Robot-assisted laparoscopic combined with endoscopic partial gastrectomy (RALE-PG) for the treatment of gastric gastrointestinal stromal tumors in challenging anatomical locations: single-center experience.

Background: Gastric gastrointestinal stromal tumors in challenging anatomical locations are difficult to remove. Methods: This study retrospectively analyzed the clinical data of 12 patients with gastric GISTs in challenging anatomical locations who underwent robot-assisted laparoscopic combined with endoscopic partial gastrectomy (RALE-PG) and manual suturing of the gastric wall. Results: This study included 12 patients with a mean age of 56.8 ± 9.8 years and a mean BMI of 23.9 ± 1.9 kg/m2. Tumors were located in the GEJ (n = 3), lesser curvature (n = 3), posterior gastric wall (n = 3) and antrum (n = 3). The cardia and pylorus were successfully preserved in all patients regardless of the tumor location. The mean tumor size was 4.5 ± 1.4 cm. The mitotic-count/50 mm2 was less than 5 in all patients (100%). There was no intraoperative tumor rupture (0%) and no conversion to open surgery (0%). The median operation time was 122 (97-240) min, and the median blood loss volume was 10 (5-30) ml. The median postoperative VAS score was 2 (2-4). The median time to first flatus was 2 (2-3) days. The median time to first fluid intake was 2 (2-3) days. The median time to first ambulation after the operation was 3 (2-4) days. No cases of anastomotic stenosis or leakage were found. The median time to drain removal for 6 patients was 5 (4-7) days. The median time to nasogastric tube removal for all patients was 2 (1-5) days. The median postoperative hospital stay was 5 (4-8) days. One patient (female/41 year) developed moderate anemia (Clavien-Dindo grade II complication). There was no unplanned readmission within 30 days after the operation. The median distance from the tumor to the resection margin was 1 (1-2) cm. R0 resection was achieved in all patients. The median follow-up period was 19 (10-25) months, and all patients survived with no recurrence or metastasis. Conclusions: RALE-PG is a safe, feasible and advantageous technique for treating GISTs in challenging anatomical locations. It can be used to accurately remove the tumor while preserving gastric function to the greatest extent, but long-term oncologic outcomes need to be evaluated in a study with a larger sample size and longer follow-up period.

Hierarchical classification-based pan-cancer methylation analysis to classify primary cancer.

Hierarchical classification offers a more specific categorization of data and breaks down large classification problems into subproblems, providing improved prediction accuracy and predictive power for undefined categories, while also mitigating the impact of poor-quality data. Despite these advantages, its application in predicting primary cancer is rare. To leverage the similarity of cancers and the specificity of methylation patterns among them, we developed the Cancer Hierarchy Classification Tool (CHCT) using the idea of hierarchical classification, with methylation data from 30 cancer types and 8239 methylome samples downloaded from publicly available databases (The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO)). We used unsupervised clustering to divide the classification subproblems and screened differentially methylated sites using Analysis of variance (ANOVA) test, Tukey-kramer test, and Boruta algorithms to construct models for each classifier module. After validation, CHCT accurately classified 1568 out of 1660 cases in the test set, with an average accuracy of 94.46%. We further curated an independent validation cohort of 677 cancer samples from GEO and assigned a diagnosis using CHCT, which showed high diagnostic potential with generally high accuracies (an average accuracy of 91.40%). Moreover, CHCT demonstrates predictive capability for additional cancer types beyond its original classifier scope as demonstrated in the medulloblastoma and pituitary tumor datasets. In summary, CHCT can hierarchically classify primary cancer by methylation profile, by splitting a large-scale classification of 30 cancer types into ten smaller classification problems. These results indicate that cancer hierarchical classification has the potential to be an accurate and robust cancer classification method.

A novel super-enhancer-related gene signature predicts prognosis and immune microenvironment for breast cancer.

BACKGROUND: This study targeted at developing a robust, prognostic signature based on super-enhancer-related genes (SERGs) to reveal survival prognosis and immune microenvironment of breast cancer. METHODS: RNA-sequencing data of breast cancer were retrieved from The Cancer Genome Atlas (TCGA), 1069 patients of which were randomly assigned into training or testing set in 1:1 ratio. SERGs were downloaded from Super-Enhancer Database (SEdb). After which, a SERGs signature was established based on the training set, with its prognostic value further validated in the testing set. Subsequently, we identified the potential function enrichment and tumor immune infiltration of the model. Moreover, in vitro experiments were completed to further explore the biological functions of ZIC2 gene (one of the risk genes in the prognostic model) in breast cancer. RESULTS: A risk score system of prognostic value was constructed with 6 SERGs (ZIC2, NFE2, FOXJ1, KLF15, POU3F2 and SPIB) to find patients in high-risk group with significantly worse prognosis in both training and testing sets. In addition, a multivariate regression was established via integrating the 6 genes with age and N stage, indicating well performance by calibration, time-dependent receiver operating characteristic (ROC) analysis and decision curve analysis (DCA). Further analysis demonstrated that tumor-associated pathological processes and pathways were significantly enriched in the high-risk group. In general, the novel SERGs signature could be applied to screen breast cancer with immunosuppressive microenvironment for the risk score was negatively correlated with ESTIMATE score, tumor-infiltration lymphocytes (such as CD4 + and CD8 + T cell), immune checkpoints and chemotactic factors. Furthermore, down-regulation of ZIC2 gene expression inhibited the cell viability, cellular migration and cell cycle of breast cancer cells. CONCLUSIONS: The novel SERGs signature could predict the prognosis of breast cancer; and SERGs might serve as potential therapeutic targets for breast cancer.

DISC1 as a prognostic biomarker correlated with immune infiltrates in gastric cancer.

Multiple mental diseases could arise in people who have the disrupted in schizophrenia 1 (DISC1) gene. However, it was unknown how DISC1 might contribute to the development of tumors and immune responses. We extracted data from the Cancer Genome Atlas (TCGA) and TISIDB databases from stomach adenocarcinoma (STAD) patients, which revealed that DISC1 overexpression was closely associated with tumor histological type (mucinous vs. tubular, OR = 2.860, CI = 1.423-5.872, p = 0.004), as well as tumor stage and grade. Furthermore, the higher the DISC1 expression, the lower the overall 10-year survival rate. Patients with low DISC1 expression had a significantly longer progression-free interval (PFI) and disease-specific survival (DSS) than patients with high DISC1 expression. However, patients with higher DISC1 expression in the T3&T4, N0&N1 and M0 subgroups had poorer prognosis in terms of OS, DSS and PFI, as could be seen in the subgroup survival analysis. Public datasets were used to predict lncRNA-miRNA-DISC1 regulation. DISC1 was significantly up-regulated in GC(gastric cancer), and its expression levels showed a moderate to strong positive correlation with infiltration levels of effector memory T cells (Tem) and central memory T cells (Tcm), and a negative correlation was observed with Th17 cells and NK CD56bright cells. In addition, concomitant with the high expression of the DISC1 gene was a decrease in MHC-I (Major Histocompatibility Complex-I)expression and an increase in MHC-II expression, and altered chemokine expression. The upregulation of CXCL12 and CXCR4 expression could be caused by an increase in DISC1 expression. The above expression variability and correlation suggest a role for DISC1 in regulating tumor immunity in GC. These findings suggest that high expression of DISC1 could be an independent prognostic factor for GC.

Realizing high-capacity all-solid-state lithium-sulfur batteries using a low-density inorganic solid-state electrolyte.

Lithium-sulfur all-solid-state batteries using inorganic solid-state electrolytes are considered promising electrochemical energy storage technologies. However, developing positive electrodes with high sulfur content, adequate sulfur utilization, and high mass loading is challenging. Here, to address these concerns, we propose using a liquid-phase-synthesized Li3PS4-2LiBH4 glass-ceramic solid electrolyte with a low density (1.491 g cm-3), small primary particle size (~500 nm) and bulk ionic conductivity of 6.0 mS cm-1 at 25 °C for fabricating lithium-sulfur all-solid-state batteries. When tested in a Swagelok cell configuration with a Li-In negative electrode and a 60 wt% S positive electrode applying an average stack pressure of ~55 MPa, the all-solid-state battery delivered a high discharge capacity of about 1144.6 mAh g-1 at 167.5 mA g-1 and 60 °C. We further demonstrate that the use of the low-density solid electrolyte increases the electrolyte volume ratio in the cathode, reduces inactive bulky sulfur, and improves the content uniformity of the sulfur-based positive electrode, thus providing sufficient ion conduction pathways for battery performance improvement.

Comprehensive research into prognostic and immune signatures of transcription factor family in breast cancer.

BACKGROUND: Breast cancer (BRCA) is the most common malignancy with high morbidity and mortality in women, and transcription factor (TF) is closely related to the occurrence and development of BRCA. This study was designed to identify a prognostic gene signature based on TF family to reveal immune characteristics and prognostic survival of BRCA. METHODS: In this study, RNA-sequence with corresponding clinical data were obtained from The Cancer Genome Atlas (TCGA) and GSE42568. Prognostic differentially expressed transcription factor family genes (TFDEGs) were screened to construct a risk score model, after which BRCA patients were stratified into low-risk and high-risk groups based on their corresponding risk scores. Kaplan-Meier (KM) analysis was applied to evaluate the prognostic implication of risk score model, and a nomogram model was developed and validated with the TCGA and GSE20685. Furthermore, the GSEA revealed pathological processes and signaling pathways enriched in the low-risk and high-risk groups. Finally, analyses regarding levels of immune infiltration, immune checkpoints and chemotactic factors were all completed to investigate the correlation between the risk score and tumor immune microenvironment (TIME). RESULTS: A prognostic 9-gene signature based on TFDEGs was selected to establish a risk score model. According to KM analyses, high-risk group witnessed a significantly worse overall survival (OS) than low-risk group in both TCGA-BRCA and GSE20685. Furthermore, the nomogram model proved great possibility in predicting the OS of BRCA patients. As indicted in GSEA analysis, tumor-associated pathological processes and pathways were relatively enriched in high-risk group, and the risk score was negatively correlated with ESTIMATE score, infiltration levels of CD4+ and CD8+T cells, as well as expression levels of immune checkpoints and chemotactic factors. CONCLUSIONS: The prognostic model based on TFDEGs could distinguish as a novel biomarker for predicting prognosis of BRCA patients; in addition, it may also be utilized to identify potential benefit population from immunotherapy in different TIME and predict potential drug targets.

Ultrasound-assisted carbon nanoparticle labeling of neoadjuvant chemotherapy for breast-conserving surgery in breast cancer.

Background: Neoadjuvant chemotherapy has gradually become an important means of breast cancer treatment; however, tumor regression following chemotherapy remains a concern. This study was conducted to investigate the effect of ultrasound-assisted carbon nanoparticle labeling in neoadjuvant chemotherapy for breast-conserving surgery in breast cancer. Methods: This was a prospective clinical trial study (clinical registration number: ChiCTR-OOC-15006844). Sixty-eight breast cancer patients confirmed by biopsy between July 2015 and January 2017 were randomly selected from the clinical data. Of these, 32 patients were screened for neoadjuvant chemotherapy, forming a consecutive, random series. An ultrasound-guided carbon nanotube was used to mark the original tumor, and sentinel lymph node biopsies were performed. After 4-6 cycles of standard neoadjuvant chemotherapy, 26 patients were selected for breast-conserving surgery. The feasibility and validity of carbon nanoparticle labeling were analyzed through the negative rate of incision margin, the volume of resected tumors, the detection rate of black-stained sentinel lymph nodes, the recurrence rate of ipsilateral breast, and postoperative survival. Results: In all, 32 patients underwent sentinel lymph node biopsy, 29 cases were detected (90.6%), the false-negative rate was 3.8% (1/26), and 0-4 sentinel lymph nodes (mean 1.8±1.1) were detected. A total of 26 patients underwent breast-conserving surgery, 5 underwent secondary excision, and 1 underwent subcutaneous adenectomy due to a positive margin. The minimum margin between the resected site and the infiltrated part was 1.0-2.1 cm (1.3±0.3 cm). The diameter of resected tumors ranged from 2.2 to 4.5 cm (3.1±0.6 cm). No recurrence or distant metastasis of ipsilateral breast tumors was observed during follow-up (the median follow-up time was 9 months). Conclusions: Ultrasound-assisted carbon nanoparticle labeling is effective for sentinel lymph node tracing before neoadjuvant chemotherapy and has a high detection rate for metastatic lymph nodes. During breast-conserving surgery, it can determine the extent of tumor resection to achieve precision surgical treatment.

Prognostic model construction and validation of esophageal cancer cellular senescence-related genes and correlation with immune infiltration.

Introduction: Cellular senescence is a cellular response to stress, including the activation of oncogenes, and is characterized by irreversible proliferation arrest. Restricted studies have provided a relationship between cellular senescence and immunotherapy for esophageal cancer. Methods: In the present study, we obtained clinical sample of colon cancer from the TCGA database and cellular senescence-related genes from MSigDB and Genecard datasets. Cellular senescence-related prognostic genes were identified by WGCNA, COX, and lasso regression analysis, and a cellular senescence-related risk score (CSRS) was calculated. We constructed a prognostic model based on CSRS. Validation was performed with an independent cohort that GSE53625. Three scoring systems for immuno-infiltration analysis were performed, namely ssGSEA analysis, ESTIMATE scores and TIDE scores. Result: Five cellular senescence-related genes, including H3C1, IGFBP1, MT1E, SOX5 and CDHR4 and used to calculate risk score. Multivariate regression analysis using cox regression model showed that cellular senescence-related risk scores (HR=2.440, 95% CI=1.154-5.159, p=0.019) and pathological stage (HR=2.423, 95% CI=1.119-5.249, p=0.025) were associated with overall survival (OS). The nomogram model predicts better clinical benefit than the American Joint Committee on Cancer (AJCC) staging for prognosis of patients with esophageal cancer with a five-year AUC of 0.946. Patients with high CSRS had a poor prognosis (HR=2.93, 95%CI=1.74-4.94, p<0.001). We observed differences in the distribution of CSRS in different pathological staging and therefore performed a subgroup survival analysis finding that assessment of prognosis by CSRS independent of pathological staging. Comprehensive immune infiltration analysis and functional enrichment analysis suggested that patients with high CSRS may develop immunotherapy resistance through mechanisms of deacetylation and methylation. Discussion: In summary, our study suggested that CSRS is a prognostic risk factor for esophageal cancer. Patients with high CSRS may have worse immunotherapy outcomes.

HPV 16 E6 promotes growth and metastasis of esophageal squamous cell carcinoma cells in vitro.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies worldwide. Increasing evidence suggests that human papillomavirus (HPV) infection may be associated with the etiology of ESCC. However, the precise role of HPV in ESCC remains unclear. METHODS AND RESULTS: Proliferation and apoptosis of ESCC cells upon infection with HPV16 E6 were detected using CCK-8 assays and Western blot analyses. The migration rate was measured with a wound healing assay, and a Transwell Matrigel invasion assay was used to detect the invasive ability. RT-qPCR was performed to detect the expression of E6AP, p53, and miR-34a. The proliferation rates were significantly higher in HPV16E6-transfected cell groups compared with the negative control groups. Bax protein expression was downregulated in HPV16E6-treated groups compared to the controls. The wound healing and Transwell Matrigel invasion assays indicated that HPV16 E6 infection could increase ESCC cell migration and invasion. Furthermore, E6AP, p53 and miR-34a expression were decreased in HPV16 E6-transfected cell lines. CONCLUSION: Our results not only provide evidence that HPV16 E6 promotes cell proliferation, migration, and invasion in ESCC, but also suggests a correlation between HPV infection and E6AP, p53 and miR-34a expression. Consequently, HPV16 E6 may play an important role in ESCC development.

Mn4+-Substituted Li-Rich Li1.2Mn0.43+Mnx4+Ti0.4-xO2 Materials with High Energy Density.

In this work, Li-rich Li1.2Mn0.43+Mnx4+Ti0.4-xO2 (LMMxTO, 0 ≤ x ≤ 0.4) oxides have been studied for the first time. X-ray diffraction (XRD) patterns show a cation-disordered rocksalt structure when x ranges from 0 to 0.2. After Mn4+ substitution, LMM0.2TO delivers a high specific capacity of 322 mAh g-1 at room temperature (30 °C, 30 mA g-1) and even 352 mAh g-1 (45 °C, 30 mA g-1) with an energy density of 1041 Wh kg-1. The reason for such a high capacity of LMM0.2TO is ascribed to the increase of both cationic (Mn) and anionic (O) redox after Mn4+ substitution, which is proved by dQ/dV curves, X-ray absorption near edge structure, DFT calculations, and in situ XRD results. In addition, the roles of Mn3+ and Ti4+ in LMM0.2TO are also discussed in detail. A ternary phase diagram is established to comprehend and further optimize the earth-abundant Mn3+-Mn4+-Ti4+ system. This work gives an innovative strategy to improve the energy density, broadening the ideas of designing Li-rich materials with better performance.

Modelling spatiotemporal trends in range shifts of marine commercial fish species driven by climate change surrounding the Antarctic Peninsula.

In recent decades, the relationships between species distributional shifts and climate change have been investigated at various geographic scales, yet there is still a gap in understanding the impacts of climate change on marine commercial fish species surrounding the Antarctic Peninsula. The dynamic bioclimate envelope model (DBEM) is a mechanistic model that encompass species distribution model and population dynamic model approaches to project the spatiotemporal change of marine commercial fish species driven by various climate change scenarios in the Southern Ocean. This paper focuses on the spatiotemporal changes of marine commercial fish species surrounding the Antarctic Peninsula under a high emissions scenario (RCP8.5) and a low emissions scenario (RCP2.6) from 1970 to 2060 following three different Earth System Models (ESMs), namely, the GFDL-ESM 2G, IPSL-CM5A-MR and MPI-ESM-MR. Results reveal that: i) The general latitudinal gradient patterns in species richness shifts poleward associated with a global abundance decrease ii) The Spp. richness in Eastern Antarctic Peninsula (EAP) is higher than in the Western Antarctic Peninsula (WAP) at the same latitude (>65°S latitude). iii) The reasons are that the krill-dependent predators in WAP could face a higher risk of depletion than that in EAP due to ocean warming and anthropogenic activities.

Tuning Oxygen Redox Reaction through the Inductive Effect with Proton Insertion in Li-Rich Oxides.

As a parent compound of Li-rich electrodes, Li2MnO3 exhibits high capacity during the initial charge; however, it suffers notoriously low Coulombic efficiency due to oxygen and surface activities. Here, we successfully optimize the oxygen activities toward reversible oxygen redox reactions by intentionally introducing protons into lithium octahedral vacancies in the Li2MnO3 system with its original structural integrity maintained. Combining structural probes, theoretical calculations, and resonant inelastic X-ray scattering results, a moderate coupling between the introduced protons and lattice oxygen at the oxidized state is revealed, which stabilizes the oxygen activities during charging. Such a coupling leads to an unprecedented initial Coulombic efficiency (99.2%) with a greatly improved discharge capacity of 302 mAh g-1 in the protonated Li2MnO3 electrodes. These findings directly demonstrate an effective concept for controlling oxygen activities in Li-rich systems, which is critical for developing high-energy cathodes in batteries.

Elucidating and Mitigating the Degradation of Cationic-Anionic Redox Processes in Li1.2Mn0.4Ti0.4O2 Cation-Disordered Cathode Materials.

Cation-disordered rock-salt oxides with the O2-/O2n- redox reaction, such as Li1.2Mn0.4Ti0.4O2 (LMTO), are critical Li-rich cathode materials for designing high-energy-density batteries. Understanding the cationic-anionic redox accompanying the structural evolution process is really imperative to further improve the performance. In this work, the cationic-anionic redox and capacity degradation mechanism of carbon-coated LMTO during (dis)charge processes are elucidated by combining in situ X-ray diffraction, X-ray absorption near-edge spectroscopy, differential electrochemical mass spectrometry, transmission electron microscopy, and electrochemical analyses. It is concluded that the redox reaction of Mn2+/Mn4+ is quite stable, while the severe degradation is mainly caused by the O2-/O2n- redox process. Moreover, we clearly clarify how the cationic-anionic interplay governs sluggish kinetics, large polarization, and capacity fading in LMTO, and reveal for the first time that a certain amount of carbon coating is capable of suppressing the irreversible lattice oxygen loss and results in an encouraging cycling performance. In summary, we elucidate the degradation of cationic-anionic redox processes in cation-disordered cathode materials and propose strategies for adjusting the electronic/ionic conductivity of the electrodes to modulate the oxygen redox reactions, setting a new direction for the design of better cation-disordered oxides.

Exploring Highly Reversible 1.5-Electron Reactions (V3+/V4+/V5+) in Na3VCr(PO4)3 Cathode for Sodium-Ion Batteries.

The development of highly reversible multielectron reaction per redox center in sodium super ionic conductor-structured cathode materials is desired to improve the energy density of sodium-ion batteries. Here, we investigated more than one-electron storage of Na in Na3VCr(PO4)3. Combining a series of advanced characterization techniques such as ex situ 51V solid-state nuclear magnetic resonance, X-ray absorption near-edge structure, and in situ X-ray diffraction, we reveal that V3+/V4+ and V4+/V5+ redox couples in the materials can be accessed, leading to a 1.5-electron reaction. It is also found that a light change on the local electronic and structural states or phase change could be observed after the first cycle, resulting in the fast capacity fade at room temperature. We also showed that the irreversibility of the phase changes could be largely suppressed at low temperature, thus leading to a much improved electrochemical performance.

Insights into the Effects of Zinc Doping on Structural Phase Transition of P2-Type Sodium Nickel Manganese Oxide Cathodes for High-Energy Sodium Ion Batteries.

P2-type sodium nickel manganese oxide-based cathode materials with higher energy densities are prime candidates for applications in rechargeable sodium ion batteries. A systematic study combining in situ high energy X-ray diffraction (HEXRD), ex situ X-ray absorption fine spectroscopy (XAFS), transmission electron microscopy (TEM), and solid-state nuclear magnetic resonance (SS-NMR) techniques was carried out to gain a deep insight into the structural evolution of P2-Na0.66Ni0.33-xZnxMn0.67O2 (x = 0, 0.07) during cycling. In situ HEXRD and ex situ TEM measurements indicate that an irreversible phase transition occurs upon sodium insertion-extraction of Na0.66Ni0.33Mn0.67O2. Zinc doping of this system results in a high structural reversibility. XAFS measurements indicate that both materials are almost completely dependent on the Ni(4+)/Ni(3+)/Ni(2+) redox couple to provide charge/discharge capacity. SS-NMR measurements indicate that both reversible and irreversible migration of transition metal ions into the sodium layer occurs in the material at the fully charged state. The irreversible migration of transition metal ions triggers a structural distortion, leading to the observed capacity and voltage fading. Our results allow a new understanding of the importance of improving the stability of transition metal layers.