Methylation-regulated tumor suppressor gene PDE7B promotes HCC invasion and metastasis through the PI3K/AKT signaling pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) has a high mortality rate, and the mechanisms underlying tumor development and progression remain unclear. However, inactivated tumor suppressor genes might play key roles. DNA methylation is a critical regulatory mechanism for inactivating tumor suppressor genes in HCC. Therefore, this study investigated methylation-related tumor suppressors in HCC to identify potential biomarkers and therapeutic targets. METHODS: We assessed genome-wide DNA methylation in HCC using whole genome bisulfite sequencing (WGBS) and RNA sequencing, respectively, and identified the differential expression of methylation-related genes, and finally screened phosphodiesterase 7B (PDE7B) for the study. The correlation between PDE7B expression and clinical features was then assessed. We then analyzed the changes of PDE7B expression in HCC cells before and after DNA methyltransferase inhibitor treatment by MassArray nucleic acid mass spectrometry. Furthermore, HCC cell lines overexpressing PDE7B were constructed to investigate its effect on HCC cell function. Finally, GO and KEGG were applied for the enrichment analysis of PDE7B-related pathways, and their effects on the expression of pathway proteins and EMT-related factors in HCC cells were preliminarily explored. RESULTS: HCC exhibited a genome-wide hypomethylation pattern. We screened 713 hypomethylated and 362 hypermethylated mCG regions in HCC and adjacent normal tissues. GO analysis showed that the main molecular functions of hypermethylation and hypomethylation were "DNA-binding transcriptional activator activity" and "structural component of ribosomes", respectively, whereas KEGG analysis showed that they were enriched in "bile secretion" and "Ras-associated protein-1 (Rap1) signaling pathway", respectively. PDE7B expression was significantly down-regulated in HCC tissues, and this low expression was negatively correlated with recurrence and prognosis of HCC. In addition, DNA methylation regulates PDE7B expression in HCC. On the contrary, overexpression of PDE7B inhibited tumor proliferation and metastasis in vitro. In addition, PDE7B-related genes were mainly enriched in the PI3K/ATK signaling pathway, and PDE7B overexpression inhibited the progression of PI3K/ATK signaling pathway-related proteins and EMT. CONCLUSION: PDE7B expression in HCC may be regulated by promoter methylation. PDE7B can regulate the EMT process in HCC cells through the PI3K/AKT pathway, which in turn affects HCC metastasis and invasion.

Siglec9 + tumor-associated macrophages predict prognosis and therapeutic vulnerability in patients with colon cancer.

BACKGROUND: Siglec9 has been identified as an immune checkpoint molecule on tumor-associated macrophages (TAMs). Nevertheless, the expression profile and clinical significance of Siglec9 + TAMs in colon cancer (CC) are still not fully understood. METHODS: Two clinical cohorts from distinct medical centers were retrospectively enrolled. Immunohistochemistry and immunofluorescence were conducted to evaluate the infiltration of immune cells. Single-cell RNA sequencing and flow cytometry were utilized to identify the impact of Siglec9 + TAMs on the tumor immune environment, which was subsequently validated through bioinformatics analysis of the TCGA database. Prognosis and the benefit of adjuvant chemotherapy (ACT) were also evaluated using Cox regression analysis and the Kaplan-Meier method. RESULTS: High infiltration of Siglec9 + TAMs was associated with worse prognosis and better benefit from 6-month ACT. Siglec9 + TAMs contributed to immunoevasion by promoting the infiltration of immunosuppressive cells and the dysfunction process of CD8 + T cells. Additionally, high infiltration of Siglec9 + TAMs was associated with the mesenchymal-featured subtype and overexpression of the VEGF signaling pathway, which was validated by the strongest communication between Siglec9 + TAMs and vascular endothelial cells. CONCLUSIONS: Siglec9 + TAMs may serve as a biomarker for prognosis and response to ACT in CC. Furthermore, the immunoevasive contexture and angiogenesis stimulated by Siglec9 + TAMs suggest potential treatment combinations for CC patients.

Comprehensive analysis of the protein phosphatase 2A regulatory subunit B56ε in pan-cancer and its role and mechanism in hepatocellular carcinoma.

BACKGROUND: B56ε is a regulatory subunit of the serine/threonine protein phosphatase 2A, which is abnormally expressed in tumors and regulates various tumor cell functions. At present, the application of B56ε in pan-cancer lacks a comprehensive analysis, and its role and mechanism in hepatocellular carcinoma (HCC) are still unclear. AIM: To analyze B56ε in pan-cancer, and explore its role and mechanism in HCC. METHODS: The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Profiling Interactive Analysis, and Tumor Immune Estimation Resource databases were used to analyze B56ε expression, prognostic mutations, somatic copy number alterations, and tumor immune characteristics in 33 tumors. The relationships between B56ε expression levels and drug sensitivity, immunotherapy, immune checkpoints, and human leukocyte antigen (HLA)-related genes were further analyzed. Gene Set Enrichment Analysis (GSEA) was performed to reveal the role of B56ε in HCC. The Cell Counting Kit-8, plate cloning, wound healing, and transwell assays were conducted to assess the effects of B56ε interference on the malignant behavior of HCC cells. RESULTS: In most tumors, B56ε expression was upregulated, and high B56ε expression was a risk factor for adrenocortical cancer, HCC, pancreatic adenocarcinoma, and pheochromocytoma and paraganglioma (all P < 0.05). B56ε expression levels were correlated with a variety of immune cells, such as T helper 17 cells, B cells, and macrophages. There was a positive correlation between B56ε expression levels with immune checkpoint genes and HLA-related genes (all P < 0.05). The expression of B56ε was negatively correlated with the sensitivity of most chemotherapy drugs, but a small number showed a positive correlation (all P < 0.05). GSEA analysis showed that B56ε expression was related to the cancer pathway, p53 downstream pathway, and interleukin-mediated signaling in HCC. Knockdown of B56ε expression in HCC cells inhibited the proliferation, migration, and invasion capacity of tumor cells. CONCLUSION: B56ε is associated with the microenvironment, immune evasion, and immune cell infiltration of multiple tumors. B56ε plays an important role in HCC progression, supporting it as a prognostic marker and potential therapeutic target for HCC.

Intratumor APOL3 delineates a distinctive immunogenic ferroptosis subset with prognosis prediction in colorectal cancer.

With the essential role of lipid transporting signaling in cancer-related immunity, apolipoprotein L3 (APOL3), a member of the apolipoprotein L gene family, demonstrated significant modulation ability in immunity. However, the expression profile and critical role of APOL3 in colorectal cancer (CRC) remain unclear. This study aimed to investigate the prognostic significance of APOL3 expression and its biological predictive value in CRC. The study enrolled multiple cohorts, consisting of 911 tumor microarray specimens of CRC patients from Zhongshan Hospital, 412 transcriptional data from The Cancer Genome Atlas, and 30 single-cell RNA sequencing (scRNA-seq) from internal and external CRC patients. APOL3 mRNA expression was directly acquired from public datasets, and APOL3 protein expression was detected using immunohistochemistry. Finally, the associations of APOL3 expression with clinical outcomes, immune context, and genomic and ferroptotic features were analyzed. Low APOL3 expression predicted poor prognosis and inferior responsiveness to 5-fluorouracil-based adjuvant chemotherapy (ACT) and targeted therapy. APOL3 fosters an immune-active microenvironment characterized by the promotion of ferroptosis, downregulation of macrophages, and upregulation of CD8+ T cell infiltration. Moreover, the expression of APOL3 in CD8+ T cells is intrinsically linked to ferroptosis and immune activation in CRC. In summary, APOL3 serves as an independent prognosticator and predictive biomarker for immunogenic ferroptosis, ACT, and targeted therapy in CRC. Furthermore, the APOL3 signaling activator could be a novel agent alone or in combination with current therapeutic strategies for CRC.

Impact of Surgical Management for Relapse After Conversion Hepatectomy for Initially Unresectable Colorectal Liver Metastasis: A Retrospective Cohort Study.

BACKGROUND: For patients with initially unresectable colorectal liver metastasis (IU-CRLM) receiving conversion therapy, disease relapse after conversion hepatectomy is common. However, few studies have focused on the assessment and management of relapse following conversion hepatectomy for IU-CRLM. METHODS: In the retrospective cohort study, 255 patients with IU-CRLM received conversion therapy and underwent subsequent R0 resection. The treatment effects of repeated liver-directed treatment (RLDT) versus non-RLDT for liver relapse were examined. Survival analysis was evaluated with the use of Cox proportional hazards methods. The importance of RLDT was further confirmed in the propensity score matching (PSM) and subgroup analyses. RESULTS: The 5-year overall survival (OS) rate after conversion hepatectomy was 34.9%. Liver relapse was observed in 208 patients. Of these patients, 106 underwent RLDT (65 underwent repeated hepatectomy and the remainder underwent ablation treatment), while 102 received only palliative chemotherapy. The relapse patients who underwent RLDT had a significantly longer OS than those who did not (hazard ratio (HR): 0.382, 95% CI: 0.259-0.563; P<0.001). In a multivariable analysis, RLDT was independently associated to prolonged survival (HR: 0.309, 95%CI: 0.181-0.529; P<0.001). In the PSM and subgroup analyses, RLDT consistently showed evidence of prolonging OS significantly. CONCLUSION: For IU-CRLM patients with liver relapse following conversion hepatectomy, the RLDT is essential for cure and prolonged survival. To avoid missing the opportunity for RLDT, intensive disease surveillance should be proposed.

Anatomical resection improves relapse-free survival in colorectal liver metastases in patients with KRAS/NRAS/BRAF mutations or right-sided colon cancer: a retrospective cohort study.

BACKGROUND: The type of liver resection (anatomical resection, AR or non-anatomical resection, NAR) for colorectal liver metastases (CRLM) is subject to debate. The debate may persist because some prognostic factors, associated with aggressive tumor biological behavior, have been overlooked. OBJECTIVE: Our study aimed to investigate the characteristics of patients who would benefit more from anatomical resection for CRLM. METHODS: Seven hundred twenty-nine patients who underwent hepatic resection of CRLM were retrospectively collected from June 2012 to May 2019. Treatment effects between AR and NAR were compared in full subgroup analyses. Tumor relapse-free survival (RFS) was evaluated by a stratified log-rank test and summarized with the use of Kaplan-Meier and Cox proportional hazards methods. RESULTS: Among 729 patients, 235 (32.2%) underwent AR and 494 (67.8%) underwent NAR. We showed favorable trends in RFS for AR compared with NAR in the patients with KRAS/NRAS/BRAF mutation (interaction P <0.001) or right-sidedness (interaction P <0.05). Patients who underwent AR had a markedly improved RFS compared with NAR in the cohorts of RAS/NRAS/BRAF mutation (median RFS 23.2 vs. 11.1 months, P <0.001) or right-sidedness (median RFS 31.6 vs. 11.5 months, P <0.001); upon the multivariable analyses, AR [gene mutation: hazard ratio (HR)=0.506, 95% CI=0.371-0.690, P <0.001; right-sidedness: HR=0.426, 95% CI=0.261-0.695, P =0.001) remained prognostic independently. In contrast, patients who underwent AR had a similar RFS compared with those who underwent NAR, in the cohorts of patients with gene wild-type tumors (median RFS 20.5 vs. 21.6 months, P =0.333). or left-sidedness (median RFS 15.8 vs. 19.5 months, P =0.294). CONCLUSIONS: CRLM patients with gene mutation or right-sidedness can benefit more from AR rather than from NAR.

Dual Breaking of Molecular Orbitals and Spatial Symmetry in an Optically Controlled Ferroelectric.

As particles carry quantified energy, photon radiation enables orbital transitions of energy levels, leading to changes in the spin state of electrons. The resulting switchable structural bistability may bring a new paradigm for manipulating ferroelectric polarization. However, the studies on molecular orbital breaking in the ferroelectric field remain blank. Here, for the first time, a new mechanism of ferroelectrics-dual breaking of molecular orbitals and spatial symmetry, demonstrated in a photochromic organic crystal with light-induced polarization switching, is formally proposed. By alternating the ultraviolet/visible light irradiation, the states of electron spin and the radial distribution p atomic orbitals experience a change, showing a reversible switch from "shoulder-to-shoulder" form to a "head-to-head" form. This reflects a reversible conversion between π and σ bonds, which induces and couples with the variation of spatial symmetry. The intersection of spatial symmetry breaking and molecular orbital breaking in ferroelectrics present in this work will be more conducive to data encryption and anticounterfeiting.

Treatment of metastatic colorectal cancer with BRAF V600E mutation: A multicenter real-world study in China.

BACKGROUND: BRAF V600E mutant-metastatic colorectal cancer (mCRC) is characterized by its short survival time. Treatment approaches vary depending on whether or not the metastases are initially resectable. The benefit of metastasectomy remains unclear, and the optimal first-line treatment is controversial. This study aimed to describe the prognosis of BRAF V600E mutant-mCRC, analyze the recurrence pattern in resectable patients, and explore the optimal first-line treatment for unresectable patients. METHODS: Patients diagnosed with BRAF V600E mutant-mCRC between February 2014 and January 2022 in five hospitals were enrolled. Date on clinical and pathological characteristics, treatment features, and survival outcomes were collected. RESULTS: Of the 220 included patients, 64 initially resectable patients had a significantly longer overall survival (OS) (37.07 vs. 20.20 months, P < 0.001) than initially unresectable patients. Of 156 unresectable patients, 54 received doublet (FOLFOX, XELOX or FOLFIRI) or triplet (FOLFOXIRI) chemotherapies (Chemo), 55 received Chemo plus Bevacizumab (Chemo+Bev), and 33 received vemurafenib plus cetuximab and irinotecan (VIC). The VIC regimen had a better progression-free survival (PFS) (12.70 months) than the Chemo (6.70 months, P < 0.001) and Chemo+Bev (8.8 months, P = 0.044) regimens. Patients treated with VIC had the best overall response rate (60.16%, P < 0.001), disease control rate (93.94%, P < 0.001) and conversional resection rate (24.24%, P = 0.003). CONCLUSIONS: Metastasectomy is beneficial to the survival of patients with BRAF V600E mutant-mCRC. For initially unresectable patients, VIC as first-line therapy is associated with a better prognosis and efficacy than doublet and triplet chemotherapy with or without bevacizumab.

B cells in tumor metastasis: friend or foe?

Metastasis is an important cause of cancer-related death. Immunotherapy may be an effective way to prevent and treat tumor metastasis in the future. Currently, many studies have focused on T cells, whereas fewer have focused on B cells and their subsets. B cells play an important role in tumor metastasis. They not only secrete antibodies and various cytokines but also function in antigen presentation to directly or indirectly participate in tumor immunity. Furthermore, B cells are involved in both inhibiting and promoting tumor metastasis, which demonstrates the complexity of B cells in tumor immunity. Moreover, different subgroups of B cells have distinct functions. The functions of B cells are also affected by the tumor microenvironment, and the metabolic homeostasis of B cells is also closely related to their function. In this review, we summarize the role of B cells in tumor metastasis, analyze the mechanisms of B cells, and discuss the current status and prospects of B cells in immunotherapy.

Apolipoprotein L3 enhances CD8+ T cell antitumor immunity of colorectal cancer by promoting LDHA-mediated ferroptosis.

Aim: Colorectal cancer (CRC) is the leading cause of cancer associated death worldwide and immune checkpoint blockade therapy only benefit a small set of CRC patients. Tumor ferroptosis of CRC reflected immune-activation in our previous findings. Understanding the mechanisms underlying how to bolster CD8+ T cells function through ferroptosis in CRC tumor microenvironment (TME) will greatly benefit cancer immunotherapy. Methods: Genes between ferroptosis and CD8+ T cell function in CRC were screened through Cox, WGCNA and differential expression analysis. Immunohistochemistry and Immunofluorescence analysis were performed. Co-immunoprecipitation were performed to determine protein-protein interaction, mRNA level was determined by qRT-PCR. RSL3 was used to induce ferroptosis, and ferroptosis levels were evaluated by measuring Transmission Electron Microscope analysis, MDA, Fe2+level and cell viability. Results: We screened APOL3 as the significant modulator for ferroptosis-related CD8+ infiltration in CRC. Next, by in vitro and in vivo, we found that increased APOL3 expression was positively correlated with sensitivity to ferroptosis and antitumor ability of CD8+ T cells. Next, we demonstrated that APOL3 can binds LDHA and promote its ubiquitylation-related degradation. Then, based on in vivo analysis and tumor specimen, we discovered the APOL3-LDHA axis can facilitate the tumor ferroptosis and cytotoxic ability of CD8+ T cells through increased IFNγ and decreased lactic acid concentration. Conclusion: The present study demonstrated that APOL3 promotes ferroptosis and immunotherapy in colorectal cancer cells. The present work provides us with a novel target to overcome drug resistance to ferroptosis and immunotherapy.

Low ferroptosis score predicts chemotherapy responsiveness and immune-activation in colorectal cancer.

BACKGROUND: Existing studies for ferroptosis and prognosis in colorectal cancer (CRC) were limited. In this study, we aim to investigate the prognostic role of ferroptosis markers in patients with CRC and exploration of its micro-environmental distributions. METHODS: Immunohistochemical staining was performed for CRC patients' tissue microarray. Selection and prognostic validation of markers were based on mRNA data from the cancer genome atlas (TCGA) database. Gene Set Enrichment Analysis (GSEA) was performed to indicate relative immune landmarks and hallmarks. Ferroptosis and immune contexture were examined by CIBERSORT. Survival outcomes were analyzed by Kaplan-Meier analysis and cox analysis. RESULTS: A panel of 42 genes was selected. Through mRNA expression difference and prognosis analysis, GPX4, NOX1 and ACSL4 were selected as candidate markers. By IHC, increased GPX4, decreased NOX1 and decreased FACL4 indicate poor prognosis and worse clinical characteristics. Ferroptosis score based on GPX4, NOX1 and ACSL4 was constructed and validated with high C-index. Low ferroptosis score can also demonstrate the better progression free survival and better adjuvant chemotherapy (ACT) responsiveness. Moreover, tumor with low ferroptosis score tend to be infiltrated with more CD4+ T cells, CD8+ T cells and less M1 macrophage. Finally, we found that IFN-γ was potentially the central molecule at the crossroad between ferroptosis and onco-immune response. CONCLUSION: Ferroptosis plays important role on CRC tumor progression, ACT response and prognosis. Ferroptosis contributes to immune-supportive responses and IFN-γ was the central molecule for this process.

CXCR6+ Tumor-Associated Macrophages Identify Immunosuppressive Colon Cancer Patients with Poor Prognosis but Favorable Response to Adjuvant Chemotherapy.

We explored the infiltration and prognostic value of CXCR6+TAMs in all stages of colon cancer (CC) patients and assessed predictive ability as a biomarker for different ACT regimens among high-risk stage II and stage III patients in both primary and validation cohorts. Two independent cohorts of 360 and 126 consecutive colon cancer patients were enrolled from two medical centers of Zhongshan Hospital. Immunofluorescence and immunohistochemistry were performed to detect the density of CXCR6+TAMs and activated CD8+ T cells. The infiltration of CXCR6+TAMs was higher in tumor tissues and increased with advanced tumor stage. A high density of CXCR6+TAMs predicted worse overall survival (OS) in all CC patients (HR = 2.49, 95% CI = (1.68, 3.70), p < 0.001), and was an independent risk factor verified by Cox regression analysis (HR = 1.68, 95% CI = (1.09, 2.59), p = 0.019). For high-risk stage II and stage III patients with a high density of CXCR6+TAMs, better disease-free survival (DFS) (HR = 0.32, 95% CI = (0.11, 0.89), p = 0.003), and OS (HR = 0.28, 95% CI = (0.07, 1.11), p = 0.014) were observed in the 6-month treatment group. There was a negative relationship between the density of CXCR6+TAMs and CD8+ T cells (R = −0.51, p < 0.001) as well as activated CD8+ T cells (R = −0.54, p < 0.001). Higher levels of IL-6 and lower levels of IL-2R and TNF-α were expressed in high-CXCR6+ TAM-density patients, which indicates that CXCR6+TAMs contribute to an immunosuppressive microenvironment. CXCR6+TAMs predicted prognosis and response to different durations of ACT in CC patients. CXCR6+TAMs were associated with an immunosuppressive microenvironment and suppressed the activation of CD8+ T cells.

Tumor-infiltrated activated B cells suppress liver metastasis of colorectal cancers.

More than 40% of patients with late-stage colorectal cancer (CRC) develop liver metastasis (LM). Which immune cells play important roles in CRC-LM and contribute to the difference between left-sided CRC (LCC) and right-sided CRC (RCC) remain unclear. By single-cell RNA sequencing (scRNA-seq), we not only find that activated B cells are significantly depleted in CRC with LM, but also find a subtype of B cells developed from activated B cells, namely immature plasma cell population alpha (iMPA), highly correlated with metastasis. Mechanistically, inhibition of the Wnt and transforming growth factor ß (TGF-ß) pathways in cancer cell promotes activated B cell migration via the SDF-1-CXCR4 axis. This study reveals that B cell subpopulations in the tumor immune microenvironment (TIME) play a key role in CRC-LM as well as in LCC and RCC. The preventive effects of modulating B cell subpopulations in CRC may provide a rationale for subsequent drug development and CRC-LM management.

The immune phenotypes and different immune escape mechanisms in colorectal cancer.

The tumor microenvironment (TME) plays a crucial role in tumor progression and metastasis. However, the immune phenotypes of colorectal cancer (CRC) and the underlying immune escape mechanism have not been studied sufficiently. A total of 1802 and 619 CRC samples from the microarray and TCGA cohorts were enrolled, respectively. The ssGSEA algorithm and unsupervised clustering were used for TME cell infiltration speculation and immune phenotype recognition in the above cohorts. A total of 447 samples from Zhongshan Hospital were collected for validation. Immunohistochemistry was performed in this cohort to quantify TME cell infiltration. The single-cell RNA-seq (scRNA-seq) data of 252,940 cells from 60 CRC samples was analyzed for further mechanistic exploration. CRC samples can be classified into three distinct immune phenotypes. Subtype 1, the immune-active subtype, was characterized by high infiltration of activated adaptive immune cells. Subtype 2, the immune-desert subtype, featured high tumor purity and low infiltration of immune and stromal cells. Subtype 3, the stroma-rich subtype, had high infiltration of stromal cells. The stroma-rich subtype conferred a significantly worse prognosis. The three subtypes had different immune escape mechanisms. The immune-active subtype has the highest immune checkpoint expression level. In comparison, the immune-desert subtype had the lowest immunogenicity and defective antigen presentation. The stroma-rich subtype lacked activated immune cells. In conclusion, distinct immune phenotypes and immune escape mechanisms may provide inspiration and direction for further research on CRC immunotherapy.

Ultrabroad Brillouin instantaneous frequency measurement with a designed linear system response.

We demonstrate an ultrabroad instantaneous frequency measurement (IFM) based on stimulated Brillouin scattering (SBS) with a designed linear system response. The linear system response is found to be the key factor that broadens the system bandwidth. It is realized by designing the sweeping method of frequency and amplitude of the local pump signal. With the improvement of linearity, the measurement error is decreased and the bandwidth of the SBS-based IFM is consequently enlarged. A Costas frequency modulated signal with an instantaneous bandwidth of 10.5 GHz is successfully measured by the designed system response. Further optimization of pump signal's characteristics extends the system bandwidth to 14.5 GHz. The measurement error of a linear frequency modulated (LFM) signal ranging from 6 GHz to 20.5 GHz is less than 1% of the instantaneous bandwidth.

An organic plastic ferroelectric with high Curie point.

Plastic ferroelectrics, featuring large entropy changes in phase transitions, hold great potential application for solid-state refrigeration due to the electrocaloric effect. Although conventional ceramic ferroelectrics (e.g., BaTiO3 and KNbO3) have been widely investigated in the fields of electrocaloric material and catalysis, organic plastic ferroelectrics with a high Curie point (T c) are rarely reported but are of great importance for the sake of environmental protection. Here, we reported an organic plastic ferroelectric, (-)-camphanic acid, which crystallizes in the P21 space group, chiral polar 2 (C2) point group, at room temperature. It undergoes plastic paraelectric-to-ferroelectric phase transition with the Aizu notation of 23F2 and high T c of 414 K, showing large entropy gain (ΔS t = 48.2 J K-1 mol-1). More importantly, the rectangular polarization-electric field (P-E) hysteresis loop was recorded on the thin film samples with a large saturated polarization (P s) of 5.2 µC cm-2. The plastic phase transition is responsible for its multiaxial ferroelectric feature. This work highlights the discovery of organic multiaxial ferroelectrics driven by the motive of combining chirality and plastic phase transition, which will extensively promote the practical application of such unique functional materials.

Target Designing Phase Transition Materials through Halogen Substitution.

Crystalline materials have received extensive attention due to their extraordinary physical and chemical properties. Among them, phase transition materials have attracted great attention in the fields of photovoltaic, switchable dielectric devices, and ferroelectric memories, etc. However, many of them suffer from low phase transition temperatures, which limits their practical application. In this work, we systematically designed crystalline materials, (TMXM)2 PtCl6 (X=F, Cl, Br, I) through halogen substitution on the cations, aiming to improving phase transition temperature. The resulting phase transition of (TMXM)2 PtCl6 (X=F, Cl, Br, I) get a significant enhancement, compared to the parent compound [(CH3 )4 N]2 PtCl6 ((TM)2 PtCl6 ). Such phase transition temperature enhancement can be attributed to the introduction of halogen atoms that increase the potential energy barrier of the cation rotation. In addition, (TMBM)2 PtCl6 and (TMIM)2 PtCl6 have a low symmetry and crystallize in the space group C2 /c and P21 21 21 , respectively. This work highlights the halogen substitution in designing crystal materials with high phase transition temperature.

Significance of Surgery in the Treatment of Colorectal Cancer Ovarian Metastases: A Retrospective Case Matching Study.

PURPOSE: Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. Ovarian metastases (OM), which are low in frequency, are reported to occur in 3-14% of women with CRC and have a poor prognosis. Studies have shown that surgical treatment may benefit patients with ovarian metastases arising from CRC. However, the precise benefit of surgery is uncertain. This study was implemented to identify treatment outcomes associated with ovarian metastases from CRC, as well as to clarify the importance of primary and metastatic lesion resection. PATIENTS AND METHODS: Between January 2008 and December 2018, the medical records of 93 patients diagnosed with CRC ovarian metastases (CRC-OM) at Zhongshan Hospital, Fudan University, Shanghai, were retrospectively analyzed. Clinicopathological characteristics as well as prognostic conditions were evaluated. Nineteen patients with only synchronous OM and 38 patients without metastases were matched to compare surgical outcomes. RESULTS: The median overall survival (OS) of the total 93 CRC-OM patients was 26 months. The median OS times of patients with ovary-only metastases (n=37) and those with other metastases (n=56) were 49 months and 20 months, respectively. Patients with only ovarian metastases had a longer OS time (p<0.001) than patients with other metastases. Patients with ovarian metastases resected (n=76) (p<0.001) had a longer OS time than those unresected (n=17). Synchronous (n=54) and metachronous (n=39) metastases indicated no significant survival difference. Patients with only ovarian metastases could achieve similar OS times to those of patients without metastases after primary and metastasis surgery. CONCLUSION: Surgical treatment is very important for CRC-OM patients. Primary and metastatic lesion resection can help achieve longer survival times.

Analysis of relapse-associated alternative mRNA splicing and construction of a prognostic signature predicting relapse in I-III colon cancer.

The literature comprehensively analyzed alternative splicing (AS) events in colon cancer is little and corresponding prognostic signature is still a lack. Based on data of TCGA, the relapse-associated ASs were comprehensively analyzed and a signature was further constructed to predict the relapse in I-III colon cancer. In total 1912 ASs of 1384 mRNA were identified as relapse-associated ASs, protein-protein interactions (PPI) and ASs-splicing factors (SF) interactions network were identified. We finally built a robust signature to predict the relapse of I-III colon cancer with a considerable AUC value in both the training group and the test group. The AUC in the entire set at 1, 3 and 5 year was 0.85, 0.83 and 0.836. Our study provided a profile of relapse-associated ASs in I-III colon cancer and built a robust signature to predict the relapse of I-III colon cancer.