifaceted impact of phased vegetation engineering measures on NPP dynamics remains unclear. In this study, the Carnegie-Ames-Stanford Approach (CASA) model was used to simulate NPP dynamics and quantify the relative contributions of LUC and climate change (CC) to NPP under two different scenarios. The results showed that the average NPP on the LP increased from 240.7 gC·m-2 to 422.5 gC·m-2 from 2001 to 2020, with 67.43% of the areas showing a significant increasing trend. LUC was the main contributor to NPP increases during the study period, and precipitation was the most important climatic factor affecting NPP dynamics. The cumulative amount of NPP change caused by LUC (ΔNPPLUC) showed a fluctuating growth trend (from 46.23 gC·m-2 to 127.25 gC·m-2), with a higher growth rate in period ΙΙ (2010-2020) than in period Ι (2001-2010), which may be related to the accumulation of vegetation biomass and the delayed effect of the GGP on NPP. The contribution rate of LUC to increased NPP in periods Ι and ΙΙ was 101.2% and 51.2%, respectively. Regarding the transformation mode, the transformation of grassland to forest had the greatest influence on ΔNPPLUC. Regarding land-use type, the increased efficiency of NPP was improved in cropland, grassland, and forest. This study provides a scientific basis for the scientific management and development of vegetation engineering measures and regional sustainable development.

Interactions between platelets and the cancer immune microenvironment.

Cancer is a leading cause of death in both China and developed countries due to its high incidence and low cure rate. Immune function is closely linked to the development and progression of tumors. Platelets, which are primarily known for their role in hemostasis, also play a crucial part in the spread and progression of tumors through their interaction with the immune microenvironment. The impact of platelets on tumor growth and metastasis depends on the type of cancer and treatment method used. This article provides an overview of the relationship between platelets and the immune microenvironment, highlighting how platelets can either protect or harm the immune response and cancer immune escape. We also explore the potential of available platelet-targeting strategies for tumor immunotherapy, as well as the promise of new platelet-targeted tumor therapy methods through further research.

Effects of mild hyperbaric oxygen therapy on timing sequence recovery of muscle fatigue in chinese university male athletes.

Objectives: This study aimed to investigate the timing sequence recovery effects of single and repeated Mild Hyperbaric Oxygen Therapy (MHOT) on muscle fatigue induced by cycling exercise through a comprehensive set of parameters. Methods: This study employed a controlled crossover design involving 12 Chinese secondary national-level male athletes. Each participant completed two identical trials over six days. Each trial consisted of a 90-min cycling exercise followed by either a Control (CON) intervention (1 atm absolute (ATA), 20.9 % oxygen, 60 min) or MHOT intervention (1.25 ATA, 26%-28 % oxygen, 60 min). Various physiological parameters including Rating of Perceived Exertion (RPE), Heart Rate (HR), Peripheral Oxygen Saturation (SpO2), Perfusion Index (PI%), Creatine Kinase (CK), Lactate Dehydrogenase (LDH), Lactic Acid (LA), Blood Urea Nitrogen (BUN), Superoxide Dismutase (SOD), Malondialdehyde (MDA), and Standing Long Jump Distance (SLJ) were measured at six different time points throughout the trials. Results: RPE revealed that the MHOT group experienced reduced subjective fatigue in comparison to the CON group (P < 0.05). Additionally, MHOT demonstrated quicker recovery in HR and PI% compared to the CON group (P < 0.05). Regarding CK, LA, BUN, SOD, and MDA levels, the MHOT group exhibited accelerated recovery post-6 intervention and at the 24-h mark after six interventions, showing significant improvement over the CON group (P < 0.05). However, no notable disparity was observed between groups concerning SpO2, LDH, and SLJ. Conclusions: Both single and repeated sessions of MHOT demonstrated efficacy in alleviating subjective fatigue and promoting recovery of heart rate and blood perfusion following muscle fatigue, ensuring parallel structure and consistency in their effects. Repeated MHOT sessions (six times) exhibit a significant reduction in levels of blood markers associated with muscle damage, metabolites, and oxidative stress. However, the impact of a single MHOT intervention was less pronounced.

Carboxylesterase Activatable Molecular Probe for Personalized Treatment Guidance by Analyte-Induced Molecular Transformation.

Accurate visualization of tumor microenvironment is of great significance for personalized medicine. Here, we develop a near-infrared (NIR) fluorescence/photoacoustic (FL/PA) dual-mode molecular probe (denoted as NIR-CE) for distinguishing tumors based on carboxylesterase (CE) level by an analyte-induced molecular transformation (AIMT) strategy. The recognition moiety for CE activity is the acetyl unit of NIR-CE, generating the pre-product, NIR-CE-OH, which undergoes spontaneous hydrogen atom exchange between the nitrogen atoms in the indole group and the phenol hydroxyl group, eventually transforming into NIR-CE-H. In cellular experiments and in vivo blind studies, the human hepatoma cells and tumors with high level of CE were successfully distinguished by both NIR FL and PA imaging. Our findings provide a new molecular imaging strategy for personalized treatment guidance.

The effects of IL-27 and IL-35 gene variation and expression levels on the susceptibility and clinical manifestations of pulmonary tuberculosis.

Inflammatory cytokines have crucial roles in the pathogenesis of tuberculosis (TB), and interleukin (IL)-27 and IL-35 have a pro-inflammatory and anti-inflammatory effect on many diseases, including infectious diseases. Therefore, we evaluated the relationship between IL-27 and IL-35 gene polymorphism, expression levels, and pulmonary TB (PTB) susceptibility. Nine single-nucleotide polymorphisms (SNPs) in the IL-27 gene (rs181206, rs153109, and rs17855750) and the IL-35 gene (rs4740, rs428253, rs9807813, rs2243123, rs2243135, and rs568408) were genotyped by the SNPscan technique in 497 patients with PTB and 501 controls. There was no significant difference regarding the genotype and allele frequencies of the above SNPs in the IL-27 and IL-35 genes between patients with PTB and controls. Haplotype analysis showed that the frequency of the GAC haplotype in the IL-35 gene was significantly decreased in patients with PTB when compared to controls (p = 0.036). Stratified analysis suggested that the frequency of the IL-27 rs17855750 GG genotype was significantly increased in patients with PTB with fever. Moreover, the lower frequency of the IL-35 rs568408 GA genotype was associated with drug-induced liver injury in patients with PTB. The IL-35 rs428253 GC genotype, as well as the rs4740 AA genotype and A allele, showed significant relationships with hypoproteinemia in patients with PTB. When compared with controls, the IL-27 level was significantly increased in patients with PTB. Taken together, IL-35 gene variation might contribute to a protective role on the susceptibility to PTB, and IL-27 and IL-35 gene polymorphisms were associated with several clinical manifestations of patients with PTB.

Nondestructive Detection of Sunflower Seed Vigor and Moisture Content Based on Hyperspectral Imaging and Chemometrics.

Sunflower is an important crop, and the vitality and moisture content of sunflower seeds have an important influence on the sunflower's planting and yield. By employing hyperspectral technology, the spectral characteristics of sunflower seeds within the wavelength range of 384-1034 nm were carefully analyzed with the aim of achieving effective prediction of seed vitality and moisture content. Firstly, the original hyperspectral data were subjected to preprocessing techniques such as Savitzky-Golay smoothing, standard normal variable correction (SNV), and multiplicative scatter correction (MSC) to effectively reduce noise interference, ensuring the accuracy and reliability of the data. Subsequently, principal component analysis (PCA), extreme gradient boosting (XGBoost), and stacked autoencoders (SAE) were utilized to extract key feature bands, enhancing the interpretability and predictive performance of the data. During the modeling phase, random forests (RFs) and LightGBM algorithms were separately employed to construct classification models for seed vitality and prediction models for moisture content. The experimental results demonstrated that the SG-SAE-LightGBM model exhibited outstanding performance in the classification task of sunflower seed vitality, achieving an accuracy rate of 98.65%. Meanwhile, the SNV-XGBoost-LightGBM model showed remarkable achievement in moisture content prediction, with a coefficient of determination (R2) of 0.9715 and root mean square error (RMSE) of 0.8349. In conclusion, this study confirms that the fusion of hyperspectral technology and multivariate data analysis algorithms enables the accurate and rapid assessment of sunflower seed vitality and moisture content, providing robust tools and theoretical support for seed quality evaluation and agricultural production practices. Furthermore, this research not only expands the application of hyperspectral technology in unraveling the intrinsic vitality characteristics of sunflower seeds but also possesses significant theoretical and practical value.

Squalene-epoxidase-catalyzed 24(S),25-epoxycholesterol synthesis promotes trained-immunity-mediated antitumor activity.

The importance of trained immunity in antitumor immunity has been increasingly recognized, but the underlying metabolic regulation mechanisms remain incompletely understood. In this study, we find that squalene epoxidase (SQLE), a key enzyme in cholesterol synthesis, is required for ß-glucan-induced trained immunity in macrophages and ensuing antitumor activity. Unexpectedly, the shunt pathway, but not the classical cholesterol synthesis pathway, catalyzed by SQLE, is required for trained immunity induction. Specifically, 24(S),25-epoxycholesterol (24(S),25-EC), the shunt pathway metabolite, activates liver X receptor and increases chromatin accessibility to evoke innate immune memory. Meanwhile, SQLE-induced reactive oxygen species accumulation stabilizes hypoxia-inducible factor 1α protein for metabolic switching into glycolysis. Hence, our findings identify 24(S),25-EC as a key metabolite for trained immunity and provide important insights into how SQLE regulates trained-immunity-mediated antitumor activity.

High expression of PPP1CC promotes NHEJ-mediated DNA repair leading to radioresistance and poor prognosis in nasopharyngeal carcinoma.

Protein phosphatase 1 catalytic subunit gamma (PPP1CC) promotes DNA repair and tumor development and progression, however, its underlying mechanisms remain unclear. This study investigated the molecular mechanism of PPP1CC's involvement in DNA repair and the potential clinical implications. High expression of PPP1CC was significantly correlated with radioresistance and poor prognosis in human nasopharyngeal carcinoma (NPC) patients. The mechanistic study revealed that PPP1CC bound to Ku70/Ku80 heterodimers and activated DNA-PKcs by promoting DNA-PK holoenzyme formation, which enhanced nonhomologous end junction (NHEJ) -mediated DNA repair and led to radioresistance. Importantly, BRCA1-BRCA2-containing complex subunit 3 (BRCC3) interacted with PPP1CC to enhance its stability by removing the K48-linked polyubiquitin chain at Lys234 to prevent PPP1CC degradation. Therefore, BRCC3 helped the overexpressed PPP1CC to maintain its high protein level, thereby sustaining the elevation of DNA repair capacity and radioresistance. Our study identified the molecular mechanism by which PPP1CC promotes NHEJ-mediated DNA repair and radioresistance, suggesting that the BRCC3-PPP1CC-Ku70 axis is a potential therapeutic target to improve the efficacy of radiotherapy.

miR-208a-3p regulated by circUQCRC2 suppresses ischemia/reperfusion-induced acute kidney injury by inhibiting CELF2-mediated tubular epithelial cell apoptosis, inflammation and ferroptosis.

BACKGROUND: Acute kidney injury (AKI) is a prevalent clinical syndrome with persistent kidney dysfunction. Renal ischemia/reperfusion (I/R) injury is a major cause of AKI. miR-208a-3p overexpression attenuated myocardial I/R injury. This study aims to investigate the role and mechanism of miR-208a-3p in I/R-induced AKI. METHODS: AKI models were established using hypoxia/reoxygenation (H/R)-exposed tubule epithelial cell HK-2 and I/R-induced mice. The function and mechanism of miR-208a-3p were investigated by gain-or loss-of-function methods using real-time PCR, CCK-8, flow cytometry, ELISA, western blot, hematoxylin-eosin staining, Tunel assay, detection of Fe2+, ROS, BUN and Creatinine, and luciferase reporter assay. RESULTS: miR-208a-3p expression was suppressed, while the expression of CELF2 and circular RNA ubiquinol-cytochrome c reductase core protein 2 (circUQCRC2) was increased in both AKI models. miR-208a-3p upregulation or circUQCRC2 silencing increased the viability, decreased the levels of proinflammatory cytokines (TNF-α, IL-1ß and IL-6), reduced apoptosis and contents of Fe2+ and ROS, elevated expression of GPX4 and SLC7A11, reduced ACSL4 expression in H/R-stimulated HK-2 cells. Also, miR-208a-3p improved kidney function by alleviating renal injury, apoptosis, inflammation and ferroptosis in AKI mouse model. CELF2 was a target gene of miR-208a-3p which was negatively modulated by circUQCRC2. Overexpression of CELF2 blocked the function of miR-208a-3p upregulation or circUQCRC2 silencing on H/R-treated HK-2 cells. Moreover, the effects of circUQCRC2 downregulation on H/R-injured cells were also reversed by miR-208a-3p inhibitor. CONCLUSIONS: miR-208a-3p regulated by circUQCRC2 could attenuate I/R-induced AKI by inhibiting CELF2-mediated tubular epithelial cell apoptosis, inflammation and ferroptosis. This study provides potential therapeutic targets for I/R-induced AKI.

SMS121, a new inhibitor of CD36, impairs fatty acid uptake and viability of acute myeloid leukemia.

Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and the second most common among children. AML is characterized by aberrant proliferation of myeloid blasts in the bone marrow and impaired normal hematopoiesis. Despite the introduction of new drugs and allogeneic bone marrow transplantation, patients have poor overall survival rate with relapse as the major challenge, driving the demand for new therapeutic strategies. AML patients with high expression of the very long/long chain fatty acid transporter CD36 have poorer survival and very long chain fatty acid metabolism is critical for AML cell survival. Here we show that fatty acids are transferred from human primary adipocytes to AML cells upon co-culturing. A drug-like small molecule (SMS121) was identified by receptor-based virtual screening and experimentally demonstrated to target the lipid uptake protein CD36. SMS121 reduced the uptake of fatty acid into AML cells that could be reversed by addition of free fatty acids and caused decreased cell viability. The data presented here serves as a framework for the development of CD36 inhibitors to be used as future therapeutics against AML.

Wild-type IDH2 is a therapeutic target for triple-negative breast cancer.

Mutations in isocitrate dehydrogenases (IDH) are oncogenic events due to the generation of oncogenic metabolite 2-hydroxyglutarate. However, the role of wild-type IDH in cancer development remains elusive. Here we show that wild-type IDH2 is highly expressed in triple negative breast cancer (TNBC) cells and promotes their proliferation in vitro and tumor growth in vivo. Genetic silencing or pharmacological inhibition of wt-IDH2 causes a significant increase in α-ketoglutarate (α-KG), indicating a suppression of reductive tricarboxylic acid (TCA) cycle. The aberrant accumulation of α-KG due to IDH2 abrogation inhibits mitochondrial ATP synthesis and promotes HIF-1α degradation, leading to suppression of glycolysis. Such metabolic double-hit results in ATP depletion and suppression of tumor growth, and renders TNBC cells more sensitive to doxorubicin treatment. Our study reveals a metabolic property of TNBC cells with active utilization of glutamine via reductive TCA metabolism, and suggests that wild-type IDH2 plays an important role in this metabolic process and could be a potential therapeutic target for TNBC.

Nardilysin-regulated scission mechanism activates polo-like kinase 3 to suppress the development of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) develops through step-wise genetic and molecular alterations including Kras mutation and inactivation of various apoptotic pathways. Here, we find that development of apoptotic resistance and metastasis of KrasG12D-driven PDAC in mice is accelerated by deleting Plk3, explaining the often-reduced Plk3 expression in human PDAC. Importantly, a 41-kDa Plk3 (p41Plk3) that contains the entire kinase domain at the N-terminus (1-353 aa) is activated by scission of the precursor p72Plk3 at Arg354 by metalloendopeptidase nardilysin (NRDC), and the resulting p32Plk3 C-terminal Polo-box domain (PBD) is removed by proteasome degradation, preventing the inhibition of p41Plk3 by PBD. We find that p41Plk3 is the activated form of Plk3 that regulates a feed-forward mechanism to promote apoptosis and suppress PDAC and metastasis. p41Plk3 phosphorylates c-Fos on Thr164, which in turn induces expression of Plk3 and pro-apoptotic genes. These findings uncover an NRDC-regulated post-translational mechanism that activates Plk3, establishing a prototypic regulation by scission mechanism.

Epidemiology of acute hepatitis C and hepatitis C virus-related cirrhosis in reproductive-age women, 1990-2019: An analysis of the Global Burden of Disease study.

Background: The current study uniquely focuses on the global incidence and temporal trends of acute hepatitis C (AHC) and hepatitis C virus (HCV)-related cirrhosis among women of reproductive age (15-49 years) from 1990-2019. The risk of vertical transmission and adverse perinatal outcomes associated with HCV infection underscores the importance of prioritising these women in HCV prevention efforts. Methods: Leveraging the Global Burden of Disease 2019 data, we calculated age-standardised incidence rates (ASIR) and assessed temporal trends via the average annual percent change from joinpoint regression. The age-period-cohort model was employed to understand further the effects of age, period, and birth cohort. Results: Over the 30 years, global incidences of AHC and HCV-related cirrhosis in reproductive-age women increased by 46.45 and 72.74%, respectively. The ASIR of AHC was highest in low sociodemographic index regions but showed a declining trend. Conversely, the ASIR of HCV-related cirrhosis displayed unfavourable trends in low, low-middle, and high sociodemographic index regions. Special attention is necessary for sub-Saharan Africa, high-income North America, Eastern Europe, and Central Asia due to their high incidence rates or increasing trends of AHC and HCV-related cirrhosis. Notably, the age-period-cohort model suggests a recent resurgence in AHC and HCV-related cirrhosis risk. Conclusions: The current study is the first to thoroughly evaluate the trends of AHC and HCV-related cirrhosis among reproductive-age women, shedding light on previously unexplored aspects of HCV epidemiology. Our findings identify critical areas where health care systems must adapt to the changing dynamics of HCV infection. The detailed stratification by region and nation further enables the development of localised prevention and treatment strategies.

A bio-inspired co-simulation crawling robot enabled by a carbon dot-doped dielectric elastomer.

Flexible actuation materials play a crucial role in biomimetic robots. Seeking methods to enhance actuation and functionality is one of the directions in which actuators strive to meet the high-performance and diverse requirements of environmental conditions. Herein, by utilizing the method of adsorbing N-doped carbon dots (NCDs) onto SiO2 to form clusters of functional particles, a NCDs@SiO2/PDMS elastomer was prepared and its combined optical and electrical co-stimulation properties were effectively harnessed to develop a biomimetic crawling robot resembling Rhagophthalmus (firefly). The introduction of NCDs@SiO2 cluster particles not only effectively improves the mechanical and dielectric properties of the elastomer but also exhibits fluorescence response and actuation response under the co-stimulation of UV and electricity, respectively. Additionally, a hybrid dielectric elastomer actuator (DEA) with a transparent SWCNT mesh electrode exhibits two notable advancements: an 826% increase in out-of-plane displacement under low electric field stimulation compared to the pure matrix and the ability of NCDs to maintain a stable excited state within the polymer for an extended duration under UV-excitation. Simultaneously, the transparent biomimetic crawling robot can stealthily move in specific environments and fluoresce under UV light.

Value of quantitative microsurface structure analysis for evaluating the invasion depth of type 0-II early gastric cancer.

Background and Aim: The microsurface structure reflects the degree of damage to the glands, which is related to the invasion depth of early gastric cancer. To evaluate the diagnostic value of quantitative microsurface structure analysis for estimating the invasion depth of early gastric cancer. Methods: White-light imaging and narrow-band imaging (NBI) endoscopy were used to visualize the lesions of the included patients. The area ratio and depth-predicting score (DPS) of each patient were calculated; meanwhile, each lesion was examined by endoscopic ultrasonography (EUS). Results: Ninety-three patients were included between 2016 and 2019. Microsurface structure is related to the histological differentiation and progression of early gastric cancer. The receiver operating characteristic curve showed that when an area ratio of 80.3% was used as a cut-off value for distinguishing mucosal (M) and submucosal (SM) type 0-II gastric cancers, the sensitivity, specificity, and accuracy were 82.9%, 80.2%, and 91.6%, respectively. The accuracies for distinguishing M/SM differentiated and undifferentiated early gastric cancers were 87.4% and 84.8%, respectively. The accuracy of EUS for distinguishing M/SM early gastric cancer was 74.9%. DPS can only distinguish M-SM1 (SM infiltration <500 µm)/SM (SM infiltration ≥500 µm) with an accuracy of 83.8%. The accuracy of using area ratio for distinguishing 0-II early gastric cancers was better than those of using DPS and EUS (P < 0.05). Conclusion: Quantitative analysis of microsurface structure can be performed to assess M/SM type 0-II gastric cancer and is expected to be effective for judging the invasion depth of gastric cancer.

The Necroptotic Process-Related Signature Predicts Immune Infiltration and Drug Sensitivity in Kidney Renal Papillary Cell Carcinoma.

BACKGROUND: It remains controversial whether the current subtypes of kidney renal papillary cell carcinoma (KIRP) can be used to predict the prognosis independently. OBJECTIVE: This observational study aimed to identify a risk signature based on necroptotic pro-cess-related genes (NPRGs) in KIRP. METHODS: In the training cohort, LASSO regression was applied to construct the risk signature from 158 NPRGs, followed by the analysis of Overall Survival (OS) using the Kaplan-Meier method. The signature accuracy was evaluated by the Receiver Operating Characteristic (ROC) curve, which was further validated by the test cohort. Wilcoxon test was used to compare the expressions of immune-related genes, neoantigen genes, and immune infiltration between differ-ent risk groups, while the correlation test was performed between NPRGs expressions and drug sensitivity. Gene set enrichment analysis was used to investigate the NPRGs' signature's biologi-cal functions. RESULTS: We finally screened out 4-NPRGs (BIRC3, CAMK2B, PYGM, and TRADD) for con-structing the risk signature with the area under the ROC curve (AUC) reaching about 0.8. The risk score could be used as an independent OS predictor. Consistent with the enriched signaling, the NPRGs signature was found to be closely associated with neoantigen, immune cell infiltration, and immune-related functions. Based on NPRGs expressions, we also predicted multiple drugs potentially sensitive or resistant to treatment. CONCLUSION: The novel 4-NPRGs risk signature can predict the prognosis, immune infiltration, and therapeutic sensitivity of KIRP.

Therapeutic vulnerabilities in triple negative breast cancer: Stem-like traits explored within molecular classification.

Triple Negative Breast Cancer (TNBC) is the most aggressive type of breast cancer (BC). Despite advances in the clinical management of TNBC, recurrence-related mortality remains a challenge. The stem-like phenotype of TNBC plays a significant role in the persistence of minimal disease residue after therapy. Individuals exhibiting stem-like characteristics are particularly prone to inducing malignant relapse accompanied by strong resistance. Therefore, stem-like traits have been broadly proposed as therapeutic vulnerabilities to treat TNBC and reduce recurrence. However, heterogeneity within TNBC often generally restricts the stability of the therapeutic efficacy. To understand the heterogeneity and manage TNBC more precisely, multiple TNBC subtyping categories have been reported, providing the basis for profile-according therapeutic regimens. To provide more insight into targeting stem-like traits to ablate TNBC and reduce recurrence in the context of heterogeneity, this paper reviewed the molecular subtyping of TNBC, identified the consensus subtypes with distinct stem-like phenotypes, characterized the stemness hierarchy of TNBC, outlined the biological models for stem-like TNBC subtypes, summarized the therapeutic vulnerabilities in stem-like traits of the subtypes, and proposed potential therapeutic regimens targeting stem-like characteristics to improve TNBC prognosis.

Gut microbial features may influence antiviral IgG levels after vaccination against viral respiratory infectious diseases: the evidence from two-sample bidirectional mendelian randomization.

BACKGROUND: Vaccination is effective in preventing viral respiratory infectious diseases through protective antibodies and the gut microbiome has been proven to regulate human immunity. This study explores the causal correlations between gut microbial features and serum-specific antiviral immunoglobulin G (IgG) levels. METHODS: We conduct a two-sample bidirectional Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary data to explore the causal relationships between 412 gut microbial features and four antiviral IgG (for influenza A, measles, rubella, and mumps) levels. To make the results more reliable, we used four robust methods and performed comprehensive sensitivity analyses. RESULTS: The MR analyses revealed 26, 13, 20, and 18 causal associations of the gut microbial features influencing four IgG levels separately. ​Interestingly, ten microbial features, like genus Collinsella, species Bifidobacterium longum, and the biosynthesis of L-alanine have shown the capacity to regulate multiple IgG levels with consistent direction (rise or fall). The ​reverse MR analysis suggested several potential causal associations of IgG levels affecting microbial features. CONCLUSIONS: The human immune response against viral respiratory infectious diseases could be modulated by changing the abundance of gut microbes, which provided new approaches for the intervention of viral respiratory infections.