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Abstract In the Loess Plateau, the impact of abandoned farmland on soil properties and enzyme activity, along with its temporal variations and potential driving factors, remains a mystery. This study was designed to systematically and comprehensively examine the variations in soil enzyme activities, particle size distribution, and stability of soil aggregates at different stages of ecological recovery in the Loess Plateau. Our findings reveal a nuanced temporal pattern: with the progression of cropland abandonment, there is a notable decrease in soil bulk density. Concurrently, a dynamic trend in enzyme activities is observed—initially exhibiting a decline, followed by an increase over extended periods of recovery. Notably, prolonged abandonment leads to marked enhancements in soil structure. Parameters such as the mean weight diameter (MWD) and geometric mean diameter (GMD) of soil aggregates show an overall increasing trend. In terms of the Relative Dissipation Index (RSI), our data indicate a sequence of control > 2 years of abandonment > 4 years > 6 years > 14 years. From this, it can be seen that fallowing may be an effective natural restoration strategy for improving the physical structure of soils in the Loess Plateau and restoring soil nutrients. However, positive changes may take a long time to become evident.

External bonding of carbon fiber–reinforced polymer (CFRP) plates is a common method for the flexural strengthening of steel beams. However, the interfacial stress concentration at the CFRP plate end can easily cause premature debonding failure of strengthened beams. Consequently, the high performance of the materials is not fully utilized, and the safety of the strengthened beams may be threatened. To address this issue, the paper proposes a simple C-shaped plate gripper to strengthen H-shaped steel beams, which can improve the anchorage at the CFRP plate end. Four-point bending tests were conducted for strengthened beams to verify gripper reliability. The strengthening effect was examined by changing the ratio of the bond length (measured from load point to the CFRP plate end) to the shear span length and anchorage types. There are three types of anchorage: in the first type, the CFRP plate is bonded only on the tensile face of the beam; in the second type, the CFRP plate is attached to the tensile face of the beam and a gripper is attached to the end of the CFRP plate; in the third type, a combination of the above two types is utilized. These types are called pure bonding, end anchorage, and hybrid strengthening, respectively. The case with an anchorage at the CFRP plate end is considerably different from the case of pure bonding. The former relies on mechanical force transfer, while the latter relies on an epoxy resin for bonding. As long as failure does not occur first in the outer section of the CFRP plate, the strain and utilization ratio of the CFRP plate, along with the related strengthening effect, will increase as the length of the CFRP plate decreases. For a strengthened beam with a CFRP plate length of 600 mm, the ultimate strain and load are 27.3% and 8.1% higher than those of the case with a CFRP plate length of 750 mm, respectively. Notably, the hybrid strengthened beams debonded suddenly and degraded to beams with only end anchorage in the subsequent loading stage. There is no obvious improvement in beams with hybrid strengthening compared with those with only end anchorage. This can be attributed to the poor surface treatment of the beams. Thus, it is necessary to improve the quality of surface treatment in the future. Compared with the cases of pure bonding, the flexural behavior is greatly improved for the cases with end anchorage for hybrid strengthened beams because the grippers can successfully impede the debonding of the CFRP plate. Herein, the debonding process was detected in real time using the piezoresistance method, which exhibits consistent results with the test phenomena.

Introduction Individualized treatment of colorectal cancer liver metastases (CRLM) remains challenging due to differences in the severity of metastatic disease and tumour biology. Exploring specific prognostic risk subgroups is urgently needed. The current study aimed to investigate the prognostic value of chromosomal instability (CIN) in patients with initially resectable CRLM and the predictive value of CIN for the efficacy of bevacizumab.Methods Ninety-one consecutive patients with initially resectable CRLM who underwent curative liver resection from 2006 to 2018 at Sun Yat-sen University Cancer Center were selected for analysis. CIN was evaluated by automated digital imaging systems. Immunohistochemistry (IHC) was performed to detect interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA) and CD31 expression in paraffin-embedded specimens. Recurrence-free survival (RFS) and overall survival (OS) were analysed using the Kaplan–Meier method and Cox regression models.Results Patients with high chromosomal instability (CIN-H) had a worse 3-year RFS rate (HR, 1.953; 95% CI, 1.001–3.810; p = 0.049) and a worse 3-year OS rate (HR, 2.449; 95% CI, 1.150–5.213; p = 0.016) than those with low chromosomal instability (CIN-L). CIN-H was identified as an independent prognostic factor for RFS (HR, 2.569; 95% CI, 1.078–6.121; p = 0.033) and OS (HR, 3.852; 95% CI, 1.173–12.645; p = 0.026) in the multivariate analysis. The protein levels of IL-6, VEGFA and CD31 were upregulated in patients in the CIN-H group compared to those in the CIN-L group in both primary tumour and liver metastases tissues. Among them, 22 patients with recurrent tumours were treated with first-line bevacizumab treatment and based on the clinical response assessment, disease control rates were adversely associated with chromosomal instability (p = 0.043).Conclusions Our study showed that high chromosomal instability is a negative prognostic factor for patients with initially resectable CRLM after liver resection. CIN may have positive correlations with angiogenesis through expression of IL-6–VEGFA axis and be used as a potential predictor of efficacy of bevacizumab.

The identification of genome-wide selection signatures can reveal the potential genetic mechanisms involved in the generation of new breeds through natural or artificial selection. In this study, we screened the genome-wide selection signatures of prolific Suffolk sheep, a new strain of multiparous mutton sheep, to identify candidate genes for reproduction traits and unravel the germplasm characteristics and population genetic evolution of this new strain of Suffolk sheep. Whole-genome resequencing was performed at an effective sequencing depth of 20× for genomic diversity and population structure analysis. Additionally, selection signatures were investigated in prolific Suffolk sheep, Suffolk sheep, and Hu sheep using fixation index (FST) and heterozygosity H) analysis. A total of 5,236.338 Gb of high-quality genomic data and 28,767,952 SNPs were obtained for prolific Suffolk sheep. Moreover, 99 selection signals spanning candidate genes were identified. Twenty-three genes were significantly associated with KEGG pathway and Gene Ontology terms related to reproduction, growth, immunity, and metabolism. Through selective signal analysis, genes such as ARHGEF4, CATIP, and CCDC115 were found to be significantly correlated with reproductive traits in prolific Suffolk sheep and were highly associated with the mTOR signaling pathway, the melanogenic pathway, and the Hippo signaling pathways, among others. These results contribute to the understanding of the evolution of artificial selection in prolific Suffolk sheep and provide candidate reproduction-related genes that may be beneficial for the establishment of new sheep breeds.

Abstract Non-alcoholic fatty liver disease (NAFLD) has emerged as one of the major causes of liver-related morbidity and mortality globally. It ranges from simple steatosis to non-alcoholic steatohepatitis (NASH) characterized by ballooning and hepatic inflammation. In the past few years, pyroptosis has been shown as a type of programmed cell death that triggers inflammation and plays a role in the development of NASH. However, the roles of pyroptosis-related genes (PRGs) in NASH remained unclear. In this study, we studied the expression level of pyroptosis-related genes (PRGs) in NASH and healthy controls, developed a diagnostic model of NASH based on PRGs and explored the pathological mechanisms associated with pyroptosis. We further compared immune status between NASH and healthy controls, analyzed immune status in different subtypes of NASH. We identified altogether twenty PRGs that were differentially expressed between NASH and normal liver tissues. Then, a novel diagnostic model consisting of seven PRGs including CASP3, ELANE, GZMA, CASP4, CASP9, IL6 and TP63 for NASH was constructed with an area under the ROC curve (AUC) of 0.978 (CI 0.965–0.99). Obvious variations in immune status between healthy controls and NASH cases were detected. Subsequently, the consensus clustering method based on differentially expressed PRGs was constructed to divide all NASH cases into two distinct pyroptosis subtypes with different immune and biological characteristics. Pyroptosis-related genes may play an important role in NASH and can provide new insights into the diagnosis and underlying mechanisms of NASH.

Abstract Mutant KRAS (KRASMUT) is often exploited by cancers to shape tumor immunity, but the underlying mechanisms are not fully understood. Here we report that tumor-specific cytotoxic T lymphocytes (CTLs) from KRASMUT cancers are sensitive to activation-induced cell death (AICD). circATXN7, an NF-κB-interacting circular RNA, governs T cell sensitivity to AICD by inactivating NF-κB. Mechanistically, histone lactylation derived from KRASMUT tumor cell-produced lactic acid directly activates transcription of circATXN7, which binds to NF-κB p65 subunit and masks the p65 nuclear localization signal motif, thereby sequestering it in the cytoplasm. Clinically, circATXN7 upregulation in tumor-specific CTLs correlates with adverse clinical outcomes and immunotherapeutic resistance. Genetic ablation of circAtxn7 in CD8+ T cells leads to mutant-selective tumor inhibition, while also increases anti-PD1 efficacy in multiple tumor models in female mice. Furthermore, targeting circATXN7 in adoptively transferred tumor-reactive CTLs improves their antitumor activities. These findings provide insight into how lymphocyte-expressed circRNAs contribute to T-cell fate decisions and anticancer immunotherapies.

To clarify the effects of weathered coal humic acid on water-stable aggregates and pore characteristics of reclaimed cambisol, this research analyzed the evolution characteristics of soil aggregates and pores. Effects of different humic acid dosages (0, 1%, 3%, and 5% by weight) and application period (1 year, 2 years, and 3 years) on soil aggregates and organic carbon components in soil water-stable aggregates were investigated. The results showed that it is advisable to have an addition of 5% weathered coal humic acid in reclaimed cambisol. The humic acid of weathered coal promoted the disintegration and transformation of water-stable aggregates and increased soil pore p > 75 μm. At 3 years, the structure of reclaimed soil was the most stable, with more robust connected pores, and the irregular pores increased. The humic acid of weathered coal has the potential to be used as an effective organic amendment for improving the quality of reclaimed cambisol.

Abstract Background The pathological tumor burden score (TBS) has been proven to be a better risk stratification tool for liver metastasis of colorectal cancer than the traditional clinical risk score (CRS). The aim of this study was to evaluate the prognostic value of the pathological tumor burden score in patients with or without neoadjuvant chemotherapy (NAC). Methods A total of 348 patients with colorectal liver metastases (CRLM) who underwent curative hepatic resection were retrospectively enrolled from September 1999 to December 2016. Univariable and multivariable Cox regression analyses were conducted to identify the independent predictors of prognosis. Kaplan–Meier curves and log-rank tests were used to determine whether TBS has enough discriminatory ability under certain grouping. Results Patients who received NAC had a higher median TBS than patients who did not receive NAC (4.07 vs. 2.69, P 3 showed a significantly worse 3-year RFS (41.1% vs. 63.6%, P 3 showed comparable 3-year RFS (33.3% vs. 26.4%, P = 0.400) and 3-year OS rates (76.5% vs. 58.2%, P = 0.064) to those who did not. Regardless of the regimen and response to NAC, there was no significant difference about 3-year RFS and 3-year OS rates between the TBS ≤ 3 and TBS > 3 groups. Conclusion Pathological TBS can be applied to predict the RFS and OS of patients suffering from CRLM who did not receive NAC. However, pathological TBS might not be regard as prognosis in patients who did receive NAC.

Background: Circulating tumor DNA (ctDNA) has emerged as a biomarker that can define the risk of recurrence after curative-intent surgery for patients with colorectal cancer (CRC). However, beyond the predictive power of postoperative ctDNA detection, the efficacy and potential limitations of ctDNA detection urgently need to be fully elucidated in a large cohort of CRC. Objectives: To define potentially cured CRC patients through ctDNA monitoring following surgery. Design: A prospective, multicenter, observational study. Methods: We enrolled 309 patients with stages I–IV CRC who underwent definitive surgery. Tumor tissues were sequenced by a custom-designed next-generation sequencing panel to identify somatic mutations. Plasma was analyzed using a ctDNA-based molecular residual disease (MRD) assay which integrated tumor-genotype-informed and tumor-genotype-naïve ctDNA analysis. The turnaround time of the assay was 10–14 days. Results: Postoperative ctDNA was detected in 5.4%, 13.8%, 15%, and 30% of patients with stage I, II, III, and IV disease, respectively, and in 17.5% of all longitudinal samples. Patients with positive postsurgery MRD had a higher recurrence rate than those with negative postsurgery MRD [hazard ratio (HR), 13.17; p < 0.0001], producing a sensitivity of 64.6%, a specificity of 94.8%, a positive predictive value (PPV) of 75.6%, and a negative predictive value (NPV) of 91.5%. Furthermore, patients with positive longitudinal MRD also had a significantly higher recurrence rate (HR, 14.44; p < 0.0001), with increased sensitivity (75.0%), specificity (94.9%), PPV (79.6%), and NPV (93.4%). Subgroup analyses revealed that adjuvant therapy did not confer superior survival for patients with undetectable or detectable MRD. In addition, MRD detection was less effective in identifying lung-only and peritoneal metastases. Conclusion: Postoperative ctDNA status is a strong predictor of recurrence independent of stage and microsatellite instability status. Longitudinal undetectable MRD could be used to define the potentially cured population in CRC patients undergoing curative-intent surgery.

Soil cadmium (Cd) contamination poses a serious threat to ecosystems, and the application of phosphorus fertilizers can reduce Cd toxicity. However, the specific effects of different phosphorus fertilizers on the subcellular distribution and chemical morphology of Cd in eggplant grown in calcareous Cd-contaminated soil remain unclear. This study examined the impact of various types and levels of phosphate fertilizers on the subcellular distribution and chemical morphology of cadmium in eggplant seedlings using a two-factor analysis. The investigation was conducted via a pot experiment utilizing a two-factor analysis. The application of 0.35 g kg−1 dicalcium phosphate significantly decreased the Cd content in the subcellular distribution and induced notable alterations in the chemical morphology of Cd in eggplant roots. Specifically, the ethanol-extracted Cd state decreased by 65.45%, and the sodium chloride-extracted Cd state decreased by 64.65%. Conversely, Cd extracted by deionized water, acetic acid, hydrochloric acid, and the residue state increased by 6.20%, 4.01%, 20.87%, and 17.85%, respectively. The application of 0.35 g kg−1 dicalcium phosphate resulted in the most significant reduction in Cd content in eggplant and modification of subcellular Cd distribution and chemical morphology in roots.

Abstract Glioma is the most common primary malignant brain tumor with limited treatment options and poor prognosis. To investigate the potential relationships between transcriptional characteristics and clinical phenotypes, we applied weighted gene co-expression network analysis (WGCNA) to construct a free-scale gene co-expression network yielding four modules in gliomas. Turquoise and yellow modules were positively correlated with the most malignant glioma subtype (IDH-wildtype glioblastomas). Of them, genes in turquoise module were mainly involved in immune-related terms and were regulated by NFKB1, RELA, SP1, STAT1 and STAT3. Meanwhile, genes in yellow module mainly participated in cell-cycle and division processes and were regulated by E2F1, TP53, E2F4, YBX1 and E2F3. Furthermore, 14 genes in turquoise module were screened as hub genes. Among them, five prognostic hub genes (TNFRSF1B, LAIR1, TYROBP, VAMP8, and FCGR2A) were selected to construct a prognostic risk score model via LASSO method. The risk score of this immune-related gene signature is associated with clinical features, malignant phenotype, and somatic alterations. Moreover, this signature showed an accurate prediction of prognosis across different clinical and pathological subgroups in three independent datasets including 1619 samples. Our results showed that the high-risk group was characterized by active immune-related activities while the low-risk group enriched in neurophysiological-related pathway. Importantly, the high-risk score of our immune signature predicts an enrichment of glioma-associated microglia/macrophages and less response to immune checkpoint blockade (ICB) therapy in gliomas. This study not only provides new insights into the molecular pathogenesis of glioma, but may also help optimize the immunotherapies for glioma patients.

Abstract Background Colorectal cancer liver metastases (CRLM) has not been identified as a unified disease entity due to the differences in the severity of metastatic disease and tumor aggressiveness. A screen for specific prognostic risk subgroups is urgently needed. The current study aimed to investigate the prognostic value of DNA ploidy, stroma fraction and nucleotyping of initially resectable liver metastases from patients with CRLM. Methods One hundred thirty-nine consecutive patients with initially resectable CRLM who underwent curative liver resection from 2006 to 2018 at Sun Yat-sen University Cancer Center were selected for analysis. DNA ploidy, stroma fraction and nucleotyping of liver metastases were evaluated using automated digital imaging systems. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox regression models. Results DNA ploidy was identified as an independent prognostic factor for RFS (HR, 2.082; 95% CI 1.053–4.115; P = 0.035) in the multivariate analysis, while stroma-tumor fraction and nucleotyping were not significant prognostic factors. A significant difference in 3-year RFS was observed among the low-, moderate- and high-risk groups stratified by a novel parameter combined with the tumor burden score (TBS) and DNA ploidy (72.5% vs. 63.2% vs. 37.3%, P = 0.007). The high-risk group who received adjuvant chemotherapy had a significantly better 3-year RFS rate than those without adjuvant chemotherapy (46.7% vs. 24.8%; P = 0.034). Conclusions Our study showed that DNA ploidy of liver metastases is an independent prognostic factor for patients with initially resectable CRLM after liver resection. The combination of DNA ploidy and TBS may help to stratify patients into different recurrence risk groups and may guide postoperative treatment among the patients.

Abstract Background Metabolic reprograming have been associated with cancer occurrence and progression within the tumor immune microenvironment. However, the prognostic potential of metabolism-related genes in colorectal cancer (CRC) has not been comprehensively studied. Here, we investigated metabolic transcript-related CRC subtypes and relevant immune landscapes, and developed a metabolic risk score (MRS) for survival prediction. Methods Metabolism-related genes were collected from the Molecular Signatures Database and metabolic subtypes were identified using an unsupervised clustering algorithm based on the expression profiles of survival-related metabolic genes in GSE39582. The ssGSEA and ESTIMATE methods were applied to estimate the immune infiltration among subtypes. The MRS model was developed using LASSO Cox regression in the GSE39582 dataset and independently validated in the TCGA CRC and GSE17537 datasets. Results We identified two metabolism-related subtypes (cluster-A and cluster-B) of CRC based on the expression profiles of 539 survival-related metabolic genes with distinct immune profiles and notably different prognoses. The cluster-B subtype had a shorter OS and RFS than the cluster-A subtype. Eighteen metabolism-related genes that were mostly involved in lipid metabolism pathways were used to build the MRS in GSE39582. Patients with higher MRS had worse prognosis than those with lower MRS (HR 3.45, P

Human telomerase reverse transcriptase (hTERT) plays an extremely important role in cancer initiation and development, including colorectal cancer (CRC). However, the precise upstream regulatory mechanisms of hTERT in different cancer types remain poorly understood. Here, we uncovered the candidate transcriptional factor of hTERT in CRC and explored its role and the corresponding molecular mechanisms in regulating hTERT expression and CRC survival with an aim of developing mechanism‐based combinational targeting therapy. The possible binding proteins at the hTERT promoter were uncovered using pull‐down/mass spectrometry analysis. The regulation of SPT6 on hTERT expression and CRC survival was evaluated in human CRC cell lines and mouse models. Mechanistic studies focusing on the synergy between SPT6 and staphylococcal nuclease and Tudor domain containing 1 (SND1) in controlling hTERT expression and CRC progression were conducted also in the above two levels. The expression correlation and clinical significance of SPT6, SND1, and hTERT were investigated in tumor tissues from murine models and patients with CRC in situ. SPT6 was identified as a possible transcriptional factor to bind to the hTERT promoter. SPT6 knockdown decreased the activity of hTERT promoter, downregulated the protein expression level of hTERT, suppressed proliferation, invasion, and stem‐like properties, promoted apoptosis induction, and enhanced chemotherapeutic drug sensitivity in vitro. SPT6 silencing also led to the delay of tumor growth and metastasis in mice carrying xenografts of human‐derived colon cancer cells. Mechanistically, SND1 interacted with SPT6 to co‐control hTERT expression and CRC cell proliferation, stemness, and growth in vitro and in vivo. SPT6, SND1, and hTERT were highly expressed simultaneously in CRC tissues, both from the murine model and patients with CRC in situ, and pairwise expression among these three factors showed a significant positive correlation. In brief, our research demonstrated that SPT6 synergized with SND1 to promote CRC development by targeting hTERT and put forward that inhibiting the SPT6‐SND1‐hTERT axis may create a therapeutic vulnerability in CRC.

BackgroundGiven the men's predominance in the prevalence of chronic subdural hematoma (CSDH), we investigated the relationship between sex differences and clinical features of CSDH.MethodsWe retrieved a large collection of clinical factors from CSDH patients between August 2011 and May 2019, and analyzed the differences and similarities in the clinical data and outcomes between men and women.ResultsIn total 1,307 CSDH patients were enrolled in this study. When we did not account for age, a greater proportion of women relative to men manifested diabetes (p = 0.001) and cardiac disease (p = 0.035) prior to the onset of CSDH. Regarding recovery outcome and recurrence rate, we observed no significant differences between men and women. The sole difference between women and men after surgery was that women experienced more complications than men (p = 0.044), and both length of hospital stay (p < 0.001, B = 0.159, Exp [B] = 1.172, 95% CI = 1.078–1.274) and the presence of cardiac disease (p = 0.002, B = 2.063, Exp [B] = 7.867, 95% CI = 2.167–28.550) were identified as independent risk factors. After accounting for age, women with CSDH exhibited more frequent disorders of consciousness at admission than men in group of ≤ 40-year-old patients (p = 0.018), while proportion of women with diabetes was higher than that of men in 41–79 year-old group (p < 0.001). However, women after surgery experienced more complications (p = 0.047), longer length of hospital stays (p = 0.005), and higher mortality at discharge (p = 0.035) than men in middle-aged group. Finally, length of hospital stay (p < 0.001, B = 0.186, Exp [B] = 1.205, 95% CI = 1.091–1.331) and cardiac disease (p = 0.017, B = 2.040, Exp [B] = 7.693, 95% CI = 1.430–41.372) impacted occurrence of complications in women 41–79-year-old, while duration of drainage catheter use (p < 0.001, B = 1.132, beta = 0.280) and complications (p < 0.001, B = 5.615, beta = 0.366) were identified as independent risk factors for length of hospital stay in the same group of women.ConclusionsAlthough sex differences did not constitute a crucial factor in all the CSDH patients, we still need to pay closer attention to disparities between men and women with respect to complications, length of hospital stay, and mortality at discharge in the various age groups (particularly with respect to 41–79 year-old women patients), to provide satisfactory management and treatment of CSDH patients.

Gliomas with chromosome 1p/19q codeletion were considered a specific tumor entity. This study was designed to reveal the biological function alterations tightly associated with 1p/19q codeletion in gliomas. Clinicopathological and RNA sequencing data from glioma patients were obtained from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. Gene set variation analysis was performed to explore the differences in biological functions between glioma subgroups stratified by 1p/19q codeletion status. The abundance of immune cells in each sample was detected using the CIBERSORT analytical tool. Single-cell sequencing data from public databases were analyzed using the t-distributed stochastic neighbor embedding (t-SNE) algorithm, and the findings were verified by in vitro and in vivo experiments and patient samples.We found that the activation of immune and inflammatory responses was tightly associated with 1p/19q codeletion in gliomas. As the most important transcriptional regulator of Galectin-9 in gliomas, the expression level of CCAAT enhancer-binding protein alpha in samples with 1p/19q codeletion was significantly decreased, which led to the downregulation of the immune checkpoints Galectin-9 and TIM-3. These results were validated in three independent datasets. The t-SNE analysis showed that the loss of chromosome 19q was the main reason for the promotion of the antitumor immune response. IHC protein staining, in vitro and in vivo experiments verified the results of bioinformatics analysis. In gliomas, 1p/19q codeletion can promote the antitumor immune response by downregulating the expression levels of the immune checkpoint TIM-3 and its ligand Galectin-9.

Background: Patients with initially unresectable colorectal liver metastases (CRLM) could achieve survival benefit from successful conversion therapy. Recently, Tumor Burden Score (TBS) was proposed as a valuable index to predict outcome following resection of CRLM. The study is aimed to investigate the association of TBS with conversion outcome. Methods: A total of 234 patients who underwent first-line treatment in our center were enrolled as training cohort. The validation cohort was developed from 89 patients in our previous study. Cut-off value of TBS was calculated to stratify patients into two groups. Significance test and logistic regression model were used to examine the prediction value of TBS for conversion outcome after first-line systemic therapy. Kaplan–Meier method and Cox proportional hazard model were applied to assess the prognostic value of TBS. Results: TBS showed good discriminatory power [area under curve (AUC) 0.726, p

Annexin A1 (ANXA1) is a calcium-dependent phospholipid-binding protein and has been implicated in multiple functions essential in cancer, including cell proliferation, apoptosis, chemosensitivity, metastasis, and invasion. However, the biological role and clinical behavior of ANXA1 in glioma remain unclear. In this study, RNA-seq (n = 1018 cases) and whole-exome sequencing (WES) (n = 286 cases) data on a Chinese cohort, RNA-seq data with different histological regions of glioblastoma blocks (n = 270 cases), and scRNA-seq data (n = 7630 cells) were used. We used the R software to perform statistical calculations and graph rendering. We found that ANXA1 is closely related to the malignant progression in gliomas. Meanwhile, ANXA1 is significantly associated with clinical behavior. Furthermore, the mutational profile revealed that glioma subtypes classified by ANXA1 expression showed distinct genetic features. Functional analyses suggest that ANXA1 correlates with the immune-related function and cancer hallmark. At a single-cell level, we found that ANXA1 is highly expressed in M2 macrophages and tumor cells of the mesenchymal subtype. Importantly, our result suggested that ANXA1 expression is significant with the patient’s survival outcome. Our study revealed that ANXA1 was closely related to immune response. ANXA1 plays a key factor in M2 macrophages and MES tumor cells. Patients with lower ANXA1 expression levels tended to experience improved survival. ANXA1 may become a valuable factor for the diagnosis and treatment of gliomas in clinical practice.

Abstract Background As the selective inhibitor of BRAF kinase, vemurafenib exhibits effective antitumor activities in patients with V600 BRAF mutant melanomas. However, acquired drug resistance invariably develops after its initial treatment. Methods Immunohistochemical staining was performed to detect the expression of iNOS and hTERT, p-p65, Epcam, CD44, PCNA in mice with melanoma xenografts. The proliferation and migration of melanoma cells were detected by MTT, tumorsphere culture, cell cycle, cell apoptosis, AO/EB assay and colony formation, transwell assay and scratch assay in vitro, and tumor growth differences were observed in xenograft nude mice. Changes in the expression of key molecules in the iNOS/hTERT signaling pathways were detected by western blot. Nucleus-cytoplasm separation, and immunofluorescence analyses were conducted to explore the location of p50/p65 in melanoma cell lines. Flow cytometry assay were performed to determine the expression of CD44. Pull down assay and ChIP assay were performed to detect the binding ability of p65 at iNOS and hTERT promoters. Additionally, hTERT promoter-driven luciferase plasmids were transfected in to melanoma cells with indicated treatment to determine luciferase activity of hTERT. Results Melatonin significantly and synergistically enhanced vemurafenib-mediated inhibitions of proliferation, colony formation, migration and invasion and promoted vemurafenib-induced apoptosis, cell cycle arresting and stemness weakening in melanoma cells. Further mechanism study revealed that melatonin enhanced the antitumor effect of vemurafenib by abrogating nucleus translocation of NF-κB p50/p65 and their binding at iNOS and hTERT promoters, thereby suppressing the expression of iNOS and hTERT. The elevated anti-tumor capacity of vemurafenib upon co-treatment with melatonin was also evaluated and confirmed in mice with melanoma xenografts. Conclusions Collectively, our results demonstrate melatonin synergizes the antitumor effect of vemurafenib in human melanoma by inhibiting cell proliferation and cancer-stem cell traits via targeting NF-κB/iNOS/hTERT signaling pathway, and suggest the potential of melatonin in antagonizing the toxicity of vemurafenib and augmenting its sensitivities in melanoma treatment.

Abstract Background The preliminary results of our phase II randomized trial reported comparable functional sphincter preservation rates and short-term survival outcomes between patients undergoing total mesorectal excision (TME) with or without preoperative concurrent chemoradiotherapy (CCRT). We now report the long-term results after a median follow-up of 71 months. Methods Between March 23, 2008 and August 2, 2012, 192 patients with T3-T4 or node-positive, resectable, mid/low rectal adenocarcinoma were randomly assigned to receive TME with or without preoperative CCRT. The following endpoints were assessed: cumulative rates of local recurrence and distant metastasis, disease-free survival (DFS), and overall survival (OS). Results The data of 184 eligible patients were analyzed: 94 patients in the TME group and 90 patients in the CCRT + TME group. In the whole cohort, the 5-year DFS and OS rates were 84.8% and 85.1%, respectively. The 5-year DFS rates were 85.2% in the CCRT + TME group and 84.3% in the TME group (P = 0.969), and the 5-year OS rates were 83.5% in the CCRT + TME group and 86.5% in the TME group (P = 0.719). The 5-year cumulative rates of local recurrence were 6.3% and 5.0% (P = 0.681), and the 5-year cumulative rates of distant metastasis were 15.0% and 15.7% (P = 0.881) in the CCRT + TME and TME groups, respectively. No significant improvements in 5-year DFS and OS were observed with CCRT by subgroup analyses. Conclusions Both treatment strategies yielded similar long-term outcomes. A selective policy towards preoperative CCRT is thus recommended for rectal cancer patients if high-quality TME surgery and enhanced chemotherapy can be performed. Trial registration ChiCTR-TRC-08000122. Registered 16 July 2008

BackgroundOur previous study reported the favorable efficacy and good tolerance associated with a modified XELOX adjuvant chemotherapy with eight cycles of capecitabine and six cycles of oxaliplatin for operated stage III colon cancer. The current study aimed to confirm the feasibility of modified XELOX chemotherapy for treating specific high-risk (T4, N2, or both) stage III colon cancer.MethodsWe selected 142 consecutive patients with high-risk stage III colon cancer who received colon tumor resection followed by modified XELOX or standard full-cycle XELOX chemotherapy from November 2007 to June 2016 at Sun Yat-sen University Cancer Center. Disease-free survival (DFS), overall survival (OS), and adverse events of patients treated with the two chemotherapy regimens were compared.ResultsSeventy-four (52.1%) patients received standard XELOX chemotherapy, and 68 (47.8%) received modified XELOX chemotherapy. Neurotoxicity was the most common adverse event in 99 (69.7%) patients. Grade 2-3 neurotoxicity, grade 2–4 thrombocytopenia and grade 3–4 leucopenia were the major severe adverse events related to the decision to treat patients with modified XELOX chemotherapy. After a median follow-up of 69 months, the modified XELOX group presented a comparable 5-year DFS rate (79.0 vs. 80.3%, P = 0.891) and 5-year OS rate (93.8 vs. 87.8%, P = 0.446) as those in the standard XELOX group. Univariate survival analysis indicated that poor tumor differentiation (HR: 2.381, 95% CI: 1.141–4.968, P = 0.021) was the only significant risk factor for DFS, but no significant prognostic factor was identified for OS.ConclusionsThe modified XELOX adjuvant chemotherapy presented a comparable oncologic efficacy as standard XELOX chemotherapy for high-risk stage III colon cancer. The modified XELOX adjuvant chemotherapy could be an alternative treatment for patients suffering severe adverse events, especially severe neurotoxicity.

The chemical and physical capabilities of shale can be altered by the interactions between fracturing fluid and shale formation, affecting the long-term reservoir productivity. To obtain information regarding how fracturing fluids with different components impact the pore structure, porosity and mineral compositions of shale reservoir rocks over time, two different types of commercial fracturing fluids (slick water and crosslinked gel) were used to react with the shales from Longmaxi Formation of Lower Silurian in the Sichuan Basin of South China. Experiments were conducted with various time intervals (1, 4 and 10 days) in a reactor at 50 MPa and 100°C, and then analytical methods including X-ray diffraction, low pressure nitrogen adsorption, field emission scanning electron microscopy and porosity measurement were used to examine the changes of mineralogical compositions, pore structure and porosity. The results demonstrated that the mineral compositions of shale samples were significantly changed after treatment with two different fracturing fluids for 4 days. The analysis of field emission scanning electron microscopy revealed that the carbonate minerals were dissolved and developed many dissolution pores after slick water treatment, while the crosslinked gel mainly caused the precipitation of carbonate minerals. After exposure to different fracturing fluids, the total pore volume and specific surface area decreased over time. Moreover, the fractal dimensions (D 1 and D 2 ) of shale showed an apparent decrease trend after treatment with two different fracturing fluids, indicating that the pore surface and structure become smooth and regular. The porosity of shale significantly decreased by 15.9% and 17.8%, respectively, after 10 days of slick water and crosslinked gel treatment. These results indicated that the injection of the two different types of fracturing fluids may negatively impact the shale gas production through reducing the nanopore structure and porosity of shale reservoir rocks.

The structure of the deep artificial neural network is similar to the structure of the biological neural network, which can be well applied to the 3D visual image recognition of aerobics movements. A lot of results have been achieved by applying deep neural networks to the 3D visual image recognition of aerobics movements, but there are still many problems to be overcome. After analyzing the expression characteristics of the convolutional neural network model for the three-dimensional visual image characteristics of aerobics, this paper builds a convolutional neural network model. The model is improved on the basis of the traditional model and unifies the process of aerobics 3D visual image segmentation, target feature extraction, and target recognition. The convolutional neural network and the deep neural network based on autoencoder are designed and applied to aerobics action 3D visual image test set for recognition and comparison. We improve the accuracy of network recognition by adjusting the configuration parameters in the network model. The experimental results show that compared with other simple models, the model based on the improved AdaBoost algorithm can improve the final result significantly when the accuracy of each model is average. Therefore, the method can improve the recognition accuracy when multiple neural network models with general accuracy are obtained, thereby avoiding the complicated parameter adjustment process to obtain a single optimal network model.

Melanoma is one of the most malignant and aggressive cancers with high cancer-related deaths. However, it is unclear whether Ku80 regulates tumor growth in human melanoma. In this study, we screened a siRNA library targeting 6024 human genes and identified Ku80 as a potential therapeutic target in melanoma cells. Knockdown of Ku80 significantly suppressed melanoma cell proliferation and induced apoptosis, as well as enhanced the antitumor effect of melatonin in melanoma in vitro and in vivo. Overexpression of Ku80, however, promoted melanoma growth and increased the insensitivity of melanoma cells to melatonin. Mechanistically, we found that Ku80 bound to the PDK1 promoter and activated the transcription of PDK1. Moreover, we showed that the binding of Ku80 at the PDK-1 promoter was HIF1-α dependent, and melatonin degraded HIF1-α in melanoma cells. Furthermore, clinical data revealed that the expression of Ku80 and PDK-1 proteins were positively correlated and elevated in the tumor tissues of melanoma patients, and high expression of Ku80 predicted a poor prognosis in melanoma. Collectively, our study demonstrated that Ku80 promoted melanoma growth and regulated antitumor activity of melatonin by targeting HIF1-α dependent PDK-1 signaling pathway, suggesting that Ku80 may be a potential molecular target for melanoma treatment. Keywords: Ku80, PDK-1, Melatonin, HIF1-α, Melanoma

Hydraulic fracturing is widely applied to economic gas production from shale reservoirs, but the effect of the shale mineral composition on the physical-chemical reactions during hydraulic fracturing is still poorly understood. To develop a foundational understanding of chemical interactions occurring on shale with different mineralogical compositions, two different types of mineral composition marine shale (carbonate-poor and carbonate-rich) from the Niutitang Formation were reacted with slick water fracturing fluid in a laboratory reactor at 100°C and 50 MPa for three days. To identify the changes of the pore structure characteristics during hydraulic fracturing, the field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), low-temperature nitrogen adsorption, and porosity measurement were performed on the original and treated shale samples. After the slick water treatment, the dissolution of pyrite in carbonate-poor shale (obtained from Youyang County, labeled as YY) was observed by FE-SEM and XRD analyses, while in carbonate-rich shale (obtained from Guzhang County, labeled as GZ), the carbonate dissolution was observed. Results from the low-temperature N2 adsorption and porosity measurement demonstrated that the variation trend of pore structure characteristics for the YY and GZ shale samples was quite different after reacting with slick water fracturing fluid. For YY shale, the specific surface area, total pore volume, and porosity increased after the reaction, whereas an opposite trend was observed in the GZ shale. Moreover, the fractal dimension analysis illustrated that the pore surface became less rough and the pore structure became more complex in the YY shale, whereas the degree of pore surface roughness and pore structure complexity of the GZ shale was reduced. The results demonstrated that the initial mineralogical composition of shale played an important role in pore structure alteration during hydraulic fracturing.

OBJECTIVES: This study aimed to evaluate the safety and efficacy of a new nickel-titanium shape memory alloy compression anastomosis ring, NiTi CAR 27, in constructing an anastomosis for colorectal cancer resection compared with conventional staples. METHODS: In total, 234 consecutive patients diagnosed with colorectal cancer receiving sigmoidectomy and anterior resection for end-to-end anastomosis from May 2010 to June 2012 were retrospectively analyzed. The postoperative clinical parameters, postoperative complications and 3-year overall survival in 77 patients using a NiTi CAR 27 compression ring (CAR group) and 157 patients with conventional circular staplers (STA group) were compared. RESULTS: There were no statistically significant differences between the patients in the two groups in terms of general demographics and tumor features. A clinically apparent anastomotic leak occurred in 2 patients (2.6%) in the CAR group and in 5 patients (3.2%) in the STA group (p=0.804). These eight patients received a temporary diverting ileostomy. One patient (1.3%) in the CAR group was diagnosed with anastomotic stricture through an electronic colonoscopy after 3 months postoperatively. The incidence of postoperative intestinal obstruction was comparable between the two groups (p=0.192). With a median follow-up duration of 39.6 months, the 3-year overall survival rate was 83.1% in the CAR group and 89.0% in the STA group (p=0.152). CONCLUSIONS: NiTi CAR 27 is safe and effective for colorectal end-to-end anastomosis. Its use is equivalent to that of the conventional circular staplers. This study suggests that NiTi CAR 27 may be a beneficial alternative in colorectal anastomosis in Chinese colorectal cancer patients.

Both natural processes and human activities affect seawater calcium carbonate saturation state (Ωarag), while the mechanisms are still far from being clearly understood. This study analysed the seawater surface Ωarag during summer and winter in Jiaozhou Bay (JZB), China, based on two cruises observations performed in January and June 2017. The ranges of Ωarag values were 1.55~2.92 in summer and 1.62~2.15 in winter. Regression analyses were conducted to identify the drivers of the change of Ωarag distribution, and then the relative contributions of temperature, mixing processes and biological processes to the spatial differences in Ωarag were evaluated by introducing the difference between total alkalinity (TA) and dissolved inorganic carbon (DIC) as a proxy for Ωarag. The results showed that biological processes were the main factor affecting the spatial differences in Ωarag, with relative contributions of 70% in summer and 50% in winter. The contributions of temperature (25% in summer and 20% in winter) and the mixing processes (5% in summer and 30% in winter) were lower. The increasing urbanization in offshore areas can further worsen acidification, therefore environmental protection in both offshore and onshore is needed.

A survey was conducted to effectively investigate the characteristics of airborne particulate pollutants PM10 and PM2.5 during the peak tourist season at Mount Wutai Buddhism scenic spot, Shanxi, China. Characteristics of the PM10 and PM2.5 in Wu Ye Temple (core incense burners), Manjusri Temple (a traffic hub), Yang Bai Lin Village (a residential district), and Nan Shan Temple (located in a primitive forest district), were determined. The results showed that the PM10 concentration was more than 1.01–1.14 times higher than the threshold (50 μg/m3) of World Health Organization Air Quality Guidelines (2005), and the PM2.5 concentration was 1.75–2.70 times higher than the above standard (25 μg/m3). Particle size analysis indicated that the distribution of fine particulate matter in Wu Ye Temple ranged from 0 to 3.30 μm. In other sampling points, the fine particulate was mainly distributed in the range of 0–5.90 μm. The particulates in Wu Ye Temple were mainly characterized by spherical, rod-like, and irregular soot aggregates (PM10) and spherical particles of dust (PM2.5). Manjusri Temple and Yang Bai Lin Village predominantly exhibited irregular soil mineral particulate matter (PM10), and amorphous ultrafine soot particulate matter (PM2.5).

By using GPS and gravity data before and after the Wenchuan Ms8.0 earthquake and combining data from geological surveys and geophysical inversion studies, an initial coseismic fault model is constructed. The dip angle changes of the fault slip distribution on the fault plane are inversed, and the inversion results show that the shape of the fault resembles a double-shovel. The Yingxiu–Beichuan Fault is approximately 330 km long, the surface fault dip angle is 65.1°, which gradually reduces with increasing depth to 0° at the detachment layer at a depth of 19.62 km. The Guanxian–Jiangyou Fault is approximately 90 km long, and its dip angle at the surface is 55.3°, which gradually reduces with increasing depth; the fault joins the Yingxiu–Beichuan Fault at 13.75 km. Coseismic slip mainly occurs above a depth of 19 km. There are five concentrated rupture areas, Yingxiu, Wenchuan, Hanwang, Beichuan, and Pingwu, which are consistent with geological survey results and analyses of the aftershock distribution. The rupture mainly has a thrust component with a small dextral strike–slip component. The maximum slip was more than 10 m, which occurred near Beichuan and Hanwang. The seismic moment is 7.84 × 1020 Nm (Mw7.9), which is consistent with the seismological results.

Schwertmannite-mediated removal of arsenic from contaminated water has attracted increasing attention. However, schwertmannite chemical synthesis behavior under different H2O2 supply rates for ferrous ions oxidation is unclear. This study investigated pH, ferrous ions oxidation efficiency, and total iron precipitation efficiency during schwertmannite synthesis by adding H2O2 into FeSO4 · 7H2O solution at different supply rates. Specific surface area and arsenic (III) removal capacity of schwertmannite have also been studied. Results showed that pH decreased from ~3.48 to ~1.96, ~2.06, ~2.12, ~2.14, or ~2.17 after 60 h reaction when the ferrous ions solution received the following corresponding amounts of H2O2: 1.80 mL at 2 h (treatment 1); 0.90 mL at 2 h and 14 h (treatment 2); 0.60 mL at 2, 14, and 26 h (treatment 3); 0.45 mL at 2, 14, 26, and 38 h (treatment 4), or 0.36 mL at 2, 14, 26, 38, and 50 h (treatment 5). Slow H2O2 supply significantly inhibited the total iron precipitation efficiency but improved the specific surface area or arsenic (III) removal capacity of schwertmannite. For the initial 50.0 μg/L arsenic (III)-contaminated water under pH ~7.0 and using 0.25 g/L schwertmannite as an adsorbent, the total iron precipitation efficiency, specific surface area of the harvested schwertmannite, and schwertmannite arsenic(III) removal efficiency were 29.3%, 2.06 m2/g, and 81.1%, respectively, in treatment 1. However, the above parameters correspondingly changed to 17.3%, 16.30 m2/g, and 96.5%, respectively, in treatment 5.

Schwertmannite (Sch) is an efficient adsorbent for arsenic(III) removal from arsenic(III)-contaminated groundwater. In this study, bio-schertmannite was synthesized in the presence of dissolved ferrous ions and Acidithiobacillus ferrooxidans LX5 in a culture media. Bio-synthesized Sch characteristics, such as total organic carbon (TOC), morphology, chemical functional groups, mineral phase, specific surface area, and pore volume were systematically studied after it was dried at 105 °C and then heated at 250–550 °C. Differences in arsenic(III) removal efficiency between 105 °C dried-sch and 250–550 °C heated-sch also were investigated. The results showed that total organic carbon content in Sch and Sch weight gradually decreased when temperature increased from 105 °C to 350 °C. Sch partly transformed to another nanocrystalline or amorphous phase above 350 °C. The specific surface area of 250 °C heated-sch was 110.06 m2/g compared to 5.14 m2/g for the 105 °C dried-sch. Total pore volume of 105 °C dried-sch was 0.025 cm3/g with 32.0% mesopore and 68.0% macropore. However, total pore volume of 250 °C heated-mineral was 0.106 cm3/g with 23.6% micropore, 33.0% mesopore, and 43.4% macropore. The arsenic(III) removal efficiency from an initial 1 mg/L arsenic(III) solution (pH 7.5) was 25.1% when 0.25 g/L of 105 °C dried-sch was used as adsorbent. However, this efficiency increased to 93.0% when using 250 °C heated-sch as adsorbent. Finally, the highest efficiency for arsenic(III) removal was obtained with sch-250 °C due to high amounts of sorption sites in agreement with the high specific surface area (SSA) obtained for this sample.

To evaluate the characteristics of atmospheric particle retention by plant leaves during the tourism season in Buddhism-based scenic areas, plants distributed in the core area of the Mount Wutai scenic area were selected for study: Populus davidiana (Po. davidiana), Rosa hugonis Hemsl. (R. hugonis), Betula platyphylla Suk. (B. platyphylla), Rosa xanthina Lindl. (R. xanthina), Periploca sepium Bunge (Pe. sepium), Spiraea salicifolia L. (S. salicifolia), Vitex negundo var. Heterophylla (V. negundo var. heterophylla) and Pinus tabuliformis Carrière (Pi. tabuliformis). Before rain, the atmospheric suspended particle-retaining weight of the plant leaves varied in the range of 6.95 ± 1.55 (Pi. tabuliformis) to 38.60 ± 18.32 mg/cm2 (Po. davidiana); the light shaded areas caused by particles on leaves were in the range of 7.25 ± 0.04 (Pi. tabuliformis) to 126.50 ± 6.66 cm2/leaf (Po. davidiana); and the atmospheric particle-retaining horizontal density of leaves varied in the range of 110 ± 2 (Pi. tabuliformis) to 255 ± 11 per cm2 (Po. davidiana). After rain, the atmospheric suspended particle-retaining quality of plant leaves varied in the range of 0.65 ± 0.23 (Pi. tabuliformis) to 3.50 ± 1.83 mg/cm2 (Po. davidiana); the light shaded areas by particles on leaves were in the range of 4.26 ± 0.02 (Pi. tabuliformis) to 45.96 ± 2.42 cm2/leaf (Po. davidiana); and the atmospheric particle-retaining horizontal density of leaves was in the range of 97 ± 2 (Pi. tabuliformis) to 147 ± 7 per cm2 (Po. davidiana). The broad-leaved plants, particularly Po. davidiana, R. hugonis and B. platyphylla, were appropriate species for purification of atmospheric particles. Plants with lower dust-retention abilities than the above three species (e.g., R. xanthina, Pe. sepium, S. salicifolia and V. negundo var. heterophylla) could be alternative plants for purification. However, the needle-leaved plant Pi. tabuliformis was not recommended as a tree species for purification of atmospheric particles in the core area of the Mount Wutai scenic area.