Development and analytical validation of a novel nasopharynx swab-based Epstein-Barr virus C promoter methylation quantitative assay for nasopharyngeal carcinoma detection.

OBJECTIVES: Epstein-Barr virus (EBV) C promoter (Cp) hypermethylation, a crucial factor for EBV latent infection of nasopharyngeal epithelial cells, has been recognized as a promising biomarker for nasopharyngeal carcinoma (NPC) detection. In this study, we develop a novel EBV Cp methylation quantification (E-CpMQ) assay and evaluate its diagnostic performance for NPC detection. METHODS: A novel qPCR assay for simultaneous quantification of methylated- and unmethylated EBV Cp was developed by the combinational modification of MethyLight and QASM, with an innovative calibrator to improve the detection accuracy and consistency. The NP swab samples and synthetic standards were used for the analytical validation of the E-CpMQ. The diagnostic efficacy of the developed E-CpMQ assay was validated in 137 NPC patients and 137 non-NPC controls. RESULTS: The E-CpMQ assay can detect the EBV Cp methylation ratio in one reaction system under 10 copies with 100 % recognition specificity, which is highly correlated to pyrosequencing with a correlation coefficient over 0.99. The calibrated E-CpMQ assay reduces the coefficient of variation by an average of 55.5 % with a total variance of less than 0.06 units standard deviation (SD). Linear methylation ratio detection range from 4.76 to 99.01 %. The sensitivity and specificity of the E-CpMQ respectively are 96.4 % (95 % CI: 91.7-98.8 %), 89.8 % (95 % CI: 83.5-94.3 %). CONCLUSIONS: The developed E-CpMQ assay with a calibrator enables accurate and reproducible EBV Cp methylation ratio quantification and offers a sensitive, specific, cost-effective method for NPC early detection.

Acetyl-CoA synthetase 2 promotes diabetic renal tubular injury in mice by rewiring fatty acid metabolism through SIRT1/ChREBP pathway.

Diabetic nephropathy (DN) is characterized by chronic low-grade renal inflammatory responses, which greatly contribute to disease progression. Abnormal glucose metabolism disrupts renal lipid metabolism, leading to lipid accumulation, nephrotoxicity, and subsequent aseptic renal interstitial inflammation. In this study, we investigated the mechanisms underlying the renal inflammation in diabetes, driven by glucose-lipid metabolic rearrangement with a focus on the role of acetyl-CoA synthetase 2 (ACSS2) in lipid accumulation and renal tubular injury. Diabetic models were established in mice by the injection of streptozotocin and in human renal tubular epithelial HK-2 cells cultured under a high glucose (HG, 30 mmol/L) condition. We showed that the expression levels of ACSS2 were significantly increased in renal tubular epithelial cells (RTECs) from the diabetic mice and human diabetic kidney biopsy samples, and ACSS2 was co-localized with the pro-inflammatory cytokine IL-1ß in RTECs. Diabetic ACSS2-deficient mice exhibited reduced renal tubular injury and inflammatory responses. Similarly, ACSS2 knockdown or inhibition of ACSS2 by ACSS2i (10 µmol/L) in HK-2 cells significantly ameliorated HG-induced inflammation, mitochondrial stress, and fatty acid synthesis. Molecular docking revealed that ACSS2 interacted with Sirtuin 1 (SIRT1). In HG-treated HK-2 cells, we demonstrated that ACSS2 suppressed SIRT1 expression and activated fatty acid synthesis by modulating SIRT1-carbohydrate responsive element binding protein (ChREBP) activity, leading to mitochondrial oxidative stress and inflammation. We conclude that ACSS2 promotes mitochondrial oxidative stress and renal tubular inflammation in DN by regulating the SIRT1-ChREBP pathway. This highlights the potential therapeutic value of pharmacological inhibition of ACSS2 for alleviating renal inflammation and dysregulation of fatty acid metabolic homeostasis in DN. Metabolic inflammation in the renal region, driven by lipid metabolism disorder, is a key factor in renal injury in diabetic nephropathy (DN). Acetyl-CoA synthetase 2 (ACSS2) is abundantly expressed in renal tubular epithelial cells (RTECs) and highly upregulated in diabetic kidneys. Deleting ACSS2 reduces renal fatty acid accumulation and markers of renal tubular injury in diabetic mice. We demonstrate that ACSS2 deletion inhibits ChREBP-mediated fatty acid lipogenesis, mitochondrial oxidative stress, and inflammatory response in RTECs, which play a major role in the progression of diabetic renal tubular injury in the kidney. These findings support the potential use of ACSS2 inhibitors in treating patients with DN.

The impact of maternal intrahepatic cholestasis during pregnancy on the growth trajectory of offspring: a population-based nested case‒control cohort study.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse fetal outcomes, yet its influence on offspring growth remains unclear. Our study dynamically tracks growth rates in children from ICP and healthy mothers and investigates the link between maternal liver function and developmental abnormalities in offspring. METHOD: Our case‒control study involved 97 women with ICP and 152 with uncomplicated pregnancies nested in a cohort of their offspring, including 50 from the ICP group and 87 from the uncomplicated pregnancy group. We collected pediatric growth and development data, with a maximum follow-up duration of 36 months. Stratified analyses of children's height, weight, and head circumference were conducted, and Spearman's rank correlation was applied to examine the relationships between maternal serological markers and pediatric growth metrics. RESULT: Maternal liver and renal functions, along with serum lipid profiles, significantly differed between the ICP and normal groups. In the ICP group, the offspring showed elevated alanine aminotransferase (ALT), direct bilirubin (DBIT), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (APOB) levels. Notably, the length-for-age z score (LAZ), weight-for-age z score (WAZ), and head circumference-for-age z score (HCZ) were lower in ICP offspring compared with those from normal pregnancies within the 1- to 12-month age range (P < 0.05). However, no significant differences in LAZ, weight-for-length z score (WLZ), BMI-for-age z score (BAZ), or HCZ were observed between groups in the 13- to 36-month age range. Maternal maximum lactate dehydrogenase (LDH) and total bile acids (TBA) levels during pregnancy were inversely correlated with LAZ and WAZ in the first year. Furthermore, offspring of mothers with ICP exhibited a greater incidence of stunting (24% vs. 6.9%, P = 0.004) and abnormal HCZ (14% vs. 3.7%, P = 0.034). CONCLUSIONS: Growth disparities in offspring of ICP-affected pregnancies were most significant within the 1- to 12-month age range. During this period, maximum maternal LDH and TBA levels were negatively correlated with LAZ and WAZ values of offspring. The observation of similar growth rates between ICP and control group offspring from 13 to 36 months suggested catch-up growth in the ICP group.

Rare Presentation of Wide QRS Tachycardia in a Patient in Their 40s.

This article describes the case of a 40-year-old individual who presented with fulminant myocarditis. Initial ECG displayed sinus tachycardia with a heart rate of 117 bpm, QS complexes in leads V1-V3, ST-segment depression in leads II, III, aVF, V5-V6, and ST-segment elevation >0.2 mV in leads V1 through V3. The initial clinical assessment suggested an acute anteroseptal myocardial infarction. However, subsequent diagnostic evaluation through coronary angiography disclosed that the coronary arteries were normal. Therefore, clinicians should carefully consider the differential diagnosis between these conditions, as their management strategies differ markedly. Two hours after admission, the patient unexpectedly developed syncope. The ECG findings were consistent with the typical characteristics of bidirectional ventricular tachycardia. Our report described the appearance and morphology as well as mechanism of bidirectional ventricular tachycardia in detail. Additionally, we delineate differential diagnoses for disease that can cause bidirectional ventricular tachycardia, such as aconite poisoning, digoxin overdose, immune checkpoint inhibitor (ICI), myocardial ischemia, and hereditary channelopathies, such as catecholaminergic polymorphic ventricular tachycardia (CPVT) and Andersen-Tawil syndrome. Therefore, clinicians should recognize this ECG finding immediately and initiate appropriate treatment promptly as these measures may be vital in saving the patient's life.

Degradation Efficiency and Mechanism of Tetracycline in Water by Activated Persulfate Using Biochar-Loaded Nano Zero-Valent Iron.

Tetracycline (TC) contamination in water is one of the key issues in global environmental protection, and traditional water treatment methods are difficult to remove antibiotic pollutants.Therefore, efficient and environmentally friendly treatment technologies are urgently needed. In this study, activated persulfate (PS) using a biochar-loaded nano zero-valent iron (BC-nZVI) advanced oxidation system was used to investigate the degradation effect, influencing factors, and mechanism of TC. BC-nZVI was prepared using the liquid-phase reduction method, and its structure and properties were analyzed by various characterization means. The results showed that nZVI was uniformly distributed on the surface or in the pores of BC, forming a stable complex. Degradation experiments showed that the BC-nZVI/PS system could degrade TC up to 99.57% under optimal conditions. The experiments under different conditions revealed that the iron-carbon ratio, dosing amount, PS concentration, and pH value all affected the degradation efficiency. Free radical burst and electron paramagnetic resonance (EPR) experiments confirmed the dominant roles of hydroxyl and sulfate radicals in the degradation process, and LC-MS experiments revealed the multi-step reaction process of TC degradation. This study provides a scientific basis for the efficient treatment of TC pollution in water.

Research Progress on the Degradation of Organic Pollutants in Water by Activated Persulfate Using Biochar-Loaded Nano Zero-Valent Iron.

Biochar (BC) is a new type of carbon material with a high specific surface area, porous structure, and good adsorption capacity, which can effectively adsorb and enrich organic pollutants. Meanwhile, nano zero-valent iron (nZVI) has excellent catalytic activity and can rapidly degrade organic pollutants through reduction and oxidation reactions. The combined utilization of BC and nZVI can not only give full play to their advantages in the adsorption and catalytic degradation of organic pollutants, but also help to reduce the agglomeration of nZVI, thus improving its efficiency in water treatment and providing strong technical support for water resources protection and environmental quality improvement. This article provides a detailed introduction to the preparation method and characterization technology, reaction mechanism, influencing factors, and specific applications of BC and nZVI, and elaborates on the research progress of BC-nZVI in activating persulfate (PS) to degrade organic pollutants in water. It has been proven experimentally that BC-nZVI can effectively remove phenols, dyes, pesticides, and other organic pollutants. Meanwhile, in response to the existing problems in current research, this article proposes future research directions and challenges, and summarizes the application prospects and development trends of BC-nZVI in water treatment. In summary, BC-nZVI-activated PS is an efficient technology for degrading organic pollutants in water, providing an effective solution for protecting water resources and improving environmental quality, and has significant application value.

Magnetic Heating Amorphous NiFe Hydroxide Nanosheets Encapsulated Ni Nanoparticles@Wood Carbon to Boost Oxygen Evolution Reaction Activity.

The oxygen evolution reaction (OER) has significant effects on the water-splitting process and rechargeable metal-air batteries; however, the sluggish reaction kinetics caused by the four-electron transfer process for transition metal catalysts hinder large-scale commercialization in highly efficient electrochemical energy conversion devices. Herein, a magnetic heating-assisted enhancement design for low-cost carbonized wood with high OER activity is proposed, in which Ni nanoparticles are encapsulated in amorphous NiFe hydroxide nanosheets (a-NiFe@Ni-CW) via direct calcination and electroplating. The introduction of amorphous NiFe hydroxide nanosheets optimizes the electronic structure of a-NiFe@Ni-CW, accelerating electron transfer and reducing the energy barrier in the OER. More importantly, the Ni nanoparticles located on carbonized wood can function as magnetic heating centers under the effect of an alternating current (AC) magnetic field, further promoting the adsorption of reaction intermediates. Consequently, a-NiFe@Ni-CW demonstrated an overpotential of 268 mV at 100 mA cm-2 for the OER under an AC magnetic field, which is superior to that of most reported transition metal catalysts. Starting with sustainable and abundant wood, this work provides a reference for highly effective and low-cost electrocatalyst design with the assistance of a magnetic field.

Efficient biosynthesis of α-aminoadipic acid via lysine catabolism in Escherichia coli.

α-Aminoadipic acid (AAA) is a nonproteinogenic amino acid with potential applications in pharmaceutical, chemical and animal feed industries. Currently, AAA is produced by chemical synthesis, which suffers from high cost and low production efficiency. In this study, we engineered Escherichia coli for high-level AAA production by coupling lysine biosynthesis and degradation pathways. First, the lysine-α-ketoglutarate reductase and saccharopine dehydrogenase from Saccharomyces cerevisiae and α-aminoadipate-δ-semialdehyde dehydrogenase from Rhodococcus erythropolis were selected by in vitro enzyme assays for pathway assembly. Subsequently, lysine supply was enhanced by blocking its degradation pathway, overexpressing key pathway enzymes and improving nicotinamide adenine dineucleotide phosphate (NADPH) regeneration. Finally, a glutamate transporter from Corynebacterium glutamicum was introduced to elevate AAA efflux. The final strain produced 2.94 and 5.64 g/L AAA in shake flasks and bioreactors, respectively. This work provides an efficient and sustainable way for AAA production.

2,4,6-TCP migrates and transforms in different cultivated soil in China: Kinetic analysis and mechanistic modeling.

Organochlorine pesticides are widely used in agriculture, wood preservation, pulp bleaching and other fields, which increased the pollution risk of cultivated land. In this study, a typical organochlorine pesticides-2,4,6-TCP was conducted as the target pollutants to investigated the migration and transformation characteristics in different cultivated soils in China. The results indicated that the adsorption of 2,4,6-TCP in soil samples was in order: black soil＞laterite＞fluvo-aquic soil, and the maximum adsorption was 71.0870, 27.0575 and 6.1292 mg/kg, respectively. The dispersion coefficient of black soil, laterite and fluvo-aquic soil was 0.0329, 0.0501 and 0.0149, and the hysteretic factor R was 5.381, 1.455 and 2.238, respectively, indicating that the migration ability of 2,4,6-TCP in different cultivated soils samples was in order: black soil＞laterite＞fluvo-aquic soil. The fitting results of one-dimensional migration model indicated that the model well reflected the migration and transformation of 2,4,6-TCP in different cultivated soil samples. Meanwhile, the Two-dimensional migration model fitting results indicated that the maximum concentration of 2,4,6-TCP of different cultivated soil samples were found along the longitudinal flow direction, reaching 40% of the initial pollution concentration at 15 m, corresponding to the center of the pollutant plume.

Syncope with QT-interval prolongation and T-wave inversion in anterior and inferior leads: Foreboder of a life-threatening condition?

Even though patients with pulmonary embolism usually present with respiratory distress and tachycardia, the patient presented with syncope only. Typical ECG changes associated with PE include right axis deviation, right bundle-branch block, S1Q3T3 pattern, arrhythmia, nonspecific ST-segment changes, QR pattern in lead V1, Brugada ECG pattern, and T-wave inversions in the precordial leads. However, his electrocardiogram showed QT-interval prolongation and simultaneous T-wave inversions in the inferior and anterior leads. This ECG pattern is crucial for diagnosing PE. The patient underwent computed tomography-pulmonary angiography, which revealed pulmonary embolism. At the same time, these ECG changes should be differentiated from those of long QT syndrome, myocardial ischemia, Takotsubo cardiomyopathy, post-pacing T-wave memory, hypertrophic cardiomyopathy, and subarachnoid hemorrhage.

Optimizing the number of valid measurements for the attenuation coefficient to assess hepatic steatosis in MAFLD patients: A study of 139 patients who underwent liver biopsy.

PURPOSE: We investigated the optimal number of valid measurements (VMs) for the attenuation coefficient (AC) to assess liver steatosis using attenuation imaging (ATI) and explored factors that may affect AC measurement in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). MATERIALS AND METHODS: A total of 139 patients with MAFLD who underwent ATI and liver biopsy were enrolled. Hepatic steatosis was graded as S0-3 according to the SAF scoring system. The AC values from 1, 2, 3, 5, and 7 VMs were compared with the degree of liver steatosis. The correlation between AC values from different VMs was analyzed. The diagnostic performance of AC from different VMs at each steatosis grade was compared. The factors related to AC were identified using linear regression analysis. RESULTS: The mean AC values from 1, 2, 3, 5, and 7 VMs were not significantly different between grades S0-3 (p=n.s. for all). Bland-Altman analysis showed the mean difference in AC values of 3 VMs and 7 VMs was 0.003 dB/cm/MHz, which was smaller compared with 2 VMs, and close to 5 VMs. The intraclass correlation coefficients of AC were all > 0.90 among different VM groups. AC values from different VMs all significantly predicted steatosis grade ≥S1, ≥S2, and S3 without significant statistical differences (p=n.s. for all). The multivariate analysis showed that the hepatic steatosis grade and triglyceride level were factors independently associated with AC. CONCLUSION: Three valid measurements of AC may be adequate to ensure the accuracy and reproducibility of hepatic steatosis assessment. The degree of liver steatosis and the triglyceride level significantly affected AC values.

A review of the photocatalytic degradation of organic pollutants in water by modified TiO2.

Organic pollutants in water bodies pose a serious environmental problem, and photocatalytic technology is an efficient and environmentally friendly water treatment method. Titanium dioxide (TiO2) is a widely used photocatalyst, but it suffers from some drawbacks such as a narrow light response range, fast charge recombination, and low photocatalytic activity. To improve the photocatalytic performance of TiO2, this article reviews the preparation methods, performance evaluation, and applications of modified TiO2 photocatalysts. Firstly, the article introduces the effects of doping modification, semiconductor composite modification, and other modification methods on the structure and properties of TiO2 photocatalysts, as well as the common characterization techniques and activity test methods of photocatalysts. Secondly, the article discusses the effects and mechanisms of modified TiO2 photocatalysts on degrading dye, pesticide, and other organic pollutants in water bodies, as well as the influencing factors. Finally, the article summarizes the main achievements and advantages of modified TiO2 photocatalysts in degrading organic pollutants in water bodies, points out the existing problems and challenges, and prospects for the development direction and future of this field.

Dual administration of lipopolysaccharide induces behavioural changes in rats relevant to psychotic disorders.

OBJECTIVE: We previously reported that dual injections of lipopolysaccharide (LPS) in mice constitute a valuable tool for investigating the contribution of inflammation to psychotic disorders. The present study investigated how immune activation affects the kynurenine pathway and rat behaviour of relevance for psychotic disorders. METHODS: Male Sprague Dawley rats were treated with either dual injections of LPS (0.5 mg/kg + 0.5 mg/kg, i.p.) or dual injections of saline. Twenty-four hours after the second injection, behavioural tests were carried out, including locomotor activity test, fear conditioning test, spontaneous alternation Y-maze test, and novel object recognition test. In a separate batch of animals, in vivo striatal microdialysis was performed, and tryptophan, kynurenine, quinolinic acid, and kynurenic acid (KYNA) in the dialysate were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). RESULTS: Dual-LPS treatment decreased spontaneous locomotion, exaggerated d-amphetamine-induced locomotor activity, and impaired recognition memory in male Sprague-Dawley rats. In vivo microdialysis showed that dual-LPS treatment elicited metabolic disturbances in the kynurenine pathway with increased extracellular levels of kynurenine and KYNA in the striatum. CONCLUSION: The present study further supports the feasibility of using the dual-LPS model to investigate inflammation-related psychotic disorders and cognitive impairments.

One Versatile Cas9-Integrated Single-Tube Duplex Quantitative Real-Time PCR System for Rapid Analysis of CRISPR/Cas-Induced Mutants.

Clustered regularly interspersed short palindromic repeat (CRISPR)/Cas9 gene editing has become a common tool for rapid crop and animal breeding, but efficiently screening out and genotyping for the CRISPR/Cas9-induced mutant lines at a low cost remains challenging. Using rice (Oryza sativa L.) samples genetically edited at the Waxy locus as an example, we developed a single-tube duplex quantitative real-time PCR assisted by an in vitro CRISPR/Cas9 cleavage (Cc-qPCR) method to screen for expected genetically edited lines, identify genotypes, and evaluate gene-editing frequency. In Cc-qPCR, genomic DNA is first cleaved at the target site by the single-guide RNA (sgRNA)/Cas9 complex and then quantified with qPCR to assess for the presence of a mutant and identify sample genotypes. Our findings suggest that Cc-qPCR can successfully identify mutants with small insertions or deletions (indels), even in mutant lines with single-base indels or substitutions. Cc-qPCR was also able to successfully identify heterozygous and homozygous mutants. The sensitivity of Cc-qPCR was determined to be as low as 0.5%, indicating that the method could be used to evaluate the editing efficiency of gene-editing systems. After testing our novel method on Waxy locus-edited rice offspring, our results show that Cc-qPCR is an accurate and effective approach to rapidly identify expected mutants and their genotypes and to evaluate editing efficiency. This method will prove useful for increasing the efficiency and range of molecular breeding techniques.

Hyperphosphorylated tau mediates neuronal death by inducing necroptosis and inflammation in Alzheimer's disease.

BACKGROUND: Progressive neuronal death is the key pathological feature of Alzheimer's disease (AD). However, the molecular mechanisms underlying the neuronal death in AD patients have not been fully elucidated. Necroptosis reportedly activates and induces neuronal death in patients with Alzheimer's disease (AD); however, the main mediators and mechanisms underlying necroptosis induction in AD remain elusive. METHODS: The function of hyperphosphorylated tau (pTau) in inducing necroptosis in neuronal cell was examined using Western blotting, RT-PCR and flow cytometry. Tau-induced inflammation was identified via RNA sequencing and transwell assay. Pharmacological methods and CRISPR-Cas9 technology were used to verify the role of necrosome proteins in pTau-stimulated neuronal death and inflammation. TauP301S model mice were treated with Nec-1 s to evaluate the role of necroptosis in tau pathology. RESULTS: Hyperphosphorylated tau could induce necroptosis in neuronal cells by promoting the formation of the RIPK1/RIPK3/MLKL necrosome. In addition, pTau significantly stimulated cell-autonomous overexpression of cytokines and chemokines via the intracellular nuclear factor kappa B (NF-κB) signaling pathway. Importantly, the RIPK1/RIPK3/MLKL axis was essential for the pTau-mediated NF-κB activation and cytokine storm. Furthermore, necroptosis stimulation, NF-κB activation, and cytokine induction have been detected in TauP301S mice and blocking necroptosis markedly ameliorated behavioral defects and excessive neuroinflammation in AD mice. CONCLUSIONS: Our study, for the first time, revealed that pTau contributes to neuronal death by inducing necroptosis and inflammation, mediated by activating the RIPK1/RIPK3/MLKL and NF-κB pathways, thereby delineating the hierarchical molecular network of neuronal necroptosis induction in AD.

Mitotically heritable epigenetic modifications of CmMYB6 control anthocyanin biosynthesis in chrysanthemum.

Flower color, which is determined by various chemical pigments, is a vital trait for ornamental plants, in which anthocyanin is a major component. However, the epigenetic regulation of anthocyanin biosynthesis remains poorly understood. During chrysanthemum cultivation, we found a heterochromatic chrysanthemum accession (YP) whose progeny generated by asexual reproduction contained both yellow-flowered (YP-Y) and pink-flowered (YP-P) plants. In this study, we aimed to elucidate the epigenetic mechanisms of different flower colors in the YP plant progeny. Metabolome and transcriptome analyses revealed that the difference in flower color between YP-Y and YP-P was caused by expression variation of the anthocyanin biosynthesis gene CmMYB6. Bisulfite sequencing revealed that methylation at the CmMYB6 promoter, especially in the CHH context, was higher in YP-Y than YP-P. After demethylation of the CmMYB6 promoter using the dCas9-TET1cd system, the flower color returned from yellow to pink. Furthermore, the methylation status of the CmMYB6 promoter was higher in YP-Y over three consecutive generations, indicating that this methylation status was heritable mitotically. Finally, investigation of other chrysanthemum cultivars showed that the methylation of CmMYB6 decreased gradually with the increase in anthocyanin content. These results lay an epigenetic foundation for the improvement of flower color in horticultural plants.

Flavonoid subclasses and CHD risk: a meta-analysis of prospective cohort studies.

Epidemiological studies have shown that higher intake of flavonoid is inversely associated with CHD risk. However, which flavonoid subclass could reduce CHD risk has remained controversial. The present meta-analysis of prospective cohort studies aimed to quantitatively assess the associations between flavonoid subclasses and CHD risk. A systematic literature search was implemented from PubMed and Web of Science databases up to March 2021, and eligible studies were identified. Multivariate-adjust relative risks (RR) with corresponding 95 % CI were pooled by using a random-effects model. A restricted cubic spline regression model was performed for non-linear dose-response analysis. A total of 19 independent prospective cohort studies with 894 471 participants and 34 707 events were included. The results showed that dietary intakes of anthocyanins (RR = 0·90; 95 % CI: 0·83, 0·98), proanthocyanidins (RR = 0·78; 95 % CI: 0·65, 0·94), flavonols (RR = 0·88; 95 % CI: 0·79, 0·98), flavones (RR = 0·94; 95 % CI: 0·89, 0·99) and isoflavones (RR = 0·90; 95 % CI: 0·83, 0·98) were negatively associated with CHD risk. Dose-response analysis showed that increment of 50 mg/d anthocyanins, 100 mg/d proanthocyanidins, 25 mg/d flavonols, 5 mg/d flavones and 0·5 mg/d isoflavones were associated with 5 % reduction in CHD risk, respectively. Sensitivity and subgroup analyses were used to further support these associations. The present results indicate that dietary intakes of fruits and vegetables abundant five flavonoid subclasses, namely anthocyanins, proanthocyanidins, flavonols, flavones and isoflavones, are associated with a lower risk of CHD.

Circular RNA circNIPBL promotes NNK-induced DNA damage in bronchial epithelial cells via the base excision repair pathway.

Environmental chemical exposure often causes DNA damage, which leads to cellular dysfunction and the development of diseases. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific carcinogen that is known to cause DNA damage, while remains unknown about the underlying mechanism. In this study, simulated doses of NNK exposure in smokers, ranging from 50 to 300 µM, were used to detect the DNA damage effects of NNK in two human bronchial epithelial cells, 16HBE and BEAS-2B. The comet assay revealed increased DNA damage in response to NNK treatment, as measured by increased Olive tail moment (OTM). NNK treatment also led to elevated foci formation and protein expression of γ-H2AX, a DNA damage sensor. Dysregulation of proliferation, cell cycle arrest and apoptosis, was also observed in NNK-treated cells. Furthermore, the most effective dose of NNK (300 µM) was used in subsequent mechanistic studies. A circular RNA circNIPBL was identified to be significantly up-regulated in NNK-treated cells, circNIPBL knockdown successfully alleviated NNK-induced DNA damage and reversed the cellular dysregulation, while circNIPBL overexpression had the opposite effect. Mechanistically, we identified an interaction between circNIPBL and PARP1, a critical enzyme of the base excision repair (BER) pathway. CircNIPBL silencing successfully alleviated the NNK-induced inhibition of BER pathway proteins, including PARP1, XRCC1, PCNA and FEN1, while overexpression of circNIPBL had the opposite effect. In summary, our study shows for the first time that circNIPBL promotes NNK-induced DNA damage and cellular dysfunction through the BER pathway. In addition, our findings reveal the crucial role of epigenetic regulation in carcinogen-induced genetic lesions and further our understanding of environmental carcinogenesis.

Taming non-stationary chimera states in locally coupled oscillators.

The imperfect traveling chimera (ITC) state is a novel non-stationary chimera pattern in which the incoherent domain of oscillators spreads into the coherent domain. We investigate the ITC state in locally coupled pendulum oscillators with heterogeneous driving forces. We introduce the heterogeneous phase value in the driving forces by two different ways, namely, the random phase from uniform distribution and random phase directions with identical amplitude. We discover two transition mechanisms from ITC to coherent state through traveling chimera-like state by taking the two different phase heterogeneity. The transition phenomena are investigated using cylindrical and polar coordinate phase spaces. In the numerical study, we propose a quantitative measurement named "spatiotemporal consistency" strength for distinguishing the ITC from the traveling one. Our research facilitates the exploration of potential applications of heterogeneous interactions in neuroscience.

A meta-analysis of prospective cohort studies of flavonoid subclasses and stroke risk.

Epidemiological studies indicate that higher intakes of flavonoids are associated with reduced stroke risk, however, which subtypes play significant roles to protect against stroke remain unclear. A systematic literature search in PubMed and Web of Science databases was performed up to Oct. 2021. Flavonoids or their subtypes (flavanol, flavanone, flavone, flavan-3-ol, isoflavone, or anthocyanin) were paired with stoke as the search term. Multivariate-adjusted relative risks (RRs) with 95% confidence intervals (CIs) for the highest versus the lowest category were pooled by using a random-effects model. Dose-response analysis was implemented by using a restricted cubic spline regression model. Ten independent prospective cohort studies with 387,076 participants and 9,564 events were included. Higher intakes of flavanones were inversely associated with stroke risk (RR = 0.85; 95%CI: 0.78, 0.93). Dose-response analysis showed that 50 mg/day increment of flavanones was associated with 11% reduction in stroke risk (RR = 0.89; 95%CI: 0.84, 0.94). Flavan-3-ols was marginally inversely associated with stroke risk (RR = 0.92; 95%CI: 0.82, 1.02). Dose-response analysis showed that 200 mg/day increment of flavan-3-ols was associated with 14% reduction in stroke risk (RR = 0.86; 95%CI: 0.75, 0.98). The non-significant association was observed with respect to other flavonoid subclasses. This study demonstrated higher intakes of flavanones and flavan-3-ols were associated with a lower risk of stroke. Dietary intakes of lemon and citrus rich in flavanones and flavan-3-ols might have beneficial functions for the protection against stroke. The findings of these associations of the present study need to be confirmed in other regions and ethnic origins.