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Radioresistance is a principal culprit for the failure of radiotherapy in hepatocellular carcinoma (HCC). Insights on the regulation genes of radioresistance and underlying mechanisms in HCC are awaiting for profound investigation. In this study, the suppressor of cytokine signaling 2 (SOCS2) were screened out by RNA-seq and bioinformatics analyses as a potential prognosis predictor of HCC radiotherapy and then were determined to promote radiosensitivity in HCC both in vivo or in vitro. Meanwhile, the measurements of ferroptosis negative regulatory proteins of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), intracellular lipid peroxidation and Fe2+ concentration suggested that a high level of ferroptosis contributed to the radiosensitization of HCC. Moreover, SOCS2 and SLC7A11 were expressed oppositely in HCC clinical tissues and tumour xenografts with different radiosensitivities. Mechanistically, the N-terminal domain of SLC7A11 was specifically recognized by the SH2-structural domain of SOCS2. While the L162 and C166 of SOCS2-BOX region could bind elongin B/C compound to co-form a SOCS2/elongin B/C complex to recruit ubiquitin molecules. Herein, SOCS2 served as a bridge to transfer the attached ubiquitin to SLC7A11 and promoted K48-linked polyubiquitination degradation of SLC7A11, which ultimately led to the onset of ferroptosis and radiosensitization of HCC. In conclusion, it was demonstrated for the first time that high-expressed SOCS2 was one of the biomarkers predicting radiosensitivity of HCC by advancing the ubiquitination degradation of SLC7A11 and promoting ferroptosis, which indicates that targeting SOCS2 may enhance the efficiency of HCC radiotherapy and improve the prognosis of patients.

Radiotherapy is one of the conventional methods for the clinical treatment of breast cancer. However, radioresistance has an adverse effect on the prognosis of breast cancer patients after radiotherapy. In this study, using bioinformatic analysis of GSE59732 and GSE59733 datasets in the Gene Expression Omnibus (GEO) database together with the prognosis database of breast cancer patients after radiotherapy, the GDF15 gene was screened out to be related to the poor prognosis of breast cancer after radiotherapy. Compared with radiosensitive parental breast cancer cells, breast cancer cells with acquired radioresistance exhibited a high level of GDF15 expression and enhanced epithelial-to-mesenchymal transition (EMT) properties of migration and invasion, as well as obvious stem-like traits, including the increases of mammosphere formation ability, the proportion of stem cells (CD44+ CD24− cells), and the expressions of stem cell-related markers (SOX2, NANOG). Moreover, knockdown of GDF15 sensitized the radioresistance cells to irradiation and significantly inhibited their EMT and stem-like traits, indicating that GDF15 promoted the radioresistance of breast cancer by enhancing the properties of EMT and stemness. Conclusively, GDF15 may be applicable as a novel prognosis-related biomarker and a potential therapeutic target for breast cancer radiotherapy.

Lung cancer has been recognized as the leading cause of cancer-related death worldwide. Despite the improvements of treatment, the distant metastasis and recurrence of lung cancer caused by therapy resistance is the biggest challenge in clinical management. Extracellular vesicles named exosomes play crucial roles in intercellular communication as signaling mediators and are involved in tumor development. In this study, we isolated exosomes from irradiated lung cancer cells and co-cultured the exosomes with other lung cancer cells. It was found that cellular growth and motility of recipient cells were facilitated. High-throughput LC–MS/MS assay of exosomal proteins and Gene Ontology enrichment analyses indicated that the metabolic enzymes ALDOA and ALDH3A1 had potential contribution in exosome-enhanced motility of recipient cells, and clinical survival analysis demonstrated the close correlations between ALDOA or ALDH3A1 expression and poor prognosis of lung cancer patients. After co-culturing with exosomes derived from irradiated cancer cells, the expressions of these metabolic enzymes were elevated and the glycolytic activity was promoted in recipient cancer cells. In conclusion, our data suggested that exosomes from irradiated lung cancer cells regulated the motility of recipient cells by accelerating glycolytic process, where exosomal ALDOA and ALDH3A1 proteins were important signaling factors.

Glioblastoma multiforme (GBM) remains a therapeutic challenge due to its aggressive nature and recurrence. This study establishes a radioresistant GBM cell model through repeated irradiation and observes a cellular senescence-like phenotype in these cells. Comprehensive genomic and transcriptomic analyses identify IFI16 as a central regulator of this phenotype and contributes to radioresistance. IFI16 activates HMOX1 transcription thereby attenuating ferroptosis by reducing lipid peroxidation, ROS production, and intracellular Fe 2+ content following irradiation. Furthermore, IFI16 interacts with the transcription factors JUND and SP1 through its pyrin domain, robustly facilitating HMOX1 expression, further inhibiting ferroptosis and enhancing radioresistance in GBM. Notably, glyburide, a sulfonylurea compound, effectively disrupts IFI16 function and enhances ferroptosis and radiosensitivity. By targeting the pyrin domain of IFI16, glyburide emerges as a potential therapeutic agent against GBM radioresistance. These findings underscore the central role of IFI16 in GBM radioresistance and offer promising avenues to improve GBM treatment. Radiotherapy is an important part of glioblastoma (GBM) treatment, but patient outcomes are often limited by resistance. Here, the authors identify a role for IFI16 in the promotion of a cellular senescence-like phenotype, inhibiting ferroptosis and driving radioresistance which can be overcome with Glyburide in preclinical GBM models.

Background Interstitial lung diseases (ILDs) can be induced and even exacerbated by radiotherapy in thoracic cancer patients. The roles of immune responses underlying the development of these severe lung injuries are still obscure and need to be investigated. Methods A severe lung damage murine model was established by delivering 16 Gy X-rays to the chest of mice that had been pre-treated with bleomycin (BLM) and thus hold ILDs. Bioinformatic analyses were performed on the GEO datasets of radiation-induced lung injury (RILI) and BLM-induced pulmonary fibrosis (BIPF), and RNA-sequencing data of the severely damaged lung tissues. The screened differentially expressed genes (DEGs) were verified in lung epithelial cell lines by qRT-PCR assay. The injured lung tissue pathology was analyzed with H&E and Masson’s staining, and immunohistochemistry staining. The macrophage chemotaxis and activity promoted by the stressed epithelial cells were determined by using a cell co-culture system. The expressions of p21 in MLE-12 and Beas-2B cells were detected by qRT-PCR, western blot, and immunofluorescence. The concentration of CCL7 in cell supernatant was measured by ELISA assay. In some experiments, Beas-2B cells were transfected with p21 -siRNA or CCL7 -siRNA before irradiation and/or BLM treatment. Results After the treatment of irradiation and/or BLM, the inflammatory and immune responses, chemokine-mediated signaling pathways were steadily activated in the severely injured lung, and p21 was screened out by the bioinformatic analysis and further verified to be upregulated in both mouse and human lung epithelial cell lines. The expression of P21 was positively correlated with macrophage infiltration in the injured lung tissues. Co-culturing with stressed Beas-2B cells or its conditioned medium containing CCL7 protein, U937 macrophages were actively polarized to M1-phase and their migration ability was obviously increased along with the damage degree of Beas-2B cells. Furthermore, knockdown p21 reduced CCL7 expression in Beas-2B cells and then decreased the chemotaxis of co-cultured macrophages. Conclusions P21 promoted CCL7 release from the severely injured lung epithelial cell lines and contributed to the macrophage chemotaxis in vitro, which provides new insights for better understanding the inflammatory responses in lung injury.

Forest rodents are important mediators of plant seed dispersal and their seed caching tactics are influenced by a variety of environmental factors; however, the role of terrain slope remains uninvestigated. We examined how the dispersal of Castanea mollissima seeds by an assemblage of scatter‐hoarding rodents in the Qinling Mountains, China, was affected by slope direction and gradient in relation to seed fate. In this study, the topographic factor, which has been frequently overlooked in previous ecological studies, was investigated. It was revealed that the sloping terrain could affect the dispersal behavior of rodents toward plant seeds and ultimately influence the direction of plant dispersal. This finding brings new insights to ecological research. Overall, rodents were 1.55 more likely to transport seed downhill than uphill, and downhill mean translocation distance was 1.41 times greater than uphill, suggesting an overarching tendency for energy conservation. When comparing steep (> 35°) with shallow (< 35°) slopes, this gradient effect was strongest on gentle slopes, with other factors likely exerting a greater influence on steeper terrain. We discuss these findings both from the perspective of rodent optimal foraging in ‘landscapes of fear’ and heterogeneous ‘energy landscapes’, as well as in the context of the counteractive pressure for trees to achieve an uphill elevational shift in response to global warming. In the Qinling Mountains, China, the impact of terrain slope on the dispersal of Castanea mollissima seeds by forest rodents was studied. It was found that rodents were more likely to transport seeds downhill and over a greater distance, with the gradient effect being strongest on gentle slopes. This study reveals the influence of the often‐overlooked topographic factor on rodent seed dispersal behavior and plant dispersal direction, bringing new insights to ecological research.

There is growing evidence to suggest that radiotherapy can paradoxically promote tumor invasion and metastatic processes, however, the underlying molecular mechanisms remain obscure. In this study, we found that exposure to X rays promoted cell invasion by triggering the epithelial mesenchymal transition (EMT) in two hepatocellular carcinoma (HCC) cell lines, HepG2 and PLC/PRF/5. This was made evident by a reduced expression of E-cadherin and enhanced expressions of N-cadherin, Vimentin and Snail. Moreover, exposure to radiation stimulated the signaling of hydrogen sulfide (H2S), a newly found gas transmitter, by upregulating the expressions of H2S-producing proteins of cysthionine-γ-lyase (CSE), cystathionine-β-synthase (CBS). Inhibition of CSE by siRNA or inhibitor not only increased the radiosensitivity but also strongly suppressed radiation-enhanced invasive properties of HCC cells. Interestingly, we found that H2S/CSE inhibition attenuated radiation-enhanced EMT, and the above effect was an end result of blockage of the radiation-activated pathway of p38 mitogen-activated protein kinase (p38MAPK). Collectively, our findings indicate that radiation could promote HCC cell invasion through EMT mediated by endogenous H2S/CSE signaling via the p38MAPK pathway.

The yak manure based biochar was produced at different temperatures of 300, 500 and 700 ℃ held for 3 h, which was characterized by BET surface area, X-ray diffraction, Fourier transform infrared spectroscopy, pH measurement, analysis, scanning electron microscopy and ultimate analysis. The resultant biochar had characteristics of high surface area, high pH, porous structure and rich nutrients such as N, P, Ca, Mg, and K, inferring that the yak manure-derived biochar could be used as a soil conditioner. The field experiment was conducted to study the effect of yak manure derived biochar amendment on the yield and biological traits of highland barley, revealing that adding biochar to soil could increase the yield and growth of highland barley in short-term although the long-term benefits remain to be quantified. The present results can be useful to fill the knowledge gap regarding the potential of yak manure derived biochar to soil improvement.

Background China is experiencing an aging population, leading to a significant demand for “Internet + nursing services” tailored for elderly individuals. However, there are many risk problems in the process of nurse service, which hinder the development of the service, and a scale is needed to assess the risk problems faced by nurses in “Internet + nursing services” for the elderly. Objective The purpose of this study is to develop an assessment scale for risk factors and outcomes related to nurses’ involvement in the “Internet + Nursing Service” for the elderly and to assess its reliability and validity. Methods Based on literature analysis, focus group, the Delphi method, and a presurvey, we designed an initial scale. The initial scale comprised two sections: risk factors and risk outcomes for nurses. In January and February of 2023, nurses engaged in “Internet + nursing services” for the elderly in Shanxi Province were chosen through a convenience sampling technique for a questionnaire survey. Subsequently, item analysis and exploratory factor analysis were employed to refine and develop a test version of the scale further. A follow-up questionnaire survey was carried out in March and April 2023 using a similar approach. The reliability and validity of the scale were assessed through confirmatory factor analysis, culminating in the formation of the final scale. Results The initial survey yielded 244 valid responses. The cumulative variance contributions of the two segments from the exploratory factor analysis were 84.584% and 90.089%, respectively. A subsequent survey garnered 220 valid responses. The confirmatory factor analysis results indicated: χ2/df = 2.086, comparative fit index (CFI) = 0.918, normative fit index (NLI) = 0.855, root mean square of residuals (RMR) = 0.045, and root mean square of error of approximation (RMSEA) = 0.070. These results demonstrate good structural, convergent, and discriminant validity. The content validity index at the item level (I-CVI) ranged between 0.875 and 1.000, while the content validity index at the scale level (S-CVI/Ave) was 0.941. Cronbach’s alpha coefficient for the entire scale stood at 0.970. Moreover, the scale exhibited a split-half reliability of 0.876 and a retest reliability of 0.980 ( p  < 0.01). Conclusion The risk factors and risk outcomes associated with nurses involved in “Internet + nursing services” for elderly individuals, as developed in this study, demonstrate strong reliability and validity. They are well suited to the Chinese national context.

Osteoclasts play a key role in the development of cancer-associated osteolytic lesions. The number and activity of osteoclasts are often enhanced by tumors. However, the origin of osteoclasts is unknown. Myeloid-derived suppressor cells (MDSCs) are one of the pre-metastatic niche components that are induced to expand by tumor cells. Here we show that the MDSCs can differentiate into mature and functional osteoclasts in vitro and in vivo. Inoculation of 5TGM1-GFP myeloma cells into C57BL6/KaLwRij mice led to a significant expansion of MDSCs in blood, spleen, and bone marrow over time. When grown in osteoclastogenic media in vitro, MDSCs from tumor-challenged mice displayed 14 times greater potential to differentiate into mature and functional osteoclasts than those from non-tumor controls. Importantly, MDSCs from tumor-challenged LacZ transgenic mice differentiated into LacZ+osteoclasts in vivo. Furthermore, a significant increase in tumor burden and bone loss accompanied by increased number of osteoclasts was observed in mice co-inoculated with tumor-challenged MDSCs and 5TGM1 cells compared to the control animals received 5TGM1 cells alone. Finally, treatment of MDSCs from myeloma-challenged mice with Zoledronic acid (ZA), a potent inhibitor of bone resorption, inhibited the number of osteoclasts formed in MDSC cultures and the expansion of MDSCs and bone lesions in mice. Collectively, these data provide in vitro and in vivo evidence that tumor-induced MDSCs exacerbate cancer-associated bone destruction by directly serving as osteoclast precursors.