Robust Least Squares Regression for Subspace Clustering: A Multi-View Clustering Perspective.

Recently, with the assumption that samples can be reconstructed by themselves, subspace clustering (SC) methods have achieved great success. Generally, SC methods contain some parameters to be tuned, and different affinity matrices can obtain with different parameter values. In this paper, for the first time, we study a method for fusing these different affinity matrices to promote clustering performance and provide the corresponding solution from a multi-view clustering (MVC) perspective. That is, we argue that the different affinity matrices are consistent and complementary, which is similar to the fundamental assumption of MVC methods. Based on this observation, in this paper, we use least squares regression (LSR), which is a typical SC method, as an example since it can be efficiently optimized and has shown good clustering performance and we propose a novel robust least squares regression method from an MVC perspective (RLSR/MVCP). Specifically, we first utilize LSR with different parameter values to obtain different affinity matrices. Then, to fully explore the information contained in these different affinity matrices and to remove noise, we further fuse these affinity matrices into a tensor, which is constrained by the tensor low-rank constraint, i.e., the tensor nuclear norm (TNN). The two steps are combined into a framework that is solved by the augmented Lagrange multiplier (ALM) method. The experimental results on several datasets indicate that RLSR/MVCP has very encouraging clustering performance and is superior to state-of-the-art SC methods.

Selection and validation of internal control genes for quantitative real-time RT‒qPCR normalization of Phlebopus portentosus gene expression under different conditions.

Phlebopus portentosus (Berk. and Broome) Boedijn is an attractive edible mushroom and is considered the only bolete for which artificial cultivation in vitro has been achieved. Gene expression analysis has become widely used in research on edible fungi and is important for elucidating the functions of genes involved in complex biological processes. Selecting appropriate reference genes is crucial to ensuring reliable RT‒qPCR gene expression analysis results. In our study, a total of 12 candidate control genes were selected from 25 traditional housekeeping genes based on their expression stability in 9 transcriptomes of 3 developmental stages. These genes were further evaluated using geNorm, NormFinder, and RefFinder under different conditions and developmental stages. The results revealed that MSF1 domain-containing protein (MSF1), synaptobrevin (SYB), mitogen-activated protein kinase genes (MAPK), TATA-binding protein 1 (TBP1), and SPRY domain protein (SPRY) were the most stable reference genes in all sample treatments, while elongation factor 1-alpha (EF1), actin and ubiquitin-conjugating enzyme (UBCE) were the most unstably expressed. The gene SYB was selected based on the transcriptome results and was identified as a novel reference gene in P. portentosus. This is the first detailed study on the identification of reference genes in this fungus and may provide new insights into selecting genes and quantifying gene expression.

Dissecting the effect of ileal faecal diversion on the intestine using single-cell sequencing.

BACKGROUND: Although ileal faecal diversion is commonly used in clinical settings, complications accompany it. Elucidating the intestinal changes caused by ileal faecal diversion will help resolve postoperative complications and elucidate the pathogenic mechanisms of associated intestinal disorders, such as Crohn's disease (CD). Therefore, our study aimed to provide new insights into the effects of ileal faecal diversion on the intestine and the potential mechanisms. METHODS: Single-cell RNA sequencing was performed on proximal functional and paired distal defunctioned intestinal mucosae from three patients with ileal faecal diversion. We also performed in vitro cellular and animal experiments, tissue staining and analysed public datasets to validate our findings. RESULTS: We found that the epithelium in the defunctioned intestine tended to be immature, with defective mechanical and mucous barriers. However, the innate immune barrier in the defunctioned intestine was enhanced. Focusing on the changes in goblet cells, we demonstrated that mechanical stimulation promotes the differentiation and maturation of goblet cells through the TRPA1-ERK pathway, indicating that the absence of mechanical stimulation may be the main cause of defects in the goblet cells of the defunctioned intestine. Furthermore, we found obvious fibrosis with a pro-fibrotic microenvironment in the defunctioned intestine and identified that monocytes may be important targets for faecal diversion to alleviate CD. CONCLUSIONS: This study revealed the different transcription landscapes of various cell subsets and the potential underlying mechanisms within the defunctioned intestine, when compared to the functional intestine, based on the background of ileal faecal diversion. These findings provide novel insights for understanding the physiological and pathological roles of the faecal stream in the intestine.

LC/MS- and GC/MS-based metabolomic profiling to determine changes in flavor quality and bioactive components of Phlebopus portentosus under low-temperature storage.

Introduction: Low temperature is the most common method used to maintain the freshness of Phlebopus portentosus during long-distance transportation. However, there is no information regarding the nutritional changes that occur in P. portentosus preserved postharvest in low temperature. Methods: In this study, the changes in flavor quality and bioactive components in fruiting bodies stored at 4 °C for different storage periods were determined through LC/MS and GC/MS analyses. Sampling was performed at 0, 3, 5, 7, and 13 days storage. Results and Discussion: Based on the results, the metabolites present in caps and stipes were different at the same period and significantly different after 7 days of storage. A total of 583 and 500 different metabolites were detected in caps and stipes, respectively, and were mainly lipids and lipid-like molecules, organic acids and derivatives, organic oxygen compounds and others. Except for prenol lipids and nucleotides, the expression levels of most metabolites increased with longer storage time. In addition, geosmin was identified as the major contributor to earthy-musty odors, and the level of geosmin was increased when the storage time was short. Conclusion: The variations in these metabolites might cause changes in flavor quality and bioactive components in P. portentosus. Variations in these metabolites were thoroughly analyzed, and the results revealed how storage processes affect the postharvest quality of P. portentosus for the first time.

Does temporary ileostomy via specimen extraction site affect the short outcomes and complications after laparoscopic low anterior resection in rectal cancer patients? A propensity score matching analysis.

PURPOSE: The purpose of the current study was to compare the outcomes of temporary stoma through the specimen extraction site (SSES) and stoma through a new site (SNS) after laparoscopic low anterior resection. METHODS: The rectal cancer patients who underwent laparoscopic low anterior resection plus temporary ileostomy were recruited in a single clinical database from Jun 2013 to Jun 2020. The SSES group and the SNS group were compared using propensity score matching (PSM) analysis. RESULTS: A total of 257 rectal cancer patients were included in this study, there were 162 patients in the SSES group and 95 patients in the SNS group. After 1:1 ratio PSM, there was no difference in baseline information (p > 0.05). The SSES group had smaller intraoperative blood loss (p = 0.016 < 0.05), shorter operation time (p < 0.01) and shorter post-operative hospital stay (p = 0.021 < 0.05) than the SNS group before PSM. However, the SSES group shorter operation time (p = 0.006 < 0.05) than the SNS group after PSM, moreover, there was no significant difference in stoma-related complications (p > 0.05). In the multivariate analysis, longer operation time was an independent factor (p = 0.019 < 0.05, OR = 1.006, 95% CI = 1.001-1.011) for the stoma-related complications. CONCLUSION: Based on the current evidence, the SSES group had smaller intraoperative blood loss, shorter operation time and shorter post-operative hospital stay before PSM, and shorter operation time after PSM. Therefore, SSES might be superior than SNS after laparoscopic low anterior resection for rectal cancer patients.

Effect of enhanced recovery after surgery on inflammatory bowel disease surgery: A meta-analysis.

BACKGROUND: The purpose of enhanced recovery after surgery (ERAS) was to reduce surgical pressure and accelerate postoperative functional recovery. Although the application of biologics in treating inflammatory bowel disease (IBD) has changed treatment strategies, most patients with IBD still require surgery. AIM: To evaluate the advantage of ERAS in IBD surgery. METHODS: The PubMed, EMBASE and Cochrane Library databases were searched from inception to March 21, 2021 to find eligible studies. The primary outcome was postoperative complications, and the secondary outcomes included operation time, time to first flatus, time to bowel movement, postoperative hospital stay and readmission. The PROSPERO registration ID of this meta-analysis is CRD42021238052. RESULTS: A total of eight studies involving 1939 patients were included in this meta-analysis. There were no differences in baseline information between the ERAS group and the non-ERAS group. After pooling up all of the data, no significant difference was found between the ERAS group and the non-ERAS group in terms of postoperative overall complications [odds ratio = 0.82, 95% confidence interval (CI) = 0.66 to 1.02, P = 0.08]. The ERAS group had a lower prevalence of anastomotic fistula (odds ratio = 0.36, 95%CI = 0.13 to 0.95, P = 0.04), less time to first flatus [mean difference (MD) = -2.03, 95%CI = -3.89 to -0.17, P = 0.03], less time to bowel movement (MD = -1.08, 95%CI = -1.60 to -0.57, P < 0.01) and shorter postoperative hospital stays (MD = -1.99, 95%CI = -3.27 to -0.71, P < 0.01) than the non-ERAS group. CONCLUSION: ERAS was effective for the quicker recovery in IBD surgery and did not lead to increased complications.

Effects of fecal stream deprivation on human intestinal barrier after loop ileostomy.

BACKGROUND AND AIM: Intestinal homeostasis is closely associated with the normal intestinal luminal physiological environment. Temporary loop ileostomy changes the intestinal structure and diverts the fecal stream, thereby disturbing the intestinal environment. This study aimed to clarify the changing situation of the human intestinal mucosa barrier in the absence of a fecal stream after loop ileostomy. METHODS: We obtained paired samples from the fed (fecal stream maintained) and unfed (no fecal stream) portions of the loop ileostomy and subjected these samples to RNA sequencing. We also determined transepithelial electrical resistance. The mucus layer thickness and content of MUC2, tight junction proteins, and common antimicrobial peptides in ileum mucosa were studied. RESULTS: Transcriptome data revealed that genes associated with enhancing the intestinal barrier function of the unfed ileum were significantly decreased and genes associated with immune defense response were significantly increased. The transepithelial electrical resistance was lower and the mucus layer thickness was thinner in the unfed ileal mucosa than in the fed ileum. The MUC2, Occludin, and zonula occludens 1 content was lower in the unfed ileum than in the fed ileum. α-Defensin 5, α-defensin 6, and lysozyme content was higher in the unfed ileum than in the enterally fed ileum. CONCLUSION: Intestinal barrier function is weakened after long-term fecal diversion, but antimicrobiota defense function is strengthened. Thus, the intestinal mucosa barrier adopts an alternative stable state during fecal diversion, which may explain the clinical paucity of cases of enterogenic infection caused by loop ileostomy.

Whole-Genome and Transcriptome Sequencing of Phlebopus portentosus Reveals Its Associated Ectomycorrhizal Niche and Conserved Pathways Involved in Fruiting Body Development.

Phlebopus portentosus (Berk. and Broome) Boedijin, a widely consumed mushroom in China and Thailand, is the first species in the order Boletaceae to have been industrially cultivated on a large scale. However, to date, the lignocellulose degradation system and molecular basis of fruiting body development in P. portentosus have remained cryptic. In the present study, genome and transcriptome sequencing of P. portentosus was performed during the mycelium (S), primordium (P), and fruiting body (F) stages. A genome of 32.74 Mb with a 48.92% GC content across 62 scaffolds was obtained. A total of 9,464 putative genes were predicted from the genome, of which the number of genes related to plant cell wall-degrading enzymes was much lower than that of some saprophytic mushrooms with specific ectomycorrhizal niches. Principal component analysis of RNA-Seq data revealed that the gene expression profiles at all three stages were different. The low expression of plant cell wall-degrading genes also confirmed the limited ability to degrade lignocellulose. The expression profiles also revealed that some conserved and specific pathways were enriched in the different developmental stages of P. portentosus. Starch and sucrose metabolic pathways were enriched in the mycelium stage, while DNA replication, the proteasome and MAPK signaling pathways may be associated with maturation. These results provide a new perspective for understanding the key pathways and hub genes involved in P. portentosus development.

Evaluation of Transanal Minimally Invasive Surgery for Rectal Benign Lesions.

Objective: To evaluate the clinical efficacy and safety of transanal minimally invasive surgery (TAMIS) for the treatment of benign rectal lesions so that patients can be provided with better surgical alternatives. Materials and Methods: A retrospective analysis was conducted on patients with rectal benign lesions who underwent TAMIS in the Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University from January 2018 to June 2019. The patients' clinical data were thoroughly recorded, such as surgical-related information, postoperative pathology, and so on. At the same time, the patients were followed up regularly and carefully after the surgery. Results: A total of 16 eligible patients were enrolled in the study. All patients underwent colonoscopy before surgery and the biopsy results showed that all the removed specimens were rectal benign tumors. All the lesions were resected with TAMIS. The average operation time was 111.94 ± 46.13 minutes. Among the 16 cases, 1 of the patients was found to have undergone peritoneal entry during operation 1 and this showed that the peritoneal cavity was penetrated during the operation. The average postoperative hospital stay was 4.56 ± 1.79 days. The final pathology of the TAMIS specimens revealed a malignant neoplasm in 10 patients, including 9 cases of rectal adenocarcinoma, 1 case of nerve endocrine tumor, and 6 cases of rectal adenoma. No long-term complications were observed during the mean follow-up time of 10.19 ± 5.14 months. Conclusions: TAMIS is a safe and effective minimally invasive surgical procedure for the treatment of rectal adenomas, which can minimize the adverse effect on anal function.

Bacterial Profiling and Dynamic Succession Analysis of Phlebopus portentosus Casing Soil Using MiSeq Sequencing.

Phlebopus portentosus (Berk. and Broome) Boedijin is a popular edible mushroom found in China and Thailand. To date, P. portentosus is the only species in the order Boletales that can be successfully cultivated worldwide. The use of a casing layer or casing soil overlaying the substrate is a crucial step in the production of this mushroom. In this study, bacterial profiling and dynamic succession analyses of casing soil during the cultivation of P. portentosus were performed. One hundred and fifty samples were collected, and MiSeq sequencing of the V3-V4 region of the 16S rRNA gene was conducted. After performing a decontamination procedure, only 38 samples were retained, including 6 casing soil-originated samples (OS), 6 casing soil samples (FHCS) and 5 upper substrate samples (FHCU) from the period of complete colonization by mycelia; 6 casing soil samples (PCS) and 5 upper substrate samples (PCU) from the primordium period; and 6 casing soil samples (FCS) and 4 upper substrate samples (FCU) from fruit body period. The results revealed that bacterial diversity increased sharply from the hyphal to the primordium stage and then decreased during harvesting. The non-metric multidimensional scaling (NMDS) ordination and analysis of similarities (ANOSIM) analysis suggested that the community composition during different stages was significantly different in casing soil. The most abundant phyla in all of the samples were Proteobacteria, Chloroflexi, Acidobacteria, Actinobacteria, Saccharibacteria, and Bacteroidetes. Burkholderia was the most abundant genus in all the samples except the OS samples. The relative abundance of Burkholderia in the FHCS samples (55.79%) decreased to 35.14% in the PCS samples and then increased to 45.60% in the FCS samples. The abundances of Acidobacterium, Rhizobium, Acidisphaera, Bradyrhizobium, and Bacillus increased from the FHCS to PCS samples. The linear discriminant analysis (LDA) effect size (LEfSe) suggested that Acidobacterium and Acidisphaera are micromarkers for PCS, whereas Bradyrhizobium, Roseiarcus, and Pseudolabrys were associated with fruit body stages. The network analyses resulted in 23 edges, including 4 negative and 19 positive edges. Extensive mutualistic interactions may occur among casing soil bacteria. Furthermore, these bacteria play important roles in mycelial elongation, primordium formations, and the production of increased yields.

Clinical significance of serum IGFBP-3 in colorectal cancer.

BACKGROUND: IGF-binding protein 3（IGFBP-3）has previously been identified as tumor marker. The present study aimed to investigate the clinical significance of serum IGFBP-3 in colorectal cancer (CRC). METHODS: Serum was collected from 70 CRC patients and 50 healthy volunteer controls. Serum IGFBP-3 and carcinoembryonic antigen (CEA) levels were measured using electrogenerated chemiluminescence immunoassay and compared between groups. Relationships between serum IGFBP-3 level and the clinical characteristics of CRC were also analyzed. A receiver operator characteristic (ROC) curve was plotted to investigate diagnostic efficacy of serum IGFBP-3 and CEA, respectively, for CRC. Data were analyzed using SPSS 13.0. RESULTS: Serum IGFBP-3 levels in CRC were lower than those of controls (4.68 [3.56, 5.77] vs 5.44 [4.77, 6.10] µg/mL, P < 0.05). Furthermore, serum IGFBP-3 levels were higher in early cancer stages (I and II) than those of advanced stages (III and IV) (4.78 [3.92, 5.49] vs 3.77 [2.65, 4.59] µg/mL, P < 0.05). In addition, patients with lymph node metastasis absent had elevated serum IGFBP-3 levels than those of patients with lymph node metastasis present (4.73 [3.92, 5.72] vs 4.11 [2.45, 4.83] µg/mL, P = 0.02). Finally, ROC curve indicated that serum IGFBP-3 had a better diagnostic power for CRC than CEA. When serum IGFBP-3 and carcinoembryonic antigen were used together to detect CRC, the AUC was 0.949, with a sensitivity of 75% and a specificity of 90%. CONCLUSIONS: Serum IGFBP-3 might be a potential biomarker for CRC.

Incidences of diabetes and prediabetes among female adult breast cancer patients after systemic treatment.

Patients with cancer frequently show glucose intolerance. This study is to estimate the status of total diabetes and prediabetes in breast cancer patients after systemic treatment through an oral glucose tolerance test (OGTT) in China. All the 119 breast cancer patients more than 3 months after systemic treatment with surgery and chemotherapy participated in the study. All the patients without the diagnosis of diabetes underwent OGTT, and fasting and 2-h glucose levels were measured to identify undiagnosed diabetes and prediabetes. Previously diagnosed diabetes were determined on the self-report and the medical record. Of the 119 breast cancer patients, with the median age of 50.1 years and the mean age of about 48 years when they were initially diagnosed with breast cancer, which showed the similar characters of China and Asia breast cancer patients, the overall incidences of total diabetes and prediabetes were 21.8 and 43.7 %, respectively. About 80 % of the diabetes were previously undiagnosed. About 80.0 % of the cases of undiagnosed diabetes and prediabetes met the criteria for elevated 2-h plasma glucose levels through OGTT but not the criteria for elevated fasting glucose levels. Our study firstly documents high incidences of previously undiagnosed diabetes and prediabetes in breast cancer patients during follow-up after systemic treatment through OGTT, indicating that greater diabetes screening, especially through OGTT, prevention, and treatment strategies among breast cancer patients, after systemic treatment for these patients is needed.

Implication from thyroid function decreasing during chemotherapy in breast cancer patients: chemosensitization role of triiodothyronine.

BACKGROUND: Thyroid hormones have been shown to regulate breast cancer cells growth, the absence or reduction of thyroid hormones in cells could provoke a proliferation arrest in G0-G1 or weak mitochondrial activity, which makes cells insensitive to therapies for cancers through transforming into low metabolism status. This biological phenomenon may help explain why treatment efficacy and prognosis vary among breast cancer patients having hypothyroid, hyperthyroid and normal function. Nevertheless, the abnormal thyroid function in breast cancer patients has been considered being mainly caused by thyroid diseases, few studied influence of chemotherapy on thyroid function and whether its alteration during chemotherapy can influence the respose to chemotherapy is still unclear. So, we aimed to find the alterations of thyroid function and non-thyroidal illness syndrome (NTIS) prevalence druing chemotherapy in breast cancer patients, and investigate the influence of thyroid hormones on chemotherapeutic efficacy. METHODS: Thyroid hormones and NTIS prevalence at initial diagnosis and during chemotherapy were analyzed in 685 breast diseases patients (369 breast cancer, 316 breast benign lesions). The influence of thyroid hormones on chemotherapeutic efficacy was evaluated by chemosensitization test, to compare chemotherapeutic efficacy between breast cancer cells with chemotherapeutics plus triiodothyronine (T3) and chemotherapeutics only. RESULTS: In breast cancer, NTIS prevalence at the initial diagnosis was higher and increased during chemotherapy, but declined before the next chemotherapeutic course. Thyroid hormones decreased signigicantly during chemotherapy. T3 can enhance the chemosensitivity of MCF-7 to 5-Fu and taxol, with progression from G0-G1 phase to S phase. The similar chemosensitization role of T3 were found in MDA-MB-231. We compared chemotherapeutic efficacy among groups with different usage modes of T3, finding pretreatment with lower dose of T3, using higher dose of T3 together with 5-Fu or during chemotherapy with 5-Fu were all available to achieve chemosensitization, but pretreatment with lower dose of T3 until the end of chemotherapy may be a safer and more efficient therapy. CONCLUSIONS: Taken together, thyroid hormones decreasing during chemotherapy was found in lots of breast cancer patients. On the other hand, thyroid hormones can enhance the chemotherapeutic efficacy through gatherring tumor cells in actively proliferating stage, which may provide a new adjuvant therapy for breast cancer in furture, especially for those have hypothyroidism during chemotherapy.

Neo-endocrinochemotherapy: a novel approach for enhancing chemotherapeutic efficacy in clinic?

Chemosensitization means enhancing the sensitivity of tumor cells to chemotherapy with certain methods for better efficacy. Tumor progression depends on stimulation of multiple hormones, decrease in hormones during chemotherapy induces G0/G1 arrest of tumor cells, which may be the main cause for chemoresistance. Some of the choriocarcinoma and testicular tumors are curable with chemotherapy only, underlying mechanism may refer high level of human chorionic gonadotropin, which has thyroid stimulating hormone like effect and even induce hyperthyroidism in these patients. Some of these patients usually have high levels of thyroid hormones or suffer thyroid crisis during chemotherapy. Possibly owning to the proliferative or metabolic promotion effect of thyroid hormones and/or other endocrine hormones, which can promote tumor cells in G0 phase metabolizing actively or stepping into division cycle again, tumors are more sensitive to chemotherapy. Both endocrinotherapy and chemotherapy are major therapies for tumor, traditional endocrinotherapy suppresses tumor progression through decreasing tumor-dependent hormones or competitively combining and blocking hormone receptors. While, chemotherapy mostly killed tumor cells that proliferate actively, because tumor cells retardant in G0 phase by endocrinotherapy are no more sensitive to chemotherapy, endocrinotherapy cannot be concurrently used with chemotherapy. Nevertheless, decrease in hormones during chemotherapy is similar to concurrently using endocrinotherapy and chemotherapy. It has been found in some basic researches that some chemotherapeutics concurrently combined with endocrine hormones can achieve better efficacy compared with chemotherapy only. It is therefore hypothesized in this article that decrease in hormones during chemotherapy causes cell cycle arrest and renders tumor cells insensitive to chemotherapy; addition of endocrine hormones to mimic the hormones and microenvironment changes during chemotherapy for patients with choriocarcinoma or testicular tumor-curable with chemotherapy only, will rescue tumor cells from cell cycle arrest rendering them sensitive to chemotherapy. This new combinative therapy of concurrently using endocrine hormones and chemotherapy is defined as choriocarcinoma-mimic chemotherapy or neo-endocrinochemotherapy to distinguish the routine term of endocrinochemotherapy and is expected to be a novel approach to enhance chemotherapeutic efficacy in clinic.

[AMPK: a novel target controlling inflammation].

The AMP-activated protein kinase (AMPK) is a pivotal serine/threonine kinase participating in the regulation of glucose, lipid as well as protein metabolism and maintenance of energy homeostasis. Recent studies demonstrated that AMPK can also inhibit nuclear factor-κB, suppress the expression of inflammatory genes and attenuate inflammatory injury through phosphorylating its downstream targets including SIRT1, PGC-lα, p53 and FoxO3a. In addition, the widely used antidiabetic metformin also exerts its anti-inflammatory effects through activating AMPK. Therefore, AMPK is emerging as a promising novel target for the development of anti-inflammatory drugs. This review summarized the anti-inflammatory effects of AMPK and the underling molecular mechanisms.