Pan-cancer analysis of Sushi domain-containing protein 4 (SUSD4) and validated in colorectal cancer.

Sushi domain-containing protein 4 (SUSD4) is a complement regulatory protein whose primary function is to inhibit the complement system, and it is involved in immune regulation. The role of SUSD4 in cancer progression has largely remained elusive. SUSD4 was studied across a variety of cancer types in this study. According to the results, there is an association between the expression level of SUSD4 and prognosis in multiple types of cancer. Further analysis demonstrated that SUSD4 expression level was related to immune cell infiltration, immune-related genes, tumor heterogeneity, and multiple cancer pathways. Additionally, we validated the function of SUSD4 in colorectal cancer cell lines and found that knockdown of SUSD4 inhibited cell growth and impacted the JAK/STAT pathway. By characterizing drug sensitivity in organoids, we found that the expression of SUSD4 showed a positive correlation trend with IC50 of Selumetinib, YK-4-279, and Piperlongumine. In conclusion, SUSD4 is a valuable prognostic indicator for diverse types of cancer, and it has the potential to be a target for cancer therapy.

Synergizing economic growth and carbon emission reduction in China: A path to coupling the MFLP and PLUS models for optimizing the territorial spatial functional pattern.

Carbon emissions caused by economic growth are the main cause of global warming, but controlling economic growth to reduce carbon emissions does not meet China's conditions. Therefore, how to synergize economic growth and carbon emission reduction is not only a sustainable development issue for China, but also significant for mitigating global warming. The territorial spatial functional pattern (TSFP) is the spatial carrier for coordinating economic development and carbon emissions, but how to establish the TSFP of synergizing economic growth and carbon emission reduction remains unresolved. We propose a decision framework for optimizing TSFP coupled with the multi-objective fuzzy linear programming and the patch-generating land use simulation model, to provide a new path to synergize economic growth and carbon emission reduction in China. To confirm the reliability, we took Qionglai City as the demonstration. The results found a significant spatiotemporal coupling between TSFP and the synergistic states between economic growth and carbon emission reduction (q ≥ 0.8220), which resolves the theoretical uncertainty about synergizing economic growth and carbon emission reduction through the path of TSFP optimization. The urban space of Qionglai City in 2025 and 2030 obtained by the decision framework was 6497.57 hm2 and 6628.72 hm2 respectively, distributed in the central and eastern regions; the rural space was 60,132.92 hm2 and 56,084.97 hm2, concentrated in the east, with a few located in the west; and the ecological space was 71,072.52 hm2 and 74,998.31 hm2, mainly located in the western and southeastern areas. Compared with the TSFP in 2020, the carbon emission intensity of the TSFP obtained by the decision framework was reduced by 0.7 and 4.7 tons/million yuan, respectively, and realized the synergy between economic growth and carbon emission reduction (decoupling index was 0.25 and 0.21). Further confirming that TSFP optimization is an effective way to synergize economic growth and carbon emission reduction, which can provide policy implications for coordinating economic growth and carbon emissions for China and even similar developing countries.

Climate and fragment area jointly affect the annual dynamics of seedlings in different functional groups in the Thousand Island Lake.

Habitat fragmentation and climate change are the two main threats to global biodiversity. Understanding their combined impact on plant community regeneration is vital for predicting future forest structure and conserving biodiversity. This study monitored the seed production, seedling recruitment and mortality of woody plants in the Thousand Island Lake, a highly fragmented anthropogenic archipelago, for 5 years. We analyzed the seed-seedling transition, seedling recruitment and mortality of different functional groups in the fragmented forests and conducted correlation analyses involving climatic factors, island area, and plant community abundance. Our results showed that: 1) shade-tolerant and evergreen species had higher seed-seedling transition, seedling recruitment and survival rate than shade-intolerant and deciduous species in time and space, and these advantages increased with the island area. 2) Seedlings in different functional groups responded differently to island area, temperature and precipitation. 3) Increasing active accumulated temperature (the sum of the mean daily temperature above 0 °C) significantly increased seedling recruitment and survival, and warming climate favored the regeneration of evergreen species. 4) The seedling mortality rate of all plant functional groups increased with the increase of island area, but the increasing strength weakened significantly with the increase of the annual maximum temperature. These results suggested that the dynamics of woody plant seedlings varied among functional groups, and can be regulated separately and jointly by fragmentation and climate.

Pan-Cancer analysis and experimental validation identify the oncogenic nature of ESPL1: Potential therapeutic target in colorectal cancer.

Introduction: Extra spindle pole bodies like 1 (ESPL1) are required to continue the cell cycle, and its primary role is to initiate the final segregation of sister chromatids. Although prior research has revealed a link between ESPL1 and the development of cancer, no systematic pan-cancer analysis has been conducted. Combining multi-omics data with bioinformatics, we have thoroughly described the function of ESPL1 in cancer. In addition, we examined the impact of ESPL1 on the proliferation of numerous cancer cell lines. In addition, the connection between ESPL1 and medication sensitivity was verified using organoids obtained from colorectal cancer patients. All these results confirm the oncogene nature of ESPL1. Methods: Herein, we downloaded raw data from numerous publicly available databases and then applied R software and online tools to explore the association of ESPL1 expression with prognosis, survival, tumor microenvironment, tumor heterogeneity, and mutational profiles. To validate the oncogene nature of ESPL1, we have performed a knockdown of the target gene in various cancer cell lines to verify the effect of ESPL1 on proliferation and migration. In addition, patients' derived organoids were used to verify drug sensitivity. Results: The study found that ESPL1 expression was markedly upregulated in tumorous tissues compared to normal tissues, and high expression of ESPL1 was significantly associated with poor prognosis in a range of cancers. Furthermore, the study revealed that tumors with high ESPL1 expression tended to be more heterogeneous based on various tumor heterogeneity indicators. Enrichment analysis showed that ESPL1 is involved in mediating multiple cancer-related pathways. Notably, the study found that interference with ESPL1 expression significantly inhibited the proliferation of tumor cells. Additionally, the higher the expression of ESPL1 in organoids, the greater the sensitivity to PHA-793887, PAC-1, and AZD7762. Discussion: Taken together, our study provides evidence that ESPL1 may implicate tumorigenesis and disease progression across multiple cancer types, highlighting its potential utility as both a prognostic indicator and therapeutic target.

Uncovering the Heterogeneity and Clinical Relevance of Circulating Tumor-Initiating Cells in Hepatocellular Carcinoma Using an Integrated Immunomagnetic-Microfluidic Platform.

Circulating tumor-initiating cells (CTICs) with stem cell-like properties play pivotal roles in tumor metastasis and recurrence. However, little is known about the biology and clinical relevance of CTICs in hepatocellular carcinoma (HCC). Here, we investigated the molecular heterogeneity and clinical relevance of CTICs in HCC using a novel integrated immunomagnetic-microfluidic platform (iMAC). We constructed the iMAC and evaluated its ability to detect CTICs using a series of spiked cell experiments. A four-channel microfluidic chip was applied to investigate the composition of CTICs in patients with primary and recurrent HCC utilizing microbeads labeled with one of four stem-related markers: epithelial cell adhesion molecule (EpCAM), CD133, CD90, and CD24. The dynamic changes of these four CTIC subsets were serially monitored during treatment courses. Finally, single-cell RNA profiling was used to reveal the molecular characteristics of the four CTIC subsets. The iMAC platform detected significantly more EpCAM+ CTICs in the blood samples from 33 HCC patients than the FDA-approved CellSearch system (0.92 ± 0.94 vs 0.23 ± 0.36, P < 0.001). The number of EpCAM+ CTICs (≥0.75/mL) detected by iMAC was a predictor of early recurrence (P = 0.007). The distinct stem-related markers' expression of CTICs could distinguish primary HCC, recurrent HCC, and TACE-resistant HCC. Single-cell transcriptional profiling proved the heterogeneity among individual CTICs and separated the four CTIC subsets into distinct phenotypes. Dissecting the heterogeneity of CTICs using the iMAC represents a novel and informative method for accurate CTIC detection and characterization. This innovative technology will enable more indepth cancer biology research and clinical cancer management than is currently available.

Short-term and long-term outcomes of natural orifice specimen extraction surgeries (NOSES) in rectal cancer: a comparison study of NOSES and non-NOSES.

Background: Natural orifice specimen extraction surgeries (NOSES) have been applied to colorectal cancer (CRC). Different types of NOSES have been proposed. Traditional laparoscopic CRC surgeries (non-NOSES) have been widely adopted in clinical practice. Therefore, the safety and feasibility of NOSES could be clarified by comparing with non-NOSES. Methods: Consecutive cases who underwent NOSE or non-NOSE rectal surgeries were retrospectively collected at the Second Affiliated Hospital of Harbin Medical University between 1 January 2013 and 31 December 2018. Other inclusion criteria included patients with adenocarcinoma of the rectum within 15 cm of the anal verge, over the age of 18 and undergoing primary laparoscopic rectal resection. Patients who were lost to follow-up or had incomplete information were excluded. Basic characteristics including gender, tumor location, age, staging, treatment, and Body Mass Index (BMI) were analyzed. Short-term outcomes including comorbidities, intra-operative blood loss, hospital stay, gas exhaust time were compared between different NOSES and non-NOSES groups. Long-term outcomes including overall survival (OS) and disease-free survival (DFS) were also analyzed. Patients were followed-up during the inpatient period, at an outpatient clinic, or by phone call. Results: A total of 196 NOSES cases and 243 non-NOSES cases were included. There was a sex difference between the two groups and other factors were comparable. Cases were divided into NOSES groups [including extra-abdominal resection (EVER), specimen extraction and extra-abdominal resection (EXER), and intra-abdominal resection and specimen extraction (IREX)] and non-NOSES groups. Differences in sex (P=0.016), BMI (with mean of 22.08, 22.00, 22.53, and 23.26 kg/m2, P=0.003), and staging (P=0.008) were observed between the four groups. There was a difference in the intra-operative blood loss between NOSES and non-NOSES groups (57.05±62.78, 52.65±68.19, 36.52±43.99 vs. 76.12±90.11 mL, P=0.002), in which NOSES groups had less blood loss. Furthermore, NOSES groups showed a better post-operative gas exhaust time (54.68±37.80, 45.06±24.69, 47.91±28.93 vs. 56.94±27.69 hours, P=0.012). NOSES groups also had fewer ileostomies (17 vs. 37, P=0.003). There was no difference in the long-term DFS and OS between the two groups. Conclusions: NOSES in rectal cancer showed better short-term outcomes and had comparable long-term outcomes compared with non-NOSE surgeries.

English learning burnout: Scale validation in the Chinese context.

While there has been considerable research on learning burnout in educational psychology, it has received little attention in language education. To fill this gap, the present study aims at exploring the construct of English learning burnout (ELB) and examining the levels of this complex construct in a large sample of 1,213 Chinese senior high school students utilizing a 15-item Senior High School English Learning Burnout Scale. A two-dimensional structure of ELB comprising exhaustion and demotivation was extracted by exploratory factor analysis and validated by confirmatory factor analysis. A descriptive analysis showed low levels of global ELB and exhaustion and a moderate level of demotivation. The findings suggest that teachers should be mindful of fostering students' self-regulated strategies to alleviate their ELB.

DEF6 has potential to be a biomarker for cancer prognosis: A pan-cancer analysis.

Introduction: DEF6 is a gene associated with the immune system and is thought to play a crucial role in autoimmunity. There are few DEF6-related studies in cancer, and it is assumed that DEF6 is a proto-oncogene. There is currently no pan-cancer analysis of DEF6, and we performed a systematic and comprehensive pan-cancer analysis of DEF6 in an attempt to reveal its role and function in cancer. Methods: The data were analyzed by mining databases available to the public and by using R software. Moreover, immunohistochemistry was used to validate the results. Results: Our results revealed that DEF6 is commonly aberrantly expressed in cancer and its expression is strongly correlated with survival prognosis in a variety of cancer types. Through correlation analysis we found that DEF6 was associated with multiple immune genes and was closely related to immune infiltration. In the enrichment analysis, DEF6 may have cross-talk with multiple cancer pathways and exert oncogenic or pro-cancer functions. In addition, we collected pathological samples from colorectal cancer patients for immunohistochemical analysis and found that patients with higher immunohistochemical scores had more lymph node metastases, higher CA199, and bigger tumor size. Discussion: Overall, DEF6 expression is closely related to cancers and has the potential to act as a cancer biomarker.

Role of Phenotypes of Circulating Tumor Cells in the Diagnosis and Treatment of Colorectal Cancer.

OBJECTIVE: To investigate the relationship between circulating tumor cells (CTCs) and their subpopulations and colorectal cancer (CRC). To explore the application of CTCs' numbers and positive rates in the diagnosis and treatment of CRC, and to assess the effect of surgery on CTCs numbers and positivity. METHODS: We identified CTCs using the CanPatrol technique after enrollment. Peripheral blood samples were collected from 74 CRC patients before anti-tumor treatment. CTCs can be divided into the following three phenotypes: epithelial CTCs (E-CTCs) (EpCAM+, Vimentin-), mesenchymal CTCs (M-CTCs) (EpCAM-, Vimentin+), and mixed CTCs (E/M-CTCs) (EpCAM+, Vimentin+). CTCs and the proportion of subtypes were statistically compared with clinicopathological characteristics. RESULTS: The positive rate of M-CTCs was significantly higher in patients with tumor size ≥5 cm (85.7% vs 49.1%, P = 0.004) and carcinoembryonic antigen (CEA) >5 ng/mL (83.3% vs 51.0% p = 0.024). Moreover, the T stage (T1 0, T2 33.3%, T3 59.4%, T4 100%, p < 0.0005) and TNM stage (stage I 11.8%, stage II 79.2%, stage III 64.3%, stage IV 100%, p < 0.0005) were correlated with the positive rate of M-CTCs. We also found that the proportion of M-CTCs was correlated with the T stage (p < 0.0005) and TNM stage (p=0.0200), but not with the N stage (p=0.6889). In survival analysis, M-CTCs >1 were found associated with worse disease-free survival (p=0.007). After treatment, the number and proportion of CTCs and M-CTCs were significantly reduced. CONCLUSION: The positive rate of M-CTCs was associated with tumor size, T stage, TNM stage, vascular invasion, and CEA. As the disease progressed, the proportion of M-CTCs gradually increased, and the survival performance was worse in patients with a high positive rate of M-CTCs.

Long-Term Outcome Comparison Between Two Specimen Extraction Approaches for Middle Rectum Cancer: A Retrospective Study.

Objective. There are few studies comparing the long-term results of natural orifice specimen extraction surgery (NOSES) and conventional laparoscopic-assisted resection (LA) in the treatment of middle rectal cancer. This retrospective analysis aimed to evaluate the reliability of NOSES. Method. From January 2013 to December 2017, all patients diagnosed with median rectal cancer in our hospital who underwent NOSES and LA were enrolled. We used propensity-score matching (PSM) to balance baseline data between the NOSES group and the laparoscopic group. The primary endpoint was overall survival (OS) and disease-free survival (DFS). We used the Kaplan-Meier method to estimate OS and DFS. Student's t-test was used to analyze the difference of continuous data. Categorical data were compared using the Kruskal-Wallis test or Fisher's exact test. Results. After PSM, 38 patients were included in each group. We found that surgical bleeding volume in the NOSES group was considerably lower than that in the LA group (49.5 ± 47.5 mL vs. 86.3 ± 83.5 mL, P = .01). From the short-term results, the first flatus and regular diet time in the NOSES group were shorter than those in the LA group (41.3 ± 25.2 vs. 54.0 ± 19.2 hours, P < .01 and 63.9 ± 42.6 hours vs. 105.1 ± 66.8 hours, P < .01, respectively). Long-term OS and DFS were not different between the groups. Conclusion. Therefore, NOSES is a reliable technique for middle rectal cancer treatment. Short-term outcomes are pointedly better than LA, while the two surgical approaches did not differ in the long-term outcomes or complication rate.

Mechanism of ammonium sharp increase during sediments odor control by calcium nitrate addition and an alternative control approach by subsurface injection.

Nitrate-driven sulfide/ferrous oxidation has been proved a cost-effective approach for river sediments in-situ odor control. However, calcium nitrate addition would sharply increase ammonium concentration in interstitial water and the mechanism was not yet clear. In this work, though sulfide and ferrous iron were efficiently oxidized, about 102% of NH4+ concentration increased in interstitial water on the first day of calcium nitrate injection (30 mg kg dwt-1), and about 31% more NH4+ increase at the 21st days was observed. To discover the mechanism of ammonium sharp release, desorption kinetics experiment was conducted and the results suggested that the short-time sharp releases of ammonium when calcium nitrate was added could be attributed to the chemical extraction of exchangeable ammonium by calcium ion. Furthermore, at the end of treatment, many genus such as Thiobacillus, Sulfurimonas, Thermomonas, and Clostridium, which were closely related to sulfide and ferrous-driven denitrification and dissimilatory nitrate reduction to ammonium (DNRA), were identified by 16S rRNA Illumina sequencing method. These findings indicated the long-time increase of ammonium might be determined by the biochemical processes (e.g. DNRA) driven by nitrate reduction. Therefore, to avoid the impact of ammonium release, an alternative subsurface injection method was introduced in this work, and the results showed that ammonium releases could be well controlled when the injection position was beneath 10 cm of the sediment surface.

Recent Advance in Source, Property, Differentiation, and Applications of Infrapatellar Fat Pad Adipose-Derived Stem Cells.

Infrapatellar fat pad (IPFP) can be easily obtained during knee surgery, which avoids the damage to patients for obtaining IPFP. Infrapatellar fat pad adipose-derived stem cells (IPFP-ASCs) are also called infrapatellar fat pad mesenchymal stem cells (IPFP-MSCs) because the morphology of IPFP-ASCs is similar to that of bone marrow mesenchymal stem cells (BM-MSCs). IPFP-ASCs are attracting more and more attention due to their characteristics suitable to regenerative medicine such as strong proliferation and differentiation, anti-inflammation, antiaging, secreting cytokines, multipotential capacity, and 3D culture. IPFP-ASCs can repair articular cartilage and relieve the pain caused by osteoarthritis, so most of IPFP-related review articles focus on osteoarthritis. This article reviews the anatomy and function of IPFP, as well as the discovery, amplification, multipotential capacity, and application of IPFP-ASCs in order to explain why IPFP-ASC is a superior stem cell source in regenerative medicine.