•Saaty-ANP misses a subclass of feedback problems, and its solution has a meaningless risk.•It is necessary to distinguish two types of alternatives.•It is necessary to examine the decision ...structure.•Rank reversal may occur in feedback problems and can be deleted with MC-ANP.
The Saaty analytic network process (Saaty-ANP) is a generalization of the analytic hierarchy process. The Markov chain-based ANP (MC-ANP) is another decision-making approach suitable for general structures. Both ANPs use a relative measurement (paired comparisons with ratio scales) to estimate tangible and intangible factors, use a stochastic matrix (SM) to solve feedback problems and obtain the same results under some conditions. The Saaty-ANP does not define the basic concepts, nor does it check the rationality of the structure, which may lead to meaningless solutions and ignore a subclass of feedback decision problems. MC-ANP separates the alternatives from the criteria and defines the attributes, criteria, criterion dominated relations (CDRs) and reasonable constraints of the CDRs by means of digraphs; it also represents CDRs as Markov chain transition diagrams and corresponding (stochastic) adjacency matrices and obtains solutions from a system of linear equations. With the MC-ANP, for the real alternative problems (Class I), the solutions are priorities of the alternatives obtained by the parametric positive left eigenvectors of the SM, and for the nominal alternative problems (Class II), the solutions are priorities of the criteria obtained by the nonnegative right eigenvector of the SM. We analyze the conditions and causes of rank reversal; note that rank reversal does not appear in Class II problems; the study offers a rank reversal ANP example (with feedback) and presents a rank-preserving method for Class I problems. We discuss the contribution of MC-ANP, how to compensate for the defects of Saaty-AHP/ANP, and present issues that need further consideration.
Abstract
CX3CR1high myeloid cells in the small intestine mediate the induction of oral tolerance by driving regulatory T (Treg) cells. Bacterial metabolites, e.g. pyruvate and lactate, induce a ...dendrite extension of CX3CR1high myeloid cells into the intestinal lumen via GPR31. However, it remains unclear whether the pyruvate–GPR31 axis is involved in the induction of oral tolerance. Here, we show that pyruvate enhances oral tolerance in a GPR31-dependent manner. In ovalbumin (OVA)-fed Gpr31-deficient mice, an OVA-induced delayed-type hypersensitivity response was substantially induced, demonstrating the defective induction of oral tolerance in Gpr31-deficient mice. The percentage of RORγt+ Treg cells in the small intestine was reduced in Gpr31-deficient mice. In pyruvate-treated wild-type mice, a low dose of OVA efficiently induced oral tolerance. IL-10 production from intestinal CX3CR1high myeloid cells was increased by OVA ingestion in wild-type mice, but not in Gpr31-deficient mice. CX3CR1high myeloid cell-specific IL-10-deficient mice showed a defective induction of oral tolerance to OVA and a decreased accumulation of OVA-specific Treg cells in the small intestine. These findings demonstrate that pyruvate enhances oral tolerance through a GPR31-dependent effect on intestinal CX3CR1high myeloid cells.
A pyruvate-GPR31 axis mediates oral tolerance
Graphical Abstract
Graphical Abstract
Sex is pivotal for reproduction, healthcare and evolution. In the fish medaka, the Y-chromosomal dmy (also dmrt1bY) serves the sex determiner, which activates dmrt1 for male sex maintenance. However, ...how dmy makes the male decision via initiating testicular differentiation has remained unknown. Here we report that autosomal gsdf serves a male sex initiator. Gene addition and deletion revealed that gsdf was necessary and sufficient for maleness via initiating testicular differentiation. We show that gsdf transcription is activated directly by dmy. These results establish the autosomal gsdf as the first male sex initiator. We propose that dmy determines maleness through activating gsdf and dmrt1 without its own participation in developmental processes of sex initiation and maintenance. gsdf may easily become a sex determiner or other autosomal genes can be recruited as new sex determiners to initiate gsdf expression. Our findings offer new insights into molecular mechanisms underlying sex development and evolution of sex-controlling genes in vertebrates.
Purpose
The purpose of this study was to evaluate the risk factors for anastomotic leakage (AL) after anterior resection for middle and low rectal cancer in order to help surgeons to decide which ...patients could benefit from a diverting stoma.
Methods
Data on 319 patients having a middle and low rectal cancer resection with anastomosis between May 2011 and October 2015 from two hospitals were included in the study. The analysis included the following variables: patient-related variables (gender, age, diabetes mellitus, ASA score, preoperative radiochemotherapy, body mass index, blood hemoglobin, and serum albumin level), tumor-related variables (K-ras status, distance of tumor from the anal verge, histopathologic grade, pathological T stage, pathological N stage, pathological M stage, TNM stage, and tumor size), and surgery-related variables (laparoscopic or open surgery, blood loss, and operative time). Univariate and multivariate regression analysis were carried out to identify risk factors for AL.
Results
The AL rate was 11.91% (38/319). Male (OR 2.898, 95% CI 1.265–6.637,
p
= 0.012), diabetes mellitus (OR 2.482, 95% CI 1.004–6.134,
p
= 0.049), K-ras mutation (OR 2.544, 95% CI 1.210–5.348,
p
= 0.014), distance of tumor from the anal verge (OR 3.445, 95% CI 1.631–7.279,
p
= 0.001), and preoperative radiochemotherapy (OR 2.790, 95% CI 1.056–7.372,
p
= 0.039) were independent risk factors of AL. One (2.63%) in 38 patients with AL presented with no risk factor of AL, 6 (15.8%) in 38 patients with 1 risk factor, 16 (42.1%) in 38 patients with 2 risk factors, 9 (23.7%) in 38 patients with 3 risk factors, and 6 (15.7%) in 38 patients with 4 risk factors. No patient with 5 risk factors in our study. AL rate increased with the elevated number of risk factors clustering in individuals.
Conclusions
K-ras mutation is first reported to be an independent risk factor for AL after sphincter-preserving surgery without diverting stoma. A diverting stoma should be performed in sphincter-preserving surgery for middle and low rectal cancer patients with 2 or more risk factors identified in this analysis.
Herpesviruses can be detected by pattern recognition receptors (PRRs), which then activate downstream adaptors, kinases and transcription factors (TFs) to induce the expression of interferons (IFNs) ...and inflammatory cytokines. IFNs further activate the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, inducing the expression of interferon-stimulated genes (ISGs). These signaling events constitute host innate immunity to defeat herpesvirus infection and replication. A hallmark of all herpesviruses is their ability to establish persistent infection in the presence of active immune response. To achieve this, herpesviruses have evolved multiple strategies to suppress or exploit host innate immune signaling pathways to facilitate their infection. This review summarizes the key host innate immune components and their regulation by herpesviruses during infection. Also we highlight unanswered questions and research gaps for future perspectives.
Objective
The study aimed to validate the role of 3D‐endorectal ultrasonography in prognosis and recurrence for patients with T3‐stage rectal cancer by evaluating the preoperative extramural depth of ...tumor invasion.
Methods
In this study, we investigated the medical records of rectal cancer patients who were admitted to Changhai Hospital's Colorectal Surgery Division. The sample group was categorized into three subgroups (T3a, T3b, and T3c) based on the extent of tumor progression (<5 mm, 5–10 mm, and >10 mm) to assess the endorectal ultrasonography diagnostic performance. The 5‐year disease‐free survival and overall survival were assessed using the Kaplan‐Meier method and a log rank test. Cox regression analysis verified the tumor invasion depth's significance as a prognostic predictor, and it was also utilized to evaluate other independent risk variables for recurrence after surgery.
Results
The study included 72 individuals with low and middle rectal cancer from January 2014 to November 2019. Twenty‐two individuals had stage T3a, 22 had stage T3b, and 28 had stage T3c based on preoperative endorectal ultrasonography. Endorectal ultrasonography had 88.0%, 86.8%, and 76.2% overall accuracy for stratifying subgroups, respectively. According to the Kaplan‐Meier curve, 5‐year OS was 100%, 83.5%, and 92.9% for T3a, T3b, and T3c (p = 0.172), and 5‐year disease‐free survival was 100%, 80.8%, and 72.9% for T3a, T3b, and T3c, respectively (p = 0.014). A distinct risk factor for 5‐year disease‐free survival was the degree of tumor infiltration (p = 0.039).
Conclusion
Preoperative T3 stage subdivision allows for categorization of prognosis and survival. Endorectal ultrasonography reports should make explicit declarations of T3a, T3b, and T3c scales.
Preoperative subclassify T3 rectal cancer can help to develop different treatment plans based on preoperative TNM staging. It is suggested that T3a, T3b, and T3c should be clearly indicated in the report of endorectal ultrasonography.
Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma (KS) and multiple types of B cell malignancies. Emerging evidence demonstrates that KSHV reprograms host-cell ...central carbon metabolic pathways, which contributes to viral persistence and tumorigenesis. However, the mechanisms underlying KSHV-mediated metabolic reprogramming remain poorly understood. Carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase (CAD) is a key enzyme of the de novo pyrimidine synthesis, and was recently identified to deamidate the NF-κB subunit RelA to promote aerobic glycolysis and cell proliferation. Here we report that KSHV infection exploits CAD for nucleotide synthesis and glycolysis. Mechanistically, KSHV vCyclin binds to and hijacks cyclin-dependent kinase CDK6 to phosphorylate Ser-1900 on CAD, thereby activating CAD-mediated pyrimidine synthesis and RelA-deamidation-mediated glycolytic reprogramming. Correspondingly, genetic depletion or pharmacological inhibition of CDK6 and CAD potently impeded KSHV lytic replication and thwarted tumorigenesis of primary effusion lymphoma (PEL) cells in vitro and in vivo. Altogether, our work defines a viral metabolic reprogramming mechanism underpinning KSHV oncogenesis, which may spur the development of new strategies to treat KSHV-associated malignancies and other diseases.
Background Breast cancer, one of the most prevalent malignancies among women worldwide, has rising incidence rates. Physical activity, particularly exercise, has emerged as a significant modifier of ...cancer prognosis, influencing both tumor biology and patient outcomes. Methods In this study, we utilized a murine breast cancer model, dividing mice into a control group and an exercise group; the latter underwent 21 days of voluntary running. We conducted RNA sequencing, bioinformatics analysis, pan-cancer analysis, and cellular experiments to investigate the underlying mechanisms influenced by exercise. Results Exercise led to a significant reduction in tumor size and weight. Post-exercise mRNA sequencing indicated a notable upregulation of THSD7B in the exercised mice, with significant alterations observed in pathways such as MicroRNAs in cancers and the Calcium signaling pathway. In a broader cancer context, THSD7B showed considerable expression variability, being significantly downregulated in several cancers, correlating with positive prognostic outcomes in PRAD, LAML, KIRC, and GBM and highlighting its potential role as a prognostic marker and therapeutic target. THSD7B expression was also negatively associated with processes of breast cancer cell proliferation, migration, and invasion. Conclusion This study underscores the dual role of exercise in modulating gene expression relevant to tumor growth and highlights the potential of THSD7B as a therapeutic target in cancer. Future research should further explore the specific mechanisms by which exercise and THSD7B influence cancer progression and develop immunotherapy-enhanced strategies to change patient outcomes in clinical settings.
SQUAMOSA promoter-binding protein-like (SPL) transcription factors are very important for the plant growth and development. Here 15
were identified in
. The conserved domains and motifs, phylogenetic ...relationships, posttranscriptional regulation, and physiological function of the 92
family genes in
,
,
,
, and
were analyzed. Sequence alignment and phylogenetic analysis showed the SPL proteins had sequence conservation, some FvSPLs could be lost or developed, and there was a closer relationship between
and
,
and
, respectively. Genes with similar motifs clustering together in the same group had their functional redundancy. Based on the function of
in
, these
could be involved in vegetative transition from juvenile to adult, morphological change in the reproductive phase, anthocyanin biosynthesis, and defense stress. Forty-eight
had complementary sequences of miR156, of which nine
in
and eight
in
as the potential targets of miR156 were reported for the first time, suggesting the conservative regulatory effects of miR156 and indicating the roles of miR156-SPL modules in plant growth, development, and defense response. It provides a basic understanding of
in Rosaceae plants.
Herpesviruses constitute a large family of disease-causing DNA viruses. Each herpesvirus strain is capable of infecting particular organisms with a specific cell tropism. Upon infection, pattern ...recognition receptors (PRRs) recognize conserved viral features to trigger signaling cascades that culminate in the production of interferons and pro-inflammatory cytokines. To invoke a proper immune response while avoiding collateral tissue damage, signaling proteins involved in these cascades are tightly regulated by post-translational modifications (PTMs). Herpesviruses have developed strategies to subvert innate immune signaling pathways in order to ensure efficient viral replication and achieve persistent infection. The ability of these viruses to control the proteins involved in these signaling cascades post-translationally, either directly
virus-encoded enzymes or indirectly through the deregulation of cellular enzymes, has been widely reported. This ability provides herpesviruses with a powerful tool to shut off or restrict host antiviral and inflammatory responses. In this review, we highlight recent findings on the herpesvirus-mediated post-translational control along PRR-mediated signaling pathways.
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