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Introduction: Despite radiotherapy being one of the major treatments for triple-negative breast cancer (TNBC), new molecular targets for its treatment are still required due to radioresistance. CDK2 plays a critical role in TNBC. However, the mechanism by which CDK2 promotes TNBC radioresistance remains to be clearly elucidated. Objectives: We aimed to elucidate the relationship between CDK2 and TRIM32 and the regulation mechanism in TNBC. Methods: We performed immunohistochemical staining to detect nuclear TRIM32, CDK2 and STAT3 on TNBC tissues. Western blot assays and PCR were used to detect the protein and mRNA level changes. CRISPR/Cas9 used to knock out CDK2. shRNA-knockdown and transfection assays also used to knock out target genes. GST pull-down analysis, immunoprecipitation (IP) assay and in vitro isomerization analysis also used. Tumorigenesis studies also used to verify the results in vitro. Results: Herein, tripartite motif-containing protein 32 (TRIM32) is revealed as a substrate of CDK2. Radiotherapy promotes the binding of CDK2 and TRIM32, thus leading to increased CDK2-dependent phosphorylation of TRIM32 at serines 328 and 339. This causes the recruitment of PIN1, involved in cis–trans isomerization of TRIM32, resulting in importin α3 binding to TRIM32 and contributing to its nuclear translocation. Nuclear TRIM32 inhibits TC45-dephosphorylated STAT3, Leading to increased transcription of STAT3 and radioresistance in TNBC. These results were validated by clinical prognosis confirmed by the correlative expressions of the critical components of the CDK2/TRIM32/STAT3 signaling pathway. Conclusions: Our findings demonstrate that regulating the CDK2/TRIM32/STAT3 pathway is a promising strategy for reducing radioresistance in TNBC.

Abstract Annexin A2 (ANXA2) is a widely reported oncogene. However, the mechanism of ANXA2 in esophageal cancer is not fully understood. In this study, we provided evidence that ANXA2 promotes the progression of esophageal squamous cell carcinoma (ESCC) through the downstream target threonine tyrosine kinase (TTK). These results are consistent with the up-regulation of ANXA2 and TTK in ESCC. In vitro experiments by knockdown and overexpression of ANXA2 revealed that ANXA2 promotes the progression of ESCC by enhancing cancer cell proliferation, migration, and invasion. Subsequently, animal models also confirmed the role of ANXA2 in promoting the proliferation and metastasis of ESCC. Mechanistically, the ANXA2/TTK complex activates the Akt/mTOR signaling pathway and accelerates epithelial-mesenchymal transition (EMT), thereby promoting the invasion and metastasis of ESCC. Furthermore, we identified that TTK overexpression can reverse the inhibition of ESCC invasion after ANXA2 knockdown. Overall, these data indicate that the combination of ANXA2 and TTK regulates the activation of the Akt/mTOR pathway and accelerates the progression of ESCC. Therefore, the ANXA2/TTK/Akt/mTOR axis is a potential therapeutic target for ESCC.

To compare the pretreatment effect of deep eutectic solvents (DESs) on corn stover, three types of DESs (acid, neutral, and alkaline) were used to pretreat corn stover, and their effects on lignin removal were investigated. Then the performance of photo-fermentation hydrogen production (PFHP) using DESs pretreated corn stover was compared and analyzed. The results showed that acid DESs had the best lignin removal efficiency, and the lignin removal percentages of choline chloride/formic acid (ChCl/Fac) and choline chloride/oxalate (ChCl/Oac) were 64.7% and 65.6%, respectively. The alkaline DESs had the second highest removal of lignin, while the neutral DESs had a poor effect on lignin removal. The comparison of hydrogen production indicated that the corn stover pretreated with ChCl/Oac had the best hydrogen production effect. In conclusion, the DESs pretreatment can obviously remove the lignin in corn stover, and then improve the hydrogen production capacity and efficiency of photo-fermentation, which provides a potential pretreatment method for the efficient utilization of straw biomass.

Abstract The relationship between total lymphocyte counts (TLCs) and survival is not well documented in rectal cancer. This study aimed to investigate the association between TLCs and disease-free survival (DFS) and identify factors associated with lymphopenia in locally advanced rectal cancer patients receiving chemoradiotherapy. Thirty-six patients with locally advanced rectal cancer were retrospectively analyzed. TLCs were evaluated before surgery (pre-S), before radiotherapy (pre-RT), and during concurrent chemoradiotherapy (CCRT). The relationship between TLCs and DFS was analyzed by univariate and multivariate analysis. Potential clinical factors associated with lymphopenia were also evaluated. Median TLC declined significantly during radiotherapy. Severe lymphopenia during CCRT was significantly associated with poorer DFS on Kaplan–Meier analysis (p = 0.01), univariate regression analysis (p = 0.036), and multivariate regression analysis (p = 0.038). Pre-S TLCs (p = 0.009) and pre-RT TLCs (p = 0.042) were significantly associated with severe lymphopenia on univariate regression analysis; however, only pre-S TLCs (p = 0.026) were significantly associated with severe lymphopenia on multivariate regression analysis. Severe lymphopenia was a predictor of poorer DFS in patients with locally advanced rectal cancer receiving adjuvant chemoradiotherapy. Pre-S TLCs were predictors of severe lymphopenia. Further study is warranted to reduce the rate of severe lymphopenia.

Abstract Background Prediction models with high accuracy rates for nonmetastatic cervical cancer (CC) patients are limited. This study aimed to construct and compare predictive models on the basis of machine learning (ML) algorithms for predicting the 5‐year survival status of CC patients through using the Surveillance, Epidemiology, and End Results public database of the National Cancer Institute. Methods The data registered from 2004 to 2016 were extracted and randomly divided into training and validation cohorts (8:2). The least absolute shrinkage and selection operator (LASSO) regression was employed to identify significant factors. Then, four predictive models were constructed, including logistic regression (LR), random forest (RF), support vector machine (SVM), and extreme gradient boosting (XGBoost). The predictive models were evaluated and compared using Receiver‐operating characteristics with areas under the curves (AUCs) and decision curve analysis (DCA), respectively. Results A total of 13,802 patients were involved and classified into training (N = 11,041) and validation (N = 2761) cohorts. By using the LASSO regression method, seven factors were identified. In the training cohort, the XGBoost model showed the best performance (AUC = 0.8400) compared to the other three models (all p

Many studies have investigated how soil water availability in shallow soil affects forest transpiration, but how deep soil water status (below 1 m depth) alters tree water use remains poorly understood. To improve our understanding of how deep soil water changes tree transpiration dynamics, we measured soil water content (SWC) in more than 20 m depths, the radial sap flow profile and the leaf area index (LAI) in the 2017 growing season in 9-, 12-, 16-, 19- and 23-year-old afforested apple (Rosaceae) trees on the Chinese Loess Plateau. SWC was also measured in long-term cultivated farmland to derive SWC before afforestation. The results showed that there was no statistical difference in SWC in shallow soil among orchards (p > 0.05), while SWC in deep soil reduced rapidly with increasing tree age. The average SWC at 1–20 m decreased from 0.27 ± 0.02 cm3 cm−3 in farmland to 0.21 ± 0.03 cm3 cm−3 in the 23-year-old orchard. Moreover, water storage in deep soil decreased by 139 mm yr−1 between the 9- and 12-year-old stands, 105 mm yr−1 between the 12- and 16-year-old stands, 44 mm yr−1 between the 16- and 19-year-old stands, and 9 mm yr−1 from the 19- to 23-year-old stands, indicating that gradually decreased SWC in deep soil has restricted tree water use. Due to the changes in SWC, growing-season transpiration and the LAI peaked in the 16-year-old orchard and then decreased with increasing stand age. Growing-season transpiration in the 23-year-old orchard was only 77% of that in the 16-year stands, despite the older trees having larger diameters at the breast height. Our results suggest that soil water availability in deep soil plays an important role in regulating trees’ transpiration.

Abstract Background Colon cancer is one of the most common diagnosed malignancies. Despite the use of surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy, and other comprehensive treatments, distant metastasis is still one of the main causes for dying of colon cancer. The common metastatic site of colon cancer is the liver, lung, and bone. In this article, we report a rare case of breast metastasis of signet ring cell carcinoma from the colon. Case presentation A 44-year-old woman was diagnosed with colon cancer and received a radical surgery of colon cancer in 2019. Combined with postoperative pathological and computed tomography (CT) images, a diagnosis of cT3N2M0 mucinous adenocarcinoma of colon (according to AJCC cancer staging manual, Version 8) was established. Adjuvant chemotherapy (XELOX: oxaliplatin 130 mg/m2 on day 1 plus capecitabine 1000 mg/m2 twice daily on days 1 to 14 every 3 weeks for 18 weeks) was performed followed by surgical resection. Fourteen months later, the patient underwent mastectomy for breast mass, which was diagnosed pathologically as metastasis of signet ring cell carcinoma from the colon. XELOX chemotherapy regimen (oxaliplatin 130 mg/m2 on day 1 plus capecitabine 1000 mg/m2 twice daily on days 1 to 14 every 3 weeks for 24 weeks) combined with bevacizumab (7.5 mg/kg on day 1) was used after the mastectomy. The patient had stable disease according to her last examination (RECIST criteria). Conclusion It is rare to find a report of a patient of colon cancer that metastasizes to breast. We hope to increase treatment experience for patients with this rare metastasis.

Cyclin-dependent kinase 16 (CDK16) is an orphan “cyclin-dependent kinase” (CDK) involved in the cell cycle, vesicle trafficking, spindle orientation, skeletal myogenesis, neurite outgrowth, secretory cargo transport, spermatogenesis, glucose transportation, cell apoptosis, cell growth and proliferation, metastasis, and autophagy. Human CDK16 is located on chromosome Xp11.3 and is related to X-linked congenital diseases. CDK16 is commonly expressed in mammalian tissues and may act as an oncoprotein. It is a PCTAIRE kinase in which Cyclin Y or its homologue, Cyclin Y-like 1, regulates activity by binding to the N- and C- terminal regions of CDK16. CDK16 plays a vital role in various cancers, including lung cancer, prostate cancer, breast cancer, malignant melanoma, and hepatocellular carcinoma. CDK16 is a promising biomarker for cancer diagnosis and prognosis. In this review, we summarized and discussed the roles and mechanisms of CDK16 in human cancers.

Abstract Histones are DNA‐binding basic proteins found in chromosomes. After the histone translation, its amino tail undergoes various modifications, such as methylation, acetylation, phosphorylation, ubiquitination, malonylation, propionylation, butyrylation, crotonylation, and lactylation, which together constitute the “histone code.” The relationship between their combination and biological function can be used as an important epigenetic marker. Methylation and demethylation of the same histone residue, acetylation and deacetylation, phosphorylation and dephosphorylation, and even methylation and acetylation between different histone residues cooperate or antagonize with each other, forming a complex network. Histone‐modifying enzymes, which cause numerous histone codes, have become a hot topic in the research on cancer therapeutic targets. Therefore, a thorough understanding of the role of histone post‐translational modifications (PTMs) in cell life activities is very important for preventing and treating human diseases. In this review, several most thoroughly studied and newly discovered histone PTMs are introduced. Furthermore, we focus on the histone‐modifying enzymes with carcinogenic potential, their abnormal modification sites in various tumors, and multiple essential molecular regulation mechanism. Finally, we summarize the missing areas of the current research and point out the direction of future research. We hope to provide a comprehensive understanding and promote further research in this field.

Revealing the water use pattern of plants influenced by coal-mining-caused land subsidence is crucial to understand plant–water interactions and guide ecological restoration. However, available information on herbaceous plants, the dominant species in most arid and semi-arid regions with abundant coal resources, remains inadequate. We investigated the water use patterns of Stipa bungeana Trin. by measuring soil water content, root distribution, and stable isotopes of hydrogen (δ2H) and oxygen (δ18O) of soil water and plant stem water both before and after a rainfall event. The results revealed that prior to rainfall, both areas exhibited a low soil water content with no discernible difference in soil drought. However, the soil waters δ2H and δ18O were found to be more enriched at varying depths within the subsidence area, indicating a heightened level of soil evaporation. Both soil water content and soil water isotopic composition responded sensitively to rainfall, with rainfall primarily replenishing the shallow layer (0–20 cm), thereby reflecting an infiltration mode dominated by piston flow. More water seeped into deeper soil layers in the subsidence area compared to the non-subsidence area, with more preferential flow. Before rainfall, the sources of plant water uptake were consistent both at shallow and deep soil layers, implying that the proportion of water uptake gradually decreased with increasing depth. After rainfall, the sources of plant water uptake differed slightly between the two soil layers. The plants in non-subsidence and subsidence areas dominantly extracted soil water at depths greater than 10 cm and 20 cm, respectively. The root system in the subsidence area was more developed than that in the non-subsidence area. Plant water uptake was primarily influenced by the spatial distribution of roots, as well as the post-rainfall water distribution, regardless of whether they were in the subsidence area or not. Although land subsidence affected soil water transport, the water uptake pattern of Stipa bungeana Trin. was similar before and after rainfall, indicating the adaptive growth of plants through their roots in the subsidence area. The high adaptability of herbs such as Stipa bungeana Trin. makes them a viable option for vegetation restoration in subsidence areas. This study has significant implications for evaluating plant–water relationships in subsidence areas due to coal mining, thereby providing a fundamental basis and valuable reference for ecological restoration and management strategies within such affected regions.

Abstract Temperature proxies for paleoclimate reconstruction have been made typically via ice cores, tree rings, stalagmites, and lake sediments. While extremely useful, these proxies can be limited spatially. Here we sampled a 98 m “soil core” from Loess Plateau of China and examined the relationship between pore water isotopic values and hydroclimate history. We extracted soil pore water for δ18O, δ2H, and 3H and measured chloride concentration. The 3H‐peak at 6 m and chloride mass balance were used to turn depth into calendar year. A 1000 year span was revealed. δ18O and δ2H values between 14–50 m were anomalously low—bracketing well the Little Ice Age period from 1420 to 1870. The identification was consistent with other standard proxies in the region and showed the same temporal dynamics of temperature anomalies. Our study shows the potential of stable isotopes of soil water for paleoclimate reconstruction in deep soils.

TMEM173 is a pattern recognition receptor detecting cytoplasmic nucleic acids and transmits cGAS related signals that activate host innate immune responses. It has also been found to be involved in tumor immunity and tumorigenesis. In this study, we first identified that the FKBP4/NR3C1 axis was a novel negative regulator of TMEM173 in human breast cancer (BC) cells. The effect of FKBP4 appeared to be at the transcriptional level of TMEM173, because it could suppress the promoter activity of TMEM173, thereby affecting TMEM173 at mRNA and protein levels. Past studies, our bioinformatics analysis, and in vitro experiments further implied that FKBP4 regulated TMEM173 via regulating nuclear translocation of NR3C1. We then demonstrated that the FKBP4/NR3C1/TMEM173 signaling pathway could regulate autophagy and proliferation of BC cells as well as dendritic cell (DC) abundance through exosome release. Our study found an unprecedented strategy used by BC to escape from TMEM173 mediated tumor suppression. Identification of the FKBP4/NR3C1 axis as a novel TMEM173 regulator would provide insights for novel anti-tumor strategy against BC among tumor microenvironment.

Water scarcity poses a formidable challenge to agricultural productivity in arid regions, and water retention agents offer promising potential in this regard. Therefore, this study proposes developing and preparing polymers with water retention properties using waste green algae as raw material to explore the effectiveness of enhanced water infiltration and reduce evaporation at different use levels (0%, 0.15%, 0.30%, 0.45% and 0.60%) and maximum mixing depths (10 cm, 20 cm, 30 cm, 40 cm and 50 cm) and determine the optimum management. The results demonstrate that the synthesized polymers exhibited a remarkable swelling rate of 143.6 g/g, along with reusability and excellent temperature stability. The polymer application rate was positively correlated with infiltration duration, with an increase from 161 min to 750 min as the application rate rose from 0% to 0.60%. Concurrently, cumulative infiltration increased from 22.6 cm to 31.1 cm, showcasing the benefits of the polymer in enhancing water retention. Intriguingly, cumulative evapotranspiration initially decreased and then increased with increasing polymer application rates. Moreover, increasing the maximum mixing depth from 10 to 50 cm while maintaining the 0.3% application rate increased the cumulative infiltration (from 22.6 cm to 31.1 cm) and infiltration rate (from 0.03 cm/min to 0.08 cm/min) while decreasing the cumulative evaporation (from 44.4 mm to 31.7 mm). Considering the cumulative infiltration, infiltration rate and evapotranspiration characteristics, an optimized polymer application rate of 0.27% at a mixing depth of 0–50 cm was recommended for efficient soil moisture management. This study highlights the potential of green algae-derived biodegradable polymers as a win–win strategy for achieving waste alleviation of water scarcity in drylands, particularly for maize and wheat cultivation in northern China.

Precipitation isoscapes have provided supporting data for numerous studies of water stable isotopes, alleviating the lack of observation data. However, the applicability of simulation data from global models to specific regional contexts remains a subject requiring further investigation, particularly concerning d-excess—an aspect often overlooked by prediction models. To bridge this gap, this study evaluates the performance of three mainstream precipitation isoscapes (OIPC3.2, RCWIP1, and RCWIP2) for the prediction of average annual δ2H, δ18O, and d-excess based on observations from the CHNIP database. The results show that while all three models can accurately reproduce δ2H and δ18O values, none are able to accurately match d-excess values. This disparity can be attributed to the absence of water-vapor source information in the models’ input variables, a key determinant influencing d-excess outcomes. Additionally, it is noteworthy that OIPC3.2 stands out as the optimal choice for δ2H and δ18O estimations, while RCWIP2 exhibits progressive enhancements over RCWIP1 in d-excess estimations. This highlights the significance of selecting highly pluralistic information variables and recognizing the impact of error propagation in such models. As a result, the advancement of isoscapes in accurately and precisely depicting precipitation isotopes, particularly d-excess, necessitates further refinement. Future avenues for improvement might involve the incorporation of water-vapor source-clustering methodologies, the selection of information-rich variables, and the autonomous construction of a dedicated d-excess simulation. This research provides valuable insights for the further refining of isoscape modeling in the future.

Abstract Direct imaging of single‐molecule and its movement is of fundamental importance in biology, but challenging. Herein, aided by the nanoconfinement effect and resultant high reaction activity within metal–organic frameworks (MOFs), the designed Ru(bpy)32+ embedded MOF complex (RuMOFs) exhibits bright electrochemiluminescence (ECL) emission permitting high‐quality imaging of ECL events at single molecule level. By labeling individual proteins of living cells with single RuMOFs, the distribution of membrane tyrosine‐protein‐kinase‐like7 (PTK7) proteins at low‐expressing cells is imaged via ECL. More importantly, the efficient capture of ECL photons generated inside the MOFs results in a stable ECL emission up to 1 h, allowing the in operando visualization of protein movements at the cellular membrane. As compared with the fluorescence observation, near‐zero ECL background surrounding the target protein with the ECL emitter gives a better contrast for the dynamic imaging of discrete protein movement. This achievement of single molecule ECL dynamic imaging using RuMOFs will provide a more effective nanoemitter to observe the distribution and motion of individual proteins at living cells.

Understanding the dynamics of soil water and nitrate in response to typical agricultural crops in dryland ecosystems are crucial for assessing ecological consequences and informing land use planning. This study was conducted in the Changwu tableland, a representative area for agricultural crop cultivation in the Loess Plateau of China. Fifteen soil profiles, including grassland, farmland, and young, mature, and old apple orchards, were sampled to investigate the effects of different land uses on soil water and nitrate dynamics using a “space-for-time” substitution approach. The results showed that the soil water content and nitrate content in farmlands were comparable to those in wild grassland. However, significant differences in soil water were observed below a depth of 2 m in apple orchards, with mature and old orchards experiencing water deficits compared to grassland of 624.9 mm and 690.0 mm, respectively. Moreover, a dried soil layer formed below a depth of 5 m in these orchards. In terms of soil nitrate, the concentration in the 0–5 m depth of apple orchards was significantly higher than that in agricultural land and grassland, and it increased with the age of the orchards. However, below 5 m, the residual nitrate stock per unit depth in apple orchards decreased to levels comparable to grassland and farmland, primarily due to the inhibitory effect of the dried soil layer on downward migration and leaching processes. Furthermore, the relationship between nitrate and soil water at 0–5 m soil depths differed during the conversion from grassland to farmland and apple orchard, with positive and negative correlations observed, respectively. This indicates that water plays a key role in influencing nitrate movement, and distinct hydrological processes occur for soil water and nitrate nitrogen under different land use change conditions. In conclusion, converting grassland and farmland to apple orchards can lead to soil water decline and nitrate accumulation in the vadose zone, posing potential threats to ecosystem sustainability and security in dryland regions. Therefore, implementing appropriate water-fertilizer management practices is crucial for promoting sustainable land use in loess drylands, with potential implications for similar areas worldwide.

Long non-coding RNA LINC00152 (cytoskeleton regulator, or LINC00152) is an 828-bp lncRNA located on chromosome 2p11.2. LINC00152 was originally discovered during research on hepatocarcinogenesis and has since been regarded as a crucial oncogene that regulates gene expression in many cancer types. LINC00152 is aberrantly expressed in various cancers, including gastric, breast, ovarian, colorectal, hepatocellular, and lung cancer, and glioma. Several studies have indicated that LINC00152 is correlated with cell proliferation, apoptosis, migration, invasion, cell cycle, epithelial-mesenchymal transition (EMT), chemotherapy and radiotherapy resistance, and tumor growth and metastasis. High LINC00152 expression in most tumors is significantly associated with poor patient prognosis. Mechanistic analysis has demonstrated that LINC00152 can serve as a competing endogenous RNA (ceRNA) by sponging miRNA, regulating the abundance of the protein encoded by a particular gene, or modulating gene expression at the epigenetic level. LINC00152 can serve as a diagnostic or prognostic biomarker, as well as a therapeutic target for most cancer types. In the present review, we discuss the roles and mechanisms of LINC00152 in human cancer, focusing on its functions in chemotherapy and radiotherapy resistance.

The long non-coding RNA (lncRNA) PVT1 was first found to activate variant translocations in the plasmacytoma of mice. Human lncPVT1 is located on chromosome 8q24.21, at the same locus as the well-known MYC oncogene. LncPVT1 has been found to promote the progression of various malignancies. Chemoresistance and radioresistance seriously affect tumor treatment efficacy and are associated with the dysregulation of physiological processes in cancer cells, including apoptosis, autophagy, stemness (for cancer stem cells, CSC), hypoxia, epithelial–mesenchymal transition (EMT), and DNA damage repair. Previous studies have also implicated lncPVT1 in the regulation of these physiological mechanisms. In recent years, lncPVT1 was found to modulate chemoresistance and radioresistance in some cancers. In this review, we discuss the mechanisms of lncPVT1-mediated regulation of cellular chemoresistance and radioresistance. Due to its high expression in malignant tumors and sensitization effect in chemotherapy and radiotherapy, lncPVT1 is expected to become an effective antitumor target and chemotherapy and radiotherapy sensitizer, which requires further study.

Evapotranspiration (ET) is a crucial process in the terrestrial water cycle, and understanding its stable isotopic evolution is essential for comprehending hydrological processes. The Craig–Gordon (C-G) model is widely used to describe isotopic fractionation during pure evaporation. However, in natural environments, ET involves both transpiration (T) and evaporation (E), and the traditional C-G model does not account for the effect of transpiration on isotopic fractionation. To address this gap, we propose the evapotranspiration-unified C-G (ET-UCG) model, which extends the C-G model by incorporating transpiration’s effect on water isotopes. We verified the validity of the ET-UCG model by comparing its simulation results with the traditional C-G model’s discrete results for a special scenario that simulated the isotopic evolution of residual water after daily transpiration consumption. Further, we simulated two different ET process scenarios using the ET-UCG model to investigate transpiration’s effect on the residual water’s isotopic composition. Our numerical experiments show that transpiration indirectly affects the degree of water isotope fractionation by reducing the true evaporation ratio, even though it does not directly produce isotope fractionation. Therefore, the isotopic composition of residual water estimated by the ET-UCG model is consistently lighter than that estimated using the traditional C-G model in the simulation of ET. Despite different T/ET conditions, the isotopic evolution process follows the same evaporation line. These results highlight the importance of considering transpiration effects when using the C-G model and provide valuable insights into ET processes with potential applications in the field.

Stereotactic body radiotherapy (SBRT) is now widely used in cancer therapy. However, the biological effects of SBRT compared with conventional radiotherapy (CRT) are not clear. The cytoskeleton plays an important role in many biological processes and cellular life activities. The effects of SBRT or CRT on the morphology and cytoskeletal structure of non-small cell lung cancer (NSCLC) cells remain unknown. Based on the biologically equivalent dose (BED) formula, we designed SBRT and CRT fractionation regimens with the same BED. The morphology was captured during radiation, and rhodamine-phalloidin immunofluorescence was used to study the cytoskeleton. A lactate dehydrogenase assay kit was used to determine the cell membrane permeability, and western blot was used to detect the cytoskeleton protein expression levels. The morphology and cytoskeleton expanded after SBRT or CRT, with an increase in cell membrane permeability and stable cytoskeleton protein levels. Besides, different dose of SBRT (10,20,30 Gy) induce similar morphology and cytoskeleton enlargement. Our findings indicate that SBRT and CRT can induce cytoskeleton reorganization and the enlargement of cell morphology (at different rates) in NSCLC. The morphology and cytoskeleton enlargement after SBRT are dose independence.

Purpose: To investigate the survival outcomes, prognostic factors and treatment modalities of stage I-III cervical esophageal carcinoma (CEC) patients using data from the Surveillance, Epidemiology, and End Results (SEER) database from the period 2004–2016.Methods: Patients with a histopathologic diagnosis of CEC were included. The primary endpoint was overall survival (OS). Univariate and multivariate analyses of OS were performed using Cox proportional hazards models, and OS was compared using the Kaplan-Meier method and log-rank test.Results: A total of 347 patients in the SEER database were enrolled. The median OS was 14.0 months, with a 5-year OS rate of 20.9%. The parameters that were found to significantly correlate with OS in the multivariate analysis were age at diagnosis [P < 0.001, hazard ratio (HR) = 1.832], sex [P < 0.001, HR= 1.867], histology [P = 0.001, HR = 0.366], surgery at the primary site [P = 0.021, HR = 0.553], radiotherapy (RT, P = 0.017, HR = 0.637) and chemotherapy (CT, P < 0.001, HR = 0.444). Comparison among the three treatment modalities demonstrated that a triple therapy regimen consisting of surgery, RT and CT was associated with a longer survival time than the other two treatment modalities before and after propensity score matching (PSM). However, triple therapy showed no significant survival benefit over double therapy (P = 0.496 before PSM and P = 0.184 after PSM).Conclusions: The survival of patients with CEC remains poor. Surgery, RT and CT were all strongly correlated with OS. We recommend a triple therapy regimen for select CEC patients based on the findings of the current study, although this recommendation should be further confirmed by prospective studies with large sample sizes.

Abstract CDP138, a CDK5 binding partner, regulates cell proliferation and migration. However, the mechanisms by which CDP138 functions in these processes remain unclear. In this study, we show that CDP138 is frequently overexpressed and that high levels of CDP138 are correlated with lymph node metastasis in lung cancer. Furthermore, we provide evidence that CDP138-depleted lung cancer cells exhibit enhanced radiosensitivity as well as reduced migration and invasion. Mechanistically, we identify GDF15, a member of the TGF-β superfamily, as a key downstream effector of CDP138. CDP138 silencing attenuates TGF-β/Smad signaling activation at least in part through the downregulation of GDF15. More importantly, the observed phenotypes caused by CDP138 knockdown are partially dependent on GDF15 inhibition. Together, our findings demonstrate that CDP138 positively modulates the TGF-β/Smad signaling pathway via GDF15 to promote radioresistance and metastasis, suggesting CDP138 as a potential oncogenic biomarker and a promising therapeutic target in the treatment of lung cancer.

Abstract The hypercoagulable state is a hallmark for patients with multiple myeloma (MM) and is associated with disease progression. Activated platelets secrete exosomes and promote solid tumor growth. However, the role of platelet-derived exosomes in MM is not fully clear. We aim to study the underlying mechanism of how platelet-derived exosomes promote MM cell growth. Flow cytometry, Western blot, proteome analysis, co-immunoprecipitation, immunofluorescence staining, and NOD/SCID mouse subcutaneous transplantation model were performed to investigate the role of exosomal LRG1 on multiple myeloma cell growth. Peripheral blood platelets in MM patients were in a highly activated state, and platelet-rich plasma from MM patients significantly promoted cell proliferation and decreased apoptotic cells in U266 and RPMI8226 cells. Leucine-rich-alpha-2-glycoprotein 1 (LRG1) was significantly enriched in MM platelet-derived exosomes. Blocking LRG1 in recipient cells using LRG1 antibody could significantly eliminate the proliferation-promoting effect of platelet-derived exosomes on MM cells. And high exosomal LRG1 was associated with poor prognosis of patients with MM. Mechanistic studies revealed that LRG1 interacted with Olfactomedin 4 (OLFM4) to accelerate MM progression by activating the epithelial-to-mesenchymal transition (EMT) signaling pathway and promoting angiogenesis. Our results revealed that blocking LRG1 is a promising therapeutic strategy for the treatment of MM.

Abstract Background Combination therapy involving immune checkpoint blockade (ICB) and other drugs is a potential strategy for converting immune-cold tumors into immune-hot tumors to benefit from immunotherapy. To achieve drug synergy, we developed a homologous cancer cell membrane vesicle (CM)-coated metal-organic framework (MOF) nanodelivery platform for the codelivery of a TLR7/8 agonist with an epigenetic inhibitor. Methods A novel biomimetic codelivery system (MCM@UN) was constructed by MOF nanoparticles UiO-66 loading with a bromodomain-containing protein 4 (BRD4) inhibitor and then coated with the membrane vesicles of homologous cancer cells that embedding the 18 C lipid tail of 3M-052 (M). The antitumor immune ability and tumor suppressive effect of MCM@UN were evaluated in a mouse model of triple-negative breast cancer (TNBC) and in vitro. The tumor immune microenvironment was analyzed by multicolor immunofluorescence staining. Results In vitro and in vivo data showed that MCM@UN specifically targeted to TNBC cells and was superior to the free drug in terms of tumor growth inhibition and antitumor immune activity. In terms of mechanism, MCM@UN blocked BRD4 and PD-L1 to prompt dying tumor cells to disintegrate and expose tumor antigens. The disintegrated tumor cells released damage-associated molecular patterns (DAMPs), recruited dendritic cells (DCs) to efficiently activate CD8+ T cells to mediate effective and long-lasting antitumor immunity. In addition, TLR7/8 agonist on MCM@UN enhanced lymphocytes infiltration and immunogenic cell death and decreased regulatory T-cells (Tregs). On clinical specimens, we found that mature DCs infiltrating tumor tissues of TNBC patients were negatively correlated with the expression of BRD4, which was consistent with the result in animal model. Conclusion MCM@UN specifically targeted to TNBC cells and remodeled tumor immune microenvironment to inhibit malignant behaviors of TNBC.

Abstract Tuning interfacial electric fields provides a powerful means to control electrocatalyst activity. Importantly, electric fields can modify adsorbate binding energies based on their polarizability and dipole moment, and hence operate independently of scaling relations that fundamentally limit performance. However, implementation of such a strategy remains challenging because typical methods modify the electric field non-uniformly and affects only a minority of active sites. Here we discover that uniformly tunable electric field modulation can be achieved using a model system of single-atom catalysts (SACs). These consist of M-N4 active sites hosted on a series of spherical carbon supports with varying degrees of nanocurvature. Using in-situ Raman spectroscopy with a Stark shift reporter, we demonstrate that a larger nanocurvature induces a stronger electric field. We show that this strategy is effective over a broad range of SAC systems and electrocatalytic reactions. For instance, Ni SACs with optimized nanocurvature achieved a high CO partial current density of ~400 mA cm−2 at >99% Faradaic efficiency for CO2 reduction in acidic media.