Citraconate promotes the malignant progression of colorectal cancer by inhibiting ferroptosis.

Metastasis is a principal factor in the poor prognosis of colorectal cancer. Recent studies have found microbial metabolites regulate colorectal cancer metastasis. By analyzing metabolomics data, we identified an essential fecal metabolite citraconate that potentially promotes colorectal cancer metastasis. Next, we tried to reveal its effect on colorectal cancer and the underlying mechanism. Firstly, the response of colorectal cancer cells (HCT116 and MC38 cells) to citraconate was assessed by Cell Counting Kit-8 assay, clonogenic assay, transwell migration and invasion assay. Moreover, we utilized an intra-splenic injection model to evaluate the effect of citraconate on colorectal cancer liver metastasis in vivo. Then molecular approaches were employed, including RNA sequencing, mass spectrometry-based metabolomics, western blot, quantitative real-time PCR, cell ferrous iron colorimetric assay and intracellular malondialdehyde measurement. In vitro, citraconate promotes the growth of colorectal cancer cells. In vivo, citraconate aggravated liver metastasis of colorectal cancer. Mechanistically, downstream genes of NRF2, NQO1, GCLC, and GCLM high expression induced by citraconate resulted in resistance to ferroptosis of colorectal cancer cells. In summary, citraconate promotes the malignant progression of colorectal cancer through NRF2-mediated ferroptosis resistance in colorectal cancer cells. Furthermore, our study indicates that fecal metabolite may be crucial in colorectal cancer development.

Resveratrol activates MAPK/ERK pathway to regulate oestrogen metabolism in type I endometrial cancer.

OBJECTIVE: Endometrial cancer (EC) is an oestrogen-dependent tumour, the occurrence of which is closely related to an imbalance of oestrogen homeostasis. Our previous studies explored the effects of Resveratrol(Res) on oestrogen metabolism. However, systematic research on the exact mechanism of action of Res is still lacking. Based on network pharmacology, molecular docking and animal experiments, the effects and molecular mechanisms of Res on endometrial cancer were investigated. METHODS: The target of Res was obtained from the high-throughput experiment and reference-guided database of TCM (HERB) and the Encyclopedia of Traditional Chinese Medicine (ETCM) databases, and the target of endometrial cancer was obtained by using the Genecards database. Venny map was used to obtain the intersection target of Res in the treatment of endometrial cancer, and the protein interaction network of the intersection target was constructed by importing the data into the STRING database. Then, the drug-disease-target interaction network was constructed based on Cytoscape 3.9.1 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for intersection targets using the OmicShare cloud platform. Res and core targets were analysed by molecular docking. EC model mice induced by MNNG were randomly divided into the control group, Res group, MNNG group, MNNG + Res group, and MNNG + Res + MAPK/ERKi group. The protein levels of ERK and p-ERK in the mouse uterus were detected by Western blot. The levels of E1, E2, E3, 16-epiE3, 17-epiE3, 2-MeOE1, 4-MeOE1, 2-MeOE2, 4-MeOE2, 3-MeOE1, 2-OHE1, 4-OHE1, 2-OHE2, 4-OHE2, and 16α-OHE1 in the serum and endometrial tissue of mice were measured by LC‒MS/MS. RESULTS: A total of 174 intersection targets of Res anti-endometrial cancer were obtained. The signalling pathways analysed by KEGG enrichment included the AGE-RAGE signalling pathway in diabetic complications, the PI3K-Akt signalling pathway and the MAPK signalling pathway. The top 10 core targets were MAPK3, JUN, TP53, CASP3, TNF, IL1B, AKT1, FOS, VEGFA and INS. Molecular docking showed that in addition to TNF, other targets had good affinity for Res, and the binding activity with MAPK3 was stable. Western blot results showed that Res increased the phosphorylation level of ERK and that MAPK/ERKi decreased ERK activation. In the LC-MS/MS analysis, the levels of 2-MeOE1, 2-MeOE2 and 4-MeOE1 in serum and uterine tissue showed a significantly decreasing trend in the MNNG group, while that of 4-OHE2 was increased (P < 0.05). The concentrations of 4-MeOE1 in serum and 2-MeOE1 and 2-MeOE2 in the endometrial tissue of mice were significantly increased after Res treatment, and those of 4-OHE2 in the serum and uterus of mice were significantly decreased (P < 0.05). Meanwhile, in the MAPK/ERKi intervention group, the effect of Res on the reversal of oestrogen homeostasis imbalance was obviously weakened. CONCLUSION: Res has multiple targets and multiple approaches in the treatment of endometrial cancer. In this study, it was found that Res regulates oestrogen metabolism by activating the MAPK/ERK pathway. This finding provides a new perspective for subsequent research on the treatment of endometrial cancer.

Gastric­type endocervical adenocarcinoma: A report of two cases.

Gastric-type endocervical adenocarcinoma (GEA) is an uncommon and highly aggressive malignancy, characterized by non-specific clinical manifestations. The limited number of documented cases poses significant challenges in achieving an early preoperative diagnosis. In the present study, two cases of GEA in female patients, aged 46 and 39 years, who presented with the chief complaint of profuse vaginal discharge are described. Both patients underwent a total hysterectomy and bilateral adnexectomy, leading to the definitive diagnosis of GEA through routine pathological and immunohistochemical examination. Following surgery, case one received conventional chemotherapy with paclitaxel and carboplatin, demonstrating no evidence of recurrence during a follow-up period of >2 years. At present, patient B has been followed up for >1 year without any signs of disease recurrence. Given the rarity and diagnostic challenges associated with GEA, further investigations into its pathogenesis and diagnostic modalities are warranted. Additionally, due to its poor prognosis, close surveillance is essential for monitoring potential recurrences. Reporting such cases is crucial in aiding clinicians to make accurate diagnoses and treatment decisions.

Replacement of fish meal with cottonseed protein concentrate in Chinese mitten crab (Eriocheir sinensis): Nutrient digestibility, growth performance, free amino acid profile, and expression of genes related to nutrient metabolism.

This study aimed to investigate the application of cottonseed protein concentrate (CPC) in Chinese mitten crabs (Eriocheir sinensis). First, the apparent digestibility coefficient (ADC) of CPC, fish meal and soybean meal were compared in crabs (21.72 ± 0.33 g). The protein ADC of CPC was 90.42%, which was significantly higher than that of soybean meal (83.16%) (P < 0.05). The ADC of Phe, Cys and Glu of CPC were significantly higher than those of fish meal, while the ADC of Ile, Leu, Lys, Met, Thr and Ala of CPC were significantly lower (P < 0.05). Second, we investigated the effects of fish meal substitution by CPC on growth performance, free amino acid profile, and expression of genes related to nutrient metabolism in crabs. Six diets were formulated by replacing 0%, 15%, 30%, 45%, 60% and 75% fish meal with CPC, namely FM, CPC15, CPC30, CPC45, CPC60, and CPC75. A total of 630 crabs (1.68 ± 0.00 g) were randomly divided into 18 tanks (3 tanks per group) and fed 3 times daily for 9 weeks. Results showed that CPC75 group significantly reduced growth performance, feed conversion efficiency, and free Ile, Leu, Lys, Met, and Thr contents in muscle (P < 0.05). The contents of free amino acids (Arg, His, Ile, Leu, Lys, Met, Phe, Thr, Val, Ala, Cys, Glu, Gly, Ser and Tyr) in hepatopancreas decreased linearly with the increase of dietary CPC level (P < 0.05). The substitution of more than 45% fish meal with CPC significantly decreased the concentration of delicious amino acids (Ala, Glu and Gly) in hepatopancreas (P < 0.05), which might adversely affect crab flavor. The expression of genes related to antioxidant capacity, protein transport, TOR pathway and lipid metabolism was significantly downregulated by increasing dietary CPC level (P < 0.05). In conclusion, based on the quadratic regression analysis of FCR and PER, the optimal replacement levels of fish meal with CPC in crab diet containing 35% fish meal were 32.36% and 35.38%, respectively. It is recommended that Ile, Leu and Thr be supplemented in addition to Met and Lys in the application of CPC.

TFTG: A comprehensive database for human transcription factors and their targets.

Transcription factors (TFs) are major contributors to gene transcription, especially in controlling cell-specific gene expression and disease occurrence and development. Uncovering the relationship between TFs and their target genes is critical to understanding the mechanism of action of TFs. With the development of high-throughput sequencing techniques, a large amount of TF-related data has accumulated, which can be used to identify their target genes. In this study, we developed TFTG (Transcription Factor and Target Genes) database (http://tf.liclab.net/TFTG), which aimed to provide a large number of available human TF-target gene resources by multiple strategies, besides performing a comprehensive functional and epigenetic annotations and regulatory analyses of TFs. We identified extensive available TF-target genes by collecting and processing TF-associated ChIP-seq datasets, perturbation RNA-seq datasets and motifs. We also obtained experimentally confirmed relationships between TF and target genes from available resources. Overall, the target genes of TFs were obtained through integrating the relevant data of various TFs as well as fourteen identification strategies. Meanwhile, TFTG was embedded with user-friendly search, analysis, browsing, downloading and visualization functions. TFTG is designed to be a convenient resource for exploring human TF-target gene regulations, which will be useful for most users in the TF and gene expression regulation research.

Advances in precision therapy of low-grade serous ovarian cancer: A review.

Low-grade serous ovarian carcinoma (LGSOC) is a rare subtype of ovarian cancer that accounts for approximately 6% to 10% of serous ovarian cancers. The clinical treatment of LGSOC is similar to that of high-grade serous ovarian carcinoma, however, its clinical and molecular characteristics are different from those of high-grade serous ovarian carcinoma. This article reviews the research on gene diagnosis, surgical treatment, chemotherapy, and biological therapy of LGSOC, providing reference for clinical diagnosis and treatment of LGSOC. Surgery is the cornerstone of LGSOC treatment and maximum effort must be made to achieve R0 removal. Although LGSOC is not sensitive to chemotherapy, postoperative platinum-based combination chemotherapy remains the first-line treatment option for LGSOC. Additional clinical trials are needed to confirm the clinical benefits of chemotherapy and explore new chemotherapy protocols. Hormone and targeted therapies may also play important roles. Some patients, particularly those with residual lesions after treatment, may benefit from hormone maintenance therapy after chemotherapy. Targeted therapies, such as MEKi, show good application prospects and are expected to change the treatment pattern of LGSOC. Continuing to further study the genomics of LGSOC, identify its specific gene changes, and combine traditional treatment methods with precision targeted therapy based on second-generation sequencing may be the direction for LGSOC to overcome the treatment bottleneck. In future clinical work, comprehensive genetic testing should be carried out for LGSOC patients to accumulate data for future scientific research, in order to find more effective methods and drugs for the treatment of LGSOC.

Palladium-Catalyzed Dearomative Heck/Suzuki Coupling of C2-Deuterated or C2-Nonsubstituted Indoles.

A palladium-catalyzed dearomative diarylation of C2-deuterated or C2-nonsubstituted indoles through domino Heck/Suzuki coupling is established. Relying on electron-deficient phosphite ligand, side reactions including intermolecular Suzuki coupling and intramolecular C-D/H arylation are inhibited and a wide range of 2,3-diarylated indolines bearing vicinal tertiary stereocenters including deuterated ones are afforded in moderate to excellent yields (up to 94%) and excellent diastereoselectivities (>20:1). The catalyst loading can be lowered to 0.02 mol % at elevated temperature.

Association of tet methylcytosine dioxygenase 2 and 5-hydroxymethylcytosine in endometrioid adenocarcinoma and its clinical significance.

BACKGROUND: Aberrant DNA methylation is a vital molecular alteration commonly detected in type I endometrial cancers (EC), and tet methylcytosine dioxygenase 2 (TET2) and 5-hydroxymethylcytosine (5hmC) play significant roles in DNA demethylation. However, little is known about the function and correlation of TET2 and 5hmC co-expressed in EC. This study intended to investigate the clinical significance of TET2 and 5hmC in EC. METHODS: The levels of TET2 and 5hmC were detected in 326 endometrial tissues by immumohistochemistry, and the correlation of their level was detected by Pearson analysis. The association between the levels of TET2 and 5hmC and clinicopathologic characteristics was analyzed. Prognostic value of TET2 and 5hmC was explored by Kaplan-Meier analysis. The Cox proportional hazard regression model was used for univariate and multivariate analyses. RESULTS: Based on the analysis results, TET2 protein level was positively correlated with 5hmC level in EC tissues (r = 0.801, P < 0.001). TET2+5hmC+ (high TET2 and high 5hmC) association was significantly associated with well differentiation, myometrial invasion, negative lymph node metastasis, and tumor stage in EC. Association of TET2 and 5hmC was confirmed as a prognostic factor (HR = 2.843, 95%CI = 1.226-3.605, P = 0.007) for EC patients, and EC patients with TET2-5hmC- level had poor overall survival. CONCLUSIONS: In summary, the association of TET2 and 5hmC was downregulated in EC tissues, and may be a potential poor prognostic indicator for EC patients. Combined detection of TET2 and 5hmC may be valuable for the diagnosis and prognosis of EC.

ACSL1-Mediated Fatty Acid ß-Oxidation Enhances Metastasis and Proliferation in Endometrial Cancer.

BACKGROUND: Gynecological malignancies, such as endometrial cancer (EC) and uterine cancer are prevalent. Increased Acyl-CoA synthetase long-chain family member 1 (ACSL1) activity may contribute to aberrant lipid metabolism, which is a potential factor that contributes to the pathogenesis of endometrial cancer. This study aimed to elucidate the potential molecular mechanisms by which ACSL1 is involved in lipid metabolism in endometrial cancer, providing valuable insights for targeted therapeutic strategies. METHODS: Xenograft mouse models were used to assess the effect of ACSL1 on the regulation of endometrial cancer progression. ACSL1 protein levels were assessed via immunohistochemistry and immunoblotting analysis. To assess the migratory potential of Ishikawa cells, wound-healing and Transwell invasion assays were performed. Changes in lipids in serum samples from mice with endometrial cancer xenotransplants were examined in an untargeted lipidomic study that combined multivariate statistical methods with liquid chromatography‒mass spectrometry (LC/MS). RESULTS: Patient sample and tissue microarray data suggested that higher ACSL1 expression is strongly associated with the malignant progression of EC. Overexpression of ACSL1 enhances fatty acid ß-oxidation and 5'-adenylate triphosphate (ATP) generation in EC cells, promoting cell proliferation and migration. Lipidomic analysis revealed that significant changes were induced by ACSL1, including changes to 28 subclasses of lipids and a total of 24,332 distinct lipids that were detected in both positive and negative ion modes. Moreover, pathway analysis revealed the predominant association of these lipid modifications with the AMPK/CPT1C/ATP pathway and fatty acid ß-oxidation. CONCLUSIONS: This study indicates that ACSL1 regulates the AMPK/CPT1C/ATP pathway, which induces fatty acid ß-oxidation, promotes proliferation and migration, and then leads to the malignant progression of EC.

A MRI radiomics-based model for prediction of pelvic lymph node metastasis in cervical cancer.

BACKGROUND: Cervical cancer (CC) is a common malignancy of the female reproductive tract, and preoperative prediction of lymph node metastasis (LNM) is essential. This study aims to design and validate a magnetic resonance imaging (MRI) radiomics-based predictive model capable of detecting LNM in patients diagnosed with CC. METHODS: This retrospective analysis incorporated 86 and 38 CC patients into the training and testing groups, respectively. Radiomics features were extracted from MRI T2WI, T2WI-SPAIR, and axial apparent diffusion coefficient (ADC) sequences. Selected features identified in the training group were then used to construct a radiomics scoring model, with relevant LNM-related risk factors having been identified through univariate and multivariate logistic regression analyses. The resultant predictive model was then validated in the testing cohort. RESULTS: In total, 16 features were selected for the construction of a radiomics scoring model. LNM-related risk factors included worse differentiation (P < 0.001), more advanced International Federation of Gynecology and Obstetrics (FIGO) stages (P = 0.03), and a higher radiomics score from the combined MRI sequences (P = 0.01). The equation for the predictive model was as follows: -0.0493-2.1410 × differentiation level + 7.7203 × radiomics score of combined sequences + 1.6752 × FIGO stage. The respective area under the curve (AUC) values for the T2WI radiomics score, T2WI-SPAIR radiomics score, ADC radiomics score, combined sequence radiomics score, and predictive model were 0.656, 0.664, 0.658, 0.835, and 0.923 in the training cohort, while these corresponding AUC values were 0.643, 0.525, 0.513, 0.826, and 0.82 in the testing cohort. CONCLUSIONS: This MRI radiomics-based model exhibited favorable accuracy when used to predict LNM in patients with CC. Relative to the use of any individual MRI sequence-based radiomics score, this predictive model yielded superior diagnostic accuracy.

Mesenteric cystic lymphatic malformation: a rare case report and review of the literature.

Background: Mesenteric cystic lymphatic malformation (LM) is a rare congenital benign malformation in adults, and its location in the mesentery of the sigmoid colon is even rarer. Case Description: We describe a rare case of LM of the mesentery in a 49-year-old woman. The patient was inadvertently identified during a physical examination 1 month earlier. Transvaginal ultrasound and magnetic resonance imaging (MRI) revealed the presence of an intrapelvic mass posterior to the uterus and right anterior to the sigmoid colon. According to the results of the ultrasound, the mass showed hypoechoic solid features with a blood flow signal, and MRI showed that the internal enhancement of the mass was uneven. According to its imaging characteristics, it was preliminarily speculated as a stromal tumor. The patient underwent laparoscopic fenestration and drainage of a sigmoid mesocolic cyst. The patient underwent laparoscopic fenestration and drainage of the sigmoid mesocolic cyst. The pathological diagnosis was cystic lymphangioma of the sigmoid mesangium. After the operation, the patient recovered well without any complications. No recurrence was observed during the 3-month follow-up. Conclusions: LM is a challenging and rare disease, and its diagnosis is difficult. However, the combination of imaging examination and endoscopic ultrasound (EUS) technology can significantly improve the accurate diagnosis rate of the disease. Complete resection is the best choice for definite diagnosis and prevention of recurrence. It has been proved that laparoscopic surgery is a safe and feasible method for the treatment of this disease.

scATAC-Ref: a reference of scATAC-seq with known cell labels in multiple species.

Chromatin accessibility profiles at single cell resolution can reveal cell type-specific regulatory programs, help dissect highly specialized cell functions and trace cell origin and evolution. Accurate cell type assignment is critical for effectively gaining biological and pathological insights, but is difficult in scATAC-seq. Hence, by extensively reviewing the literature, we designed scATAC-Ref (https://bio.liclab.net/scATAC-Ref/), a manually curated scATAC-seq database aimed at providing a comprehensive, high-quality source of chromatin accessibility profiles with known cell labels across broad cell types. Currently, scATAC-Ref comprises 1 694 372 cells with known cell labels, across various biological conditions, >400 cell/tissue types and five species. We used uniform system environment and software parameters to perform comprehensive downstream analysis on these chromatin accessibility profiles with known labels, including gene activity score, TF enrichment score, differential chromatin accessibility regions, pathway/GO term enrichment analysis and co-accessibility interactions. The scATAC-Ref also provided a user-friendly interface to query, browse and visualize cell types of interest, thereby providing a valuable resource for exploring epigenetic regulation in different tissues and cell types.

[Platelet-to-lymphocyte ratio as a biomarker for predicting coronary artery lesions in Chinese children with Kawasaki disease: a Meta analysis]. / è¡€å°æ¿ä¸Žæ·‹å·´ç»†èƒžæ¯”å€¼å¯¹ä¸­å›½å·å´Žç— æ‚£å„¿å† çŠ¶åŠ¨è„‰ç— å˜é¢„æµ‹ä»·å€¼çš„Meta分析.

OBJECTIVES: To systematically evaluate the value of the platelet-to-lymphocyte ratio (PLR) in predicting coronary artery lesions (CAL) in Chinese children with Kawasaki Disease (KD). METHODS: A comprehensive search was conducted in databases including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Data, China Biomedical Literature Database, and China Science and Technology Journal Database from inception to December 2022. The quality of the included literature was assessed using the Newcastle-Ottawa Scale, and a Meta analysis was performed using Stata 15.1. RESULTS: A total of ten published reports, involving 3 664 Chinese children with KD, were included in this Meta analysis, of whom 1 328 developed CAL. The Meta analysis revealed a sensitivity of 0.78 (95%CI: 0.71-0.83), specificity of 0.71 (95%CI: 0.61-0.80), overall diagnostic odds ratio of 8.69 (95%CI: 5.02-15.06), and an area under the curve of the summary receiver operating characteristic of 0.82 (95%CI: 0.78-0.85) for PLR in predicting CAL in the children with KD. The sensitivity, specificity, and area under the curve of summary receiver operating characteristic were lower for PLR alone compared to PLR in combination with other indicators. Sensitivity analysis demonstrated the stability of the Meta analysis results with no significant changes upon excluding individual studies. However, a significant publication bias was observed (P<0.001). CONCLUSIONS: PLR demonstrates certain predictive value for CAL in Chinese children with KD.

Recent advances in biopolymers-based carbon materials for supercapacitors.

Supercapacitors as potential candidates for novel green energy storage devices demonstrate a promising future in promoting sustainable energy supply, but their development is impeded by limited energy density, which can be addressed by developing high-capacitance electrode materials with efforts. Carbon materials derived from biopolymers have received much attention for their abundant reserves and environmentally sustainable nature, rendering them ideal for supercapacitor electrodes. However, the limited capacitance has hindered their widespread application, resulting in the proposal of various strategies to enhance the capacity properties of carbon electrodes. This paper critically reviewed the recent research progress of biopolymers-based carbon electrodes. The advances in biopolymers-based carbon electrodes for supercapacitors are presented, followed by the strategies to improve the capacitance of carbon electrodes which include pore engineering, doping engineering and composite engineering. Furthermore, this review is summarized and the challenges of biopolymer-derived carbon electrodes are discussed. The purpose of this review is to promote the widespread application of biopolymers in the domain of supercapacitors.

MCSNet+: Enhanced Convolutional Neural Network for Detection and Classification of Tribolium and Sitophilus Sibling Species in Actual Wheat Storage Environments.

Insect pests like Tribolium and Sitophilus siblings are major threats to grain storage and processing, causing quality and quantity losses that endanger food security. These closely related species, having very similar morphological and biological characteristics, often exhibit variations in biology and pesticide resistance, complicating control efforts. Accurate pest species identification is essential for effective control, but workplace safety in the grain bin associated with grain deterioration, clumping, fumigator hazards, and air quality create challenges. Therefore, there is a pressing need for an online automated detection system. In this work, we enriched the stored-grain pest sibling image dataset, which includes 25,032 annotated Tribolium samples of two species and five geographical strains from real warehouse and another 1774 from the lab. As previously demonstrated on the Sitophilus family, Convolutional Neural Networks demonstrate distinct advantages over other model architectures in detecting Tribolium. Our CNN model, MCSNet+, integrates Soft-NMS for better recall in dense object detection, a Position-Sensitive Prediction Model to handle translation issues, and anchor parameter fine-tuning for improved matching and speed. This approach significantly enhances mean Average Precision (mAP) for Sitophilus and Tribolium, reaching a minimum of 92.67 ± 1.74% and 94.27 ± 1.02%, respectively. Moreover, MCSNet+ exhibits significant improvements in prediction speed, advancing from 0.055 s/img to 0.133 s/img, and elevates the recognition rates of moving insect sibling species in real wheat storage and visible light, rising from 2.32% to 2.53%. The detection performance of the model on laboratory-captured images surpasses that of real storage facilities, with better results for Tribolium compared to Sitophilus. Although inter-strain variances are less pronounced, the model achieves acceptable detection results across different Tribolium geographical strains, with a minimum recognition rate of 82.64 ± 1.27%. In real-time monitoring videos of grain storage facilities with wheat backgrounds, the enhanced deep learning model based on Convolutional Neural Networks successfully detects and identifies closely related stored-grain pest images. This achievement provides a viable solution for establishing an online pest management system in real storage facilities.

Correlation between cerebral cortex changes and clinical features in patients with neuromyelitis optica spectrum disorder with normal-appearing brain tissue: a case-control study.

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system. However, whether and how cortical changes occur in NMOSD with normal-appearing brain tissue, or whether any cortical changes correlate with clinical characteristics, is not completely clear. The current study recruited 43 patients with NMOSD who had normal-appearing brain tissue and 45 healthy controls matched for age, sex, and educational background from December 2020 to February 2022. A surface-based morphological analysis of high-resolution T1-weighted structural magnetic resonance images was used to calculate the cortical thickness, sulcal depth, and gyrification index. Analysis showed that cortical thickness in the bilateral rostral middle frontal gyrus and left superior frontal gyrus was lower in the patients with NMOSD than in the control participants. Subgroup analysis of the patients with NMOSD indicated that compared with those who did not have any optic neuritis episodes, those who did have such episodes exhibited noticeably thinner cortex in the bilateral cuneus, superior parietal cortex, and pericalcarine cortex. Correlation analysis indicated that cortical thickness in the bilateral rostral middle frontal gyrus was positively correlated with scores on the Digit Symbol Substitution Test and negatively correlated with scores on the Trail Making Test and the Expanded Disability Status Scale. These results are evidence that cortical thinning of the bilateral regional frontal cortex occurs in patients with NMOSD who have normal-appearing brain tissue, and that the degree of thinning is correlated with clinical disability and cognitive function. These findings will help improve our understanding of the imaging characteristics in NMOSD and their potential clinical significance.

Unsymmetric N-heterocyclic carbene ligand enabled nickel-catalysed arylation of bulky primary and secondary amines.

The arylation of sterically hindered amines represents one of the long-standing challenges in synthetic chemistry. Herein, we report a highly efficient Ni-catalysed arylation of sterically hindered primary and secondary amines with aryl chlorides or phenol derivatives enabled by an unsymmetric N-heterocyclic carbene (NHC) ligand. The protocol provides general, efficient, and scalable access to various sterically demanding anilines in excellent yields under mild conditions. A wide range of functional groups and heterocycles are compatible (>50 examples), including those present in biologically relevant molecules. Computational studies suggest that the unsymmetric bulky and flexible NHC ligand was critical to balance the oxidative addition and reductive elimination elementary steps, thus promoting this challenging transformation.

Online temperature-monitoring technology for grain storage: a three-dimensional visualization method based on an adaptive neighborhood clustering algorithm.

BACKGROUND: Post-harvest quality assurance is a crucial link between grain production and end users. It is essential to ensure that grain does not deteriorate due to heating during storage. To visualize the temperature distribution of a grain pile, the present study proposed a three-dimensional (3D) temperature field visualization method based on an adaptive neighborhood clustering algorithm (ANCA). The ANCA-based visualization method contains four calculation modules. First, discrete grain temperature data, obtained by sensors, are collected and interpolated using back propagation (BP) neural networks to model the temperature field. Then a new adaptive neighborhood clustering algorithm is applied to divide interpolation data into different categories by combining spatial characteristics and spatiotemporal information. Next, the Quickhull algorithm is used to compute the boundary points of each cluster. Finally, the polyhedrons determined by boundary points are rendered into different colors and are constructed in a 3D temperature model of the grain pile. RESULTS: The experimental results show that ANCA is much better than the DBSCAN and MeanShift algorithms on compactness (around 95.7% of tested cases) and separation (approximately 91.3% of tested cases). Moreover, the ANCA-based visualization method for grain pile temperatures has a shorter rendering time and better visual effects. CONCLUSION: This research provides an efficient 3D visualization method that allows managers of grain depots to obtain temperature field information for bulk grain visually in real time to help them protect grain quality during storage. © 2023 Society of Chemical Industry.

SEanalysis 2.0: a comprehensive super-enhancer regulatory network analysis tool for human and mouse.

Super-enhancers (SEs) play an essential regulatory role in various biological processes and diseases through their specific interaction with transcription factors (TFs). Here, we present the release of SEanalysis 2.0 (http://licpathway.net/SEanalysis), an updated version of the SEanalysis web server for the comprehensive analyses of transcriptional regulatory networks formed by SEs, pathways, TFs, and genes. The current version added mouse SEs and further expanded the scale of human SEs, documenting 1 167 518 human SEs from 1739 samples and 550 226 mouse SEs from 931 samples. The SE-related samples in SEanalysis 2.0 were more than five times that in version 1.0, which significantly improved the ability of original SE-related network analyses ('pathway downstream analysis', 'upstream regulatory analysis' and 'genomic region annotation') for understanding context-specific gene regulation. Furthermore, we designed two novel analysis models, 'TF regulatory analysis' and 'Sample comparative analysis' for supporting more comprehensive analyses of SE regulatory networks driven by TFs. Further, the risk SNPs were annotated to the SE regions to provide potential SE-related disease/trait information. Hence, we believe that SEanalysis 2.0 has significantly expanded the data and analytical capabilities of SEs, which helps researchers in an in-depth understanding of the regulatory mechanisms of SEs.

Study on the effect and mechanisms of piperine against cervical cancer based on network pharmacology and experimental validation.

Piperine has immunomodulatory and anti-inflammatory properties, and its potential in treating cervical cancer needs further exploration. Using data from The Cancer Genome Atlas (TCGA), we identified immune-related differentially expressed genes (IRDEGs) in cervical cancer. Predicted targets of piperine were compared with cervical cancer-associated genes from various databases. Protein-protein interaction (PPI) network analysis, enrichment of GO and KEGG pathways, and molecular docking were performed. Kaplan-Meier survival analysis was done to assess prognostic significance. In vitro and in vivo experiments were conducted to confirm findings. We obtained 403 IRDEGs, 125 piperine targets, and 7037 cervical cancer genes. PPI network analysis revealed potential targets and pathways regulated by piperine. Molecular docking showed good binding activity of piperine with specific targets. In vitro, piperine inhibited cervical cancer cell proliferation, migration, and invasion, and promoted apoptosis. In vivo, piperine suppressed tumor growth and downregulated expression of IL-1ß and NLRP3 in tumor cells. Piperine also downregulated expression of IL-17A, IL-21, IL-22, and RORγt, and decreased the number of Th17 cells in tumor tissues. Piperine may inhibit cervical cancer progression through modulation of Th17 cell activation mediated by the NLRP3/IL-1ß axis. Further studies are warranted to explore the potential of piperine as an immunomodulatory agent in cervical cancer treatment.