Application of the pedicle axis view in percutaneous screw placement for type III fracture dislocation of the sacroiliac joint.

AIM: To investigate the clinical application of axial view projection of the pedicle in percutaneous screw placement for type III fracture dislocation of the sacroiliac joint. METHODS: Percutaneous sacroiliac screw fixation was performed in 29 patients with type III sacroiliac joint fractures under X-ray fluoroscopy (C-arm) using axial view projection of the pedicle after preoperative traction reduction and preoperative preparation. The study included 19 males and 10 females, aged 20 to 75 years old, with a mean age of 42.1 ± 3.4 years. RESULTS: The total operative time ranged between 44 and 135 min, with a mean of 95.5 ± 9.4 min. The intraoperative fluoroscopy time ranged between 15 and 42 s, with a mean of 25 ± 4.7 s. The intraoperative blood loss ranged between 5 and 10 ml, with a mean of 7.1 ± 1.3 ml. According to the Matta scoring system, excellent outcomes were achieved in 25 cases, whereas good outcomes were achieved in 4 cases. Based on the definition by Neo et al., pedicle screw positions were categorized into four grades: grade 0 (33 screws), grade I (2 screws), grade II (2 screws), and grade III (0 screws). Excellent outcomes were achieved in 94.6% of Grade 0 and I screws. According to Majeed's functional score, 21 cases achieved excellent outcomes, whereas 8 cases achieved good outcomes. The 29 patients were followed between 3 and 18 months, with a mean of 7.1 ± 1.2 months. All patients achieved anatomical reduction with accurate screw placement and successful healing of their fractures, with no cases of bone penetration or neurovascular injury. CONCLUSION: Axial view imaging of the pedicle using fluoroscopy is a convenient and rapid fluoroscopy method for percutaneous screw placement for type III fracture dislocation of the sacroiliac joint, with a high rate of success, good safety, and short fluoroscopy time.

Thrombospondin-2 holds prognostic value and is associated with metastasis and the mismatch repair process in gastric cancer.

BACKGROUND: This study aims to investigate thrombospondin 2 (TSP2) expression levels in gastric cancer (GC) and determine the relationship between TSP2 and clinical characteristics and prognosis. METHODS: The online database Gene Expression Profile Interactive Analysis (GEPIA) was used to analyse TSP2 mRNA expression levels in GC. The Kaplan-Meier plotter prognostic analysis tool was used to evaluate the influence of TSP2 expression on clinical prognosis in GC patients. TSP2 expression levels were analysed in paraffin-embedded GC samples and adjacent normal tissues by immunohistochemistry. The relationship between the clinicopathological characteristics and prognosis of GC patients was assessed. Transwell experiments were used to evaluate the effect of TSP2 on HGC27 and AGS cell invasion and migration. The EdU experiment was used to detect the effect of transfection of TSP2 on cell proliferation, and the flow cytometry experiment was used to detect the effect of TSP2 on cell apoptosis and the cell growth cycle. Western blotting (Wb) technology was used to detect MMP, E-cadherin, N-cadherin, Vimentin, Snail, AKT, PI3K, and VEGF protein expression in HGC27 cells. RESULTS: Compared with normal tissues, TSP2 mRNA expression in GC was significantly upregulated and was closely related to the clinical stage of GC. High TSP2 expression significantly affected the OS, FP and PPS of patients with GC. Among these patients, TSP2 expression levels did not affect the prognosis of patients with GC in the N0 subgroup but significantly affected the prognosis of patients with GC in the N (1 + 2 + 3) subgroup. TSP2 protein expression levels were significantly higher in GC tissue compared with normal tissues (P < 0.01). The overall survival (OS) and relapse-free survival (RFS) of patients with high TSP2 expression were lower than those of patients with low TSP2 expression. Cells transfected with the TSP2-silencing sequence exhibited increased apoptosis and inhibition of proliferation, migration and invasion. AKT and PI3K expression in cells was significantly downregulated (P < 0.01). AKT, PI3K and VEGF expression in cells transfected with the TSP2 silencing sequence was significantly reduced. Proliferation, migration, invasion ability, and TSP2 expression levels significantly correlated with mismatch repair genes, such as PMS2, MSH6, MSH2, and MLH1 (P < 0.05). CONCLUSION: TSP2 expression is significantly increased in GC. TSP2 expression is closely related to metastasis and the mismatch repair process in GC patients and affects GC patient prognosis. The mechanism may involve regulating gastric cancer cell proliferation and migration by modulating the VEGF/PI3K/AKT signalling pathway. TSP2 is a potential marker and therapeutic target for the prognosis of GC patients.

High Fe and Mn groundwater in the Nanchang, Poyang Lake Basin of China: hydrochemical characteristics and genesis mechanisms.

Based on the water quality test data of 257 groups of phreatic groundwater and 165 groups of confined groundwater in the Nanchang area and the redox conditions, acid-base conditions and the organic matter content in groundwater, we identified hydrochemical characteristics and genesis of groundwater with high Fe and Mn contents in Nanchang. The results showed that Fe and Mn exceeded the standard in both phreatic and confined groundwater. The over-standard rates of Fe and Mn in groundwater were 8.56-11.52% and 33.07-36.36%, respectively. The degree of pollution Fe and Mn in the confined groundwater is higher than that in the phreatic groundwater, and the degree of pollution caused by Mn is higher than that caused by Fe. The high Fe and Mn contents in groundwater were caused by the release of Fe and Mn minerals from the native environment due to changes in the groundwater environment of the study area. A mild redox environment (Eh < 100) and low pH value are favorable for Fe and Mn enrichment in groundwater. The presence of organic matter accelerates microbial activity and promotes the release of Fe and Mn from aquifer sediments. Therefore, the change in the native environment played an important role in the increase in Fe and Mn content in the study area.

Relationship between Tertiary Lymphoid Structure and the Prognosis and Clinicopathologic Characteristics in Solid Tumors.

Background: An increasing number of studies had shown that tertiary lymphoid structure (TLS) plays an important role in tumor progression. However, the prognostic role of TLS in various tumors remains controversial. This meta-analysis aims to investigate the clinicopathological and prognostic values of TLS in solid tumors. Methods: A systematic search was conducted in PubMed, EMBASE and Cochrane Library undated to November 2, 2020. Odds ratios of clinical parameters, hazard ratio (HR) of overall survival (OS), relapse-free survival (RFS), disease-free survival (DFS) and relapse rate were calculated in order to evaluate the relationship between TLS expression and clinicopathological or prognostic values in different tumors. Result: 27 eligible studies including 6647 patients with different types of tumors were analyzed. High TLS expression was associated with a longer OS (HR = 0.66, 95% CI: 0.50 - 0.86, P = 0.002) and RFS (HR = 0.61, 95% CI: 0.47 - 0.79, P = 0.0001). Moreover, high TLS levels in tumor were associated with a low risk of recurrence (HR = 0.43, 95% CI: 0.32 - 0.57, P < 0.0001). However, there was no relationship between TLS expression and DFS. Meanwhile, high TLS expression was associated with smaller tumor size (P < 0.00001) and higher tumor infiltrating lymphocytes (TILs). Furthermore, the subgroup analysis showed high TLS expression that may be associated with a lower clinical grading and N stage in breast cancer and colorectal cancer. Conclusion: High TLS expression is associated with the longer OS and RFS in solid tumors, and a lower risk of cancer relapse. Meanwhile, high TLS expression is also associated with a smaller tumor size, higher infiltration of TILs, lower clinical grading and N stage in the tumor. Therefore, high TLS expression in the tumor is a favorable prognostic biomarker for solid tumor patients.

Polybrominated diphenyl ethers and polychlorinated biphenyls in mangrove sediments of Shantou, China: Occurrence, profiles, depth-distribution, and risk assessment.

Surface and columnar sediments were collected from four mangrove Wetlands in Shantou coastal areas of South China to investigate the level, distribution, possible sources and ecotoxicological risks of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs). Total concentration of 14 PBDEs (∑14PBDEs) and 41 PCBs (∑41PCBs) varied from 0.61 to 180 ng/g and 42-636 pg/g dry weight (dw) in surface sediments, respectively. The concentration of PBDEs was much higher than that of PCBs. Compared with other mangrove Wetlands around the world, PCBs levels in the studied area were relatively low, while the concentrations of PBDE were at higher level. Decabromodiphenyl ether (BDE-209) was the predominant PBDEs homologue in all sediment samples, indicating the extensive use of deca-BDE in this area. Penta-CBs and hexa-CBs were the main homologues of PCBs. Spatial variations showed that the concentration of PBDEs might be mainly affected by anthropogenic activities in specific sites of this region, whereas dry and wet deposition might be an important input source of PCBs in this area. Although accurate sediment chronology was not available, higher concentrations of PBDEs and PCBs were still found in some deeper sediment layers, suggesting that new input quantity tends to decrease with the increase of control. Risk assessment showed that penta-BDEs and deca-BDE may have potential negative ecological effects on the ecological of Shantou mangrove sediments, while the effects of PCBs can be neglected.

Amputation Triggered by Gefitinib: An Unusual Clinical Presentation.

Gefitinib is an epidermal growth factor tyrosine kinase inhibitor used as a targeted chemotherapeutic agent in the treatment of lung cancer and other solid malignancies. The most common adverse effects of gefitinib include dermatological side effects and gastrointestinal symptoms, with rare reports of vascular side effects such as myocardial infarction and stroke. We recently reported a case of a patient with diabetes and multiple comorbidities who developed a serious lower limb vascular adverse event after gefitinib treatment, ultimately leading to amputation surgery. This is the first reported case of lower extremity amputation following gefitinib therapy in a patient with type 2 diabetes mellitus and lung adenocarcinoma. This case highlights the potential risk of amputation in diabetic patients receiving targeted therapies like gefitinib, especially in those with vascular complications. It emphasizes the importance of exercising extra caution when dealing with these patients.

Enhancement effect of biochar addition on anaerobic co-digestion of pig manure and corn straw under biogas slurry circulation.

Based on the semi-continuous anaerobic co-digestion (AcoD) reactor, the effects of biochar addition on the internal environmental changes and gas production characteristics were studied under the condition of biogas slurry recirculation. The results showed that the addition of biochar enhanced the degradation and metabolic pathways of acetate and propionate, thereby reducing the concentrations of volatile fatty acids (VFAs), total ammonia and chemical oxygen demand by 55 %, 41 % and 61 %, respectively. The buffer system formed by the combination of NH4+ and VFAs of C2-C5 was also enhanced, thereby improving the stability of the system. The addition of biochar effectively increased the relative abundance of Bacteroidetes, Chloroflexi, Spirochaetota and Synergistota, and enhanced three methanogenic metabolic pathways. This study provides scientific support for the application of biochar to solve the system inhibition in mixed substrate semi-continuous AcoD process and provides technical support for the stable operation of biogas project.

[Evaluation of Shallow Groundwater Quality and Optimization of Monitoring Indicators in Nanchang].

In the process of groundwater environmental monitoring, while ensuring the representativeness of groundwater quality evaluation, the number of monitoring indicators should be optimized as much as possible, which is of great significance to groundwater environmental management. Based on monitoring data of shallow groundwater in Nanchang in 2014 and 2019, the chemical characteristics of water and the changes in water quality were analyzed via statistical analysis, a Piper three-line diagram, and the entropy-weighted water quality index (EWQI). Furthermore, a key indicator optimization method based on water quality evaluation was constructed by coupling stepwise multiple linear regression analysis. The feasibility of this method was also evaluated. The results showed that the water chemistry type of groundwater in 2014 and 2019 was mainly HCO3-Ca, and the five abnormal indicators pH value, NO3-, I-, Fe, and Mn were the main influencing factors of water quality change. The water quality in 2019 was generally higher than that in 2014, which was considered as overall "moderate," and the average EWQI values of the two years were 53.72 and 82.34, respectively. The optimal model EWQImin-4 constructed based on the key indicator optimization method could better represent the actual EWQI; the key indicators included Mn, NO3-, TH, Fe, pH value, and I-; and the determination coefficient (R2) and percentage error (PE) values were 0.865 and 10.61%, respectively. Therefore, the optimization method of groundwater monitoring indicators based on entropy-weighted water quality evaluation could be used as an important reference for optimizing monitoring indicators and provide a method for regional groundwater environmental management.

Tumor neoantigens: Novel strategies for application of cancer immunotherapy.

Neoantigen-targeted immunotherapy is a rapidly advancing field that holds great promise for treating cancer. The recognition of antigens by immune cells is a crucial step in tumor-specific killing, and neoantigens generated by mutations in cancer cells possess high immunogenicity and are selectively expressed in tumor cells, making them an attractive therapeutic target. Currently, neoantigens find utility in various domains, primarily in the realm of neoantigen vaccines such as DC vaccines, nucleic acid vaccines, and synthetic long peptide vaccines. Additionally, they hold promise in adoptive cell therapy, encompassing tumor-infiltrating cells, T cell receptors, and chimeric antigen receptors which are expressed by genetically modified T cells. In this review, we summarized recent progress in the clinical use of tumor vaccines and adoptive cell therapy targeting neoantigens, discussed the potential of neoantigen burden as an immune checkpoint in clinical settings. With the aid of state-of-the-art sequencing and bioinformatics technologies, together with significant advancements in artificial intelligence, we anticipated that neoantigens will be fully exploited for personalized tumor immunotherapy, from screening to clinical application.

Targeting LAYN inhibits colorectal cancer metastasis and tumor-associated macrophage infiltration induced by hyaluronan oligosaccharides.

The accumulation of hyaluronan oligosaccharides (oHA) in colorectal cancer (CRC) is closely related to tumor metastasis, but the underlying mechanism remains unclear. In this study, we first described that LAYN, a novel HA receptor, was upregulated in CRC tissue. Aberrant LAYN expression correlated with CRC metastasis and poor prognosis and positively correlated with tumor-associated macrophage (TAM) infiltration and M2 macrophage polarization in the tumor environment. Both in vitro and in vivo studies demonstrated that LAYN is activated by oHA and subsequently induces CRC metastasis and macrophage infiltration. Mechanistic studies demonstrated that oHA activates LAYN by binding to the 60-68th amino acid region of the extracellular segment. oHA-induced LAYN activation promoted metastasis and CCL20 secretion through the NF-kB pathway in CRC cells. Furthermore, targeting LAYN using a blocking antibody prevented oHA-mediated tumor metastasis, TAM infiltration and M2 polarization. This study revealed the LAYN activation mechanism and identified a potential target for the treatment of CRC tumor exhibiting high oHA levels.

Tumour budding is a novel marker in breast cancer: the clinical application and future prospects.

Breast cancer (BC) is a group of markedly heterogeneous tumours. There are many subtypes with different biological behaviours and clinicopathological characteristics, leading to significantly different prognosis. Despite significant advances in the treatment of BC, early metastatic is a critical factor for poor prognosis in BC patients. Tumour budding (TB) is considered as the first step process of tumour metastasis and is related to the epithelial-mesenchymal transition (EMT). TB has been observed in a variety of cancers, such as colorectal and gastric cancer, and had been considered as a distinct clinicopathological characteristics for early metastasis. However, TB evaluation standards and clinical application are not uniform in BC, as well as its molecular mechanism is not fully understood. Here, we reviewed the interpretation criteria, mechanism, clinicopathological characteristics and clinical application prospects of TB in BC. Key messagesCurrently, tumour budding is a poor prognosis for various solid tumours, also in breast cancer.Tumour budding is based on epithelial-mesenchymal transition and tumour microenvironment factors and is presumed to be an early step in the metastatic process.Breast cancer tumour budding still needs multi-centre experiments. We summarize the current research on breast cancer tumour budding, analyse the method of discriminating breast cancer tumour budding and explore the prognostic role and mechanism in breast cancer.

Targeting PELP1 Attenuates Angiogenesis and Enhances Chemotherapy Efficiency in Colorectal Cancer.

Abnormal angiogenesis is one of the important hallmarks of colorectal cancer as well as other solid tumors. Optimally, anti-angiogenesis therapy could restrain malignant angiogenesis to control tumor expansion. PELP1 is as a scaffolding oncogenic protein in a variety of cancer types, but its involvement in angiogenesis is unknown. In this study, PELP1 was found to be abnormally upregulated and highly coincidental with increased MVD in CRC. Further, treatment with conditioned medium (CM) from PELP1 knockdown CRC cells remarkably arrested the function of human umbilical vein endothelial cells (HUVECs) compared to those treated with CM from wildtype cells. Mechanistically, the STAT3/VEGFA axis was found to mediate PELP1-induced angiogenetic phenotypes of HUVECs. Moreover, suppression of PELP1 reduced tumor growth and angiogenesis in vivo accompanied by inactivation of STAT3/VEGFA pathway. Notably, in vivo, PELP1 suppression could enhance the efficacy of chemotherapy, which is caused by the normalization of vessels. Collectively, our findings provide a preclinical proof of concept that targeting PELP1 to decrease STAT3/VEGFA-mediated angiogenesis and improve responses to chemotherapy due to normalization of vessels. Given the newly defined contribution to angiogenesis of PELP1, targeting PELP1 may be a potentially ideal therapeutic strategy for CRC as well as other solid tumors.

Micro-ecology restoration of colonic inflammation by in-Situ oral delivery of antibody-laden hydrogel microcapsules.

In-situ oral delivery of therapeutic antibodies, like monoclonal antibody, for chronic inflammation treatment is the most convenient approach compared with other administration routes. Moreover, the abundant links between the gut microbiota and colonic inflammation indicate that the synergistic or antagonistic effect of gut microbiota to colonic inflammation. However, the antibody activity would be significantly affected while transferring through the gastrointestinal tract due to hostile conditions. Moreover, these antibodies have short serum half-lives, thus, require to be frequently administered with high doses to be effective, leading to low patient tolerance. Here, we develop a strategy utilizing thin shell hydrogel microcapsule fabricated by microfluidic technique as the oral delivering carrier. By encapsulating antibodies in these microcapsules, antibodies survive in the hostile gastrointestinal environment and rapidly release into the small intestine through oral administration route, achieving the same therapeutic effect as the intravenous injection evaluated by a colonic inflammation disease model. Moreover, the abundance of some intestinal microorganisms as the indication of the improvement of inflammation has remarkably altered after in-situ antibody-laden microcapsules delivery, implying the restoration of micro-ecology of the intestine. These findings prove our microcapsules are exploited as an efficient oral delivery agent for antibodies with programmable function in clinical application.

Endostatin induces normalization of blood vessels in colorectal cancer and promotes infiltration of CD8+ T cells to improve anti-PD-L1 immunotherapy.

Introduction: The purpose of this study was to evaluate recombinant human endostatin (rHE)-induced normalization of the tumor vasculature in colorectal cancer (CRC) and to evaluate the therapeutic effects of combined treatment with rHE and a programmed death ligand-1 (PD-L1) inhibitor. Methods: A mouse subcutaneous tumorigenesis model was established to evaluate the antitumor effects of endostatin combined with a PD-L1 inhibitor on CRC. Intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM-DW MRI) was used to evaluate changes in the intratumor microcirculation in response to combined treatment with endostatin and a PD-L1 inhibitor. The infiltration density and function of CD8+ T cells in tumors were evaluated using flow cytometry. Finally, clinical specimens were used to evaluate the expression area of tumor vascular pericytes and CD8+ T cells in tumor tissues. Results: The antitumor effects of endostatin combined with a PD-L1 inhibitor were significantly greater than those of endostatin or a PD-L1 inhibitor alone. On the ninth day of intervention, the endostatin group showed significantly higher pseudo diffusion parameter (D*) and microvascular volume fraction (F) values in tumors than those in the control group or PD-L1 group. After 27 days of intervention, the endostatin groups showed significantly lower levels of vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-ß than those in the control group. Treatment of CD8+ T cells with endostatin for 24 h did not alter the expression levels of markers of reduced T-cell activity. However, endostatin reversed the VEGF-mediated inhibition of the secretion of interferon (IFN)-γ from T cells. The results in CRC clinical samples showed that treatment with endostatin induced significantly higher infiltration of CD8+ T cells compared with treatment that did not include endostatin. Furthermore, the expression area of pericytes was significantly positively related to the infiltration density of CD8+ T cells and overall survival time. Conclusion: Endostatin improved the antitumor effects of PD-L1 inhibitors on CRC, significantly increased the activity of CD8+ T cells, and synergistically improved the tumor treatment effect of the two inhibitors.

Targeting FAPα-expressing hepatic stellate cells overcomes resistance to antiangiogenics in colorectal cancer liver metastasis models.

Vessel co-option has been demonstrated to mediate colorectal cancer liver metastasis (CRCLM) resistance to antiangiogenic therapy. The current mechanisms underlying vessel co-option have mainly focused on "hijacker" tumor cells, whereas the function of the "hijackee" sinusoidal blood vessels has not been explored. Here, we found that the occurrence of vessel co-option in bevacizumab-resistant CRCLM xenografts was associated with increased expression of fibroblast activation protein α (FAPα) in the co-opted hepatic stellate cells (HSCs), which was dramatically attenuated in HSC-specific conditional Fap-knockout mice bearing CRCLM allografts. Mechanistically, bevacizumab treatment induced hypoxia to upregulate the expression of fibroblast growth factor-binding protein 1 (FGFBP1) in tumor cells. Gain- or loss-of-function experiments revealed that the bevacizumab-resistant tumor cell-derived FGFBP1 induced FAPα expression by enhancing the paracrine FGF2/FGFR1/ERK1/-2/EGR1 signaling pathway in HSCs. FAPα promoted CXCL5 secretion in HSCs, which activated CXCR2 to promote the epithelial-mesenchymal transition of tumor cells and the recruitment of myeloid-derived suppressor cells. These findings were further validated in tumor tissues derived from patients with CRCLM. Targeting FAPα+ HSCs effectively disrupted the co-opted sinusoidal blood vessels and overcame bevacizumab resistance. Our study highlights the role of FAPα+ HSCs in vessel co-option and provides an effective strategy to overcome the vessel co-option-mediated bevacizumab resistance.

Treatment of Pauwels type III femoral neck fracture with medial femoral neck support screw: a biomechanical and clinical study.

A femoral neck fracture is currently one of the most common types of fracture in clinical practice. The incidence continues to increase due to traffic accidents, trauma, and osteoporosis. This research includes a biomechanical study and a clinical retrospective study. In the biomechanical studies, three groups' effects (Control Group: 3CCS, DHS group, and study Group: 3CCS + mFNSS group) were compared by vertical compression tests, torsion tests, and fatigue tests. All the data were collected and analyzed. We subsequently performed a retrospective analysis of 131 patients with femoral neck fractures. The operative time, intraoperative blood loss, quality of postoperative fracture reduction, and follow-up observation of fracture healing, screw retreatment rates and fixation failure rates, as well as femoral head necrosis rates and hip function in two groups with 3CCS and 3CCS + mFNSS were compared. By the biomechanical study, we found that 3CCS + Mfnss group were biomechanically superior to 3CCS group and superior to the DHS group in terms of resistance to torsion. However, it was less effective than the DHS group in compressive strength and fatigue resistance. In terms of clinical application, 3CCS + mFNSS group was found to have lower screw retreatment rates and femoral head necrosis rates, and to have better fracture healing rates than group with 3CCS, indicating that medial support screws can effectively resist the vertical shear forces of fracture ends and promote the stability and healing of fracture ends, as well as to reduce the incidence of postoperative complications.

Studies on the degradation of corn straw by combined bacterial cultures.

In this study, the combined bacteria (CB) were constructed by Phanerochaete chrysosporium, Trametes versicolor and Pleurotus ostreatus, which have a good ability to degrade lignocellulose, and the optimum degradation conditions and internal degradation mechanism of combined bacteria were investigated. The results showed that under conditions of temperature (32 °C), pH (3.5), solid-liquid ratio (10%), culture time (20 d), the degradation rates of lignin, cellulose and hemicellulose were 43.36%, 31.29%, 48.36%, respectively. The construction of combined bacteria significantly enhances the degradation ability of lignocellulose, and showed good correlation and coordination mechanism.

Anaerobic digestion of corn straw pretreated by ultrasonic combined with aerobic hydrolysis.

Corn straw (CS) was pretreated by ultrasonic combined aerobic with biogas slurry as medium for anaerobic digestion (AD), that strengthened the degradation efficiency CS, varied in the composition of digestion slurry, thereby the methane production was increased. Central combinatorial design (CCD) test was used to treat CS at ultrasonic power (200, 400, and 600 W), time (10, 20, and 30 min) and AD for 25 days, at 37 ± 1℃. According to data showed that the pH and volatile fatty acids (VFAs) affected methane production directly. With an ultrasonic power 309 W, time 26 min, it reached the maximum content of VFAs with 16.24 g/L, the cumulative methane production achieved the highest with 198.56 mL/g VS, which was 46.73% higher than unpretreated raw material as CK. Ultrasonic-aerobic hydrolysis pretreatment can obtain higher VFAs and methane production content in a short period of time that is great significance to biogas engineering.

Long Noncoding RNA KCNQ1OT1 is a Prognostic Biomarker and mediates CD8+ T cell exhaustion by regulating CD155 Expression in Colorectal Cancer.

Background: Long noncoding RNA KCNQ1 opposite strand/antisense transcript 1 (lncRNA KCNQ1OT1) is abnormally expressed in various solid tumors. The purpose of this study was to explore the prognostic value and potential functional role of lncRNA KCNQ1OT1 across cancers. Methods: We performed a meta-analysis of published literature to evaluate the prognostic value of lncRNA KCNQ1OT1 across cancers. Verification, functional analysis, and genomic variation analysis were performed using the GEPIA, TIMER, and LnCeVar databases. According to the immune cell infiltration level, we established a prognostic model of lncRNA KCNQ1OT1 expression using public datasets of TIMER. We used quantitative real-time polymerase chain reaction (RT-qPCR) and western blot to detect the expression levels of lncRNA KCNQ1OT1 and the CD155 protein in colorectal cancer (CRC) tissues and cell lines. Then, a lncRNA KCNQ1OT1-knockdown cell line was cocultured to explore the role of lncRNA KCNQ1OT1 and CD155 in the T cell response by flow cytometric analysis. Results: Our results showed that the high expression of lncRNA KCNQ1OT1 was significantly related to poor overall survival across cancers, especially CRC. Interestingly, we found that COAD patients with high lncRNA KCNQ1OT1 expression and high CD8+ T cell infiltration levels had a worse prognosis than those with low lncRNA KCNQ1OT1 expression and high CD8+ T cell infiltration levels. Moreover, lncRNA KCNQ1OT1 and CD155 showed significantly higher expression in CRC tissue than in normal tissue, and lncRNA KCNQ1OT1 expression was positively correlated with CD155 expression in CRC. Finally, knockdown of lncRNA KCNQ1OT1 reduced CD155 expression in HCT116 and SW620 cells and enhanced the immune response in coculture with CD8+ T cells. Conclusions: High lncRNA KCNQ1OT1 expression is significantly correlated with poor prognosis of CRC patients and mediates the CD8+ T cell response in CRC. These findings indicate that lncRNA KCNQ1OT1 is a prognostic biomarker and potential immune therapeutic target for enhancing the CD8+ T cell response in CRC.

Comprehensive Analysis of N6-Methyladenosine-Related lncRNA Signature for Predicting Prognosis and Immune Cell Infiltration in Patients with Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most common tumor worldwide. Aberrant N6-methyladenosine (m6A) modification can influence the progress of the CRC. Additionally, long noncoding RNA (lncRNA) plays a critical role in CRC and has a close relationship with m6A modification. However, the prognostic potential of m6A-related lncRNAs in CRC patients still remains to be clarified. METHODS: We use "limma" R package, "glmnet" R package, and "survival" R package to screen m6A-related-lncRNAs with prognostic potential. Then, we comprehensively analysed and integrated the related lncRNAs in different TNM stages from TCGA database using the LASSO Cox regression. Meanwhile, the relationship between functional enrichment of m6A-related lncRNAs and immune microenvironment in CRC was also investigated using the TCGA database. A prognostic model was constructed and validated to determine the association between m6A-related lncRNAs in different TNM stages and the prognosis of CRC. RESULT: We demonstrated that three related m6A lncRNAs in different TNM stages were associated with the prognosis of CRC patients. Patients from the TCGA database were classified into the low-risk and the high-risk groups based on the expression of these lncRNAs. The patients in the low-risk group had longer overall survival than the patients in the high-risk group (P < 0.001). We further constructed and validated a prognostic nomogram based on these genes with a C-index of 0.80. The receiver operating characteristic curves confirmed the predictive capacity of the model. Meanwhile, we also found that the low-risk group has the correlation with the dendritic cell (DC). Finally, we discovered the relationship between the m6A regulators and the three lncRNAs. CONCLUSION: The prognostic model based on three m6A-related lncRNAs exhibits superior predictive performance, providing a novel prognostic model for the clinical evaluation of CRC patients.