[Analysis of Temporal and Spatial Carbon Stock Changes and Driving Mechanism in Xinjiang Region by Coupled PLUS-InVEST-Geodector Model].

Based on the goal of "dual-carbon" strategy, it is important to explore the impacts of land use change on carbon stock and the drivers of spatial differentiation of carbon stock in Xinjiang. Here, we predicted the land use types in Xinjiang in 2035 under different scenarios and analyzed the impacts of land use on carbon stock, which is of great theoretical and practical importance for policy formulation, land use structure adjustment, and carbon neutrality target achievement in Xinjiang. The coupled PLUS-InVEST-Geodector model was used to explore the spatial and temporal patterns of carbon stock change under the scenarios of rapid development, natural change, arable land protection, and ecological protection in Xinjiang in 2035 and to quantitatively reveal the attribution of influences on the changes in carbon stock from the perspectives of land use change and the combination of nature-socioeconomic-accessibility. The results showed that： ① From 1990 to 2020, the area of arable land and construction land in Xinjiang increased, and in terms of the transfer direction, it was mainly shifted from unutilized land to grassland. ② On the time scale, the carbon stock in Xinjiang showed the fluctuation of "decrease-increase-decrease," with an overall increasing trend. The transfer of unutilized land to grassland was the main reason for the increase in carbon stock； on the spatial scale, the carbon stock in the Altai Mountains in the north, the Tianshan Mountains in the middle, and the Kunlun Mountains in the south was higher, whereas the carbon stock in the Tarim Basin and the Junggar Basin was lower. ③ In 2035, the carbon stock of the natural development and rapid development scenarios decreased by 27.24 Tg and 71.17 Tg compared with 2020, respectively, and the ecological protection and arable land protection scenarios increased by 492.55 Tg and 46.67 Tg. The ecological protection scenario could significantly increase the carbon stock of the Xinjiang Region compared with that in the other scenarios, and the distribution pattern of the carbon stock in the four scenarios was more or less the same as that in 2020. In addition to land transformation, soil erosion intensity was the main driver of spatial differentiation of carbon stocks in Xinjiang （q value of 0.3501）, followed by net primary productivity of vegetation. The results of multifactor interactions showed that the spatial differentiation of carbon stocks in Xinjiang was the result of the joint action of multiple factors. All the factors had a synergistic enhancement under the interactions. The interaction between soil erosion intensity and the net primary productivity of vegetation was the main driver of the spatial differentiation of carbon stocks in Xinjiang.

Palmatine reverse aristolochic acid-induced heart failure through activating EGFR pathway via upregulating IKBKB.

Aristolochic acid (AA) is renowned for engendering nephrotoxicity and teratogenicity. Previous literature has reported that AA treatment resulted in heart failure (HF) via inflammatory pathways. Yet, its implications in HF remain comparatively uncharted territory, particularly with respect to underlying mechanisms. In our study, the zebrafish model was employed to delineate the cardiotoxicity of AA exposure and the restorative capacity of a phytogenic alkaloid palmatine (PAL). PAL restored morphology and blood supply in AA-damaged hearts by o-dianisidine staining, fluorescence imaging, and Hematoxylin and Eosin staining. Furthermore, PAL attenuated the detrimental effects of AA on ATPase activity, implying myocardial energy metabolism recovery. PAL decreased the co-localization of neutrophils with cardiomyocytes, implying an attenuation of the inflammatory response induced by AA. A combination of network pharmacological analysis and qPCR validation shed light on the therapeutic mechanism of PAL against AA-induced heart failure via upregulation of the epidermal growth factor receptor (EGFR) signaling pathway. Subsequent evaluations using a transcriptological testing, inhibitor model, and molecular docking assay corroborated PAL as an IKBKB enzyme activator. The study underscores the possible exploitation of the EGFR pathway as a potential therapeutic target for PAL against AA-induced HF, thus furthering the continued investigation of the toxicology and advancement of protective pharmaceuticals for AA.

[Characteristics and influence factors of rainfall redistribution in eight typical plantations in the loess area in West Shanxi, China]. / 晋西黄土区8ç§å ¸åž‹æž—åˆ†é™é›¨å†åˆ†é ç‰¹å¾ä¸Žå½±å“å› ç´ .

Aiming for clarifying the potential distribution characteristics of canopy rainfall partitioning of the loess area, we explored the process of rainfall partitioning across eight typical forest stands (Pinus tabuliformis forest, Robinia pseudoacacia forest, Platycladus orientalis forest, mixed forest of Robinia pseudoacacia-Pinus tabuliformis, mixed forest of Platycladus orientalis-Robinia pseudoacacia, Quercus wutaishanica forest, Populus davidiana forest, mixed forest of Quercus wutaishanica-Populus davidiana), and used boosted regression trees (BRT) to quantify the relative influences of stand structures and meteorological environment factors. We established multiple regression relationships according to the most influential factors extracted by BRT, and applied to the dataset of mining to verify the performance of the BRT-derived predictive model. The results showed that the percentages of throughfall (TF), stemflow (SF), and canopy interception (Ic) in total precipitation were 24.5%-95.1%, 0-13.6%, and 0.7%-55.7% among eight typical forest stands, respectively. For the individual rainfall threshold of TF, coniferous forest (3.06±1.21 mm) was significantly higher than broad-leaved forest (1.97±0.52 mm), but there was no significant difference between coniferous forest and broad-leaved mixed forest (3.01±0.98 mm). There was no significant difference in the individual rainfall threshold of SF among different composition stands. BRT analysis showed that stand structure factors accounted for a relatively small proportion for TF and SF, respectively. By contrast, stand structure factors dominated the Ic. Rainfall was the most important factor in determining TF and SF. Tree height was the most important factor in determining Ic, followed by rainfall, canopy area, diameter at breast height, and stand density. Compared with the general linear function and the power function, the prediction effect of BRT prediction model constructed here on TF and SF had been further improved, and the prediction of canopy interception still needed to explore. In conclusion, the BRT model could better quantitatively evaluate the effects of stand structure and meteorological environmental factors on rainfall partitioning components, and the performance of the BRT predictive model could satisfy and lay the foundation for the optimization strategy for stand configuration.

Poisoning Mechanism Map for Metal Hydride Hydrogen Storage Materials.

The effective utilization of hydrogen storage materials (HSMs) is hindered by impurity gas poisoning, posing a significant challenge for large-scale applications. This study elucidates the poisoning mechanisms of various impurities gases (CO, CO2, O2, Ar, He, CH4, N2) on ZrCo, Pd, U and LaNi5. Impurities gases are categorized into active and inactive types based on their effecting behaviors and mechanisms on the hydrogenation of HSMs. During the hydrogenation process, active impurities chemically poison the hydrogenation reaction by limiting hydrogen absorption at interface, while inactive impurities physically hinder hydrogenation reaction by impeding hydrogen diffusion in hydrogen-impurity mixed gas. In situ Scanning Tunneling Microscope clarifies these behaviors, and a novel criterion based on hydrogen spontaneous dissociation energy is introduced to explain and predict impurity-substrate interaction characteristics. The novel findings of this work provide a comprehensive framework for designing long-lived HSMs with poisoning resistance, guiding the development of more resilient hydrogen storage systems.

Comparisons of laparoscopic and robotic pancreaticoduodenectomy using barbed and conventional sutures for pancreaticojejunostomy: a propensity score matching study.

BACKGROUND: There are limited data on the effect of different sutures and surgical approaches on the quality of pancreaticojejunostomy in minimally invasive pancreaticoduodenectomy (MIPD). This study compares the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) between the use of barbed sutures (BSs) and conventional sutures (CSs). METHODS: A retrospective cohort study was conducted on 253 consecutive patients who had undergone MIPD from July 2016 to April 2023. Patients were excluded if conversion to open surgery or open anastomosis was necessary. 220 patients were enrolled and divided into BS (n = 148) and CS (n = 72) groups. After 1:1 propensity score matching (PSM), 67 cases remained in each group. Univariate and multivariate analyses identified factors associated with CR-POPF. Comparisons were also made between laparoscopic (LPD) and robotic (RPD) pancreaticoduodenectomy. RESULTS: After PSM, BSs were associated with significantly lower rates of CR-POPF (7.5 vs. 22.4%, P = 0.015) and severe complications (Clavien-Dindo ≥ III) (7.5vs. 19.4%, P = 0.043). No significant differences were found in operative time, length of postoperative hospital stay, or other major morbidities. Multivariate analyses revealed BMI ≥ 22 kg/m2 (OR = 5.048, 95% CI: 1.256-20.287, P = 0.023) and the use of BSs (OR = 0.196, 95% CI: 0.059-0.653, P = 0.008) as the independent predictors of CR-POPF. There were no significant differences in postoperative outcomes between the LPD and RPD groups, but RPD was associated with significantly shorter operative time (402.8 min vs. 429.4 min, P = 0.015). CONCLUSIONS: In conclusion, using BSs for PJ during MIPD is feasible and has the potential to reduce CR-POPF and severe complications.

Temperature-dependent microbial mechanism and accumulation of volatile fatty acids in primary sludge pretreated with peroxymonosulfate.

For revealing the influence of temperature on volatile fatty acids (VFAs) generation from primary sludge (PS) during the anaerobic fermentation process facilitated by peroxymonosulfate (PMS), five fermentation groups (15, 25, 35, 45, and 55 °C) were designed. The results indicated that the production of VFAs (5148 mg COD/L) and acetic acid (2019 mg COD/L) reached their peaks at 45 °C. High-throughput sequencing technology disclosed that Firmicutes, Proteobacteria, and Actinobacteria was the dominant phyla, carbohydrate metabolism and membrane transport were the most vigorous at 45 °C. Additionally, higher temperature and PMS exhibit synergistic effects in promoting VFAs accumulation. This study unveiled the mechanism of the effect of the pretreatment of PS with PMS on the VFAs production, which established a theoretical foundation for the production of VFAs.

Learning curve of robotic pancreatoduodenectomy by a single surgeon with extensive laparoscopic pancreatoduodenectomy experience.

With the development of robotic systems, robotic pancreatoduodenectomies (RPDs) have been increasingly performed. However, the number of cases required by surgeons with extensive laparoscopic pancreatoduodenectomy (LPD) experience to overcome the learning curve of RPD remains unclear. Therefore, we aimed to analyze and explore the impact of different phases of the learning curve of RPD on perioperative outcomes. Clinical data were prospectively collected and retrospectively analyzed for 100 consecutive patients who underwent RPD performed by a single surgeon. This surgeon had previous experience with LPD, having performed 127 LPDs with low morbidity. The learning curve for RPD was analyzed using the cumulative sum (CUSUM) method based on operation time, and perioperative outcomes were compared between the learning and proficiency phases. Between April 2020 and November 2022, one hundred patients (56 men, 44 women) were included in this study. Based on the CUSUM curve of operation time, the learning curve for RPD was divided into two phases: phase I was the learning phase (cases 1-33) and phase II was the proficiency phase (cases 34-100). The operation time during the proficiency phase was significantly shorter than that during the learning phase. In the learning phase of RPD, no significant increases were observed in estimated blood loss, conversion to laparotomy, severe complications, postoperative pancreatic hemorrhage, clinical pancreatic fistula, or other perioperative complications compared to the proficiency phases of either RPD or LPD. A surgeon with extensive prior experience in LPD can safely surmount the RPD learning curve without increasing morbidity in the learning phase. The proficiency was significantly improved after accumulating experience of 33 RPD cases.

A novel hsa_circ_0006903 circular RNA promotes tumor development and dendritic cells activated expression in infantile hemangioma.

Background: Increasing reports revealed that circular RNAs (circRNAs) and immune cells infiltration were related with tumor development. However, its role in infantile hemangioma (IH) is unknown. We will explore a novel hsa_circ_0006903-based ceRNA network and investigate the landscape of dendritic cells activated expression in IH. Material and methods: Differentially expressed circRNAs (DECs) were identified from Gene Expression Omnibus (GEO) database. Regulatory networks and functional enrichment analysis were constructed. CIBERSORT was used to characterize immune cells composition. qRT-PCR was performed to detect the expression of hsa_circ_0006903 in cell lines. Then, the role of hsa_circ_0006903 in IH were validated in vitro using transwell assay. Immunofluorescence was applied to the colocalization of CD11b for dendritic cells activated as a biomarker in IH tissues. Results: Using GEO database, a total of 67 DECs were screened out in IH. Hsa_circ_0006903 was the most significant DECs. Then, a novel hsa_circ_0006903 circular RNA-ceRNA network was constructed. Mechanistically, functional enrichment analysis showed that the p53 signaling pathway played the most important roles, and hsa_circ_0006903/miR-6721-5p/CACNA2D2 and hsa_circ_0006903/miR-4786-3p/ATP13A4 axis were identified. CACNA2D2, ATP13A4, and P53 were significantly downregulated in IH cell lines. We validated that dendritic cell activated was significantly overexpressed. Moreover, CD11b as a biomarker of dendritic cells activated were tested in IH tissues. Finally, hsa_circ_0006903 was significantly overexpressed, and hsa_circ_0006903 promoted infantile hemangioma cell proliferation, invasion, and migration in vitro. Conclusion: Overall, our study revealed that a novel hsa_circ_0006903 promoted tumor progression, and indicated a potential biomarker CD11b of dendritic cells activated in IH.

Robotic Versus Laparoscopic Pancreaticoduodenectomy for Pancreatic Cancer: Evaluation and Analysis of Surgical Efficacy.

BACKGROUND: Evidence is limited for the treatment of pancreatic cancer among minimally invasive pancreatoduodenectomy. METHODS: This retrospective analysis evaluated patients who underwent robotic pancreaticoduodenectomy (RPD) or laparoscopic pancreaticoduodenectomy (LPD) from April 2016 to April 2023. Their baseline and perioperative data, including operative time, R0 resection rates, and severe complications rates, were analyzed, and the follow-up data, such as disease-free survival (DFS) and overall survival (OS), were collected. RESULTS: A total of 253 cases of LPD and RPD were performed, and 101 cases with pancreatic cancer were included, of which 54 were LPD and 47 were RPD. The conversion rate (4.3% vs. 29.6%, p = 0.001) and blood loss (400 vs. 575 mL, p < 0.05) were lower in the RPD group. No significant difference was observed between the two groups in terms of operative time, vessel resection rates, and TNM-stage diagnosis; however, R0 resection rates (80.9% vs. 70.4%) and lymph node harvest (24.2 vs. 21.9) had a higher tendency in the RPD group, and postoperative length of stay was shorter in the RPD cohort (11 vs. 13 days). Moreover, improved 1- to 3-years DFS (75.7%, 61.7%, and 36.0% vs. 59.0%, 35.6%, and 21.9%) and OS (94.7%, 84.7%, and 50.8% vs. 84.1%, 63.6%, and 45.5%) was found in the RPD group in comparison with the LPD group. CONCLUSIONS: RPD had advantages in surgical safety and oncological outcomes compared with LPD, but was similar to the latter in perioperative outcomes. Long-term outcomes require further study.

Molecular-docking electrolytes enable high-voltage lithium battery chemistries.

Ideal rechargeable lithium battery electrolytes should promote the Faradaic reaction near the electrode surface while mitigating undesired side reactions. Yet, conventional electrolytes usually show sluggish kinetics and severe degradation due to their high desolvation energy and poor compatibility. Here we propose an electrolyte design strategy that overcomes the limitations associated with Li salt dissociation in non-coordinating solvents to enable fast, stable Li chemistries. The non-coordinating solvents are activated through favourable hydrogen bond interactions, specifically Fδ--Hδ+ or Hδ+-Oδ-, when blended with fluorinated benzenes or halide alkane compounds. These intermolecular interactions enable a dynamic Li+-solvent coordination process, thereby promoting the fast Li+ reaction kinetics and suppressing electrode side reactions. Utilizing this molecular-docking electrolyte design strategy, we have developed 25 electrolytes that demonstrate high Li plating/stripping Coulombic efficiencies and promising capacity retentions in both full cells and pouch cells. This work supports the use of the molecular-docking solvation mechanism for designing electrolytes with fast Li+ kinetics for high-voltage Li batteries.

Inducing One-Step Dehydrogenation of Magnesium Borohydride via Confinement in Robust Dodecahedral Nitrogen-Doped Porous Carbon Scaffold.

A dodecahedral activated N-doped porous carbon scaffold is synthesized and used for the nanoconfinement of Mg(BH4)2. The optimized mesoporous scaffold possesses an accumulated pore width of 2.65 nm, high specific surface area (3955.9 m2 g-1), and large pore volume (2.15 cm3 g-1), providing ample space for the confinement of Mg(BH4)2 particles and numerous surface active sites for interactions with the same. The confined Mg(BH4)2 system features a dehydrogenation onset temperature of 81.5 °C, an extremely high capacity of 10.2 wt% H2, and an almost single-step dehydrogenation profile. Moreover, the system exhibits superior capacity retention of 82.7% after 20 cycles at a moderate temperature of 250 °C. Precise activation control enables a transformation from microporous carbon materials to mesoporous ones, and hence the efficient nanoconfinement of Mg(BH4)2 and realization of one-step dehydrogenation. The evolution of borohydride intermediates is systematically revealed throughout the cycling process. Density functional theory calculations demonstrate defective N heteroatoms within the scaffold are vital in reducing the strength of B─H bonds, and the N-doped carbon can facilitate decomposition of the irreversible MgB12H12 intermediate. This study opens up new avenues for designing robust carbon scaffolds doped with heteroatoms and analyzing intermediate evolution in nanoconfined Mg-based borohydride systems.

How has carbon storage changed in the Yili-Tianshan region over the past three decades and into the future? What has driven it to change?

Predicting future land use changes and assessing carbon storage remain challenging. Nowadays, how nature and socioeconomics drive changes in carbon storage is a hot topic in research. In this study, through the projection of land use type and the integration of the PLUS, Integrated Valuation of Ecosystem Services and Trade-offs (InVEST), and Geodetector models, we constructed a framework for assessing carbon storage in different land use scenarios. Utilizing this framework, it is possible to project land use change and estimate carbon storage based on different development scenarios. We applied the framework to the Yili Tianshan region and identified the main driving forces for carbon storage change. Further, we estimated the carbon storage in the Yili Tianshan region in 2035 under four scenarios (RE, NE, EP, and CLP). The results showed the following: 1) Between 1990 and 2020, there was an increase in the forest area and water bodies in the Yili-Tianshan region, mainly from bare land. 2) As shown on the time scale, carbon storage increases in the Yili-Tianshan region with a W-shaped fluctuation by converting grasslands and bare land into forests. On a spatial scale, the carbon storage was lower in the center and higher on both sides in the Yili-Tianshan region. 3) In 2035- RE, 2035-ND, and 2035-EP scenarios, the carbon storage was increased by 4.30 Tg, 6.67 Tg, and 12.08 Tg; in the 2035-CLP scenario, it was decreased by 14.63 Tg. The Yili-Tianshan region experienced a notable rise in carbon storage under the 2035-EP scenario compared to the other three scenarios. 4) Soil type played a significant role in the spatial differentiation of carbon storage in Yili-Tianshan (q value 0.5958), followed by population density (0.5394). The changes in carbon storage in the Yili-Tianshan region are the result of synergistic effects of multiple factors, in which the soil type∩soil erosion intensity are the most important. This research could provide a reference method for improving regional carbon storage.

Effects of water replenishment on lake water quality and trophic status: An 11-year study in cold and arid regions.

Water replenishment is an important measure for maintaining and improving the aquatic environmental quality of lakes. The problems of water quality deterioration and water shortage can be alleviated by introducing water of higher quality. However, the mechanism of water replenishment in the improvement of the water quality and trophic status of lakes remains unclear. This study investigated water replenishment in Wuliangsuhai Lake (WLSHL) from 2011 to 2021 by collecting seasonal water samples and conducting laboratory analyses. Water replenishment was found to be capable of significantly improving lake water quality and alleviating eutrophication. It is worth noting that single long-term water replenishment measures have limitations in improving the water quality and trophic status. The whole process was divided into three stages according to the water quality and trophic status, namely the buffer period, decline period, and stable period. During the buffer period, the water quality and trophic status showed only slight improvement because of the small amount of water replenishment and the low proportion of higher-quality water from the Yellow River. In the decline period, with increasing water replenishment, the proportion of higher-quality water from the Yellow River gradually increased, leading to the most significant and stable degree of improvement. In the stable period, increases in the amount of water replenishment had little effect on improving the water quality and trophic status, which is attributable to the balance between internal pollutants (lake water-sediment), and the balance between internal-external pollutants (lake water-irrigation return flow + Yellow River water). On the premise of stable water quality, with eutrophication control as the management goal, the optimal water replenishment would be approximately 10.58 ×108 m3. Further necessary measures for solving aquatic environmental problems include the combination of sediment dredging, optimization of the water replenishment route, and implementation of quality management in water replenishment.

To elucidate the mechanism of "Scrophulariae Radix-Fritillaria" in goiter by integrated metabolomics and serum pharmaco-chemistry.

The pharmacodynamic substances in "Scrophulariae Radix-Fritillaria" and the molecular mechanisms underlying its therapeutic effects against goiter were analyzed through metabolomics and serum pharmaco-chemistry. A rat model of goiter was established using propylthiouracil (PTU), and the animals were treated using "Scrophulariae Radix-Fritillaria." The efficacy of the drug pair was evaluated in terms of thyroid gland histopathology and blood biochemical indices. Serum and urine samples of the rats were analyzed by UPLC-Q-TOF/MS. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed to screen potential biomarkers in urine and the corresponding metabolic pathways. The blood components of "Scrophulariae Radix-Fritillaria" were also identified, and their correlation with urine biomarkers was analyzed in order to screen for potential bioactive compounds. "Scrophulariae Radix-Fritillaria" mitigated injury to thyroid tissues and normalized the levels of the thyroid hormones FT3, FT4, and TSH. We also identified 22 urine biomarkers related to goiter, of which 19 were regulated by "Scrophulariae Radix-Fritillaria." Moreover, urine biomarkers are involved in tryptophan metabolism, steroid hormone biosynthesis, and beta-alanine metabolism, and these pathways may be targeted by the drug pair. In addition, 47 compounds of "Scrophulariae Radix-Fritillaria" were detected by serum pharmacochemistry, of which nine components, namely, syringic acid, paeonol, cedrol, and cis-ferulic acid, fetisinine, aucubigenin, linolenic acid, ussuriedine, and 5-(methylsulfanyl)pentanenitrile, were identified as potential effective substances against goiter. To summarize, we characterized the chemical components and mechanisms of "Scrophulariae Radix-Fritillaria" involved in the treatment of goiter, and our findings provide an experimental basis for its clinical application.

Upgrading Electrolyte Antioxidant Chemistry by Constructing Potential Scaling Relationship.

Rational design of advanced electrolytes to improve the high-voltage capability has been attracting wide attention as one critical solution to enable next-generation high-energy-density batteries. However, the limited understanding of electrolyte antioxidant chemistry as well as the lack of valid quantization approaches have resulted in knowledge gap, which hinders the formulation of new electrolytes. Herein, we construct a standard curve based on representative solvation structures to quantify the oxidation stability of ether-based electrolytes, which reveals the linear correlation between the oxidation potential and the atomic charge of the least oxidation-resistant solvent. Dictated by the regularity between solvation composition and oxidation potential, a (Trifluoromethyl)cyclohexane-based localized high-concentration electrolyte dominated by anion-less solvation structures was designed to optimize the cycling performance of 4.5 V 30 µm-Li||3.8 mAh cm-2-LiCoO2 batteries, which maintained 80 % capacity retention even after 440 cycles. The consistency of experimental and computational results validates the proposed principles, offering a fundamental guideline to evaluate and design aggressive electrochemical systems.

Reliability and Validity of the Chinese Version of the Revised Sociosexual Orientation Inventory.

The Revised Sociosexual Orientation Inventory (SOI-R) is a measurement tool for assessing an individual's willingness to engage in uncommitted sexual relations. Despite its widespread use in various contexts, no studies have validated the use of this instrument in China. Therefore, the current study aimed to assess the reliability and validity of an existing Chinese translation of the SOI-R. A total of 2,209 participants were recruited and randomly divided into two groups: exploratory factor analysis was conducted on one group and confirmatory factor analysis on the other, with 161 participants from the total sample recruited to assess the test-retest reliability. Criterion validity was measured by testing the correlations between sociosexuality and sexual desire, mate value, sexual attitudes, and personality traits. The results confirmed a three-factor structure (sociosexual behaviors, attitudes, and desire) for the SOI-R. Furthermore, the findings demonstrated good reliability (internal consistency and test-retest stability) and validity (criterion validity, convergent validity, and discriminant validity) of the SOI-R, supporting its suitability as an assessment tool for sociosexual orientation in China.

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.