Magnetic nanoparticles and possible synergies with cold atmospheric plasma for cancer treatment.

The biomedical applications of magnetic nanoparticles (MNPs) have gained increasing attention due to their unique biological, chemical, and magnetic properties such as biocompatibility, chemical stability, and high magnetic susceptibility. However, several critical issues still remain that have significantly halted the clinical translation of these nanomaterials such as the relatively low therapeutic efficacy, hyperthermia resistance, and biosafety concerns. To identify innovative approaches possibly creating synergies with MNPs to resolve or mitigate these problems, we delineated the anti-cancer properties of MNPs and their existing onco-therapeutic portfolios, based on which we proposed cold atmospheric plasma (CAP) to be a possible synergizer of MNPs by enhancing free radical generation, reducing hyperthermia resistance, preventing MNP aggregation, and functioning as an innovative magnetic and light source for magnetothermal- and photo-therapies. Our insights on the possible facilitating role of CAP in translating MNPs for biomedical use may inspire fresh research directions that, once actualized, gain mutual benefits from both.

MDM2 inhibitors in cancer immunotherapy: Current status and perspective.

Murine double minute 2 (MDM2) plays an essential role in the cell cycle, apoptosis, DNA repair, and oncogene activation through p53-dependent and p53-independent signaling pathways. Several preclinical studies have shown that MDM2 is involved in tumor immune evasion. Therefore, MDM2-based regulation of tumor cell-intrinsic immunoregulation and the immune microenvironment has attracted increasing research attention. In recent years, immune checkpoint inhibitors targeting PD-1/PD-L1 have been widely used in the clinic. However, the effectiveness of a single agent is only approximately 20%-40%, which may be related to primary and secondary drug resistance caused by the dysregulation of oncoproteins. Here, we reviewed the role of MDM2 in regulating the immune microenvironment, tumor immune evasion, and hyperprogression during immunotherapy. In addition, we summarized preclinical and clinical findings on the use of MDM2 inhibitors in combination with immunotherapy in tumors with MDM2 overexpression or amplification. The results reveal that the inhibition of MDM2 could be a promising strategy for enhancing immunotherapy.

USP49 promotes adenocarcinoma of the esophagogastric junction malignant progression via activating SHCBP1-ß-catenin-GPX4 axis.

Adenocarcinoma of the esophagogastric junction (AEG) has received widespread attention because of its increasing incidence. However, the molecular mechanism underlying tumor progression remains unclear. Here, we report that the downregulation of Ubiquitin-specific peptidase 49 (USP49) promotes ferroptosis in OE33 and OE19 cells, thereby inhibiting cell proliferation in vitro and in vivo, whereas the overexpression of USP49 had the opposite effect. In addition, USP49 downregulation promoted AEG cell radiotherapy sensitivity. Moreover, overexpression of Glutathione PeroXidase 4 (GPX4) reversed the ferroptosis and proliferation inhibition induced by USP49 knockdown. Mechanistically, USP49 deubiquitinates and stabilizes Shc SH2-domain binding protein 1 (SHCBP1), subsequently facilitating the entry of ß-catenin into the nucleus to enhance GPX4 transcriptional expression. Finally, high USP49 expression was correlated with shorter overall survival in patients with AEG. In summary, our findings identify USP49 as a novel regulator of ferroptosis in AEG cells, indicating that USP49 may be a potential therapeutic target in AEG.

The potential of Burkholderia gladioli KRS027 in plant growth promotion and biocontrol against Verticillium dahliae revealed by dual transcriptome of pathogen and host.

Verticillium dahliae is a destructive, soil-borne pathogen that causes significant losses on numerous important dicots. Recently, beneficial microbes inhabiting the rhizosphere have been exploited and used to control plant diseases. In the present study, Burkholderia gladioli KRS027 demonstrated excellent inhibitory effects against Verticillium wilt in cotton seedlings. Plant growth and development was promoted by affecting the biosynthesis and signaling pathways of brassinosteroids (BRs), gibberellins (GAs), and auxins, consequently promoting stem elongation, shoot apical meristem, and root apical tissue division in cotton. Furthermore, based on the host transcriptional response to V. dahliae infection, it was found that KRS027 modulates the plants to maintain cell homeostasis and respond to other pathogen stress. Moreover, KRS027 induced disruption of V. dahliae cellular structures, as evidenced by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses. Based on the comparative transcriptomic analysis between KRS027 treated and control group of V. dahliae, KRS027 induced substantial alterations in the transcriptome, particularly affecting genes encoding secreted proteins, small cysteine-rich proteins (SCRPs), and protein kinases. In addition, KRS027 suppressed the growth of different clonal lineages of V. dahliae strains through metabolites, and volatile organic compounds (VOCs) released by KRS027 inhibited melanin biosynthesis and microsclerotia development. These findings provide valuable insights into an alternative biocontrol strategy for Verticillium wilt, demonstrating that the antagonistic bacterium KRS027 holds promise as a biocontrol agent for promoting plant growth and managing disease occurrence.

Glycosylation editing: an innovative therapeutic opportunity in precision oncology.

Cancer is still one of the most arduous challenges in the human society, even though humans have found many ways to try to conquer it. With our incremental understandings on the impact of sugar on human health, the clinical relevance of glycosylation has attracted our attention. The fact that altered glycosylation profiles reflect and define different health statuses provide novel opportunities for cancer diagnosis and therapeutics. By reviewing the mechanisms and critical enzymes involved in protein, lipid and glycosylation, as well as current use of glycosylation for cancer diagnosis and therapeutics, we identify the pivotal connection between glycosylation and cellular redox status and, correspondingly, propose the use of redox modulatory tools such as cold atmospheric plasma (CAP) in cancer control via glycosylation editing. This paper interrogates the clinical relevance of glycosylation on cancer and has the promise to provide new ideas for laboratory practice of cold atmospheric plasma (CAP) and precision oncology therapy.

Functional analysis of the mating type genes in Verticillium dahliae.

BACKGROUND: Populations of the plant pathogenic fungus Verticillium dahliae display a complex and rich genetic diversity, yet the existence of sexual reproduction in the fungus remains contested. As pivotal genes, MAT genes play a crucial role in regulating cell differentiation, morphological development, and mating of compatible cells. However, the functions of the two mating type genes in V. dahliae, VdMAT1-1-1, and VdMAT1-2-1, remain poorly understood. RESULTS: In this study, we confirmed that the MAT loci in V. dahliae are highly conserved, including both VdMAT1-1-1 and VdMAT1-2-1 which share high collinearity. The conserved core transcription factor encoded by the two MAT loci may facilitate the regulation of pheromone precursor and pheromone receptor genes by directly binding to their promoter regions. Additionally, peptide activity assays demonstrated that the signal peptide of the pheromone VdPpg1 possessed secretory activity, while VdPpg2, lacked a predicted signal peptide. Chemotactic growth assays revealed that V. dahliae senses and grows towards the pheromones FO-a and FO-α of Fusarium oxysporum, as well as towards VdPpg2 of V. dahliae, but not in response to VdPpg1. The findings herein also revealed that VdMAT1-1-1 and VdMAT1-2-1 regulate vegetative growth, carbon source utilization, and resistance to stressors in V. dahliae, while negatively regulating virulence. CONCLUSIONS: These findings underscore the potential roles of VdMAT1-1-1 and VdMAT1-2-1 in sexual reproduction and confirm their involvement in various asexual processes of V. dahliae, offering novel insights into the functions of mating type genes in this species.

Insights into the biocontrol and plant growth promotion functions of Bacillus altitudinis strain KRS010 against Verticillium dahliae.

BACKGROUND: Verticillium wilt, caused by the fungus Verticillium dahliae, is a soil-borne vascular fungal disease, which has caused great losses to cotton yield and quality worldwide. The strain KRS010 was isolated from the seed of Verticillium wilt-resistant Gossypium hirsutum cultivar "Zhongzhimian No. 2." RESULTS: The strain KRS010 has a broad-spectrum antifungal activity to various pathogenic fungi as Verticillium dahliae, Botrytis cinerea, Fusarium spp., Colletotrichum spp., and Magnaporthe oryzae, of which the inhibition rate of V. dahliae mycelial growth was 73.97% and 84.39% respectively through confrontation test and volatile organic compounds (VOCs) treatments. The strain was identified as Bacillus altitudinis by phylogenetic analysis based on complete genome sequences, and the strain physio-biochemical characteristics were detected, including growth-promoting ability and active enzymes. Moreover, the control efficiency of KRS010 against Verticillium wilt of cotton was 93.59%. After treatment with KRS010 culture, the biomass of V. dahliae was reduced. The biomass of V. dahliae in the control group (Vd991 alone) was 30.76-folds higher than that in the treatment group (KRS010+Vd991). From a molecular biological aspect, KRS010 could trigger plant immunity by inducing systemic resistance (ISR) activated by salicylic acid (SA) and jasmonic acid (JA) signaling pathways. Its extracellular metabolites and VOCs inhibited the melanin biosynthesis of V. dahliae. In addition, KRS010 had been characterized as the ability to promote plant growth. CONCLUSIONS: This study indicated that B. altitudinis KRS010 is a beneficial microbe with a potential for controlling Verticillium wilt of cotton, as well as promoting plant growth.

Transcriptome analysis of Gossypium hirsutum cultivar Zhongzhimian No.2 uncovers the gene regulatory networks involved in defense against Verticillium dahliae.

BACKGROUND: Cotton is globally important crop. Verticillium wilt (VW), caused by Verticillium dahliae, is the most destructive disease in cotton, reducing yield and fiber quality by over 50% of cotton acreage. Breeding resistant cotton cultivars has proven to be an efficient strategy for improving the resistance of cotton to V. dahliae. However, the lack of understanding of the genetic basis of VW resistance may hinder the progress in deploying elite cultivars with proven resistance. RESULTS: We planted the VW-resistant Gossypium hirsutum cultivar Zhongzhimian No.2 (ZZM2) in an artificial greenhouse and disease nursery. ZZM2 cotton was subsequently subjected to transcriptome sequencing after Vd991 inoculation (6, 12, 24, 48, and 72 h post-inoculation). Several differentially expressed genes (DEGs) were identified in response to V. dahliae infection, mainly involved in resistance processes, such as flavonoid and terpenoid quinone biosynthesis, plant hormone signaling, MAPK signaling, phenylpropanoid biosynthesis, and pyruvate metabolism. Compared to the susceptible cultivar Junmian No.1 (J1), oxidoreductase activity and reactive oxygen species (ROS) production were significantly increased in ZZM2. Furthermore, gene silencing of cytochrome c oxidase subunit 1 (COX1), which is involved in the oxidation-reduction process in ZZM2, compromised its resistance to V. dahliae, suggesting that COX1 contributes to VW resistance in ZZM2. CONCLUSIONS: Our data demonstrate that the G. hirsutum cultivar ZZM2 responds to V. dahliae inoculation through resistance-related processes, especially the oxidation-reduction process. This enhances our understanding of the mechanisms regulating the ZZM2 defense against VW.

Current status of controlled onco-therapies based on metal organic frameworks.

Despite consecutive efforts devoted to the establishment of innovative therapeutics for cancer control, cancer remains as a primary global public health concern. Achieving controlled release of anti-cancer agents may add great value to the field of oncology that requires the involvement of nanotechnologies. Metal organic frameworks (MOFs) hold great promise in this regard owing to their unique structural properties. MOFs can act as superior candidates for drug delivery given their porous structure and large loading area, and can be prepared into anti-cancer therapeutics by incorporating stimuli-sensitive components into the ligands or nodes of the framework. By combing through chemical and physical features of MOFs favorable for onco-therapeutic applications and current cancer treatment portfolios taking advantages of these characteristics, this review classified MOFs feasible for establishing controlled anti-cancer modalities into 6 categories, outlined the corresponding strategies currently available for each type of MOF, and identified understudied areas and future opportunities towards innovative MOF design for improved or expanded clinical anti-cancer applications.

Associations between preparedness, perceived stress, depression, and quality of life in family caregivers of patients with a temporary enterostomy.

PURPOSE: To investigate the preparedness, perceived stress, risk of depression, and quality of life of family caregivers of patients receiving a temporary enterostomy, to provide a reference for improving the long-term care and quality of life of patients receiving a temporary enterostomy. METHODS: We enrolled 181 family caregivers of patients in a hospital in China from 2021 to 2023. Responses to the General Information Questionnaire, the Chinese Caregiver Preparedness Scale, the Chinese Perceived Stress Scale, the Chinese bilingual version of the Patient Health Questionnaire-2, and the 12-item Short Form Survey were collected online. RESULTS: Pearson's correlation analysis revealed that family caregivers' risk of depression was negatively correlated with their preparedness, the physical component summary score, and the mental component summary score but was positively correlated with perceived stress. Multiple linear regression analysis identified factors influencing caregiver preparedness. CONCLUSIONS: These findings help healthcare personnel to identify high-risk individuals among family caregivers of patients receiving a temporary enterostomy. This provides a basis for formulating well-planned, dynamic health education programs that meet patients' needs for disease-related knowledge and care.

TMEM160 promotes tumor immune evasion and radiotherapy resistance via PD-L1 binding in colorectal cancer.

BACKGROUND: The effectiveness of anti-programmed cell death protein 1(PD-1)/programmed cell death 1 ligand 1(PD-L1) therapy in treating certain types of cancer is associated with the level of PD-L1. However, this relationship has not been observed in colorectal cancer (CRC), and the underlying regulatory mechanism of PD-L1 in CRC remains unclear. METHODS: Binding of TMEM160 to PD-L1 was determined by co-immunoprecipitation (Co-IP) and GST pull-down assay.The ubiquitination levels of PD-L1 were verified using the ubiquitination assay. Phenotypic experiments were conducted to assess the role of TMEM160 in CRC cells. Animal models were employed to investigate how TMEM160 contributes to tumor growth.The expression and clinical significance of TMEM160 and PD-L1 in CRC tissues were evaluated by immunohistochemistry(IHC). RESULTS: In our study, we made a discovery that TMEM160 interacts with PD-L1 and plays a role in stabilizing its expression within a CRC model. Furthermore, we demonstrated that TMEM160 hinders the ubiquitination-dependent degradation of PD-L1 by competing with SPOP for binding to PD-L1 in CRC cells. Regarding functionality, the absence of TMEM160 significantly inhibited the proliferation, invasion, metastasis, clonogenicity, and radioresistance of CRC cells, while simultaneously enhancing the cytotoxic effect of CD8 + T cells on tumor cells. Conversely, the upregulation of TMEM160 substantially increased these capabilities. In severely immunodeficient mice, tumor growth derived from lentiviral vector shTMEM160 cells was lower compared with that derived from shNC control cells. Furthermore, the downregulation of TMEM160 significantly restricted tumor growth in immune-competent BALB/c mice. In clinical samples from patients with CRC, we observed a strong positive correlation between TMEM160 expression and PD-L1 expression, as well as a negative correlation with CD8A expression. Importantly, patients with high TMEM160 expression exhibited a worse prognosis compared with those with low or no TMEM160 expression. CONCLUSIONS: Our study reveals that TMEM160 inhibits the ubiquitination-dependent degradation of PD-L1 that is mediated by SPOP, thereby stabilizing PD-L1 expression to foster the malignant progress, radioresistance, and immune evasion of CRC cells. These findings suggest that TMEM160 holds potential as a target for the treatment of patients with CRC.

Insights into the role of the N6-methyladenosine reader IGF2BP3 in the progression of oral squamous cell carcinoma and its connection to cell-cycle control.

The genome of oral squamous cell carcinoma (OSCC) has been extensively characterized via bulk sequencing, revealing a multitude of genetic changes. The gene IGF2BP3, which encodes for the insulin-like growth factor 2 mRNA-binding protein 3, has been observed to be highly expressed in several types of cancer. This finding suggests that IGF2BP3 may play a significant role in the initiation and advancement of cancer. Nevertheless, the mechanisms by which IGF2BP3 contribute to OSCC are yet to be fully understood. In this study, we have observed that IGF2BP3 exhibits overexpression in OSCC. Based on our findings from bulk sequencing analysis, we have concluded that IGF2BP3 could potentially serve as a biomarker for predicting poor prognosis in OSCC. Moreover, it has been demonstrated that IGF2BP3 exhibits a significant association with the initiation and advancement of tumors both in vivo and in vitro. The evaluation of IGF2BP3 expression levels in relation to the cell cycle stage was conducted using single-cell RNA sequencing data. Tumor cells characterized by elevated IGF2BP3 expression demonstrated a higher percentage of cells in the G2/M transition phase. This study presents new findings indicating that the molecular target IGF2BP3 can serve as a prognostic indicator for tumors and has an impact on the development and progression of OSCC by influencing the regulation of the cell cycle.

Effects of Designed Herbal Formula on Growth Performance, Blood Indices, Organ Traits, and Cecum Microbiology in Broilers.

The objective of this study was to investigate the effect of the designed herbal formula (DHF) on growth performance, blood indices, organ traits, and cecum microbiology in broilers. A total of 96 male broilers of 1 d were selected and randomly assigned to two groups with six replicates of eight broilers each. The control (CON) and the basal diet containing 1.0% DHF (Astragali radix, Atractylodes macrocephala Koidz., Isatis tinctoria Linnaeus, and Citri reticulatae pericarpium, 2:1:1:2) were fed separately. The experiment was conducted for 35 days. The results showed that the DHF diet increased body weight and decreased the feed conversion ratio (FCR) (p < 0.05). At 21 days, the spleen, thymus, lymphocytes, and thrombocytes were increased (p < 0.05), and pancreas, duodenum, heterophils, and mean corpuscular hemoglobin (MCH) were decreased (p < 0.05). At 35 days, the heart, pancreas, white blood cell, heterophils, hemoglobin, MCH and mean corpuscular hemoglobin concentration (MCHC) were decreased, while lymphocytes and middle cells were increased (p < 0.05). The results of microbial diversity analysis showed that the DHF diet decreased the microbial diversity of the cecum. Firmicutes and Bacteroidetes were the dominant phyla, where the DHF diet increased the relative abundances of Bacteroides uniformis, Bacteroides vulgatus, and Faecalibacterium prausnitzii, and then decreased the relative abundance of Shigella sonnei. In conclusion, DHF played a positive role in improving the growth performance, immune performance, and relative abundance of Bacteroides uniformis, Bacteroides vulgatus, and Faecalibacterium prausnitzii in cecum microbiology in broilers, and has the potential to be used as a novel feed additive.

An effective electricity worker identification approach based on Yolov3-Arcface.

To address the issues of low efficiency and high complexity of detection models for electric power workers in distribution rooms, the electric power worker identification approach is proposed. The ArcFace loss function is used as the coordinate regression loss of the target box. According to the score, the template box with the highest score is selected for prediction, which speeds up the rate of convergence. Dimensional clustering is used to set template boxes for bounding box prediction. The experimental results show that the improved YOLOv3 is a high-performance and lightweight model. The electric power worker identification approach proposed in this paper has a high-speed recognition process, accurate recognition results. The effectiveness of the approach is verified with better detection performance and robustness.

Residual behavior of dinotefuran and its metabolites during Huangjiu fermentation and their effects on flavor.

Yellow rice wine (Huangjiu) is a traditional Chinese alcoholic beverage. However, there is a risk of pesticide residues in Huangjiu due to pesticide indiscriminate use. In this study, the residues of dinotefuran and its metabolites during Huangjiu fermentation and their effects on flavor substances were studied. The initial concentrations of dinotefuran ranged from 856.3 to 1874.9 µg/L, and its half-life was no more than 3.65 d. At 24 d of Huangjiu fermentation, the terminal residues of dinotefuran, 1-methyl-3-(tetrahydro-3-furylmethyl)urea (UF) and 1-methyl-3-(tetrahydro-3-furylmethyl)guanidine (DN) were 195.1-535.3 µg/L, 38.33-48.70 µg/L and 37.8-74.1 µg/L, respectively. Twenty potential degradation compounds were identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS), and their toxicity was evaluated. Finally, the effect of dinotefuran on physicochemical properties and total phenol content of Huangjiu were analyzed. The risk of rancidity was significantly increased and bitter amino acids were formed. These findings provide a guidance and the safe production of Huangjiu.

Characterization of the Endophytic Bacillus subtilis KRS015 Strain for Its Biocontrol Efficacy Against Verticillium dahliae.

Endophytes play important roles in promoting plant growth and controlling plant diseases. Verticillium wilt is a vascular wilt disease caused by Verticillium dahliae, a widely distributed soilborne pathogen that causes significant economic losses on cotton each year. In this study, an endophyte KRS015, isolated from the seed of the Verticillium wilt-resistant Gossypium hirsutum 'Zhongzhimian No. 2', was identified as Bacillus subtilis by morphological, phylogenetic, physiological, and biochemical analyses. The volatile organic compounds (VOCs) produced by KRS015 or its cell-free fermentation extract had significant antagonistic effects on various pathogenic fungi, including V. dahliae. KRS015 reduced Verticillium wilt index and colonization of V. dahliae in treated cotton seedlings significantly; the disease reduction rate was ∼62%. KRS015 also promoted plant growth, potentially mediated by the growth-related cotton genes GhACL5 and GhCPD-3. The cell-free fermentation extract of KRS015 triggered a hypersensitivity response, including reactive oxygen species (ROS) and expression of resistance-related plant genes. VOCs from KRS015 also inhibited germination of conidia and the mycelial growth of V. dahliae, and were mediated by growth and development-related genes such as VdHapX, VdMcm1, Vdpf, and Vel1. These results suggest that KRS015 is a potential agent for controlling Verticillium wilt and promoting growth of cotton.

Epidermal growth factor potentiates EGFR(Y992/1173)-mediated therapeutic response of triple negative breast cancer cells to cold atmospheric plasma-activated medium.

Cold atmospheric plasma (CAP) holds promise as a cancer-specific treatment that selectively kills various types of malignant cells. We used CAP-activated media (PAM) to utilize a range of the generated short- and long-lived reactive species. Specific antibodies, small molecule inhibitors and CRISPR/Cas9 gene-editing approaches showed an essential role for receptor tyrosine kinases, especially epidermal growth factor (EGF) receptor, in mediating triple negative breast cancer (TNBC) cell responses to PAM. EGF also dramatically enhanced the sensitivity and specificity of PAM against TNBC cells. Site-specific phospho-EGFR analysis, signal transduction inhibitors and reconstitution of EGFR-depleted cells with EGFR-mutants confirmed the role of phospho-tyrosines 992/1173 and phospholipase C gamma signaling in up-regulating levels of reactive oxygen species above the apoptotic threshold. EGF-triggered EGFR activation enhanced the sensitivity and selectivity of PAM effects on TNBC cells. The proposed approach based on the synergy of CAP and EGFR-targeted therapy may provide new opportunities to improve the clinical management of TNBC.

Applications of Innovation Technologies for Personalized Cancer Medicine: Stem Cells and Gene-Editing Tools.

Personalized medicine is a new approach toward safer and even cheaper treatments with minimal side effects and toxicity. Planning a therapy based on individual properties causes an effective result in a patient's treatment, especially in a complex disease such as cancer. The benefits of personalized medicine include not only early diagnosis with high accuracy but also a more appropriate and effective therapeutic approach based on the unique clinical, genetic, and epigenetic features and biomarker profiles of a specific patient's disease. In order to achieve personalized cancer therapy, understanding cancer biology plays an important role. One of the crucial applications of personalized medicine that has gained consideration more recently due to its capability in developing disease therapy is related to the field of stem cells. We review various applications of pluripotent, somatic, and cancer stem cells in personalized medicine, including targeted cancer therapy, cancer modeling, diagnostics, and drug screening. CRISPR-Cas gene-editing technology is then discussed as a state-of-the-art biotechnological advance with substantial impacts on medical and therapeutic applications. As part of this section, the role of CRISPR-Cas genome editing in recent cancer studies is reviewed as a further example of personalized medicine application.

Influence of urbanization on schistosomiasis infection risk in Anhui Province based on sixteen year's longitudinal surveillance data: a spatio-temporal modelling study.

BACKGROUND: Urbanization greatly affects the natural and social environment of human existence and may have a multifactoral impact on parasitic diseases. Schistosomiasis, a common parasitic disease transmitted by the snail Oncomelania hupensis, is mainly found in areas with population aggregations along rivers and lakes where snails live. Previous studies have suggested that factors related to urbanization may influence the infection risk of schistosomiasis, but this association remains unclear. This study aimed to analyse the effect of urbanization on schistosomiasis infection risk from a spatial and temporal perspective in the endemic areas along the Yangtze River Basin in China. METHODS: County-level schistosomiasis surveillance data and natural environmental factor data covering the whole Anhui Province were collected. The urbanization level was characterized based on night-time light data from the Defense Meteorological Satellite Program Operational Linescan System (DMSP-OLS) and the National Polar-Orbiting Partnership's Visible Infrared Imaging Radiometer Suite (NPP-VIIRS). The geographically and temporally weighted regression model (GTWR) was used to quantify the influence of urbanization on schistosomiasis infection risk with the other potential risk factors controlled. The regression coefficient of urbanization was tested for significance (α = 0.05), and the influence of urbanization on schistosomiasis infection risk was analysed over time and across space based on significant regression coefficients. Variables studied included climate, soil, vegetation, hydrology and topography. RESULTS: The mean regression coefficient for urbanization (0.167) is second only to the leached soil area (0.300), which shows that the urbanization is the most important influence factors for schistosomiasis infection risk besides leached soil area. The other important variables are distance to the nearest water source (0.165), mean minimum temperature (0.130), broadleaf forest area (0.105), amount of precipitation (0.073), surface temperature (0.066), soil bulk density (0.037) and grassland area (0.031). The influence of urbanization on schistosomiasis infection risk showed a decreasing trend year by year. During the study period, the significant coefficient of urbanization level increased from - 0.205 to - 0.131. CONCLUSIONS: The influence of urbanization on schistosomiasis infection has spatio-temporal heterogeneous. The urbanization does reduce the risk of schistosomiasis infection to some extend, but the strength of this influence decreases with increasing urbanization. Additionally, the effect of urbanization on schistosomiasis infection risk was greater than previous reported natural environmental factors. This study provides scientific basis for understanding the influence of urbanization on schistosomiasis, and also provides the feasible research methods for other similar studies to answer the issue about the impact of urbanization on disease risk.

IFNγ synergies with cold atmospheric plasma in triggering colorectal cancer cell ferroptosis via the IFNγ/IFNR2/APC/TCF4/GPX4 axis.

Colorectal cancer accounts for the second most common cancer-related lethality. Intestinal stem cells are responsible for enteric homeostasis maintenance that, once being transformed, become colorectal cancer stem cells. Arresting cancer stemness represents an innovative strategy for colorectal cancer management. Using intestinal stem cell organoids as the primary model, we screened common inflammatory cytokines to identify key players targeting cancer stemness. We also explored the downstream signaling that drives the functionalities of the identified cytokine through both experimental investigations and computational predictions. As the results, we identified IFNγ as the key cytokine capable of arresting intestinal stem cells via the IFNγ/IFNGR2/APC/TCF4/GPX4 axis, proposed its role in killing colorectal cancer stem cells via triggering GPX4-dependent ferroptosis, and demonstrated its synergistic anti-cancer effect with cold atmospheric plasma in killing colorectal cancer cells that is worthy to be experimentally validated.