Selenomethionine Inhibited HADV-Induced Apoptosis Mediated by ROS through the JAK-STAT3 Signaling Pathway.

Adenovirus (HAdV) can cause severe respiratory infections in children and immunocompromised patients. There is a lack of specific therapeutic drugs for HAdV infection, and the study of anti-adenoviral drugs has far-reaching clinical implications. Elemental selenium can play a specific role as an antioxidant in the human immune cycle by non-specifically binding to the amino acid methionine in body proteins. Methods: The antiviral mechanism of selenomethionine was explored by measuring cell membrane status, intracellular DNA status, cytokine secretion, mitochondrial membrane potential, and ROS production. Conclusions: Selenomethionine improved the regulation of ROS-mediated apoptosis by modulating the expression of Jak1/2, STAT3, and BCL-XL, which led to the inhibition of apoptosis. It is anticipated that selenomethionine will offer a new anti-adenoviral therapeutic alternative.

Gender-Specific Trajectories of Non-Suicidal Self-Injury among Adolescents: Predictive Roles of Distal and Proximal Risk Factors.

Non-suicidal self-injury (NSSI) is considered a strong risk factor for suicide. Although NSSI is prevalent among adolescents and varies by gender, few studies have examined the gender-specific trajectory of NSSI and its predictors. This study examined the trajectory of NSSI among Chinese adolescent boys and girls separately, and the roles of distal (i.e., childhood maltreatment and its specific subtypes) and proximal risk factors (i.e., emotional dysregulation, peer victimization) on their trajectories. A total of 3290 Chinese adolescents (Mage = 13.08; SD = 0.84; 57.6% boys) participated in assessments at three time points. Latent class growth models identified three trajectories for boys: Low stable (92.5%), moderate increasing (5.0%) and high decreasing (2.5%). Four trajectories were identified for girls: Low stable (87.9%), moderate increasing (7.6%), high decreasing (3.0%) and high stable (1.5%). Multinomial logistic regression analyses revealed that both emotional dysregulation and emotional abuse predicted the trajectories of moderate increasing, high decreasing and high stable for girls, as well as predicted moderate increasing and high decreasing trajectories for boys. Peer victimization served as a significant risk factor predicting the moderate increasing and high decreasing trajectories only for girls, while overall childhood maltreatment was a remarkable predictor for the moderate increasing and high decreasing trajectories of boys. The findings highlighted the importance of gender differences in understanding the progression of NSSI and the key predictors, informing effective strategies for prevention and intervention.

18F-Labeled dihydropyridines via Hantzsch reaction for positron emission tomography of P-glycoprotein dysfunction.

Despite the availability of various 11C-labeled positron emission tomography (PET) tracers for assessing P-glycoprotein (P-gp) function, there are still limitations related to complex metabolism, high lipophilicity, and low baseline uptake. This study aimed to address these issues by exploring a series of customized dihydropyridines (DHPs) with enhanced stability and reduced lipophilicity as alternative PET tracers for P-gp dysfunction. Compared with verapamil and the rest DHPs, dimethyl 4-(4-fluorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (1) exhibited superior cellular uptake differences between the human gastric cancer cell line SGC7901 and its drug-resistant counterpart. [18F]1 is successfully synthesized using a novel "hot-Hantzsch" approach in 22.1 ± 0.1 % radiochemical yields. MicroPET/CT imaging demonstrated that the uptake of [18F]1 in the brains of P-gp blocked mice increased by > 3 times compared to the control group. Additionally, [18F]1 displayed favorable lipophilicity (log D = 2.3) and excellent clearance characteristics, making it a promising tracer candidate with low background noise and high contrast.

Application of Hip Pericapsular Nerve Block Combined With Spinal Anesthesia in the Treatment of Elderly Patients With Femoral Intertrochanteric Fracture.

OBJECTIVE: To investigate the effect of pericapsular nerve group (PENG) block combined with spinal anesthesia in the treatment of elderly patients with intertrochanteric fractures through "rapid diagnosis and treatment channel" PFNA internal fixation. METHODS: 52 elderly patients were randomly divided into the observation group (26 patients, PENG block combined with spinal anesthesia) and the control group (26 patients, spinal anesthesia alone). The general health, mean arterial pressure (MAP), and heart rate (HR) of both groups were compared at various stages: immediately before the administration of pain analgesia, during the positioning of spinal epidural anesthesia, at the beginning and end of the surgery, and 2 hours after surgery. Additionally, VAS scores at rest and during passive straight leg elevation by 15° were evaluated at 12 hours, 24 hours, 48 hours, 72 hours, and 7 days after surgery. RESULTS: The MAP and HR in the observation group under spinal anesthesia in the lateral position were lower than those in the control group (P < 0.05). Additionally, the VAS scores of the observation group during positioning and at 12 hours and 24 hours after surgery were lower than those in the control group under spinal epidural anesthesia (both P < 0.05). CONCLUSION: The application of ultrasound-guided PENG block combined with lumbar anesthesia can reduce pain when in lateral position, stabilize perioperative vital signs, and result in high satisfaction.

Determining Whether an Individual is 18 Years or Older Based on the Third Molar Root Pulp Visibility in East China.

OBJECTIVES: To investigate the age-related changes of the mandibular third molar root pulp visibility in individuals in East China, and to explore the feasibility of applying this method to determine whether an individual is 18 years or older. METHODS: A total of 1 280 oral panoramic images were collected from the 15-30 years old East China population, and the mandibular third molar root pulp visibility in all oral panoramic images was evaluated using OLZE 0-3 four-stage method, and the age distribution of the samples at each stage was analyzed using descriptive statistics. RESULTS: Stages 0, 1, 2 and 3 first appeared in 16.88, 19.18, 21.91 and 25.44 years for males and in 17.47, 20.91, 22.01 and 26.01 years for females. In all samples, individuals at stages 1 to 3 were over 18 years old. CONCLUSIONS: It is feasible to determine whether an individual in East China is 18 years or older based on the mandibular third molar root pulp visibility on oral panoramic images.

Extracellular Matrix Remodeling Alleviates Memory Deficits in Alzheimer's Disease by Enhancing the Astrocytic Autophagy-Lysosome Pathway.

Extracellular matrix (ECM) remodeling is strongly linked to Alzheimer's disease (AD) risk; however, the underlying mechanisms are not fully understood. Here, it is found that the injection of chondroitinase ABC (ChABC), mimicking ECM remodeling, into the medial prefrontal cortex (mPFC) reversed short-term memory loss and reduced amyloid-beta (Aß) deposition in 5xFAD mice. ECM remodeling also reactivated astrocytes, reduced the levels of aggrecan in Aß plaques, and enhanced astrocyte recruitment to surrounding plaques. Importantly, ECM remodeling enhanced the autophagy-lysosome pathway in astrocytes, thereby mediating Aß clearance and alleviating AD pathology. ECM remodeling also promoted Aß plaque phagocytosis by astrocytes by activating the astrocytic phagocytosis receptor MERTK and promoting astrocytic vesicle circulation. The study identified a cellular mechanism in which ECM remodeling activates the astrocytic autophagy-lysosomal pathway and alleviates AD pathology. Targeting ECM remodeling may represent a potential therapeutic strategy for AD and serve as a reference for the treatment of this disease.

Adaptive neural fault-tolerant prescribed performance control of a rehabilitation exoskeleton for lower limb passive training.

This article studies the passive tracking problem of a wearable exoskeleton for lower limb rehabilitation therapy in the face of unmodeled dynamics, interactive friction, disturbance, prescribed performance constraints, and actuator faults. Adaptive neural networks and a smooth performance function are incorporated to establish a novel fault-tolerant tracking scheme, which can not only compensate for the nonlinear uncertainties and disturbance, but also handle the actuator fault with guaranteed tracking performance. A state feedback controller is presented by using the full state information and an output feedback controller is developed when the angular velocity is unavailable. The differential explosion issue of the backstepping technique is resolved by constructing a first-order filter and the unmeasurable velocity is estimated by a nonlinear observer. Semiglobal uniform boundedness stabilities of the exoskeleton system are proved via the Lyapunov direct method. The tracking performances of the designed control approaches are tested by comparative simulations.

Microbial metabolite butyrate modulates granzyme B in tolerogenic IL-10 producing Th1 cells to regulate intestinal inflammation.

CD4+ T cells play a critical role in regulating autoimmune diseases, and intestinal microbial metabolites control various immune responses. Granzyme B (GzmB)-producing CD4+ T cells have been recently reported to participate in the pathogenesis of autoimmune diseases. Here, we found that GzmbB-deficient CD4+ T cells induced more severe colitis in Rag1-/- mice than wild-type (WT) CD4+ T cells. Germ-free (GF) mice exhibited a lower expression of GzmB in intestinal CD4+ T cells compared to specific pathogen-free (SPF) mice. Intestinal microbial metabolite butyrate increased GzmB expression in CD4+ T cells, especially in IL-10-producing Th1 cells, through HDAC inhibition and GPR43, but not GPR41 and GPR109a. Butyrate-treated GzmB-deficient CD4+ T cells demonstrated more severe colitis compared to butyrate-treated WT CD4+ T cells in the T cell transfer model. Butyrate altered intestinal microbiota composition, but altered microbiota did not mediate butyrate induction of intestinal CD4+ T cell expression of GzmB in mice. Blimp1 was involved in the butyrate induction of GzmB in IL-10-producing Th1 cells. Glucose metabolism, including glycolysis and pyruvate oxidation, mediated butyrate induction of GzmB in Th1 cells. In addition, we found that IKZF3 and NR2F6 regulated GzmB expression induced by butyrate. Together, our studies underscored the critical role of GzmB in mediating gut bacterial metabolite butyrate regulation of T cell tolerance at the mucosal surface.

Temporal turnover of viral biodiversity and functional potential in intertidal wetlands.

As the central members of the microbiome networks, viruses regulate the composition of microbial communities and drive the nutrient cycles of ecosystems by lysing host cells. Therefore, uncovering the dynamic patterns and the underlying ecological mechanisms mediating the tiniest viral communities across space and through time in natural ecosystems is of crucial importance for better understanding the complex microbial world. Here, the temporal dynamics of intertidal viral communities were investigated via a time-series sampling effort. A total of 1911 viral operational taxonomic units were recovered from 36 bimonthly collected shotgun metagenomes. Functionally important auxiliary metabolic genes involved in carbohydrate, sulfur, and phosphorus metabolism were detected, some of which (e.g., cysH gene) were stably present within viral genomes over time. Over the sampling period, strong and comparable temporal turnovers were observed for intertidal viromes and their host microbes. Winter was determined as the pivotal point for the shifts in viral diversity patterns. Notably, the viral micro-diversity covaried with the macro-diversity, following similar temporal patterns. The relative abundances of viral taxa also covaried with their host prokaryotes. Meanwhile, the virus-host relationships at the whole community level were relatively stable. Further statistical analyses demonstrated that the dynamic patterns of viral communities were highly deterministic, for which temperature was the major driver. This study provided valuable mechanistic insights into the temporal turnover of viral communities in complex ecosystems such as intertidal wetlands.

Encapsulation of Lactobacillus plantarum in W1/O/W2 double emulsions stabilized with the high-intensity ultrasound-treated pea protein and pectin.

This study focuses on developing a water-in-oil-in-water (W1/O/W2) double emulsion system using high-intensity ultrasound (HIU)-treated pea protein isolate (HIU-PPI) and pectin to encapsulate Lactobacillus plantarum (L. plantarum). The effects of ultrasound treatment on pea protein isolate (PPI) characteristics such as solubility, particle size, emulsification, surface hydrophobicity, and surface free sulfhydryl group were examined, determining optimal HIU processing conditions was 400 W for 10 min. The developed W1/O/W2 double emulsion system based on HIU-PPI demonstrated effective encapsulation and protection of L. plantarum, especially at the HIU-PPI concentration of 4 %, achieving an encapsulation efficiency of 52.65 %. Incorporating both HIU-PPI and pectin as emulsifiers increased the particle size and significantly enhanced the emulsion's viscosity. The highest bacterial encapsulation efficiency of the emulsion, 59.94 %, was attained at a HIU to pectin concentration ratio of 3:1. These emulsions effectively encapsulate and protect L. plantarum, with the concentration of HIU-PPI being a critical factor in enhancing probiotic survival under simulated gastrointestinal digestion. However, the concurrent utilization of pectin and HIU-PPI as emulsifiers did not provide a notable advantage compared to the exclusive use of HIU-PPI in enhancing probiotic viability during in vitro simulated digestion. This research offers valuable perspectives for the food industry on harnessing environmentally friendly, plant-based proteins as emulsifiers in probiotic delivery systems. It underscores the potential of HIU-modified pea protein and pectin in developing functional food products that promote the health benefits of probiotics.

An Attention-Based Hemispheric Relation Inference Network for Perinatal Brain Age Prediction.

Brain anatomical age is an effective feature to assess the status of the brain, such as atypical development and aging. Although some deep learning models have been developed for estimating infant brain age, the performance of these models was unsatisfactory because few of them considered the developmental characteristics of brain anatomy during the perinatal period-the most rapid and complex developmental stage across the lifespan. The present study proposed an attention-based hemispheric relation inference network (HRINet) that takes advantage of the nature of brain structural lateralization during early development. This model captures the inter-hemispheric relationship using a graph attention mechanism and transmits lateralization information as features to describe the interactive development between bilateral hemispheres. The HRINet was used to estimate the brain age of 531 preterm and full-term neonates from the Developing Human Connectome Project (dHCP) database based on two metrics (mean curvature and sulcal depth) characterizing the folding morphology of the cortex. Our results showed that the HRINet outperformed other benchmark models in fitting the perinatal brain age, with mean absolute error of 0.53 and determination coefficient of 0.89. We also verified the generalizability of the HRINet on an extra independent dataset collected from the Gansu Provincial Maternity and Child-care Hospital. Furthermore, by applying the best-performing model to an independent dataset consisting of 47 scans of preterm infants at term-equivalent age, we showed that the predicted age was significantly lower than the chronological age, suggesting a delayed development of premature brains. Our results demonstrate the effectiveness and generalizability of the HRINet in estimating infant brain age, providing promising clinical applications for assessing neonatal brain maturity.

6-benzylaminopurine highly sensitive analysis by SPR sensor with bifunctional magnetic molecularly imprinted polymers nanoparticles.

A highly sensitive Surface Plasmon Resonance (SPR) sensor coupled magnetic molecularly imprinted polymers nanoparticles (MMIPs NPs) was developed and validated for the determination of 6-benzylaminopurine (6-BA) in vegetables. MMIPs NPs were synthesized using methacrylic acid (MAA) and sodium p-styrene sulfonate (SSS) as functional monomers. The SPR exhibited a linear dependence on 6-BA concentration in the range 5-300 pg/mL with a low limit of detection (3.02 pg/mL) and limit of quantitation (10.08 pg/mL). The SPR signal of 6-BA-captured MAA/SSS-MMIPs NPs is higher than those of the structural analogues (6-KT and 2-IP: 1.72 and 2.12 times) and the non-structural analogues (2, 4-D and NAA: 2.31 and 2.57 times), indicating the SPR sensor has good selectivity for 6-BA. The recovery of the established method was between 93.8% and 108.6% with a coefficient of variation less than 9.2% in four vegetables. This SPR sensor shows great potential in detecting 6-BA in more vegetables.

Correlation between vitamin D levels and blood pressure in elderly hypertensive patients with osteoporosis.

Objectives: The association between vitamin D and blood pressure in elderly patients with hypertension complicated by osteoporosis remains unclear. The objective of this study is to explore whether vitamin D deficiency contributes to elevated blood pressure in elderly individuals with both hypertension and osteoporosis. Methods: This study represents a single-center retrospective observational investigation carried out at the Zhongshan Hospital Affiliated to Xiamen University. Ambulatory blood pressure, bone density, vitamin D levels, and additional laboratory parameters were collected upon admission. The association between vitamin D and ambulatory blood pressure outcomes was assessed using Spearman correlation tests and partial correlation analyses. The relationship between vitamin D and changes in blood pressure was analyzed through Generalized Additive Models, and threshold analysis was conducted to explore potential thresholds. Results: 139 patients with newly diagnosed osteoporosis were consecutively included (mean age 73 years, 84.9% female). There is a negative correlation between 25-(OH) D3 and 24 h mean systolic blood pressure (mSBP), diurnal mSBP, nocturnal mSBP, maximum SBP, respectively. The results of the generalized additive model analysis show that there is a nonlinear relationship between 25-(OH) D3 and 24 h mSBP, diurnal mSBP, nocturnal mSBP, respectively. After determining the critical point of 25-(OH) D3 as 42 nmol/L, a segmented linear regression model was used to calculate the effect size and 95% confidence interval on both sides of the critical point. When 25-(OH) D3 is ≤42 nmol/L, it significantly negatively correlates with 24 h, diurnal, and nocturnal mean SBP. Conversely, when 25-(OH) D3 exceeds 42 nmol/L, there is no statistically significant association with 24 h, diurnal, or nocturnal mSBP. Conclusion: There was a significant negative correlation between vitamin D levels and blood pressure levels in elderly patients with hypertension and osteoporosis.

[Retracted] ATP­binding cassette transporter A7 accelerates epithelial­to­mesenchymal transition in ovarian cancer cells by upregulating the transforming growth factor­ß signaling pathway.

[This retracts the article DOI: 10.3892/ol.2018.9366.].

Decreased Tiam1-mediated Rac1 activation is responsible for impaired directional persistence of chondrocyte migration in microtia.

The human auricle has a complex structure, and microtia is a congenital malformation characterized by decreased size and loss of elaborate structure in the affected ear with a high incidence. Our previous studies suggest that inadequate cell migration is the primary cytological basis for the pathogenesis of microtia, however, the underlying mechanism is unclear. Here, we further demonstrate that microtia chondrocytes show a decreased directional persistence during cell migration. Directional persistence can define a leading edge associated with oriented movement, and any mistakes would affect cell function and tissue morphology. By the screening of motility-related genes and subsequent confirmations, active Rac1 (Rac1-GTP) is identified to be critical for the impaired directional persistence of microtia chondrocytes migration. Moreover, Rho guanine nucleotide exchange factors (GEFs) and Rho GTPase-activating proteins (GAPs) are detected, and overexpression of Tiam1 significantly upregulates the level of Rac1-GTP and improves directional migration in microtia chondrocytes. Consistently, decreased expression patterns of Tiam1 and active Rac1 are found in microtia mouse models, Bmp5se/J and Prkralear-3J/GrsrJ. Collectively, our results provide new insights into microtia development and therapeutic strategies of tissue engineering for microtia patients.

Selenium bioaccumulation in Daphnia pulex via aqueous and dietary exposure.

Pit lakes are currently being investigated as a way to store and reclaim waste materials in the Alberta Oil Sands (AOS) region, Canada. Lake Miwasin (LM) is a pilot-scale pit lake consisting of treated fine tailings overlayed with oil sands process-affected water (OSPW) blended with fresh surface water. In October 2021, the surface water contained a mean concentration of 1.33 ± 0.04 µg/L dissolved selenium (Se), slightly above the Canadian Council of Ministers of Environment water quality guideline for long-term protection of aquatic life (1 µg Se/L). This study assessed the bioaccumulation of Se by the cladoceran Daphnia pulex under laboratory conditions through both aqueous and dietary exposure routes for comparison to field-collected specimens. In 12-day semi-static tests, lab-cultured D.pulex were exposed to water, and algae grown in media spiked with selenate. Results showed that Se bioaccumulation by lab-cultured D. pulex increased in all exposure treatments from days 5 to 12, with maximum Se concentrations of 3.08-3.47 µg/g dry weight (dw) observed within the exposure range tested. Interestingly, lower Se bioaccumulation concentrations (1.26-1.58 µg/g dw) were observed in the highest dissolved Se and dietary Se treatments, suggesting potential internal regulatory mechanisms. In addition, native D. pulex (LM) collected from Lake Miwasin and cultured in-house were exposed in 8-day semi-static tests to Lake Miwasin surface water and algae cultured in Lake Miwasin surface water. Selenium bioaccumulation in native D. pulex (LM) ranged from 2.00 to 2.04 µg/g dw at day 8 and was not significantly different (p > 0.05) compared to Se concentrations in D. pulex collected from Lake Miwasin (2.15 ± 0.28 µg/g) in summer 2022.

Exercise blood pressure, cardiorespiratory fitness, fatness and cardiovascular risk in children and adolescents.

Cardiovascular disease remains the leading cause of mortality on a global scale. Individuals who possess risk factors for cardiovascular disease, such as high blood pressure (BP) and obesity, face an elevated risk of experiencing organ-specific pathophysiological changes. This damage includes pathophysiological changes in the heart and peripheral vascular systems, such as ventricular hypertrophy, arterial stiffening, and vascular narrowing and stenosis. Consequently, these damages are associated with an increased risk of developing severe cardiovascular outcomes including stroke, myocardial infarction, heart failure, and coronary heart disease. Among all the risk factors associated with cardiovascular disease, high blood pressure emerges as the most prominent. However, conventional resting BP measurement methods such as auscultatory or oscillometric methods may fail to identify many individuals with asymptomatic high BP. Recently, exercise BP has emerged as a valuable diagnostic tool for identifying real (high) blood pressure levels and assessing underlying cardiovascular risk, in addition to resting BP measurements in adults. Furthermore, numerous established factors, such as low cardiorespiratory fitness and high body fatness, have been confirmed to contribute to exercise BP and the associated cardiovascular risk. Modifying these factors may help reduce high exercise BP and, consequently, alleviate the burden of cardiovascular disease. A significant body of evidence has demonstrated cardiovascular disease in later life have their origins in early life. Children and adolescents with these cardiovascular risk factors also possess a greater propensity to develop cardiovascular diseases later in life. Nevertheless, the majority of previous studies on the clinical utility of exercise BP have been conducted in middle-to-older aged populations, often with pre-existing clinical conditions. Therefore, there is a need to investigate further of the factors influencing exercise BP in adolescence and its association with cardiovascular risk in early life. Our previously published work showed that exercise BP is a potential useful method to detect adolescents with increased cardiovascular risk. Children and adolescents with cardiovascular risk factors are more likely to develop cardiovascular diseases later in life. However, previous studies on the clinical utility of exercise BP have largely focused on middle-to-older aged populations with pre-existing clinical conditions. Therefore, there is a need to investigate further the factors influencing exercise BP in adolescence and its association with future cardiovascular risk. Our previous studies, which focused on exercise BP measured at submaximal intensity, have shown that exercise BP is a potentially useful method for identifying adolescents at increased cardiovascular risk. Our previous findings suggest that improving cardio-respiratory fitness and reducing body fatness may help to reduce the risk of developing cardiovascular disease and improve overall cardiovascular health. These findings have important implications for the development of effective prevention and early detection strategies, which can contribute to improved public health outcomes.

Bone-metastatic lung adenocarcinoma cells bearing CD74-ROS1 fusion interact with macrophages to promote their dissemination.

Approximately 40% of patients with lung adenocarcinoma (LUAD) often develop bone metastases during the course of their disease. However, scarcely any in vivo model of LUAD bone metastasis has been established, leading to a poor understanding of the mechanisms underlying LUAD bone metastasis. Here, we established a multiorgan metastasis model via the left ventricular injection of luciferase-labeled LUAD cells into nude mice and then screened out lung metastasis (LuM) and bone metastasis (BoM) cell subpopulations. BoM cells exhibited greater stemness and epithelial-mesenchymal transition (EMT) plasticity than LuM cells and initially colonized the bone and subsequently disseminated to distant organs after being reinjected into mice. Moreover, a CD74-ROS1 fusion mutation (C6; R34) was detected in BoM cells but not in LuM cells. Mechanistically, BoM cells bearing the CD74-ROS1 fusion highly secrete the C-C motif chemokine ligand 5 (CCL5) protein by activating STAT3 signaling, recruiting macrophages in tumor microenvironment and strongly inducing M2 polarization of macrophages. BoM cell-activated macrophages produce a high level of TGF-ß1, thereby facilitating EMT and invasion of LUAD cells via TGF-ß/SMAD2/3 signaling. Targeting the CD74-ROS1/CCL5 axis with Crizotinib (a ROS1 inhibitor) and Maraviroc (a CCL5 receptor inhibitor) in vivo strongly impeded bone metastasis and secondary metastasis of BoM cells. Our findings reveal the critical role of the CD74-ROS1/STAT3/CCL5 axis in the interaction between LUAD bone metastasis cells and macrophages for controlling LUAD cell dissemination, highlighting the significance of the bone microenvironment in LUAD bone metastasis and multiorgan secondary metastasis, and suggesting that targeting CD74-ROS1 and CCL5 is a promising therapeutic strategy for LUAD bone metastasis.

Metabolic pathway-based subtyping reveals distinct microenvironmental states associated with diffuse large B-cell lymphoma outcomes.

Diffuse large B-cell lymphoma (DLBCL) is a biologically and clinically heterogeneous disease that requires personalized clinical treatment. Assigning patients to different risk categories and cytogenetic abnormality and genetic mutation groups has been widely applied for prognostic stratification of DLBCL. Increasing evidence has demonstrated that dysregulated metabolic processes contribute to the initiation and progression of DLBCL. Metabolic competition within the tumor microenvironment is also known to influence immune cell metabolism. However, metabolism- and immune-related stratification has not been established. Here, 1660 genes involved in 84 metabolic pathways were selected and tested to establish metabolic clusters (MECs) of DLBCL. MECs established based on independent lymphoma datasets distinguished different survival outcomes. The CIBERSORT algorithm and EcoTyper were applied to quantify the relative abundance of immune cell types and identify variation in cell states for 13 lineages comprising the tumor micro environment among different MECs, respectively. Functional characterization showed that MECs were an indicator of the immune microenvironment and correlated with distinctive mutational characteristics and oncogenic signaling pathways. The novel immune-related MECs exhibited promising clinical prognostic value and potential for informing DLBCL treatment decisions.

Function and mechanism of action of the TRPV1 channel in the development of triple-negative breast cancer.

Transient receptor potential channel subfamily vanilloid 1 (TRPV1) is a member of the transient receptor potential family of nonselective cationic transmembrane channel proteins that are involved in the regulation of calcium homeostasis. It is expressed in various tumor types and has been implicated in the regulation of cancer growth, metastasis, apoptosis, and cancer-related pain. TRPV1 is highly expressed in triple-negative breast cancer (TNBC), and both its agonists and antagonists may exert anti-cancer effects. In this review, we provide an overview of the effect of TRPV1 on TNBC development and its influence on immunotherapy in an attempt to facilitate the development of future treatment strategies.