Meta-analysis of the traditional Chinese medicine care model in relieving postoperative pain in patients with anorectal diseases.

Objective: To explore the effect of traditional Chinese medicine (TCM) nursing on relieving postoperative pain in patients with anorectal diseases. Method: Three English and three Chinese databases (PubMed, Embase, the Cochrane Library, the China National Knowledge Internet, Wanfang Data and the China Science and Technology Journal Database) were systematically searched for case-controlled or prospective studies evaluating the impact of TCM nursing on postoperative pain in patients with anorectal diseases from the date of library construction until June 20, 2022. The Newcastle-Ottawa Scale was adopted to evaluate the quality of the observational studies. The effect of TCM care on pain based on the Visual Analogue Scale (VAS), the effective pain relief rate, the wound healing time and the length of hospital stay were systematically analysed. Result: After a systematic search and screening, a total of 15 documents were included in this study. The systematic evaluation showed that TCM care reduced the VAS score (mean difference (MD): 1.15（95 % Confidence Interval (CI): 1.96, -1.06; P < 0.00001) compared with conventional postoperative care methods. As TCM nursing time increased, there was a trend towards decreased VAS scores. Furthermore, TCM care was effective in providing pain relief (OR: 4.78; 95 % CI: 2.93,7.79; P < 0.00001) and reducing wound healing time (MD: 4.44; 95 % CI: 5.60, -3.27; P < 0.00001) and length of hospital stay (MD: 4.87; 95 % CI: 5.93, -3.82; P < 0.00001). Conclusion: Traditional Chinese medicine nursing has a positive effect on the postoperative clinical results of patients with anorectal diseases, especially in relieving postoperative pain. The effect of traditional Chinese medicine nursing in relieving short-term postoperative pain in patients with anorectal diseases is obvious. However, there is no uniform standard for TCM nursing projects, which may lead to heterogeneity.

The male and female genomes of golden pompano (Trachinotus ovatus) provide insights into the sex chromosome evolution and rapid growth.

INTRODUCTION: Golden pompano (Trachinotus ovatus) is economically significant important for offshore cage aquaculture in China and Southeast Asian countries. Lack of high-quality genomic data and accurate gene annotations greatly restricts its genetic breeding progress. OBJECTIVES: To decode the mechanisms of sex determination and rapid growth in golden pompano and facilitate the sex- and growth-aimed genetic breeding. METHODS: Genome assemblies of male and female golden pompano were generated using Illumina, PacBio, BioNano, genetic maps and Hi-C sequencing data. Genomic comparisons, whole genome re-sequencing of 202 F1 individuals, QTL mapping and gonadal transcriptomes were used to analyze the sex determining region, sex chromosome evolution, SNP loci, and growth candidate genes. Zebrafish model was used to investigate the functions of growth candidate gene. RESULTS: Female (644.45 Mb) and male (652.12 Mb) genomes of golden pompano were assembled and annotated at the chromosome level. Both genomes are highly conserved and no new or highly differentiated sex chromosomes occur. A 3.5 Mb sex determining region on LG15 was identified, where Hsd17b1, Micall2 and Lmx1a were putative candidates for sex determination. Three SNP loci significantly linked to growth were pinpointed, and a growth-linked gene gpsstr1 was identified by locus BSNP1369 (G â†’ C, 17489695, Chr23). Loss of sstr1a (homologue of gpsstr1) in zebrafish caused growth retardation. CONCLUSION: This study provides insights into sex chromosome evolution, sex determination and rapid growth of golden pompano.

N6-methyladenosine modification promotes hepatocarcinogenesis through circ-CDYL-enriched and EpCAM-positive liver tumor-initiating exosomes.

CircRNAs play multiple roles in a variety of cellular processes. We found that Circ-CDYL is highly enriched in early HCC plasma exosomes. Moreover, EpCAM+ HCC cells and exosomes had significant Circ-CDYL levels. We postulated that Circ-CDYL-enriched and EpCAM-positive exosomes would function as liver tumor-initiating exosomes (LTi-Exos). As predicted, intercellular transfer of LTi-Exos activates the HDGF-PI3K-AKT-mTOR and HIF1AN-NOTCH2 axes in recipient cells, promoting malignancy. Upstream, we found that the N6-methyladenosine (m6A) modification of Circ-CDYL exerted its action in HCC cells through a dual mechanism. First, it stimulated back-splicing processes via YTHDC1 to promote Circ-CDYL biogenesis. Second, it facilitates the active sorting of Circ-CDYL into exosomes via hnRNPA2/B1. Clinically, the combination of LTi-Exos and plasma alpha-fetoprotein (AFP) provides a promising early diagnostic biomarker for HCC with an AUC of 0.896. This study highlights the effect and mechanism by which m6A modification promotes hepatocarcinogenesis via modulation of the tumor microenvironment by LTi-Exos.

Astragalus mongholicus Bunge and Curcuma aromatica Salisb. inhibits liver metastasis of colon cancer by regulating EMT via the CXCL8/CXCR2 axis and PI3K/AKT/mTOR signaling pathway.

BACKGROUND: One of the most challenging aspects of colon cancer (CC) prognosis and treatment is liver-tropic metastasis. Astragalus mongholicus Bunge-Curcuma aromatica Salisb. (AC) is a typical medication combination for the therapy of many malignancies. Our previous studies found that AC intervention inhibits liver metastasis of colon cancer (LMCC). Nevertheless, the comprehensive anti-metastasis mechanisms of AC have not been uncovered. METHODS: In bioinformatics analysis, RNA-seq data of CC and LMCC patients were collected from TCGA and GEO databases, and differentially expressed genes (DEGs) were identified. The biological processes and signaling pathways involved in DEGs were enriched by GO and KEGG. The protein-protein interaction (PPI) network of DEGs was established and visualized using the Cytocape software, followed by screening Hub genes in the PPI network using Degree value as the criterion. Subsequently, the expression and survival relevance of Hub gene in COAD patients were verified. In the experimental study, the effects of AC on the inhibition of colon cancer growth and liver metastasis were comprehensively evaluated by cellular and animal models. Finally, based on the results of bioinformatics analysis, the possible mechanisms of AC inhibition of colon cancer EMT and liver metastasis were explored by in vivo and in vitro pharmacological experiments. RESULTS: In this study, we obtained 2386 DEGs relevant to LMCC from the COAD (colon adenocarcinoma) and GSE38174 datasets. Results of GO gene function and KEGG signaling pathway enrichment analysis suggested that cellular EMT (Epithelial-mesenchymal transition) biological processes, Cytokine-cytokine receptor interaction and PI3K/Akt signaling pathways might be closely related to LMCC mechanism. We then screened for CXCL8, the core hub gene with the highest centrality within the PPI network of DEGs, and discovered that CXCL8 expression was negatively correlated with the prognosis of COAD patients. In vitro and in vivo experimental evidence presented that AC significantly inhibited colon cancer cell proliferation, migration and invasion ability, and suppressed tumor growth and liver metastasis in colon cancer orthotopic transplantation mice models. Concomitantly, AC significantly reduced CXCL8 expression levels in cell supernatants and serum. Moreover, AC reduced the expression and transcription of genes related to the PI3K/AKT pathway while suppressing the EMT process in colon cancer cells and model mice. CONCLUSIONS: In summary, our research predicted the potential targets and pathways of LMCC, and experimentally demonstrated that AC might inhibit the growth and liver metastasis in colon cancer by regulating EMT via the CXCL8/CXCR2 axis and PI3K/AKT/mTOR signaling pathway, which may facilitate the discovery of mechanisms and new therapeutic strategies for LMCC.

How dignity-related distress interacts with quality of life in young adult patients with cancer during the active treatment stage: A network analysis.

OBJECTIVE: Young adult patients with cancer are a growing concern. By means of network analysis, this study aimed to explore the interplay between dignity-related distress and quality of life (QoL) in young adult patients with cancer when they undergo active treatments. METHODS: In this cross-sectional study, 309 young adults aged 18-39 and diagnosed with malignant tumors were recruited from an oncology center in China between September 2020 and August 2021. Participants completed the Patient Dignity Inventory and SF-36 questionnaires. Network analysis was applied to examine the network structure. RESULTS: Overall, the core facets of dignity-related distress were negatively related to QoL and its corresponding domains, either directly or indirectly. Developmental distress played a central role among estimated networks and strongly interplayed with most QoL domains, especially the mental domains. Symptom distress was the only facet consistently interplayed with the physical domains of QoL (i.e., physical function and bodily pain). The social aspects were also revealed in the association between limited social support and vitality. CONCLUSIONS: Early attention must be paid to guarantee the need of preserving dignity and enhancing QoL for young adult patients.

Microstructure and Mechanical Properties of Composites Obtained by Spark Plasma Sintering of Ti3SiC2-15 vol.%Cu Mixtures.

Method of soft metal (Cu) strengthening of Ti3SiC2 was conducted to increase the hardness and improve the wear resistance of Ti3SiC2. Ti3SiC2/Cu composites containing 15 vol.% Cu were fabricated by Spark Plasma Sintering (SPS) in a vacuum. The effect of the sintering temperature on the phase composition, microstructure and mechanical properties of the composites was investigated in detail. The as-synthesized composites were thoroughly characterized by scanning electron micrography (SEM), optical micrography (OM) and X-ray diffractometry (XRD), respectively. The results indicated that the constituent of the Ti3SiC2/Cu composites sintered at different temperatures included Ti3SiC2, Cu3Si and TiC. The formation of Cu3Si and TiC originated from the reaction between Ti3SiC2 and Cu, which was induced by the presence of Cu and the de-intercalation of Si atoms Ti3SiC2. OM analysis showed that with the increase in the sintering temperature, the reaction between Ti3SiC2 and Cu was severe, leading to the Ti3SiC2 getting smaller and smaller. SEM measurements illustrated that the uniformity of the microstructure distribution of the composites was restricted by the agglomeration of Cu, controlling the mechanical behaviors of the composites. At 1000 °C, the distribution of Cu in the composites was relatively even; thus, the composites exhibited the highest density, relatively high hardness and compressive strength. The relationships of the temperature, the current and the axial dimension with the time during the sintering process were further discussed. Additionally, a schematic illustration was proposed to explain the related sintering characteristic of the composites sintered by SPS. The as-synthesized Ti3SiC2/Cu composites were expected to improve the wear resistance of polycrystalline Ti3SiC2.

Glycemic Variability Is Independently Associated With Poor Prognosis in Five Pediatric ICU Centers in Southwest China.

Background: Glucose variability (GV) is a common complication of dysglycemia in critically ill patients. However, there are few studies on the role of GV in the prognosis of pediatric patients, and there is no consensus on the appropriate method for GV measurement. The objective of this study was to determine the "optimal" index of GV in non-diabetic critically ill children in a prospective multicenter cohort observational study. Also, we aimed to confirm the potential association between GV and unfavorable outcomes and whether this association persists after controlling for hypoglycemia or hyperglycemia. Materials and Methods: Blood glucose values were recorded for the first 72 h and were used to calculate the GV for each participant. Four different metrics [SD, glycemic lability index (GLI), mean absolute glucose (MAG), and absolute change of percentage (ACACP)] were considered and compared to identify the "best" GV index associated with poor prognosis in non-diabetic critically ill children. Among the four metrics, the SD was most commonly used in previous studies, while GLI- and MAG-integrated temporal information, that is the rate and magnitude of change and the time interval between glucose measurements. The fourth metric, the average consecutive ACACP, was introduced in our study, which can be used in real-time clinical decisions. The primary outcome of this study was the 28-day mortality. The receiver operating characteristic (ROC) curve analysis was conducted to compare the predictive power of different metrics of GV for the primary outcome. The GV index with the largest area under ROC curve (AUC) was chosen for subsequent multivariate analyses. Multivariate Cox regression analysis was performed to identify the potential predictors of the outcome. To compare the contribution in 28-day mortality prognosis between glycemic variability and hyper- or hypoglycemia, performance metrics were calculated, which included AUC, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results: Among 780 participants, 12.4% (n = 97) died within 28 days after admission to the pediatric intensive care unit (PICU). Statistically significant differences were found between survivors and non-survivors in terms of four GV metrics (SD, GLI, MAG, and ACACP), in which MAG (AUC: 0.762, 95% CI: 0.705-0.819, p < 0.001) achieved the largest AUC and showed a strong independent association with ICU mortality. Subsequent addition of MAG to the multivariate Cox model for hyperglycemia resulted in further quantitative evolution of the model statistics (AUC = 0.651-0.681, p = 0.001; IDI: 0.017, p = 0.044; NRI: 0.224, p = 0.186). The impact of hyperglycemia (adjusted hazard ratio [aHR]: 1.419, 95% CI: 0.815-2.471, p = 0.216) on outcome was attenuated and no longer statistically relevant after adjustment for MAG (aHR: 2.455, 95% CI: 1.411-4.270, p = 0.001). Conclusions: GV is strongly associated with poor prognosis independent of mean glucose level, demonstrating more predictive power compared with hypoglycemia and hyperglycemia after adjusting for confounding factors. GV metrics that contain information, such as time and rate of change, are the focus of future research; thus, the MAG may be a good choice. The findings of this study emphasize the crucial role of GVs in children in the PICU. Clinicians should pay more attention to GV for clinical glucose management.

Microstructure and Tribological Properties of Spark-Plasma-Sintered Ti3SiC2-Pb-Ag Composites at Elevated Temperatures.

Ti3SiC2-PbO-Ag composites (TSC-PA) were successfully prepared using the spark plasma sintering (SPS) technique. The ingredient and morphology of the as-synthesized composites were elaborately investigated. The tribological properties of the TSC-PA pin sliding against Inconel 718 alloys disk at room temperature (RT) to 800 °C were examined in air. The wear mechanisms were argued elaborately. The results showed that the TSC-PA was mainly composed of Ti3SiC2, Pb, and Ag. The average friction coefficient of TSC-PA gradually decreased from 0.72 (RT) to 0.3 (800 °C), with the temperature increasing from RT to 800 °C. The wear rate of TSC-PA showed a decreasing trend, with the temperature rising from RT to 800 °C. The wear rate of Inconel 718 exhibited positive wear at RT and negative wear at elevated temperatures. The tribological property of TSC-PA was related to the tribo-chemistry, and the abrasive and adhesive wear.

[Anti-colorectal cancer mechanism of Astragali Radix-Curcumae Rhizoma-Paridis Rhizoma based on network pharmacology and experimental verification].

The present study explored the underlying mechanism of Astragali Radix-Curcumae Rhizoma-Paridis Rhizoma(AR-CR-PR) in the treatment of colorectal cancer(CRC) by network pharmacology and molecular docking and animal tests and verified the core targets based on the orthotopic transplantation model in nude mice. The active components of AR-CR-PR were retrieved from databases such as TCMSP. The targets of drugs and the disease were obtained from PubChem, SwissTargetPrediction, TTD, and DrugBank, and the intersection targets were imported into STRING for the analysis of the protein-protein interaction(PPI). Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses were performed through DAVID. AutoDock Vina was used to perform molecular docking and binding ability prediction between the active components and the core targets. The effects of AR-CR-PR on tumor growth, metastasis, and phosphorylation of core target proteins in tumor tissues based on the orthotopic transplantation model in nude mice. As revealed by network pharmacology, AR-CR-PR contained nine core components, such as quercetin, curcumin, and ß-ecdysone, and the key targets included protein kinase B(AKT1), mitogen-activated protein kinase 3(MAPK3), MAPK1, and epithelial growth factor receptor(EGFR), which was indicated that the anti-CRC effect of AR-CR-PR was presumedly achieved by regulating tumor cell proliferation, apoptosis, migration, and angiogenesis through PI3 K-AKT, MAPK and other signaling pathways. The results of molecular docking showed that the nine core components had strong binding abilities to AKT1 and MAPK3. The results in vivo showed that AR-CR-PR could reduce the volume of the orthotopic tumor, inhibit liver metastasis, and decrease the phosphorylation of AKT1 and MAPK3 in the CRC model. The mechanism of AR-CR-PR in the intervention of CRC may be related to the activation of PI3 K-AKT and MAPK signaling pathway. This study provides a scientific basis for the clinical application of AR-CR-PR in the treatment of CRC and ideas for modern research on AR-CR-PR.

Astragalus mongholicus Bunge-Curcuma aromatica Salisb. suppresses growth and metastasis of colorectal cancer cells by inhibiting M2 macrophage polarization via a Sp1/ZFAS1/miR-153-3p/CCR5 regulatory axis.

Colorectal cancer (CRC) is regarded as one of the commonest cancer types around the world. Due to the poor understanding on the causes of CRC formation and progression, this study sets out to investigate the physiological mechanisms by which Astragalus mongholicus Bunge-Curcuma aromatica Salisb. (ARCR) regulates CRC growth and metastasis, and the role in which M2 macrophage polarization plays in this process. An orthotopic-transplant model of CRC was established to evaluate the influence of ARCR on the polarization of M2 macrophage and the growth and metastasis of tumors. Next, the binding affinity among Sp1, ZFAS1, miR-153-5p, and CCR5 was identified using multiple assays. Finally, after co-culture of bone marrow-derived macrophages (BMDM) with CRC cell line CT26.WT, the cell proliferative, invasive, and migrated abilities were assessed in gain- or loss-of-function experiments. ARCR inhibited the infiltration of M2 macrophages into tumor microenvironment to suppress the CRC growth and metastasis in vivo. Additionally, ARCR inhibited the transcription of ZFAS1 by reducing Sp1 expression to repress M2 macrophage polarization. Moreover, ZFAS1 competitively binds to miR-153-3p to upregulate the CCR5 expression. Finally, ARCR suppressed the polarization of M2 macrophages to inhibit the tumor growth and tumor metastasis in CRC by mediating the Sp1/ZFAS1/miR-153-3p/CCR5 regulatory axis. Collectively, ARCR appears to suppress the CRC cell growth and metastasis by suppressing M2 macrophage polarization via Sp1/ZFAS1/miR-153-3p/CCR5 regulatory axis. 1. ARCR suppress the CRC cell growth and metastasis 2. ZFAS1 promotes CCR5 expression by competitively binding to miR-153-3p. 3. Sp1 promotes M2 macrophage polarization by activating ZFAS1 via miR-153-3p/CCR5. 4. The study unveiled a protective target against CRC.

Immune-related gene-based prognostic index for predicting survival and immunotherapy outcomes in colorectal carcinoma.

Introduction: Colorectal cancer shows high incidence and mortality rates. Immune checkpoint blockade can be used to treat colorectal carcinoma (CRC); however, it shows limited effectiveness in most patients. Methods: To identify patients who may benefit from immunotherapy using immune checkpoint inhibitors, we constructed an immune-related gene prognostic index (IRGPI) for predicting the efficacy of immunotherapy in patients with CRC. Transcriptome datasets and clinical information of patients with CRC were used to identify differential immune-related genes between tumor and para-carcinoma tissue. Using weighted correlation network analysis and Cox regression analysis, the IRGPI was constructed, and Kaplan-Meier analysis was used to evaluate its predictive ability. We also analyzed the molecular and immune characteristics between IRGPI high-and low-risk subgroups, performed sensitivity analysis of ICI treatment, and constructed overall survival-related receiver operating characteristic curves to validate the IRGPI. Finally, IRGPI genes and tumor immune cell infiltration in CRC model mice with orthotopic metastases were analyzed to verify the results. Results: The IRGPI was constructed based on the following 11 hub genes: ADIPOQ, CD36, CCL24, INHBE, UCN, IL1RL2, TRIM58, RBCK1, MC1R, PPARGC1A, and LGALS2. Patients with CRC in the high-risk subgroup showed longer overall survival than those in the low-risk subgroup, which was confirmed by GEO database. Clinicopathological features associated with cancer progression significantly differed between the high- and low-risk subgroups. Furthermore, Kaplan-Meier analysis of immune infiltration showed that the increased infiltration of naïve B cells, macrophages M1, and regulatory T cells and reduced infiltration of resting dendritic cells and mast cells led to a worse overall survival in patients with CRC. The ORC curves revealed that IRGPI predicted patient survival more sensitive than the published tumor immune dysfunction and rejection and tumor inflammatory signature. Discussion: Thus, the low-risk subgroup is more likely to benefit from ICIs than the high-risk subgroup. CRC model mice showed higher proportions of Tregs, M1 macrophages, M2 macrophages and lower proportions of B cells, memory B cell immune cell infiltration, which is consistent with the IRGPI results. The IRGPI can predict the prognosis of patients with CRC, reflect the CRC immune microenvironment, and distinguish patients who are likely to benefit from ICI therapy.

Effect of Vacancy Behavior on Precipitate Formation in a Reduced-Activation V-Cr-Mn Medium-Entropy Alloy.

In this work, we studied the evolution of vacancy-like defects and the formation of brittle precipitates in a reduced-activation V-Cr-Mn medium-entropy alloy. The evolution of local electronic circumstances around Cr and Mn enrichments, the vacancy defects, and the CrMn3 precipitates were characterized by using scanning electron microscopy with energy-dispersive spectroscopy, X-ray diffraction, and positron annihilation spectroscopy. The microstructure measurements showed that the Mn and Cr enrichments in the as-cast sample significantly evolved with temperature, i.e., from 400 °C, the Cr/Mn-segregated regions gradually dissolved into the matrix and then disappeared, and from 900 °C to 1000 °C, they existed as CrMn3 precipitates. The crystallite size of the phase corresponding to CrMn3 precipitates was about 29.4 nm at 900 °C and 43.7 nm at 1000 °C. The positron annihilation lifetime results demonstrated that the vacancies mediated the migration of Cr and Mn, and Cr and Mn segregation finally led to the formation of CrMn3 precipitates. The coincidence Doppler broadening results showed that the characteristic peak moved to the low-momentum direction, due to an increase in the size of the vacancy defects at the interface and the formation of CrMn3 precipitates.

Tribo-oxide Competition and Oxide Layer Formation of Ti3SiC2/CaF2 Self-Lubricating Composites during the Friction Process in a Wide Temperature Range.

Ti3SiC2/CaF2 composites were prepared by the spark plasma sintering (SPS) process. Both the microstructure of Ti3SiC2/CaF2 and the influence of test temperature on the tribological behavior of the Ti3SiC2/CaF2composites were investigated. The synergistic effect of friction and oxidation was evaluated by analyzing the worn surface morphology. The results showed that Ti3SiC2/CaF2 were still brittle materials after adding CaF2, which was in agreement with Ti3SiC2. The hardness, relative density, flexural strength and compressive strength of the Ti3SiC2/CaF2 composites were slightly lower than those of Ti3SiC2, and the addition of CaF2 decreased the decomposition temperature of Ti3SiC2 from 1350 to 1300 °C. Simultaneously, as the temperature of the test increased, the friction coefficient of Ti3SiC2/CaF2 showed a downward trend (from 0.81 to 0.34), and its the wear rate was insensitive.

Standardized Astragalus Mongholicus Bunge-Curcuma Aromatica Salisb. Extract Efficiently Suppresses Colon Cancer Progression Through Gut Microbiota Modification in CT26-Bearing Mice.

Altered gut microbiota and a damaged colon mucosal barrier have been implicated in the development of colon cancer. Astragalus mongholicus Bunge-Curcuma aromatica Salisb. (ACE) is a common herbal drug pair that widely used clinically to treat cancer. However, whether the anti-cancer effect of ACE is related to gut microbiota remains unclear yet. We standardized ACE and investigated the effects of ACE on tumour suppression and analyze the related mechanisms on gut microbiota in CT26 colon cancer-bearing mice in the present study. Firstly, four flavonoids (calycosin-7-glucoside, ononin, calycosin, formononetin) and three astragalosides (astragaloside A, astragaloside II, astragaloside I) riched in Astragalus mongholicus Bunge, three curcumins (bisdemethoxycurcumin, demethoxycurcumin, curcumin) and four essential oils (curdione, curzerene, germacrone and ß-elemene) from Curcuma aromatica Salisb., in concentrations from 0.08 to 2.07 mg/g, were examined in ACE. Then the results in vivo studies indicated that ACE inhibited solid tumours, liver and spleen metastases of colon cancer while simultaneously reducing pathological tissue damage. Additionally, ACE regulated gut microbiota dysbiosis and the short chain fatty acid content in the gut, repaired intestinal barrier damage. ACE treatment suppressed the overgrowth of conditional pathogenic gut bacteria, including Escherichia-Shigella, Streptococcus and Enterococcus, while the probiotic gut microbiota like Lactobacillus, Roseburia, Prevotellaceae_UCG-001 and Mucispirillum were increased. More interestingly, the content level of SCFAs such as propionic acid and butyric acid was increased after ACE administration, which further mediates intestinal SDF-1/CXCR4 signalling pathway to repair the integrity of the intestinal barrier, decrease Cyclin D1 and C-myc expressions, eventually suppress the tumor the growth and metastasis of colon cancer. To sum up, the present study demonstrated that ACE could efficiently suppress colon cancer progression through gut microbiota modification, which may provide a new explanation of the mechanism of ACE against colon cancer.

A comparative integrated multi-omics analysis identifies CA2 as a novel target for chordoma.

BACKGROUND: Chordoma is a rare mesenchymal malignancy, with a high recurrence rate and unclear tumorigenic mechanism. Genetic alterations, epigenetic regulators, and chromatin spatial organization play crucial roles in the initiation and progression of chordoma. In the current study, we aim to uncover the novel therapeutical targets for chordoma via using integrated multi-omics analysis. METHODS: The RNA-sequencing (RNA-seq), assay for transposable accessible chromatin by high-throughput sequencing (ATAC-seq), and Hi-C were performed between chordoma and human nucleus pulposus (HNP), along with imageological examination and clinical information. The expressions of identified targets were validated by clinical samples and their functions were further evaluated by cell and animal experiments via gene knockdown and inhibitors. RESULTS: The integrated multi-omics analysis revealed the important roles of bone microenvironment in chordoma tumorigenesis. By comparing the hierarchical structures, CA2 (carbonic anhydrase II) and THNSL2 (threonine synthase-like 2) were identified in the switched compartments, cell-specific boundaries, and loops. Additionally, CA2 was highly expressed in chordoma but barely found in HNP. The cell growth and migration of chordoma cells were dramatically suppressed via inhibition of CA2 either with genetic deletion or pharmaceutical treatment with Dorzolamide HCl. Furthermore, Dorzolamide HCl also regulated the bone microenvironment by blocking the osteoclast differentiation of bone marrow monocytes. CONCLUSION: This study uncovers the roles of bone microenvironment in the chordoma tumorigenesis and identifies CA2 as a novel therapeutic target for chordoma. Besides, our findings suggest Dorzolamide HCl as a promising therapeutic option for chordoma.

Cotton D genome assemblies built with long-read data unveil mechanisms of centromere evolution and stress tolerance divergence.

BACKGROUND: Many of genome features which could help unravel the often complex post-speciation evolution of closely related species are obscured because of their location in chromosomal regions difficult to accurately characterize using standard genome analysis methods, including centromeres and repeat regions. RESULTS: Here, we analyze the genome evolution and diversification of two recently diverged sister cotton species based on nanopore long-read sequence assemblies and Hi-C 3D genome data. Although D genomes are conserved in gene content, they have diversified in gene order, gene structure, gene family diversification, 3D chromatin structure, long-range regulation, and stress-related traits. Inversions predominate among D genome rearrangements. Our results support roles for 5mC and 6mA in gene activation, and 3D chromatin analysis showed that diversification in proximal-vs-distal regulatory-region interactions shape the regulation of defense-related-gene expression. Using a newly developed method, we accurately positioned cotton centromeres and found that these regions have undergone obviously more rapid evolution relative to chromosome arms. We also discovered a cotton-specific LTR class that clarifies evolutionary trajectories among diverse cotton species and identified genetic networks underlying the Verticillium tolerance of Gossypium thurberi (e.g., SA signaling) and salt-stress tolerance of Gossypium davidsonii (e.g., ethylene biosynthesis). Finally, overexpression of G. thurberi genes in upland cotton demonstrated how wild cottons can be exploited for crop improvement. CONCLUSIONS: Our study substantially deepens understanding about how centromeres have developed and evolutionarily impacted the divergence among closely related cotton species and reveals genes and 3D genome structures which can guide basic investigations and applied efforts to improve crops.

Metabonomics study on orthotopic transplantion mice model of colon cancer treated with Astragalus membranaceus-Curcuma wenyujin in different proportions via UPLC-Q-TOF/MS.

Metabolomics, an important part of systems biology, can reveal the complex pathogenesis of many diseases and mechanism of Chinese materia medica (CMM). Astragalus membranaceus-Curcuma wenyujin (AC) was a classic drug pair that has a good clinical effect on gastrointestinal inflammation and many tumors. Our previous research proved that AC can inhibit tumor growth and metastasis especially the colorectal cancer (CRC), also promote the normalization of tumor blood vessels, but its optimal ratio and the specific mechanism is still not clear. In this study, colon cancer mice of orthotopic transplantion model was used to screen the best proportion, UPLC-Q-TOF/MS metabolomics analysis method was established to explore the pathogenesis of colon cancer and the molecular mechanism of AC. The correlation analysis of metabolite changes and tumor growth was analyzed by R language. The result showed that AC at the ratio of 2:1 showed the best effect on inhibiting tumor growth, also the liver and spleen metastasis rate. A total of 23 potential biomarkers were detected in the serum of colon cancer mice by the analysis of Progenesis QI (Version 2.4) software. Among this, 11 metabolites including purines, steroids, phytosphingosine and l-palmitoylcarnitine were up-regulated in CC mice, while 12 metabolites like amino acids, deoxyribose and dihydrobiopterin were down-regulated in CC mice. After the treatment of AC for 15 days, 8 biomarkers were up-regulated, and 9 biomarkers down-regulated. Especially, AC at the ratio of 2:1 showed a significant callback effect on metabolic biomarkers, such as hypoxanthine, xanthosine, 7-methylxanthine, all-trans-retinoic acid, dihomo-γ-linolenic acid. 8 metabolic pathways: Aminoacyl-tRNA biosynthesis, Nicotinate and nicotinamide metabolism, Phenylalanine, tyrosine and tryptophan biosynthesis, Valine, leucine and isoleucine biosynthesis, Phenylalanine metabolism, Caffeine metabolism, Retinol metabolism, Alanine, aspartate and glutamate metabolism were selected as the model group disturbed metabolic pathways after the enrichment of MetaboAnalyst 4.0 online analysis software. And compared with the model group, Valine, leucine and isoleucine biosynthesis, Aminoacyl-tRNA biosynthesis, Caffeine metabolism pathway and Retinol metabolism pathways were altered after the intervention of AC. The correlation analysis results showed that various endogenous metabolites in serum have a strong correlation with tumor weight, such as hypoxanthine, which provides a basis for the selection of clinical markers. The results showed that AC can partially regulate metabolic disorder of CC mice by reversing the changes of metabolites, so as to inhibit the growth and metastasis of colon cancer, especially at the ratio of 2:1. These findings can provide a scientific basis for exploring the diagnostic biomarkers of colon cancer, and for clinical application of AC in the treatment of CRC program.

The evolutionary origin and domestication history of goldfish (Carassius auratus).

Goldfish have been subjected to over 1,000 y of intensive domestication and selective breeding. In this report, we describe a high-quality goldfish genome (2n = 100), anchoring 95.75% of contigs into 50 pseudochromosomes. Comparative genomics enabled us to disentangle the two subgenomes that resulted from an ancient hybridization event. Resequencing 185 representative goldfish variants and 16 wild crucian carp revealed the origin of goldfish and identified genomic regions that have been shaped by selective sweeps linked to its domestication. Our comprehensive collection of goldfish varieties enabled us to associate genetic variations with a number of well-known anatomical features, including features that distinguish traditional goldfish clades. Additionally, we identified a tyrosine-protein kinase receptor as a candidate causal gene for the first well-known case of Mendelian inheritance in goldfish-the transparent mutant. The goldfish genome and diversity data offer unique resources to make goldfish a promising model for functional genomics, as well as domestication.

Erratum: Author Correction: Improved Brassica rapa reference genome by single-molecule sequencing and chromosome conformation capture technologies.

[This corrects the article DOI: 10.1038/s41438-018-0071-9.].

Insulin Glargine and Acarbose in the treatment of elderly patients with diabetes.

OBJECTIVE: To investigate the clinical efficacy of insulin glargine combined with acarbose in the treatment of elderly patients with diabetes. METHODS: One hundred and forty-four elderly patients with diabetes who received treatment between December 2016 and December 2017 in Binzhou People's Hospital, China, were selected and divided into a control group and an observation group, 72 each, using random number table. The control group was treated with insulin glargine, while the observation group was treated with insulin glargine combined with acarbose. The therapeutic effect, improvement of quality of life and adverse reactions were compared between the two groups. RESULTS: After treatment, fasting blood glucose (FBG), 2h postprandial blood glucose (PBG) and glycosylated hemoglobin (Hb Alc) of the two groups were lower than those before treatment, and the decrease degree of the observation group was significantly larger than that of the control group (P<0.05). The time needed for blood glucose reaching the standard level and daily insulin dosage of the observation group were significantly lower than that of the control group, and the differences were statistically significant (P<0.05). SF-36 scale score of the observation group was significantly better than the control group, and the difference was statistically significant (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). CONCLUSION: The combination of insulin Glargine and Acarbose can significantly control the blood glucose level of elderly patients with diabetes, improve the biochemical indicators, and enhance the quality of life. It is worth promotion in clinical practice.