Counting triangles in graphs without vertex disjoint odd cycles

Given two graphs $H$ and $F$, the maximum possible number of copies of $H$ in an $F$-free graph on $n$ vertices is denoted by $\mathrm{ex}(n, H, F)$. Let $(\ell+1) \cdot F$ denote $\ell+1$ vertex disjoint copies of $F$. In this paper, we determine the exact value of $\mathrm{ex}(n, C_3, (\ell+1)\cdot C_{2k+1})$ and its extremal graph, which generalizes some known results

G2C: A Generator-to-Classifier Framework Integrating Multi-Stained Visual Cues for Pathological Glomerulus Classification

Pathological glomerulus classification plays a key role in the diagnosis of nephropathy. As the difference between different subcategories is subtle, doctors often refer to slides from different staining methods to make decisions. However, creating correspondence across various stains is labor-intensive, bringing major difficulties in collecting data and training a vision-based algorithm to assist nephropathy diagnosis. This paper provides an alternative solution for integrating multi-stained visual cues for glomerulus classification. Our approach, named generator-to-classifier (G2C), is a two-stage framework. Given an input image from a specified stain, several generators are first applied to estimate its appearances in other staining methods, and a classifier follows to combine visual cues from different stains for prediction (whether it is pathological, or which type of pathology it has). We optimize these two stages in a joint manner. To provide a reasonable initialization, we pre-train the generators in an unlabeled reference set under an unpaired image-to-image translation task, and then fine-tune them together with the classifier. We conduct experiments on a glomerulus type classification dataset collected by ourselves (there are no publicly available datasets for this purpose). Although joint optimization slightly harms the authenticity of the generated patches, it boosts classification performance, suggesting more effective visual cues are extracted in an automatic way. We also transfer our model to a public dataset for breast cancer classification, and outperform the state-of-the-arts significantly.Comment: Accepted by AAAI 201

Two stability theorems for Kℓ+1r\mathcal{K}_{\ell + 1}^{r}-saturated hypergraphs

An $\mathcal{F}$-saturated $r$-graph is a maximal $r$-graph not containing any member of $\mathcal{F}$ as a subgraph. Let $\mathcal{K}_{\ell + 1}^{r}$ be the collection of all $r$-graphs $F$ with at most $\binom{\ell+1}{2}$ edges such that for some $\left(\ell+1\right)$-set $S$ every pair $\{u, v\} \subset S$ is covered by an edge in $F$. Our first result shows that for each $\ell \geq r \geq 2$ every $\mathcal{K}_{\ell+1}^{r}$-saturated $r$-graph on $n$ vertices with $t_{r}(n, \ell) - o(n^{r-1+1/\ell})$ edges contains a complete $\ell$-partite subgraph on $(1-o(1))n$ vertices, which extends a stability theorem for $K_{\ell+1}$-saturated graphs given by Popielarz, Sahasrabudhe and Snyder. We also show that the bound is best possible. Our second result is motivated by a celebrated theorem of Andr\'{a}sfai, Erd\H{o}s and S\'{o}s which states that for $\ell \geq 2$ every $K_{\ell+1}$-free graph $G$ on $n$ vertices with minimum degree $\delta(G) > \frac{3\ell-4}{3\ell-1}n$ is $\ell$-partite. We give a hypergraph version of it. The \emph{minimum positive co-degree} of an $r$-graph $\mathcal{H}$, denoted by $\delta_{r-1}^{+}(\mathcal{H})$, is the maximum $k$ such that if $S$ is an $(r-1)$-set contained in a edge of $\mathcal{H}$, then $S$ is contained in at least $k$ distinct edges of $\mathcal{H}$. Let $\ell\ge 3$ be an integer and $\mathcal{H}$ be a $\mathcal{K}_{\ell+1}^3$-saturated $3$-graph on $n$ vertices. We prove that if either $\ell \ge 4$ and $\delta_{2}^{+}(\mathcal{H}) > \frac{3\ell-7}{3\ell-1}n$; or $\ell = 3$ and $\delta_{2}^{+}(\mathcal{H}) > 2n/7$, then $\mathcal{H}$ is $\ell$-partite; and the bound is best possible. This is the first stability result on minimum positive co-degree for hypergraphs

Adverse Effects of Simulated Hyper- and Hypo-Phosphatemia on Endothelial Cell Function and Viability

Dysregulation of phosphate homeostasis as occurs in chronic kidney disease is associated with cardiovascular complications. It has been suggested that both hyperphosphatemia and hypophosphatemia can cause cardiovascular disease. The molecular mechanisms by which high or low serum phosphate levels adversely affect cardiovascular function are poorly understood. The purpose of this study was to explore the mechanisms of endothelial dysfunction in the presence of non-physiologic phosphate levels.We studied the effects of simulated hyper- and hypophosphatemia in human umbilical vein endothelial cells in vitro. We found both simulated hyperphosphatemia and hypophosphatemia decrease eNOS expression and NO production. This was associated with reduced intracellular calcium, increased protein kinase C β2 (PKCβ2), reduced cell viability, and increased apoptosis. While simulated hyperphosphatemia was associated with decreased Akt/p-Akt, Bcl-xl/Bax ratios, NFkB-p65 and p-Erk abundance, simulated hypophosphatemia was associated with increased Akt/p-Akt and Bcl-xl/Bax ratios and p-Mek, p38, and p-p38 abundance.This is the first demonstration of endothelial dysfunction with hypophosphatemia. Our data suggests that both hyperphosphatemia and hypophosphatemia decrease eNOS activity via reduced intracellular calcium and increased PKCβ2. Hyperphosphatemia also appears to reduce eNOS transcription via reduced signaling through PI3K/Akt/NF-kB and MAPK/NF-kB pathways. On the other hand, hypophosphatemia appears to activate these pathways. Our data provides the basis for further studies to elucidate the relationship between altered phosphate homeostasis and cardiovascular disease. As a corollary, our data suggests that the level of phosphate in the culture media, if not in the physiologic range, may inadvertently affect experimental results

Regulation of MUTYH, a DNA Repair Enzyme, in Renal Proximal Tubular Epithelial Cells

MUTYH is a DNA repair enzyme that initiates a base excision repair (BER) by recognizing and removing 8-Oxoguanine (8-oxoG) and its paired adenine. We demonstrated that both TGF-β1 and H2O2 treatment led to an increased 8-oxoG in cultured human proximal tubule epithelial (HK-2) cells, while the former induced epithelial-mesenchymal transition and the latter caused cell apoptosis. Without stimulation, HK-2 cells showed MUTYH expression in mitochondria. TGF-β1 triggered a transient upregulation of mitochondrial MUTYH and induced the expression of nuclear isoforms, while H2O2 showed no role on MUTYH expression. Ureteral obstruction (UUO) mice exhibited high 8-oxoG reactivity with tubulointerstitial lesions. After obstruction, the MUTYH expression was increased only in tubules at day 3 and decreased with obvious tubular atrophy at day 10. Particularly, MUTYH was primarily located in normal tubular cytoplasm with a dominant mitochondrial form. A few cells with nuclear MUTYH expression were observed in the fibrotic interstitium. We confirmed that increased MUTYH expression was upregulated and positively correlated with the severity of kidney fibrosis. Thus, renal fibrosis caused a cell-type-specific and time-dependent response of oxidative DNA repairs, even within the same tissues. It suggests that intervention of MUTYH might be effective for therapies

Contemporary survival and anticoagulation of patients with atrial fibrillation: A community based cohort study in China

BackgroundsThe understanding of death in patients with atrial fibrillation (AF) in China is limited. This study aimed to assess the contemporary survival of AF patients in China and to explore risk factors for deaths.MethodsThis was a prospective community-based cohort study including 559 AF patients, who were followed-up from July 2015 to December 2020.ResultsDuring 66-month follow-up, there were 200 deaths (56.5% cardiovascular, 40.0% non-cardiovascular, and 3.5% unknown causes) among 559 AF patients with the median age of 76 years. The top three causes of death were heart failure (33.0%), ischemic stroke (17.0%) and cancer (16.5%). Multivariate Cox regression analysis indicated baseline variables positively associated with all-cause death were age (HR: 1.10, 95% CI: 1.08–1.13), AF subtype (HR: 1.37, 95% CI: 1.08–1.73), prior myocardial infarction (HR: 3.40, 95% CI: 1.48–7.78), previous tumor (HR: 2.61, 95% CI: 1.37–4.98), hypoglycemic therapy at baseline (HR: 1.81, 95% CI: 1.13–2.91), but body weight (HR: 0.98, 95% CI: 0.97–1.00) and use of calcium channel blocker (CCB) (HR: 0.62, 95% CI: 0.41–0.95) played a protective role to all-cause death. Of patients who were alive at the end of follow-up, 24.0% were on oral anticoagulants (OAC) alone, 4.5% on dual antithrombotic therapy, 33.1% on antiplatelet agents alone and 38.4% weren't on any antithrombotic medication.ConclusionIschemic stroke still remains one of the leading causes of death and OAC is seriously underused in AF patients in China. Independent risk factors for death are age, AF subtype, previous tumor, prior myocardial infarction, hypoglycemic therapy, low body weight and no CCB use.Clinical Trial Registrationhttp://www.chictr.org.cn/ (ChiCTR-ICR-15007036)

The Prevalence of Immunologic Injury in Renal Allograft Recipients with De Novo Proteinuria

Post-transplant proteinuria is a common complication after renal transplantation; it is associated with reduced graft and recipient survival. However, the prevalence of histological causes has been reported with considerable variation. A clinico-pathological re-evaluation of post-transplant proteinuria is necessary, especially after dismissal of the term “chronic allograft nephropathy,” which had been considered to be an important cause of proteinuria. Moreover, urinary protein can promote interstitial inflammation in native kidney, whether this occurs in renal allograft remains unknown. Factors that affect the graft outcome in patients with proteinuria also remain unclear. Here we collected 98 cases of renal allograft recipients who developed proteinuria after transplant, histological features were characterized using Banff scoring system. Cox proportional hazard regression models were used for graft survival predictors. We found that transplant glomerulopathy was the leading (40.8%) cause of post-transplant proteinuria. Immunological causes, including transplant glomerulopathy, acute rejection, and chronic rejection accounted for the majority of all pathological causes of proteinuria. Nevertheless, almost all patients that developed proteinuria had immunological lesions in the graft, especially for interstitial inflammation. Intraglomerular C3 deposition was unexpectedly correlated with the severity of proteinuria. Moreover, the severity of interstitial inflammation was an independent risk factor for graft loss, while high level of hemoglobin was a protective factor for graft survival. This study revealed a predominance of immunological parameters in renal allografts with post-transplant proteinuria. These parameters not only correlate with the severity of proteinuria, but also with the outcome of the graft

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field