Homosalate and ERK Knockdown in the Modulation of Aurelia coerulea Metamorphosis by Regulating the PI3K Pathway and ERK Pathway.

Metamorphosis control is pivotal in preventing the outbreak of jellyfish, and it is often studied using common model organisms. The widespread use of the ultraviolet blocking agent homosalate in cosmetics poses a threat to marine ecosystems. Although the impact of homosalate on marine organisms has been extensively examined, there is a notable absence of research on its effects on jellyfish metamorphosis and the underlying mechanisms, warranting further investigation. In this study, we first established a study model by using 5-methoxy-2-methylindole to induce Aurelia coerulea metamorphosis, and selected homosalate as a PI3K agonist and an ERK agonist, while we used YS-49 as a specific PI3K agonist, as well as ERK knockdown, to observe their effect on the metamorphosis of Aurelia coerulea. The results showed that an Aurelia coerulea metamorphosis model was established successfully, and the PI3K agonist homosalate, YS-49, and the knockdown of ERK molecules could significantly delay the metamorphosis development of Aurelia coerulea. We propose that activating PI3K/Akt and inhibiting the ERK pathway are involved in the delayed development of Aurelia coerulea, which provides a new strategy for the prevention and control of jellyfish blooms.

Exploring the Mechanism of Ferroptosis Induction by Sappanone A in Cancer: Insights into the Mitochondrial Dysfunction Mediated by NRF2/xCT/GPX4 Axis.

Non-small cell lung cancer (NSCLC), a major subtype of lung cancer, encompasses squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. Compared to small cell lung cancer, NSCLC cells grow and divide more slowly, and their metastasis occurs at a later stage. Currently, chemotherapy is the primary treatment for this disease. Sappanone A (SA) is a flavonoid compound extracted from the plant Caesalpinia sappan, known for its antitumor, redox-regulating, and anti-inflammatory properties. Recent studies have investigated the interaction of SA with mitochondrial pathways in regulating cell death through the Nrf-2/GPX-4/xCT axis. This study specifically explores the mechanism by which SA affects mitochondrial morphology and structure through the regulation of mitophagy and mitochondrial biogenesis in tumor cells. The study primarily utilizes second-generation transcriptomic sequencing data and molecular docking techniques to elucidate the role of SA in regulating programmed cell death in tumor cells. The omics results indicate that SA treatment significantly targets genes involved in oxidative phosphorylation, mitophagy, mitochondrial dynamics, and oxidative stress. Further findings confirmed that the Nrf-2/GPX4/xCT pathway serves as a crucial target of SA in the treatment of NSCLC. Knockdown of Nrf-2 (si-Nrf-2) and Nrf-2 overexpression (ad-Nrf-2) were shown to modulate the therapeutic efficacy of SA to varying degrees. Additionally, modifications to the GPX4/xCT genes significantly affected the regulatory effects of SA on mitochondrial autophagy, biogenesis, and energy metabolism. These regulatory mechanisms may be mediated through the caspase pathway and ferroptosis-related signaling. Molecular biology experiments have demonstrated that SA intervention further inhibits the phosphorylation of FUNDC1 at Tyr18 and downregulates TOM20 expression. SA treatment was found to reduce the expression of PGC1α, Nrf-1, and Tfam, resulting in a decrease in mitochondrial respiration and energy metabolism. Overexpression of Nrf-2 was shown to counteract the regulatory effects of SA on mitophagy and mitochondrial biogenesis. Confocal microscopy experiments further revealed that SA treatment increases mitochondrial fragmentation, subsequently inducing mitochondrial pathway-mediated programmed cell death. However, genetic modification of the Nrf-2/GPX4/xCT pathway significantly altered the regulatory effects of SA on tumor cells. In conclusion, SA has been identified as a promising therapeutic agent for NSCLC. The mitochondrial pathway-mediated apoptosis and ferroptosis may represent key mechanisms in regulating tumor cell death. Targeting the Nrf-2/GPX-4/xCT axis offers a novel therapeutic approach for maintaining mitochondrial homeostasis within the cellular microenvironment.

Biosynthesis and Signaling of Strigolactones Act Synergistically With That of ABA and JA to Enhance Verticillium dahliae Resistance in Cotton (Gossypium hirsutum L.).

Verticillium wilt (VW) caused by the soil-borne fungal pathogen Verticillium dahliae reduces cotton productivity and quality. Numerous studies have explored the genetic and molecular mechanisms regulating VW resistance in cotton, but the role and mechanism of strigolactone (SL) is still elusive. We investigated the function of SL in cotton's immune response to V. dahliae infection by exogenously applying SL analog, blocking or enhancing biosynthesis of endogenous SLs in combination with comparative transcriptome analysis and by exploring cross-talk between SL and other phytohormones. Silencing GhDWARF27 and applying the SL analog GR24 or overexpressing GhDWARF27 decreased and enhanced V. dahliae resistance, respectively. Transcriptome analysis revealed SL-mediated activation of abscisic acid (ABA) and jasmonic acid (JA) biosynthesis and signaling pathways. Enhanced ABA biosynthesis and signaling led to increased activity of antioxidant enzymes and reduced buildup of excess reactive oxygen species. Enhanced JA biosynthesis and signaling facilitated transcription of JA-dependent disease resistance genes. One of the components of the SL signal transduction pathway, GhD53, was found to interact with GhNCED5 and GhLOX2, the key enzymes of ABA and JA biosynthesis, respectively. We revealed the molecular mechanism underlying SL-enabled V. dahliae resistance and provided potential solutions for improving VW resistance in cotton.

Advances in Cotton Genomics, Genetics and Breeding.

The cotton is an industrial crop of global significance, providing its fibers for the predominant textile material and its seed accumulating abundant oil and protein for other utilizations [...].

Systematic pharmacology and experimental validation to elucidate the inflammation-associated mechanism of Huanglian Wendan (HLWD) decoction in the treatment of MAFLD associated with atherosclerosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Metabolic-associated fatty liver disease (MAFLD) and atherosclerosis are very common disorders that frequently coexist. The therapeutic efficacy of Huanglian Wendan (HLWD) decoction, a traditional Chinese medicine (TCM) prescription, is satisfactory in treating MAFLD associated with atherosclerosis. However, the underlying mechanisms through which HLWD exerts its effects need to be elucidated. Given the complex composition of HLWD and its multiple therapeutic targets, pharmacological investigation is challenging. AIM OF THIS STUDY: This study aimed to identify the effective compounds in HLWD and elucidate the mechanisms involved in its therapeutic effect on MAFLD associated with atherosclerosis. MATERIALS AND METHODS: We used a systematic pharmacology method to identify effective compounds present in HLWD and determine the mechanism by which it affects MAFLD associated with atherosclerosis. The effective components of HLWD were identified through ultrahigh-performance liquid chromatography-q exactive-orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). Next, a comprehensive in silico method was used to predict potential related targets and disease targets for these compounds to establish corresponding pathways. The accuracy of our assumed systemic pharmacology results was determined by conducting follow-up experiments. RESULTS: By conducting UHPLC-Q-Orbitrap HRMS combined with network analysis, we identified 18 potentially active components of HLWD and assessed the inflammatory regulatory mechanism by which it affects MAFLD associated with atherosclerosis on the basis of 52 key targets. We used a high-fat, high-cholesterol (HFHC)-induced mice model of MAFLD associated with atherosclerosis to confirm our results. We found that administering HLWD significantly improved the appearance of their liver and reduced their body weight, liver weight, blood lipids, hepatic damage, and hepatic pathology. HLWD also decreased atherosclerotic lesion areas, foam cells, and inflammatory cells in the aorta. HLWD showed anti-inflammatory effects, suppressed M1 polarization, and promoted M2 polarization in the liver and aorta. HLWD might also regulate peroxisome proliferator-activated receptor-γ (PPARγ)/nuclear factor kappa-B (NF-κB) signaling to influence macrophage polarization and inflammation. CONCLUSIONS: Our results showed that HLWD protected against HFHC diet-induced MAFLD associated with atherosclerosis by regulating PPARγ/NF-κB signaling, thus adjusting macrophage polarization and inflammation. Additionally, pharmacochemistry research, network pharmacology analysis, and experimental verification can be combined to form a comprehensive model used in studies on TCM.

The application of real-time indocyanine green fluorescence cholangiography in laparoscopic living donor left lateral sectionectomy.

Background: The judgment of the division point of the bile duct has always been one of the difficulties of laparoscopic left lateral sectionectomy (LLLS). The purpose of this study was to assess the effects of indocyanine green (ICG) fluorescence cholangiography during LLLS on the occurrence of biliary complications in both donors and recipients. The optimal dose and injection time of ICG were also investigated. Methods: This is a retrospective cohort study. From October 2016 to December 2022, the clinical data of 103 donors who underwent LLLS and relevant recipients were retrospectively analyzed. According to whether ICG fluorescence cholangiography was used, they were divided into a non-ICG group (n=46) and an ICG group (n=57). Biliary complications were observed and the optimal dose and injection time of ICG were explored. Results: Three donors in the non-ICG group suffered from bile leakage. Four grafts had multiple bile duct openings and biliary complications were observed in the relevant recipients who received these grafts in the non-ICG group. Two recipients had bile leakage, and the other two had biliary stenosis. There was no biliary complications both in donors and recipients in the ICG group. The fluorescence intensity of the liver was 108.1±17.6 at a dose of 0.004 mg/kg 90 minutes after injection, significantly weaker than that at 0.05 mg/kg 30 minutes (200.3±17.6, P=0.001) and 90 minutes after injection (140.2±15.4, P=0.001). The fluorescence intensity contrast value at a dose of 0.004 mg/kg was stronger than that at 0.05 mg/kg, both measured 90 minutes after injection (0.098±0.032 vs. 0.078±0.022, P=0.021). Conclusions: ICG fluorescence cholangiography is safe and feasible in LLLS. It reduces biliary complications in both donors and recipients. The optimal ICG dose was 0.004 mg/kg, and 90 minutes after injection was the best observation time. ICG fluorescence cholangiography is recommended for routine use in LLLS.

Development and Validation of a Carbohydrate Metabolism-Related Model for Predicting Prognosis and Immune Landscape in Hepatocellular Carcinoma Patients.

OBJECTIVE: The activities and products of carbohydrate metabolism are involved in key processes of cancer. However, its relationship with hepatocellular carcinoma (HCC) is unclear. METHODS: The cancer genome atlas (TCGA)-HCC and ICGC-LIRI-JP datasets were acquired via public databases. Differentially expressed genes (DEGs) between HCC and control samples in the TCGA-HCC dataset were identified and overlapped with 355 carbohydrate metabolism-related genes (CRGs) to obtain differentially expressed CRGs (DE-CRGs). Then, univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses were applied to identify risk model genes, and HCC samples were divided into high/low-risk groups according to the median risk score. Next, gene set enrichment analysis (GSEA) was performed on the risk model genes. The sensitivity of the risk model to immunotherapy and chemotherapy was also explored. RESULTS: A total of 8 risk model genes, namely, G6PD, PFKFB4, ACAT1, ALDH2, ACYP1, OGDHL, ACADS, and TKTL1, were identified. Moreover, the risk score, cancer status, age, and pathologic T stage were strongly associated with the prognosis of HCC patients. Both the stromal score and immune score had significant negative/positive correlations with the risk score, reflecting the important role of the risk model in immunotherapy sensitivity. Furthermore, the stromal and immune scores had significant negative/positive correlations with risk scores, reflecting the important role of the risk model in immunotherapy sensitivity. Eventually, we found that high-/low-risk patients were more sensitive to 102 drugs, suggesting that the risk model exhibited sensitivity to chemotherapy drugs. The results of the experiments in HCC tissue samples validated the expression of the risk model genes. CONCLUSION: Through bioinformatic analysis, we constructed a carbohydrate metabolism-related risk model for HCC, contributing to the prognosis prediction and treatment of HCC patients.

[Application of reverse traction device in preoperative treatment of high-energy tibial plateau fracture].

Objective: To investigate the effectiveness of the reverse traction device in the preoperative treatment of high-energy tibial plateau fractures. Methods: A retrospective study was conducted to analyze the clinical data of 33 patients with high-energy tibial plateau fractures who met the selection criteria between December 2020 and December 2023. All patients were treated by open reduction and internal fixation. According to the preoperative traction method, they were divided into the observation group (16 cases, treated with a reverse traction device on the day of admission) and the control group (17 cases, treated with heel traction on the day of admission). There was no significant difference in baseline data such as gender, age, body mass index, affected side, cause of injury, fracture Schatzker classification between the two groups ( P>0.05). Preoperative waiting time, preoperative related complications (nail channel loosening, nail channel oozing, nail channel infection, soft tissue necrosis, soft tissue infection, deep vein thrombosis of the lower extremity, etc.), operation time, and total hospitalization time were recorded and compared between the two groups. On the 4th day after traction, visual analogue scale (VAS) score was used to evaluate the pain relief of the patients, the swelling value of the affected limb was measured, and the Immobilization Comfort Questionnaire (ICQ) score was used to evaluate the perioperative hospital comfort of the patients. Results: Both groups of patients completed the operation successfully, and the operation time, total hospitalization time, and preoperative waiting time of the observation group were significantly less than those of the control group ( P<0.05). There was no preoperative related complications in the observation group; in the control group, 3 patients had nail channel loosening and oozing, and 2 cases had the deep vein thrombosis of the lower extremity; the difference in the incidence of complication between the two groups was significant ( P<0.05). On the 4th day after traction, the ICQ score, VAS score, and limb swelling value of the observation group were significantly better than those of the control group ( P<0.05). X-ray films showed that the tibial plateau fracture separation and lower limb alignment recovered after calcaneal traction in the control group, but not as obvious as in the observation group. The fracture gap in the observation group significantly reduced, the tibial plateau alignment was good, and the lateral angulation deformity was corrected. Conclusion: The use of reverse traction treatment in patients with high-energy tibial plateau fractures on admission can accelerate the swelling around the soft tissues to subside, reduce patients' pain, shorten the preoperative waiting time, improve the patients' preoperative quality of life, and contribute to the shortening of the operation time, with a good effectiveness.

Metabolic Engineering of Escherichia coli for Bioproduction of (R)-3-Hydroxybutyric Acid through a Three-Pronged Approach.

(R)-3-Hydroxybutyric acid (R-3HB) is an important chiral chemical with extensive applications in the agricultural, food, and chemical industries. The synthesis of R-3HB by microbial fermentation is of interest due to its remarkable stereoselectivity and economy. However, the low production of R-3HB failed to meet the needs of large-scale industrial production. In this study, an engineered strain for the efficient biosynthesis of R-3HB was constructed through a three-pronged approach encompassing biosynthetic pathway optimization, engineering of NADPH regenerators, and central metabolism regulation. The engineered strain Q5081 produced 75.7 g/L R-3HB, with a productivity of 1.26 g/L/h and a yield of 0.34 g/g glucose in fed-batch fermentation, showing the highest reported titer and productivity of R-3HB to date. We also performed transcriptome sequencing and annotation to illustrate the mechanism underlying the enhanced R-3HB production. The systematic metabolic engineering by a three-pronged approach demonstrated the feasibility of improving the biosynthesis, and the engineered strain Q5081 has the potential for widespread applications in the industrial production of R-3HB.

DNA methylation profiles of ovarian cysts resemble ovarian tissues but not endometrial tissues.

INTRODUCTION: Endometriosis is a heritable, complex chronic inflammatory disease, for which much of the causal pathogenic mechanism remain unknown.Despite the high prevalence of ovarian chocolate cyst, its origin is still under debate. METHODS: Prevailing retrograde menstruation model predicts that ectopic endometrial cells migrate and develop into ovarian chocolate cyst. However, other models were also proposed. Genome-wide association studies (GWASs) have proved successful in identifying common genetic variants of moderate effects for various complex diseases. RESULTS: A growing body of evidence shows that the remodeling of retrograde endometrial tissues to the ectopic endometriotic lesions involves multiple epigenetic alterations, such as DNA methylation, histone modification, and microRNA expression.Because DNA methylation states exhibit a tissue specific pattern, we profiled the DNA methylation for ovarian cysts and paired eutopic endometrial and ovarian tissues from four patients. Surprisingly, DNA methylation profiles showed the ovarian cysts were closely grouped with normal ovarian but not endometrial tissues. CONCLUSIONS: These results suggested alterative origin of ovarian cysts or strong epigenetic reprogramming of infiltrating endometrial cells after seeding the ovarian tissue. The data provide contributing to the pathogenesis and pathophysiology of endometriosis.

Contributions of soil organic carbon-induced root- and soil properties complexity to water flow in eastern China.

Water flow within the soils affects the efficiency of materials transfer mediated by water. Soil organic carbon (SOC) as an important role in active water flow events can drive the complexity of root-soil synthesis by improving root and soil properties. However, contributions of SOC-induced root- and soil properties complexity to water flow are not well understood. In this study, dye tracing experiments at the three forest stands (oak, pine, and bamboo forests) were conducted to explore water flow patterns, i.e., preferential flow paths (PFP), stream buffer zones (SBZ), and water flow zones (WFZ). X-ray microtomography (CT) scanning was performed to reconstruct the root architecture. The partial least squares path model was applied to quantitatively explore the effects of root- and soil properties on water flow. The results showed that the index of water flow connectivity (IWFC) in the PFP and WFZ patterns decreased with increasing soil depth, while IWFC in the SBZ pattern increased at first and then decreased. In the PFP pattern, soil physical properties had the larger total effects (TE = 0.624) on IWFC change compared with root properties (TE = 0.257). In the SBZ pattern, the total effects of root properties controlling IWFC change (TE = 0.510) were greater than soil physical properties (TE = -0.386). Both of them can equally affect the IWFC in the WFZ pattern. In conclusion, the influences of SOC by driving the changes of soil properties on gravity-driven convective flow process were dramatically stronger than root properties, while SOC could primarily drive the changes of root properties and thereby affect capillary-driven convective flow process. The present results can provide a scientific basis for sustainable forestry management and also a better understanding of the forestry hydrology.

Zinc Oxide Nanoparticles and Zinc Sulfate Alleviate Boron Toxicity in Cotton (Gossypium hirsutum L.).

Boron toxicity significantly hinders the growth and development of cotton plants, therefore affecting the yield and quality of this important cash crop worldwide. Limited studies have explored the efficacy of ZnSO4 (zinc sulfate) and ZnO nanoparticles (NPs) in alleviating boron toxicity. Nanoparticles have emerged as a novel strategy to reduce abiotic stress directly. The precise mechanism underlying the alleviation of boron toxicity by ZnO NPs in cotton remains unclear. In this study, ZnO NPs demonstrated superior potential for alleviating boron toxicity compared to ZnSO4 in hydroponically cultivated cotton seedlings. Under boron stress, plants supplemented with ZnO NPs exhibited significant increases in total fresh weight (75.97%), root fresh weight (39.64%), and leaf fresh weight (69.91%). ZnO NPs positively affected photosynthetic parameters and SPAD values. ZnO NPs substantially reduced H2O2 (hydrogen peroxide) by 27.87% and 32.26%, MDA (malondialdehyde) by 27.01% and 34.26%, and O2- (superoxide anion) by 41.64% and 48.70% after 24 and 72 h, respectively. The application of ZnO NPs increased the antioxidant activities of SOD (superoxide dismutase) by 82.09% and 76.52%, CAT (catalase) by 16.79% and 16.33%, and POD (peroxidase) by 23.77% and 21.66% after 24 and 72 h, respectively. ZnO NP and ZnSO4 application demonstrated remarkable efficiency in improving plant biomass, mineral nutrient content, and reducing boron levels in cotton seedlings under boron toxicity. A transcriptome analysis and corresponding verification revealed a significant up-regulation of genes encoding antioxidant enzymes, photosynthesis pathway, and ABC transporter genes with the application of ZnO NPs. These findings provide valuable insights for the mechanism of boron stress tolerance in cotton and provide a theoretical basis for applying ZnO NPs and ZnSO4 to reduce boron toxicity in cotton production.

Near-Infrared Spectroscopy Analysis of the Phytic Acid Content in Fuzzy Cottonseed Based on Machine Learning Algorithms.

Cottonseed is rich in oil and protein. However, its antinutritional factor content, of phytic acid (PA), has limited its utilization. Near-infrared (NIR) spectroscopy, combined with chemometrics, is an efficient and eco-friendly analytical technique for crop quality analysis. Despite its potential, there are currently no established NIR models for measuring the PA content in fuzzy cottonseeds. In this research, a total of 456 samples of fuzzy cottonseed were used as the experimental materials. Spectral pre-treatments, including first derivative (1D) and standard normal variable transformation (SNV), were applied, and the linear partial least squares (PLS), nonlinear support vector machine (SVM), and random forest (RF) methods were utilized to develop accurate calibration models for predicting the content of PA in fuzzy cottonseed. The results showed that the spectral pre-treatment significantly improved the prediction performance of the models, with the RF model exhibiting the best prediction performance. The RF model had a coefficient of determination in prediction (R2p) of 0.9114, and its residual predictive deviation (RPD) was 3.9828, which indicates its high accuracy in measuring the PA content in fuzzy cottonseed. Additionally, this method avoids the costly and time-consuming delinting and crushing of cottonseeds, making it an economical and environmentally friendly alternative.

Site-Selective Distal C(sp3)-H Bromination of Aliphatic Amines as a Gateway for Forging Nitrogen-Containing sp3 Architectures.

Herein, we disclose a new strategy that rapidly and reliably incorporates bromine atoms at distal, secondary C(sp3)-H sites in aliphatic amines with an excellent and predictable site-selectivity pattern. The resulting halogenated building blocks serve as versatile linchpins to enable a series of carbon-carbon and carbon-heteroatom bond-formations at remote C(sp3) sites, thus offering a new modular and unified platform that expediates the access to advanced sp3 architectures possessing valuable nitrogen-containing saturated heterocycles of interest in medicinal chemistry settings.

Zinc Oxide Nanoparticles Alleviate Salt Stress in Cotton (Gossypium hirsutum L.) by Adjusting Na+/K+ Ratio and Antioxidative Ability.

Soil salinization poses a threat to the sustainability of agricultural production and has become a global issue. Cotton is an important cash crop and plays an important role in economic development. Salt stress has been harming the yield and quality of many crops, including cotton, for many years. In recent years, soil salinization has been increasing. It is crucial to study the mechanism of cotton salt tolerance and explore diversified materials and methods to alleviate the salt stress of cotton for the development of the cotton industry. Nanoparticles (NPs) are an effective means to alleviate salt stress. In this study, zinc oxide NPs (ZnO NPs) were sprayed on cotton leaves with the aim of investigating the intrinsic mechanism of NPs to alleviate salt stress in cotton. The results show that the foliar spraying of ZnO NPs significantly alleviated the negative effects of salt stress on hydroponic cotton seedlings, including the improvement of above-ground and root dry and fresh weight, leaf area, seedling height, and stem diameter. In addition, ZnO NPs can significantly improve the salt-induced oxidative stress by reducing the levels of MDA, H2O2, and O2- and increasing the activities of major antioxidant enzymes, such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT). Furthermore, RNA-seq showed that the foliar spraying of ZnO NPs could induce the expressions of CNGC, NHX2, AHA3, HAK17, and other genes, and reduce the expression of SKOR, combined with the CBL-CIPK pathway, which alleviated the toxic effect of excessive Na+ and reduced the loss of excessive K+ so that the Na+/K+ ratio was stabilized. In summary, our results indicate that the foliar application of ZnO NPs can alleviate high salt stress in cotton by adjusting the Na+/K+ ratio and regulating antioxidative ability. This provides a new strategy for alleviating the salt stress of cotton and other crops, which is conducive to the development of agriculture.

Prediction of the survival status and tumor microenvironment in colorectal cancer through genotyping analysis based on toll-like receptors.

BACKGROUND: Colorectal cancer (CRC) ranks third in both the incidence and mortality rates among male and female cancers, and it is the leading digestive system cancer. Due to the inter- and intratumor heterogeneity of cancer, the TNM system is insufficient for predicting prognosis, necessitating the use of molecular biomarkers for prognostic prediction. Toll-like receptors (TLRs) have been associated with CRC survival rates. This study focused on the investigation of the role and potential value of TLRs in CRC genotyping to aid in immunotherapy for CRC patients. METHODS: Differential gene expression analysis was performed on CRC transcriptomic data from The Cancer Genome Atlas database. TLRs were referred from the literature, and their intersection with differentially expressed genes (DEGs) in CRC yielded TLR-DEGs. The expression patterns of TLR-DEGs were predicted using the STRING website, and copy number variations of TLR-DEGs were analyzed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on TLR-DEGs. ConsensusClusterPlus R package was used for clustering CRC patients, and ESTIMATE and GSEAbase were employed to analyze immune characteristics of different subtypes. Immune phenotyping scores and tumor immune dysfunction and exclusion scores were evaluated. DEGs of different subtypes were analyzed, followed by GO and KEGG enrichment analyses, the protein-protein interaction (PPI) network analysis, and further selection of hub genes. The sensitivity of drugs was assessed using the identified hub genes. RESULTS: We identified 37 TLR-DEGs, and the PPI analysis revealed their coexpression, although they were distributed on different chromosomes. Enrichment analyses indicated that the 37 TLR-DEGs were linked to cancer cell immune response. Based on these TLR-DEGs, CRC patients were classified into three subtypes. Cluster2 exhibited lower survival rates and higher immune infiltration levels and predicted poorer response to immune checkpoint inhibitor therapy. The intersection of DEGs from cluster2 and cluster1 with DEGs from cluster2 and cluster3 yielded a set of 426 commonly shared DEGs. Enrichment analyses revealed that these shared DEGs might regulate immune cell viability. Eight common hub genes for different subtypes were further identified to predict drug-related correlations. CONCLUSION: The developed TLR genotyping was used to predict the survival status and tumor microenvironment of CRC, providing a foundation for understanding the molecular mechanisms of TLR signaling and deepening its clinical significance.

Ex vivo liver resection and auto-transplantation as an alternative for the treatment of liver malignancies: Progress and challenges.

Hepatectomy is still the major curative treatment for patients with liver malignancies. However, it is still a big challenge to remove the tumors in the central posterior area, especially if their location involves the retrohepatic inferior vena cava and hepatic veins. Ex vivo liver resection and auto-transplantation (ELRA), a hybrid technique of the traditional liver resection and transplantation, has brought new hope to these patients and therefore becomes a valid alternative to liver transplantation. Due to its technical difficulty, ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver resection and liver transplantation. The efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases, especially in the advanced alveolar echinococcosis. Recently, the application of ELRA for liver malignances has gained more attention. However, standardization of clinical practice norms and international consensus are still lacking. The prognostic impact in these oncologic patients also needs further evaluation. In this review, we summarized the principles and recent progresses on ELRA.