Induced Pluripotent Stem Cells Facilitate the Development and Evaluation of Cancer Vaccines.

Cancer vaccines are an approach to elicit amplified antigen-specific immune responses. Induced pluripotent stem cells (iPSCs) have potential utility for the development of universal vaccines due to their intrinsic antigenic epitopes. Concurrently, iPSCs can undergo pluripotent differentiation and are thus a stable source of both antigen-presenting cells for producing immune cell-based vaccines and tumor organoids for facilitating the exploration and adaptive assessment of tumor vaccines. This review describes the specific contributions of iPSCs to vaccine development, summarizes their diverse developmental trajectories, and discusses the obstacles to their application along with potential solutions.

[Thinking on the application of reinforcing and reducing techniques of moxibustion in the staged differentiation and treatment of prostate cancer].

The effect of reinforcing and reducing techniques of moxibustion depends on types of moxibustion, operation methods and characteristics of acupoints. According to the ups and downs of pathogenic factors and healthy qi during the occurrence and development of prostate cancer, three stages are divided, namely, the stage of initial accumulation of cancer toxicity, the stage of the deficiency of healthy qi and toxin retention, and the stage of yang deficiency and cold stagnation. In the stage of initial accumulation of cancer toxicity, zangfu function is impaired and the dampness, heat and stasis toxin are accumulated in the body; due to which, the reducing technique of moxibustion should be dominant and the healthy qi be supported in combination. In treatment, the wheat-grain sized cone moxibustion, suppurative moxibustion and garlic-isolated moxibustion are applicable. The reducing purpose of moxibustion is obtained by delivering an appropriate increased number of moxa cones, large dosage and strong stimulation at acupoints. In the stage of the deficiency of healthy qi and toxin retention, qi movement is weakened and cancer toxin consumes yin; the reinforcing healthy qi and removing pathogenic factors should be operated simultaneously. In treatment, mild moxibustion and suppurative moxibustion can be used. The reduced number of moxa cones, moderate dosage of moxibustion and mild stimulation at acupoints should be considered to gently adjust the conditions of deficiency and excess. In the stage of yang deficiency and cold stagnation, spleen and kidney yang is deficient, and the meridians are blocked by cold and damp pathogens. In treatment, the reinforcing technique of moxibustion should be used specially and eliminating pathogenic factors be combined. Monkshood cake-insulated moxibustion, salt-insulated moxibustion and wheat-grain sized cone moxibustion can be adopted. The less number of moxa cones, small dosage and appropriately increased frequency of treatment should be considered to produce the gentle and sustained stimulation at acupoints so as to excite the healthy qi and promote the transformation of qi and blood.

Simultaneous In Vivo Imaging of Neutrophil Elastase and Oxidative Stress in Atherosclerotic Plaques Using a Unimolecular Photoacoustic Probe.

Atherosclerosis is a primary global health concern due to its high morbidity and mortality. This disease is characterized by a complex interplay of chronic inflammation, oxidative stress, and proteolytic enzymes. Traditional imaging techniques struggle to capture the dynamic biochemical processes within atherosclerotic plaques. Herein, we have developed a novel unimolecular photoacoustic probe (UMAPP) that combines specific recognition sites for neutrophil elastase (NE) and the redox pair O2•‒/GSH into a cohesive molecular platform, allowing in vivo monitoring of oxidative stress and activated neutrophils within plaques. UMAPP features a boron-dipyrromethene (BODIPY) core linked to a hydrophilic NE-cleavable tetrapeptide, and dual oxidative stress-responsive catechol moieties, enabling NE-mediated modulation of photoinduced electron transfer, affecting the photoacoustic intensity at 685 nm (PA685), while oxidation and reduction of the catechol groups by O2•‒ and GSH lead to reversible, ratiometric changes in the photoacoustic spectrum. Preliminary applications of UMAPP have successfully differentiated between atherosclerotic and healthy mice, assessed the impact of pneumonia on plaque composition, and validated the probe's efficacy in drug-treatment studies, detecting molecular changes prior to observable histopathological alterations. UMAPP's integrated molecular imaging approach holds significant promise for advancing the diagnosis and management of atherosclerosis by enabling earlier and more precise detection of vulnerable plaques.

Mechanism of Autocatalytic Reduction of CO2 over MgCO3 to High Value-Added Chemicals: A DFT & AIMD Study.

Calcination of MgCO3 is an important industrial reaction, but it causes significant and unfavorable CO2 production. Calcination in a reducing green hydrogen atmosphere can substantially reduce CO2 release and produce high value-added products such as CO or hydrocarbons, but the mechanism is still unclear. Here, the in situ transformation process of MgCO3 interacting with hydrogen and the specific formation mechanism of the high value-added products are thoroughly investigated based on reaction thermodynamic, ab initio molecular dynamics (AIMD) simulations, and density functional theory (DFT) calculations. The reaction thermodynamic parameters of MgCO3 coupled with hydrogen to produce CO or methane are calculated, revealing that increasing and decreasing the thermal reductive decomposition temperature favors the production of CO and methane, respectively. Kinetically, the energy barriers of each possible production pathway for the dominant products CO and methane are further calculated in conjunction with the AIMD simulation results of the transformation process. The results suggest that CO is produced via the MgO catalytic-carboxyl pathway (CO2*→ COOH*trans→ COOH*cis→ CO*→ CO), which is autocatalyzed by MgO derived from the thermal reductive decomposition of MgCO3. For the mechanism of methane formation, it prefers to be produced by the stepwise interaction of carbonates in the MgCO3 laminates with hydrogen adsorbed on their surfaces (direct conversion pathway: sur-O-CO → sur-O-HCO → sur-O-HCOH → sur-O-HC → sur-O-CH2 → sur-O-CH3 → sur-O + CH4*).

Awareness and preparedness level of medical workers for radiation and nuclear emergency response.

Radiological science and nuclear technology have made great strides in the twenty-first century, with wide-ranging applications in various fields, including energy, medicine, and industry. However, those developments have been accompanied by the inherent risks of exposure to nuclear radiation, which is a source of concern owing to its potentially adverse effects on human health and safety and which is of particular relevance to medical personnel who may be exposed to certain cancers associated with low-dose radiation in their working environment. While medical radiation workers have seen a decrease in their occupational exposure since the 1950s thanks to improved measures for radiation protection, a concerning lack of understanding and awareness persists among medical professionals regarding these potential hazards and the required safety precautions. This issue is further compounded by insufficient capabilities in emergency response. This highlights the urgent need to strengthen radiation safety education and training to ensure the well-being of medical staff who play a critical role in radiological and nuclear emergencies. This review examines the health hazards of nuclear radiation to healthcare workers and the awareness and willingness and education of healthcare workers on radiation protection, calling for improved training programs and emergency response skills to mitigate the risks of radiation exposure in the occupational environment, providing a catalyst for future enhancement of radiation safety protocols and fostering of a culture of safety in the medical community.

Overcoming cancer drug-resistance calls for novel strategies targeting abnormal alternative splicing.

Abnormal gene alternative splicing (AS) events are strongly associated with cancer progression. Here, we summarize AS events that contribute to the development of drug resistance and classify them into three categories: alternative cis-splicing (ACS), alternative trans-splicing (ATS), and alternative back-splicing (ABS). The regulatory mechanisms underlying AS processes through cis-acting regulatory elements and trans-acting factors are comprehensively described, and the distinct functions of spliced variants, including linear spliced variants derived from ACS, chimeric spliced variants arising from ATS, and circRNAs generated through ABS, are discussed. The identification of dysregulated spliced variants, which contribute to drug resistance and hinder effective cancer treatment, suggests that abnormal AS processes may together serve as a precise regulatory mechanism enabling drug-resistant cancer cell survival or, alternatively, represent an evolutionary pathway for cancer cells to adapt to changes in the external environment. Moreover, this review summarizes recent advancements in treatment approaches targeting AS-associated drug resistance, focusing on cis-acting regulatory elements, trans-acting factors, and specific spliced variants. Collectively, gaining an in-depth understanding of the mechanisms underlying aberrant alternative splicing events and developing strategies to target this process hold great promise for overcoming cancer drug resistance.

Broadening anticancer spectrum by preprocessing and treatment of T- lymphocytes expressed FcγRI and monoclonal antibodies for refractory cancers.

Background: Chimeric antigen receptor T (CAR-T) cell therapies have achieved remarkable success in the treatment of hematological tumors. However, given the distinct features of solid tumors, particularly heterogeneity, metabolic aggressiveness, and fewer immune cells in tumor microenvironment (TME), the practical utility of CAR-T cells for solid tumors remains as a challenging issue. Meanwhile, although anti-PD-1 monoclonal antibody (mAb) has shown clinical efficacy, most mAbs also show limited clinical benefits for solid tumors due mainly to the issues associated with the lack of immune cells in TME. Thus, the infiltration of targeted immunological active cells into TME could generate synergistic efficacy for mAbs. Methods: We present a combinational strategy for solid tumor treatment, which combines armored-T cells to express Fc-gamma receptor I (FcγRI) fragment on the surfaces for targeting various tumors with therapeutically useful mAbs. Choosing CD20 and HER-2 as the targets, we characterized the in vitro and in vivo efficacy and latent mechanism of the combination drug by using flow cytometry, ELISA and other methods. Results: The combination and preprocessing of armored T-cells with corresponding antibody of Rituximab and Pertuzumab exerted profound anti-tumor effects, which is demonstrated to be mediated by synergistically produced antibody-dependent cellular cytotoxicity (ADCC) effects. Meanwhile, mAb was able to carry armored-T cell by preprocessing for the infiltration to TME in cell derived xenograft (CDX) model. Conclusions: This combination strategy showed a significant increase of safety profiles from the reduction of antibody doses. More importantly, the present strategy could be a versatile tool for a broad spectrum of cancer treatment, with a simple pairing of engineered T cells and a conventional antibody.

The impact of Library Size and Scale of Testing on Virtual Screening.

Virtual libraries for ligand discovery have recently increased 10,000-fold, and this is thought to have improved hit rates and potencies from library docking. This idea has not, however, been experimentally tested in direct comparisons of larger-vs-smaller libraries. Meanwhile, though libraries have exploded, the scale of experimental testing has little changed, with often only dozens of high-ranked molecules investigated, making interpretation of hit rates and affinities uncertain. Accordingly, we docked a 1.7 billion molecule virtual library against the model enzyme AmpC ß-lactamase, testing 1,521 new molecules and comparing the results to the same screen with a library of 99 million molecules, where only 44 molecules were tested. Encouragingly, the larger screen outperformed the smaller one: hit rates improved by two-fold, more new scaffolds were discovered, and potency improved. Overall, 50-fold more inhibitors were found, supporting the idea that there are many more compounds to be discovered than are being tested. With so many compounds evaluated, we could ask how the results vary with number tested, sampling smaller sets at random from the 1521. Hit rates and affinities were highly variable when we only sampled dozens of molecules, and it was only when we included several hundred molecules that results converged. As docking scores improved, so too did the likelihood of a molecule binding; hit rates improved steadily with docking score, as did affinities. This also appeared true on reanalysis of large-scale results against the σ2 and dopamine D4 receptors. It may be that as the scale of both the virtual libraries and their testing grows, not only are better ligands found but so too does our ability to rank them.

Bitopic Ligands Support the Presence of a Metastable Binding Site at the ß2 Adrenergic Receptor.

Metastable binding sites (MBS) have been observed in a multitude of molecular dynamics simulations and can be considered low affinity allosteric binding sites (ABS) that function as stepping stones as the ligand moves toward the orthosteric binding site (OBS). Herein, we show that MBS can be utilized as ABS in ligand design, resulting in ligands with improved binding kinetics. Four homobivalent bitopic ligands (1-4) were designed by molecular docking of (S)-alprenolol ((S)-ALP) in the cocrystal structure of the ß2 adrenergic receptor (ß2AR) bound to the antagonist ALP. Ligand 4 displayed a potency and affinity similar to (S)-ALP, but with a >4-fold increase in residence time. The proposed binding mode was confirmed by X-ray crystallography of ligand 4 in complex with the ß2AR. This ligand design principle can find applications beyond the ß2AR and G protein-coupled receptors (GPCRs) as a general approach for improving the pharmacological profile of orthosteric ligands by targeting the OBS and an MBS simultaneously.

METTL1-mediated tRNA m7G methylation and translational dysfunction restricts breast cancer tumorigenesis by fueling cell cycle blockade.

BACKGROUND: RNA modifications of transfer RNAs (tRNAs) are critical for tRNA function. Growing evidence has revealed that tRNA modifications are related to various disease processes, including malignant tumors. However, the biological functions of methyltransferase-like 1 (METTL1)-regulated m7G tRNA modifications in breast cancer (BC) remain largely obscure. METHODS: The biological role of METTL1 in BC progression were examined by cellular loss- and gain-of-function tests and xenograft models both in vitro and in vivo. To investigate the change of m7G tRNA modification and mRNA translation efficiency in BC, m7G-methylated tRNA immunoprecipitation sequencing (m7G tRNA MeRIP-seq), Ribosome profiling sequencing (Ribo-seq), and polysome-associated mRNA sequencing were performed. Rescue assays were conducted to decipher the underlying molecular mechanisms. RESULTS: The tRNA m7G methyltransferase complex components METTL1 and WD repeat domain 4 (WDR4) were down-regulated in BC tissues at both the mRNA and protein levels. Functionally, METTL1 inhibited BC cell proliferation, and cell cycle progression, relying on its enzymatic activity. Mechanistically, METTL1 increased m7G levels of 19 tRNAs to modulate the translation of growth arrest and DNA damage 45 alpha (GADD45A) and retinoblastoma protein 1 (RB1) in a codon-dependent manner associated with m7G. Furthermore, in vivo experiments showed that overexpression of METTL1 enhanced the anti-tumor effectiveness of abemaciclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor. CONCLUSION: Our study uncovered the crucial tumor-suppressive role of METTL1-mediated tRNA m7G modification in BC by promoting the translation of GADD45A and RB1 mRNAs, selectively blocking the G2/M phase of the cell cycle. These findings also provided a promising strategy for improving the therapeutic benefits of CDK4/6 inhibitors in the treatment of BC patients.

The relationship between coffee-related factors and cortical and hippocampal structure: a triangulation of evidence approach and Mendelian randomization research.

Objective: Existing studies have reported sustained changes in the cortical structure of rats due to coffee-related factors, which are speculated to occur in the human body. However, there is a lack of research on this topic. Additionally, previous observational studies have found the impact of diseases on cortical structure and the potential therapeutic effects of coffee on these diseases. Our aim was to study the causal effects of coffee-related factors on the human brain using SNPs (single nucleotide polymorphisms). We will connect these discovered causal effects to the impact of diseases on the brain. Through triangulating evidence, we will reveal the potential active areas of coffee in preventing diseases. Methods: We utilized GWAS data from multiple cohorts and their databases, selecting instrumental variables for genetic prediction of coffee intake and plasma levels of caffeine and its direct metabolites. We applied these instrumental variables to individual data on cortical thickness and surface area, as well as hippocampal volume, from the ENIGMA and CHARGE consortium for Mendelian randomization analysis (MR). Triangular evidence was obtained by integrating existing evidence through a specified retrieval strategy, calculating the overlap between coffee's effects on brain regions and disease-related brain regions to identify potential regions of action. Results: The MR analysis yielded 93 positive results for 9 exposures, among which theobromine, a metabolite in the caffeine pathway, was found to be associated with increased hippocampal volume. For cortical structure, theobromine in the caffeine pathway was associated with a decrease in total surface area, while theobromine and caffeine in the pathway were associated with an increase in total thickness. The overlap rate of triangular evidence showed no difference in both overall and subgroup analyses, indicating a high overlap between the effects of coffee on brain regions and disease. Conclusions: From predicted outcomes from causal effects, coffee intake-related factors may have lasting effects on cortical structure. Additionally, theobromine and theophylline have the greatest impact on certain brain gyri, rather than caffeine. Triangulation evidence indicates that disease and coffee intake-related factors act on the same cortical regions, suggesting the presence of potential shared or antagonistic pathways.

Effects of artificial light with different spectral compositions on refractive development and matrix metalloproteinase 2 and tissue inhibitor of metalloproteinases 2 expression in the sclerae of juvenile guinea pigs.

Artificial light can affect eyeball development and increase myopia rate. Matrix metalloproteinase 2 (MMP-2) degrades the extracellular matrix, and induces its remodeling, while tissue inhibitor of matrix MMP-2 (TIMP-2) inhibits active MMP-2. The present study aimed to look into how refractive development and the expression of MMP-2 and TIMP-2 in the guinea pigs' remodeled sclerae are affected by artificial light with varying spectral compositions. Three weeks old guinea pigs were randomly assigned to groups exposed to five different types of light: natural light, LED light with a low color temperature, three full spectrum artificial lights, i.e. E light (continuous spectrum in the range of ~390-780 nm), G light (a blue peak at 450 nm and a small valley 480 nm) and F light (continuous spectrum and wavelength of 400 nm below filtered). A-scan ultrasonography was used to measure the axial lengths of their eyes, every two weeks throughout the experiment. Following twelve weeks of exposure to light, the sclerae were observed by optical and transmission electron microscopy. Immunohistochemistry, Western blot and RT-qPCR were used to detect the MMP-2 and TIMP-2 protein and mRNA expression levels in the sclerae. After four, six, eight, ten, and twelve weeks of illumination, the guinea pigs in the LED and G light groups had axial lengths that were considerably longer than the animals in the natural light group while the guinea pigs in the E and F light groups had considerably shorter axial lengths than those in the LED group. Following twelve weeks of exposure to light, the expression of the scleral MMP-2 protein and mRNA were, from low to high, N group, E group, F group, G group, LED group; however, the expression of the scleral TIMP-2 protein and mRNA were, from high to low, N group, E group, F group, G group, LED group. The comparison between groups was statistically significant (p<0.01). Continuous, peaks-free or valleys-free artificial light with full-spectrum preserves remodeling of scleral extracellular matrix in guinea pigs by downregulating MMP-2 and upregulating TIMP-2, controlling eye axis elongation, and inhibiting the onset and progression of myopia.

Efficacy, safety, and survival of neoadjuvant immunotherapy plus chemotherapy in locally advanced esophageal squamous cell carcinoma: A real-world retrospective study.

BACKGROUND: This study aims to analyze the efficacy and safety of neoadjuvant programmed cell death-1 (PD-1) blockade plus chemotherapy in real-world applications. Additionally, we report survival outcomes with a median follow-up of 40.1 months. METHODS: From January 2018 to October 2022, we retrospectively recruited patients with esophageal squamous cell carcinoma (ESCC) who underwent surgery after receiving PD-1 blockade (immunotherapy) plus chemotherapy at Jiangsu Cancer Hospital. RESULTS: A total of 132 eligible ESCC patients were included, and R0 resection was achieved in 131 cases (99.2 %). A complete pathological response rate (ypT0N0) was observed in 32 patients (24.2 %), and the objective response rate was 59.1 %. The most common grade 3-4 treatment-related adverse events (TRAEs) were leukopenia (18.2 %) and neutropenia (15.9 %). Three cases (2.3 %) of grade 3 immune-related AEs were observed, including increased ALT (0.8 %), rash (0.8 %), and encephalitis (0.8 %). The 1-year disease-free survival (DFS) and overall survival (OS) rates were 68.2 % and 89.4 %, respectively, and the 2-year DFS and OS rates were 55.1 % and 78.6 %, respectively. The pathological responses of 103 cases (94.5 % of 109) of the index lymph node (ILN) were categorized as the worst regression subgroup. In these cases, using the pathological response of the ILN to indicate the status of other lymph nodes would not result to a missed therapeutic lymph node dissection. CONCLUSIONS: Neoadjuvant immunotherapy plus chemotherapy is safe and effective for ESCC, with observable survival benefits. The pathological response of the ILN after neoadjuvant therapy may have important value in guiding therapeutic lymph node dissection.

Donafenib inhibits PARP1 expression and induces DNA damage, in combination with PARP1 inhibitors promotes apoptosis in liver cancer cells.

Liver cancer is a prevalent malignant tumor globally. The newly approved first-line drug, donafenib, is a novel oral small molecule multi-tyrosine kinase inhibitor that has significant antitumor effects on liver cancer. This study aims to investigate the antitumor effects of donafenib on liver cancer and to explore its potential mechanisms. Donafenib significantly inhibited the viability of Huh-7 and HCCLM3 cells, inhibited malignant cell proliferation, and promoted cell apoptosis, as demonstrated by CCK-8, EdU, and Calcein/PI (propidium iodide) staining experiments. The results of DNA damage detection experiments and western blot analysis indicate that donafenib caused considerable DNA damage in liver cancer cells. The analysis of poly (ADP-ribose) polymerase 1 (PARP1) in liver cancer patients using online bioinformatics data websites such as TIMER2.0, GEPIA, UALCAN, cBioPortal, Kaplan-Meier Plotter, and HPA revealed a high expression of PARP1, which is associated with poor prognosis. Molecular docking and western blot analysis demonstrated that donafenib can directly target and downregulate the protein expression of PARP1, a DNA damage repair protein, thereby promoting DNA damage in liver cancer cells. Western blot and immunofluorescence detection showed that the group treated with donafenib combined with PARP1 inhibitor had significantly higher expression of γ-H2AX and 8-OHdG compared to the groups treated with donafenib or PARP1 inhibitors alone, the combined treatment suppresses the expression of the antiapoptotic protein Bcl2 and enhances the protein expression level of the proapoptotic protein Bcl-2-associated X protein (BAX). These data suggest that the combination of donafenib and a PARP1 inhibitor results in more significant DNA damage in cells and promotes cell apoptosis. Thus, the combination of donafenib and PARP1 inhibitors has the potential to be a treatment option for liver cancer.

On characteristics of K0 value and shear behaviour of loess using triaxial test.

Compared with conventional soils, such as sand and clay, little knowledge on the coefficient of lateral earth pressure at-rest (K0) has been established for loess in the current literature. This paper presents an experimental investigation on K0 of compacted loess and the associated impacts on undrained shear behaviour. By adopting a K0 consolidation module in the triaxial system, the K0 stress state for loess samples was achieved through a unique feedback control. During the K0 consolidation, the deviatoric stress (q) increases progressively with the premise that the volumetric strain (εv) of the sample equals to the axial strain (εa). The results show that the K0 value of compacted loess is in a range of 0.28 to 0.53, which is dependent on the packing density and the clay content. A distinguishable decrease of K0 was found in the course of K0 consolidation for the loosely compacted loess sample, whereas a similar trend was not observed in the dense sample. In the undrained shear stage, all loess specimens revealed contractive response in the stress path (q-p') diagram, which can be quantified by a modified collapsibility index (Ic). The index is consistently higher for the K0 consolidated loess samples than for the isotropic ones. The experimental results indicate a strong impact of the initial stress state on the shear behaviour of compacted loess.

Stepwise Protonation of Three-Dimensional Covalent Organic Frameworks for Enhancing Hydrogen Peroxide Photosynthesis.

Three-dimensional covalent organic frameworks (3D COFs), recognized for their tailorable structures and accessible active sites, offer a promising platform for developing advanced photocatalysts. However, the difficulty in the synthesis and functionalization of 3D COFs hinders their further development. In this study, we present a series of 3D-bcu-COFs with 8 connected porphyrin units linked by linear linkers through imine bonds as a versatile platform for photocatalyst design. The photoresponse of 3D-bcu-COFs was initially modulated by functionalizing linear linkers with benzo-thiadiazole or benzo-selenadiazole groups. Furthermore, taking advantage of the well-exposed porphyrin and imine sites in 3D-bcu-COFs, their photocatalytic activity was optimized by stepwise protonation of imine bonds and porphyrin centers. The dual protonated COF with benzo-selenadiazole groups exhibited enhanced charge separation, leading to an increased photocatalytic H2O2 production under visible light. This enhancement demonstrates the combined benefits of linker functionalization and stepwise protonation on photocatalytic efficiency.

The influence of environmental factors on the job burnout of physical education teachers in tertiary education.

This study takes environmental factors and individual factors as variables to explore the deep internal mechanism of the impact of a comprehensive environment on higher education physical education (PE) teachers' job burnout. Little research has been done on how environmental factors affect the internal mechanism of college and university PE teachers' job burnout through individual factors (e.g., professional pressure and teaching efficacy). In this study, the participants were 231 PE teachers from seven comprehensive universities, and four questionnaires were administered to measure the participants' job burnout, perceived overall environment, teaching efficacy, and occupational stress. Research has found that environmental factors have a significant negative impact on occupational stress, and occupational stress plays an important mediating role between environment and occupational burnout. Research has shown that differences in external environments lead to varying levels of personal stress among college physical education teachers, which in turn affects their level of occupational burnout. The study concludes that a good social, working, and living environment helps to reduce the work pressure on PE teachers, improves their sense of teaching efficacy, and inhibits the occurrence of teachers' job burnout.

Macrophage colony-stimulating factor and its role in the tumor microenvironment: novel therapeutic avenues and mechanistic insights.

The tumor microenvironment is a complex ecosystem where various cellular and molecular interactions shape the course of cancer progression. Macrophage colony-stimulating factor (M-CSF) plays a pivotal role in this context. This study delves into the biological properties and functions of M-CSF in regulating tumor-associated macrophages (TAMs) and its role in modulating host immune responses. Through the specific binding to its receptor colony-stimulating factor 1 receptor (CSF-1R), M-CSF orchestrates a cascade of downstream signaling pathways to modulate macrophage activation, polarization, and proliferation. Furthermore, M-CSF extends its influence to other immune cell populations, including dendritic cells. Notably, the heightened expression of M-CSF within the tumor microenvironment is often associated with dismal patient prognoses. Therefore, a comprehensive investigation into the roles of M-CSF in tumor growth advances our comprehension of tumor development mechanisms and unveils promising novel strategies and approaches for cancer treatment.

Widely Targeted Metabolomics Analysis Reveals Metabolites Important for Antioxidant Properties and Quality Traits in Different Fruit Parts of Aurantii Fructus Immatures.

In traditional Chinese medicine, Aurantii Fructus Immatures (AFIs) have been utilized for more than 2000 years. The proportions of different fruit parts are crucial for evaluating AFI quality in China. However, the basis for this statement's substance is unclear. Differences in quality are intimately correlated with a plant's metabolite composition. On the basis of a widely targeted metabolome, this study intended to investigate the metabolite composition and evaluate the antioxidant capacity of the peel and pulp of an AFI. Metabolites were identified and quantified by UHPLC-QqQ-MS. To assess their antioxidant ability, DPPH and ABTS assays were carried out. There were 1327 chemical compounds identified by UHPLC-QqQ-MS. After screening the differential metabolites using a multivariate statistical analysis, it was found that there were 695 significant differences in the metabolites between the peel and the pulp. Among them, it was discovered that the content of active ingredients in the peel group was higher than that in the pulp group. Furthermore, the aqueous extracts from the peel showed stronger antioxidant capacities than those from the pulp. The metabolites and antioxidant capacities were significantly different between the peel and the pulp. This study of different fruit parts might provide a guide for AFI quality assessments.