An evaluation model of hepatic steatosis based on CT value and serum uric acid/HDL cholesterol ratio can predict intrahepatic recurrence of colorectal cancer liver metastasis.

BACKGROUND: Intrahepatic recurrence is one of the main causes of treatment failure in patients with colorectal cancer liver metastasis (CRLM). Hepatic steatosis was reported to provide fertile soil for metastasis. The effect of irinotecan-inducted hepatic steatosis on the progression of liver metastasis remains to be verified. Therefore, we aim to clarify the effect of hepatic steatosis on postoperative intrahepatic recurrence in CRLM and whether it is relevant to irinotecan-based chemotherapy. METHODS: Data for a total of 284 patients undergoing curative surgical treatment for CRLMs were retrospectively reviewed between March 2007 and June 2018. Hepatic steatosis score (HSS) was established by combining Liver to Spleen CT ratio (LSR) and Uric acid to HDL-cholesterol ratio (UHR) to detect the presence of hepatic steatosis. RESULTS: The evaluation model is consistent with pathological results and has high prediction ability and clinical application value. Patients with HSS high risk (HSS-HR) had significantly worse prognosis than those with HSS low risk (HSS-LR) (3-year intrahepatic RFS: 42.7% vs. 29.4%, P = 0.003; 5-year OS: 45.7% vs. 26.5%, P = 0.002). Univariate and multivariate analysis confirmed its essential role in the prediction of intrahepatic RFS. Besides, patients treated with preoperative irinotecan chemotherapy were more likely to end up with HSS-HR than those with non-irinotecan chemotherapy (63.3% vs. 21.8%, P < 0.001). Furthermore, irinotecan chemotherapy is relevant to worse prognosis in baseline HSS-HR patients. CONCLUSION: In summary, patients with HSS-HR had significantly worse 5-year OS and 3-year intrahepatic RFS. Irinotecan chemotherapy is more likely to lead to HSS-HR and pre-existing hepatic steatosis may be a worse prognostic factor limiting patients underwent IRI-based chemotherapy.

Efficacy and Safety of Neoadjuvant Subcutaneous Envafolimab in dMMR/MSI-H Locally Advanced Colon Cancer.

BACKGROUND: Neoadjuvant immunotherapy with programmed death-ligand 1 blockade for colon cancer, especially for mismatch repair-deficient (dMMR)/high microsatellite instability (MSI-H) colon cancer, has gained considerable attention recently. OBJECTIVE: This study aimed to assess the safety and efficacy of neoadjuvant subcutaneous envafolimab in patients with dMMR/MSI-H locally advanced colon cancer. METHODS: Patients with dMMR/MSI-H locally advanced colon cancer treated with envafolimab at Sun Yat-sen University Cancer Center and Yunnan Cancer Hospital from October 2021 to July 2023 were retrospectively reviewed and analyzed. The primary endpoint was the pathological complete response (CR) rate, and secondary endpoints were treatment-related adverse events and complete clinical response rate. RESULTS: Overall, 15 patients were analyzed. After neoadjuvant immunotherapy with envafolimab, six patients achieved a CR, with five partial responses, and four stable disease. Three patients achieving a complete clinical response chose to accept a "watch and wait" strategy, and surgery was performed in 12 patients. Postoperative pathology results revealed seven patients achieved pathological CRs, and five patients achieved tumor regression grade 2, with 66.7% of the total CR rate. The most common treatment-related adverse events were pruritus and rash (40%), with no severe cases. No recurrences occurred over a 7.9-month follow-up. CONCLUSIONS: Envafolimab yielded promising surgical outcomes and safety in dMMR/MSI-H locally advanced colon cancer, representing a promising treatment modality for this population.

Unveiling the Research Landscape and Emerging Trends in Cell Cycle for Cancer Immunotherapy: A Bibliometric Analysis (1990-2022).

BACKGROUND The direct and indirect roles of the cell cycle in immunology of the tumor microenvironment (TME) are topics of intense scientific interest. Therefore, this study aimed to investigate the knowledge domain and hotspots related to the cell cycle for cancer immunology applications. MATERIAL AND METHODS The Web of Science Core Collection (WoSCC) was used as a powerful tool for identifying articles related to cell cycle for cancer immunology applications. Co-occurrence relationships were examined with R, VOSviewer, and CiteSpace software. Related research hotspots and possible future trends were also examined. RESULTS A total of 1844 qualified English-language documents were obtained in WoSCC between 1999 and 2022, with a 7.66% annual growth rate. These eligible studies were co-authored by 2246 institutions in 51 countries/regions, with the greatest article number being published in the United States (36%, 664/1844), followed by China (19%, 351/1844) and Germany (4.5%, 83/1844). The top 3 institutions with the most publications and the top 3 academic journals (n=390 in total) on this topic that published the most articles were identified. Key nodes from the co-cited network were aggregated and identified to reveal the shift in cell cycle for cancer immunology applications. Notably, the current research hotspots in this field include "tumor progression", "chemotherapy", "resistance", "clinical trial", and "target population". CONCLUSIONS This study revealed field profiles, research hotspots, and future directions of cell cycle dysregulation-related immunology, and the findings will offer a vigorous roadmap for further studies in the combination therapy of cell cycle inhibitors and immune checkpoint inhibitors for treating various cancers. Our results can shed more light on relevant research in this field.

A neutrophil extracellular traps-related classification predicts prognosis and response to immunotherapy in colon cancer.

Neutrophil extracellular traps (NETs) have been categorized as a form of inflammatory cell death mode of neutrophils (NETosis) involved in natural immunity and the regulation of adaptive immunity. More and more studies revealed the ability of NETs to reshape the tumor immune microenvironment (TIME) by limiting antitumor effector cells, which may impair the efficacy of immunotherapy. To explore whether NETs-related genes make vital impacts on Colon carcinoma (COAD), we have carried out a systematic analysis and showed several findings in the present work. First, we obtained the patient's data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset, aiming to detect two NETs-associated subtypes by consensus clustering. For the purpose of annotating the roles of NETs-related pathways, gene ontology enrichment analyses were adopted. Next, we constructed a 6 novel NETs-related genes score using the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model. We found that the NETs risk score was notably upregulated in COAD patient samples, and its levels were notably correlated with tumor clinicopathological and immune traits. Then, according to NETs-associated molecular subtypes and the risk signature, this study compared immune cell infiltration calculated through the estimate, CIBERSORT, TIMER, ssGSEA algorithms, tumor immune dysfunction, as well as exclusion (TIDE). Furthermore, we confirm that MPO(myeloperoxidase) was significantly upregulated in COAD patient samples, and its levels were significantly linked to tumor malignancy and clinic outcome. Moreover, multiplex immunohistochemistry (mIHC) spatial analysis confirmed that MPO was closely related to Treg and PD-1 + Treg in spatial location which suggested MPO may paly an important role in TIME formation. Altogether, the obtained results indicated that a six NETs-related genes prognostic signature was conducive to estimating the prognosis and response of chemo-/immuno-therapy of COAD patients.

Heterologous Expression of Dehydration-Inducible MfbHLH145 of Myrothamnus flabellifoli Enhanced Drought and Salt Tolerance in Arabidopsis.

Myrothamnus flabellifolia is the only woody resurrection plant found in the world. It has a strong tolerance to drought and can survive long-term exposure to desiccated environments. However, few genes related to its drought tolerance have been functionally characterized and the molecular mechanisms underlying the stress tolerance of M. flabellifolia are largely unknown. In this study, we isolated a dehydration-inducible bHLH transcription factor gene MfbHLH145 from M. flabellifolia. Heterologous expression of MfbHLH145 enhanced the drought and salt tolerance of Arabidopsis. It can not only promote root system development under short-term stresses, but also improve growth performance under long-term treatments. Further investigation showed that MfbHLH145 contributes to enhanced leaf water retention capacity through the promotion of stomatal closure, increased osmolyte accumulation, and decreased stress-induced oxidative damage through an increase in antioxidant enzyme activities. These results suggest that MfbHLH145 may be involved in the positive regulation of stress responses in M. flabellifolia. This study provides insight into the molecular mechanism underlying the survival of M. flabellifolia in extreme dehydration conditions.

Heterologous Expression of Dehydration-Inducible MfWRKY17 of Myrothamnus Flabellifolia Confers Drought and Salt Tolerance in Arabidopsis.

: As the only woody resurrection plant, Myrothamnus flabellifolia has a strong tolerance to drought and can survive long-term in a desiccated environment. However, the molecular mechanisms related to the stress tolerance of M. flabellifolia are largely unknown, and few tolerance-related genes previously identified had been functionally characterized. WRKYs are a group of unique and complex plant transcription factors, and have reported functions in diverse biological processes, especially in the regulation of abiotic stress tolerances, in various species. However, little is known about their roles in response to abiotic stresses in M. flabellifolia. In this study, we characterized a dehydration-inducible WRKY transcription factor gene, MfWRKY17, from M. flabellifolia. MfWRKY17 shows high degree of homology with genes from Vitis vinifera and Vitis pseudoreticulata, belonging to group II of the WRKY family. Unlike known WRKY17s in other organisms acting as negative regulators in biotic or abiotic stress responses, overexpression of MfWRKY17 in Arabidopsis significantly increased drought and salt tolerance. Further investigations indicated that MfWRKY17 participated in increasing water retention, maintaining chlorophyll content, and regulating ABA biosynthesis and stress-related gene expression. These results suggest that MfWRKY17 possibly acts as a positive regulator of stress tolerance in the resurrection plant M. flabellifolia.

Genome-wide identification and characterization of TIFY family genes in Moso Bamboo (Phyllostachys edulis) and expression profiling analysis under dehydration and cold stresses.

The proteins containing the TIFY domain belong to a plant-specific family of putative transcription factors and could be divided into four subfamilies: ZML, TIFY, PPD and JAZ. They not only function as key regulators of jasmonate hormonal response, but are also involved in responding to abiotic stress. In this study, we identified 24 TIFY genes (PeTIFYs) in Moso bamboo (Phyllostachys edulis) of Poaceae by analyzing the whole genome sequence. One PeTIFY belongs to TIFY subfamily, 18 and five belong to JAZ and ZML subfamilies, respectively. Two equivocal gene models were re-predicted and a putative retrotransposition event was found in a ZML protein. The distribution and conservation of domain or motif, and gene structure were also analyzed. Phylogenetic analysis with TIFY proteins of Arabidopsis and Oryza sativa indicated that JAZ subfamily could be further divided to four groups. Evolutionary analysis revealed intragenomic duplication and orthologous relationship between P. edulis, O. sativa, and B. distachyon. Calculation of the non-synonymous (Ka) and synonymous (Ks) substitution rates and their ratios indicated that the duplication of PeTIFY may have occurred around 16.7 million years ago (MYA), the divergence time of TIFY family among the P. edulis-O. sativa, P. edulis-B. distachyon, and O. sativa-B. distachyon was approximately 39 MYA, 39 MYA, and 45 MYA, respectively. They appear to have undergone extensive purifying selection during evolution. Transcriptome sequencing revealed that more than 50% of PeTIFY genes could be up-regulated by cold and dehydration stresses, and some PeTIFYs also share homology to know TIFYs involved in abiotic stress tolerance. Our results made insights into TIFY family of Moso bamboo, an economically important non-timber forest resource, and provided candidates for further identification of genes involved in regulating responses to abiotic stress.

Genome-Wide Identification, Characterization, and Stress-Responsive Expression Profiling of Genes Encoding LEA (Late Embryogenesis Abundant) Proteins in Moso Bamboo (Phyllostachys edulis).

Late embryogenesis abundant (LEA) proteins have been identified in a wide range of organisms and are believed to play a role in the adaptation of plants to stress conditions. In this study, we performed genome-wide identification of LEA proteins and their coding genes in Moso bamboo (Phyllostachys edulis) of Poaceae. A total of 23 genes encoding LEA proteins (PeLEAs) were found in P. edulis that could be classified to six groups based on Pfam protein family and homologous analysis. Further in silico analyses of the structures, gene amount, and biochemical characteristics were conducted and compared with those of O. sativa (OsLEAs), B. distachyon (BdLEAs), Z. mays (ZmLEAs), S. bicolor (SbLEAs), Arabidopsis, and Populus trichocarpa. The less number of PeLEAs was found. Evolutionary analysis revealed orthologous relationship and colinearity between P. edulis, O. sativa, B. distachyon, Z. mays, and S. bicolor. Analyses of the non-synonymous (Ka) and synonymous (Ks)substitution rates and their ratios indicated that the duplication of PeLEAs may have occurred around 18.8 million years ago (MYA), and divergence time of LEA family among the P. edulis-O. sativa and P. edulis-B. distachyon, P. edulis-S. bicolor, and P. edulis-Z. mays was approximately 30 MYA, 36 MYA, 48 MYA, and 53 MYA, respectively. Almost all PeLEAs contain ABA- and (or) stress-responsive regulatory elements. Further RNA-seq analysis revealed approximately 78% of PeLEAs could be up-regulated by dehydration and cold stresses. The present study makes insights into the LEA family in P. edulis and provides inventory of stress-responsive genes for further functional validation and transgenic research aiming to plant genetic improvement of abiotic stress tolerance.

Molecular cloning and characterization of a novel freezing-inducible DREB1/CBF transcription factor gene in boreal plant Iceland poppy (Papaver nudicaule).

DREB1 of the AP2/ERF superfamily plays a key role in the regulation of plant response to low temperatures. In this study, a novel DREB1/CBF transcription factor, PnDREB1, was isolated from Iceland poppy (Papaver nudicaule), a plant adaptive to low temperature environments. It is homologous to the known DREB1s of Arabidopsis and other plant species. It also shares similar 3D structure, and conserved and functionally important motifs with DREB1s of Arabidopsis. The phylogenetic analysis indicated that the AP2 domain of PnDREB1 is similar to those of Glycine max, Medicago truncatula, and M. sativa. PnDREB1 is constitutively expressed in diverse tissues and is increased in roots. qPCR analyses indicated that PnDREB1 is significantly induced by freezing treatment as well as by abscissic acid. The expression levels induced by freezing treatment were higher in the variety with higher degree of freezing tolerance. These results suggested that PnDREB1 is a novel and functional DREB1 transcription factor involved in freezing response and possibly in other abiotic stresses. Furthermore, the freezing-induction could be suppressed by exogenous gibberellins acid, indicating that PnDREB1 might play some role in the GA signaling transduction pathway. This study provides a basis for better understanding the roles of DREB1 in adaption of Iceland poppy to low temperatures.