More on Rainbow Cliques in Edge-Colored Graphs

In an edge-colored graph $G$, a rainbow clique $K_k$ is a $k$-complete subgraph in which all the edges have distinct colors. Let $e(G)$ and $c(G)$ be the number of edges and colors in $G$, respectively. In this paper, we show that for any $\varepsilon>0$, if $e(G)+c(G) \geq (1+\frac{k-3}{k-2}+2\varepsilon) {n\choose 2}$ and $k\geq 3$, then for sufficiently large $n$, the number of rainbow cliques $K_k$ in $G$ is $\Omega(n^k)$. We also characterize the extremal graphs $G$ without a rainbow clique $K_k$, for $k=4,5$, when $e(G)+c(G)$ is maximum. Our results not only address existing questions but also complete the findings of Ehard and Mohr (Ehard and Mohr, Rainbow triangles and cliques in edge-colored graphs. {\it European Journal of Combinatorics, 84:103037,2020}).Comment: 16page

Purification and expression of a novel bacteriocin, JUQZ-1, against Pseudomonas syringae pv. Actinidiae (PSA), secreted by Brevibacillus laterosporus Wq-1, isolated from the rhizosphere soil of healthy kiwifruit

Kiwifruit canker, caused by Pseudomonas syringae pv. actinidiae (PSA), has led to significant losses in the kiwifruit industry each year. Due to the drug resistance feature of PSA, biological control is currently the most promising method. Developing biocontrol bacteria against PSA could help solve the issue of drug resistance generated during the chemical control of PSA to a certain extent. In this research, a Wq-1 strain that demonstrated excellent inhibitory activity against PSA was isolated from the rhizosphere soil of healthy kiwifruit. Based on the morphological characteristics and phylogenetic analysis of the 16S rRNA gene sequence, the isolated strain was identified as Brevibacillus laterosporus Wq-1. Bacteriostatic proteins were isolated from the cell-free culture filtrate of strain Wq-1 and were found to have a molecular weight of approximately 12 kDa, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Liquid chromatography–tandem mass spectrometry (LC–MS/MS) detection revealed that there were several peptides in the target band that were consistent with protein 01021 in the genome. The gene of the 01021 protein was cloned into the plasmid pPICZa, and the recombinant bacteriocin was successfully expressed using the Pichia pastoris X33 expression system. The recombinant protein 01021 effectively inhibited the growth of PSA. This is the first report of the protein’s antimicrobial activity, distinguishing it from previously identified bacteriocins. Therefore, we named this bacteriocin JUQZ-1. In addition, our results showed that the protein JUQZ-1 not only exhibited a broad bacteriostatic spectrum but also high thermal and pH stability suitable for harsh environmental conditions., JUQZ-1, a protein with antimicrobial properties and strong environmental tolerance, may serve as a promising alternative to antibiotics

The obesity paradox in osteoporosis risk among older adults is mostly driven by women:a population-based prospective study

Objectives: The obesity paradox is common among older adults at risk for various diseases. Although this paradox has also been observed in the association between obesity and osteoporosis, the available evidence remains controversial. This study aimed to investigate the association between obesity and OP risk in an older population. Methods: A cross-sectional and prospective study was conducted using data from 177,734 participants in the UK Biobank. The association of body mass index (BMI), waist circumference (WC), and fat percentage with BMD was examined using Spearman correlation analysis with baseline BMD data. Cox proportional hazards regression analysis was used to investigate the association between obesity and OP risk. Restricted cubic spline (RCS) were used to assess the nonlinear associations of BMI, WC, and fat percentage with OP. Results: Baseline cross-sectional analyses revealed a significant positive association between BMI, WC, and fat percentage with BMD in women, whereas this association was very weak in men. A total of 8,998 OP patients were identified during a median follow-up period of 13.7 years. Cox analyses showed that obesity as defined by BMI, WC, and fat percentage was associated with a 33%, 23%, and 31% reduction in the risk of OP in older women but not in men, respectively. Conjoint analysis showed that lower BMI was associated with increased risk of OP in older adults, whereas the lowest risk was observed in women with higher BMI and higher body fat. RCS revealed an inverse J-shaped nonlinear association between obesity metrics and OP risk in women. Conclusion: Lower BMI is an independent risk factor for OP in older adults, and the obesity paradox for OP risk exists only in women.</p

Metabolic syndrome increases osteoarthritis risk:findings from the UK Biobank prospective cohort study

Objective: The association between Metabolic Syndrome (MetS), its components, and the risk of osteoarthritis (OA) has been a topic of conflicting evidence in different studies. The aim of this present study is to investigate the association between MetS, its components, and the risk of OA using data from the UK Biobank. Methods: A prospective cohort study was conducted in the UK Biobank to assess the risk of osteoarthritis (OA) related to MetS. MetS was defined according to the criteria set by the International Diabetes Federation (IDF). Additionally, lifestyle factors, medications, and the inflammatory marker C-reactive protein (CRP) were included in the model. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). The cumulative risk of OA was analyzed using Kaplan–Meier curves and log-rank tests. To explore potential nonlinear associations between MetS components and OA risk, a restricted cubic splines (RCS) model was employed. In addition, the polygenic risk score (PRS) of OA was calculated to characterize individual genetic risk. Results: A total of 45,581 cases of OA were identified among 370,311 participants, with a median follow-up time of 12.48 years. The study found that individuals with MetS had a 15% higher risk of developing OA (HR = 1.15, 95%CI:1.12–1.19). Additionally, central obesity was associated with a 58% increased risk of OA (HR = 1.58, 95%CI:1.5–1.66), while hyperglycemia was linked to a 13% higher risk (HR = 1.13, 95%CI:1.1–1.15). Dyslipidemia, specifically in triglycerides (HR = 1.07, 95%CI:1.05–1.09) and high-density lipoprotein (HR = 1.05, 95%CI:1.02–1.07), was also found to be slightly associated with OA risk. When stratified by PRS, those in the high PRS group had a significantly higher risk of OA compared to those with a low PRS, whereas no interaction was found between MetS and PRS on OA risks. Furthermore, the presence of MetS significantly increased the risk of OA by up to 35% in individuals with elevated CRP levels (HR = 1.35, 95% CI:1.3–1.4). Conclusion: MetS and its components have been found to be associated with an increased risk of OA, particularly in individuals with elevated levels of CRP. These findings highlight the significance of managing MetS as a preventive and intervention measure for OA.</p

Neutrophil-to-lymphocyte ratio and incident end-stage renal disease in Chinese patients with chronic kidney disease: results from the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE)

Abstract Background Chronic kidney disease (CKD) leads to end-stage renal failure and cardiovascular events. An attribute to these progressions is abnormalities in inflammation, which can be evaluated using the neutrophil-to-lymphocyte ratio (NLR). We aimed to investigate the association of NLR with the progression of end stage of renal disease (ESRD), cardiovascular disease (CVD) and all-cause mortality in Chinese patients with stages 1–4 CKD. Methods Patients with stages 1–4 CKD (18–74 years of age) were recruited at 39 centers in 28 cities across 22 provinces in China since 2011. A total of 938 patients with complete NLR and other relevant clinical variables were included in the current analysis. Cox regression analysis was used to estimate the association between NLR and the outcomes including ESRD, CVD events or all-cause mortality. Results Baseline NLR was related to age, hypertension, serum triglycerides, total serum cholesterol, CVD history, urine albumin to creatinine ratio (ACR), chronic kidney disease-mineral and bone disorder (CKD-MBD), hyperlipidemia rate, diabetes, and estimated glomerular filtration rate (eGFR). The study duration was 4.55 years (IQR 3.52–5.28). Cox regression analysis revealed an association of NLR and the risk of ESRD only in patients with stage 4 CKD. We did not observe any significant associations between abnormal NLR and the risk of either CVD or all-cause mortality in CKD patients in general and CKD patients grouped according to the disease stages in particular. Conclusion Our results suggest that NLR is associated with the risk of ESRD in Chinese patients with stage 4 CKD. NLR can be used in risk assessment for ESRD among patients with advanced CKD; this application is appealing considering NLR being a routine test. Trial registration ClinicalTrials.gov Identifier NCT03041987. Registered January 1, 2012. (retrospectively registered) ( https://www.clinicaltrials.gov/ct2/show/NCT03041987?term=Chinese+Cohort+Study+of+Chronic+Kidney+Disease+%28C-STRIDE%29&rank=1 )https://deepblue.lib.umich.edu/bitstream/2027.42/148285/1/12967_2019_Article_1808.pd

Long-term exposure to ambient NO2 increase oral cancer prevalence in Southern China: a 3-year time-series analysis

BackgroundWhile the correlation between cancer and air pollutants is well-established, research on the delayed effects of NO2 on oral cancer remains limited.MethodsWe collected data on nitrogen dioxide (NO2) along with diagnosed cases of oral cancer in Guangxi, China, and analyzed the correlation between exposure to NO2 and the prevalence of oral cancer.ResultsThe study included 1,841 participants diagnosed with oral malignancies, consisting of 1,179 males (64.0%) and 662 females (36.0%), with a mean age of 55.9 ± 14.0 years. The NO2 concentration is 20.2 ± 10.4 μg/m3. The highest cumulative effects of NO2 exposure were observed at a 3-year cumulative lag, with a relative risk (RR) of 1.115 (95% CI: 1.102–1.128). For males, the most pronounced effect of NO2 also occurred at a 3-year lag (RR = 1.110, 95% CI: 1.094–1.127). Similarly, among females, the significant cumulative impact of NO2 was found at a 3-year lag (RR = 1.123, 95% CI: 1.101–1.145). For individuals under 60 years of age, the cumulative impact of NO2 peaked at the same 3-year lag (RR = 1.102, 95% CI: 1.085–1.120). For individuals aged 60 and above, the highest cumulative impact of NO2 was also detected at a 3-year lag (RR = 1.132, 95% CI: 1.112–1.152). For the group with normal BMI, the highest cumulative effect of NO2 exposure was also observed at the 3-year lag period (RR = 1.289, 95% CI: 1.217–1.365), consistent with the findings for other groups.ConclusionThese findings suggest a significant lagged effect of long-term NO2 exposure on oral cancer, with varying associations between NO2 and oral cancer across different ages and genders

Hsa-miR-196a2 Rs11614913 Polymorphism Contributes to Cancer Susceptibility: Evidence from 15 Case-Control Studies

BACKGROUND: MicroRNAs (miRNAs) are a family of endogenous, small and noncoding RNAs that negatively regulate gene expression by suppressing translation or degrading mRNAs. Recently, many studies investigated the association between hsa-miR-196a2 rs11614913 polymorphism and cancer risk, which showed inconclusive results. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a meta-analysis of 15 studies that included 9,341 cancer cases and 10,569 case-free controls. We assessed the strength of the association, using odds ratios (ORs) with 95% confidence intervals (CIs). Overall, individuals with the TC/CC genotypes were associated with higher cancer risk than those with the TT genotype (OR=1.18, 95% CI=1.03-1.34, P<0.001 for heterogeneity test). In the stratified analyses, we observed that the CC genotype might modulate breast cancer risk (OR=1.11, 95%CI=1.01-1.23, Pheterogeneity=0.210) and lung cancer risk (OR=1.25, 95%CI=1.06-1.46, Pheterogeneity=0.958), comparing with the TC/TT genotype. Moreover, a significantly increased risk was found among Asian populations in a dominant model (TC/CC versus TT, OR=1.24, 95% CI=1.07-1.43, Pheterogeneity=0.006). CONCLUSIONS: These findings supported that hsa-miR-196a2 rs11614913 polymorphism may contribute to the susceptibility of cancers

Extensive Crosstalk between O-GlcNAcylation and Phosphorylation Regulates Akt Signaling

O-linked N-acetylglucosamine glycosylations (O-GlcNAc) and O-linked phosphorylations (O-phosphate), as two important types of post-translational modifications, often occur on the same protein and bear a reciprocal relationship. In addition to the well documented phosphorylations that control Akt activity, Akt also undergoes O-GlcNAcylation, but the interplay between these two modifications and the biological significance remain unclear, largely due to the technique challenges. Here, we applied a two-step analytic approach composed of the O-GlcNAc immunoenrichment and subsequent O-phosphate immunodetection. Such an easy method enabled us to visualize endogenous glycosylated and phosphorylated Akt subpopulations in parallel and observed the inhibitory effect of Akt O-GlcNAcylations on its phosphorylation. Further studies utilizing mass spectrometry and mutagenesis approaches showed that O-GlcNAcylations at Thr 305 and Thr 312 inhibited Akt phosphorylation at Thr 308 via disrupting the interaction between Akt and PDK1. The impaired Akt activation in turn resulted in the compromised biological functions of Akt, as evidenced by suppressed cell proliferation and migration capabilities. Together, this study revealed an extensive crosstalk between O-GlcNAcylations and phosphorylations of Akt and demonstrated O-GlcNAcylation as a new regulatory modification for Akt signaling

Estimated GFR and the Effect of Intensive Blood Pressure Lowering After Acute Intracerebral Hemorrhage

BackgroundThe kidney-brain interaction has been a topic of growing interest. Past studies of the effect of kidney function on intracerebral hemorrhage (ICH) outcomes have yielded inconsistent findings. Although the second, main phase of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) suggests the effectiveness of early intensive blood pressure (BP) lowering in improving functional recovery after ICH, the balance of potential benefits and harms of this treatment in those with decreased kidney function remains uncertain.Study DesignSecondary analysis of INTERACT2, which randomly assigned patients with ICH with elevated systolic BP (SBP) to intensive (target SBP<140mmHg) or contemporaneous guideline-based (target SBP<180mmHg) BP management.Setting & Participants2,823 patients from 144 clinical hospitals in 21 countries.PredictorsAdmission estimated glomerular filtration rates (eGFRs) of patients were categorized into 3 groups based on the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation: normal or high, mildly decreased, and moderately to severely decreased (>90, 60-90, and <60mL/min/1.73m2, respectively).OutcomesThe effect of admission eGFR on the primary outcome of death or major disability at 90 days (defined as modified Rankin Scale scores of 3-6) was analyzed using a multivariable logistic regression model. Potential effect modification of intensive BP lowering treatment by admission eGFR was assessed by interaction terms.ResultsOf 2,623 included participants, 912 (35%) and 280 (11%) had mildly and moderately/severely decreased eGFRs, respectively. Patients with moderately/severely decreased eGFRs had the greatest risk for death or major disability at 90 days (adjusted OR, 1.82; 95% CI, 1.28-2.61). Effects of early intensive BP lowering were consistent across different eGFRs (P=0.5 for homogeneity).LimitationsGeneralizability issues arising from a clinical trial population.ConclusionsDecreased eGFR predicts poor outcome in acute ICH. Early intensive BP lowering provides similar treatment effects in patients with ICH with decreased eGFRs

Learning to generalize to new tasks/domains with limited data

The goal of Artificial Intelligence (AI) research is to develop a system that not only performs tasks comparably to humans (e.g., understanding language and vision) but also learns new tasks similarly to humans. While the former has been well-achieved with the recent advances of large AI models, the latter still remains a challenge for AI researchers. The key trait of human beings is the ability to generalize knowledge from past experience, achieving satisfactory performance on new tasks with minimal to no learning (i.e., limited data). In this thesis, I focus on three areas of study with different problem settings, proposing learning-based algorithms to improve the system's generalization ability to unseen tasks or domains when data is limited. My first focus is on meta-learning, which aims to acquire common knowledge from a set of tasks to facilitate learning of new tasks with few examples. A popular approach is to capture the common knowledge in the form of a global initialization. To further handle the case where tasks are from different distributions, recent developments propose to condition the global initialization with some task-specific feature-based representations. My work further considers utilizing the task optimization process to derive the task representation, which contains additional information about the quality of the global initialization to inidividual task learning. As a result, task representation learned in this way can be better used to adapt the global initialization to a more beneficial one. The method is evaluated in two real-world application domains: few-shot image classification and user cold-start recommendations, to demonstrate its effectiveness. Meta-learning derives common knowledge by assuming that all tasks are available at once. However, in real-world situations, tasks are often learned in a sequential manner, where access to previous tasks' data is restricted. This setting falls under another field of study termed continual learning (CL). Unlike most CL works that focus on preventing forgetting of previous tasks, my research focuses more on how to leverage knowledge gained from previous tasks to enhance performance on the current task - an ability known as forward transfer, which is of great significance especially when the data from a single task is limited. With specific application to incremental updates of recommender systems, where data arriving at different periods can be treated as different tasks, and incrementally updating the recommender system can be seen as a form of CL, it is possible to mine the historical trends from the past tasks to achieve forward transfer, i.e., to improve performance on the current task/period. In this regard, I develop a model generation method that learns to leverage models from the past periods to generate a more superior model for the current period. A recurrent neural network design is adopted for the meta-model generator to leverage its ability of capturing the sequential patterns. My third research focuses on generalizing across domains. Different from tasks, domains are specifically defined by variations in input distribution. When the target domain is completely inaccessible during training, and the model learns to generalize from multiple source domains, the problem is termed domain generalization (DG). A common pitfall of the existing DG methods is the risk of overfitting to the source domains. To address this issue, some works propose to use interpolation between source data to cover the unseen region within the convex hull of the source domains. My research further explores the potential of extrapolation to extend beyond the convex hull and achieve better generalization. To avoid the adverse effects caused by uncontrolled extrapolation, a strategy is carefully designed to generate the sample weights based on gradients and learned towards flatter minima. Experiments demonstrate that the proposed strategy can better cover the regions outside the source domains, and the resultant loss minima are flatter and wider, better aligning with the target optima.Doctor of Philosoph