Olfactory perception complexity induced by key odorants perceptual interactions of alcoholic beverages: Wine as a focus case example.

The odorants in alcoholic beverages are frequently experienced as complex mixtures, and there is a complex array of influence factors and interactions involved during consumption that deeply increase its olfactory perception complexity, especially the complexity induced by perceptual interactions between different odorants. In this review, the effect of olfactory perceptual interactions and other factors related to the complexity of olfactory perception of alcoholic beverages are discussed. The classification, influencing factors, and mechanisms of olfactory perceptual interactions are outlined. Recent research progress as well as the methodologies applied in these studies on perceptual interactions between odorants observed in representative alcoholic beverages, especially wine, are briefly summarized. In the future, unified theory or systematic research methodology need to be established, since up to now, the rules of perceptual interaction between multiple odorants, which is critical to the alcoholic beverage industry to improve the flavor of their products, are still not revealed.

Cold Exposure Alleviates T2DM Through Plasma-Derived Extracellular Vesicles.

Purpose: Anecdotal reports have praised the benefits of cold exposure, exemplified by activities like winter swimming and cold water immersion. Cold exposure has garnered acclaim for its potential to confer benefits and potentially alleviate diabetes. We posited that systemic cold temperature (CT, 4-8°C) likely influences the organism's blood components through ambient temperature, prompting our investigation into the effects of chronic cold exposure on type 2 diabetic (T2DM) mice and our initial exploration of how cold exposure mitigates the incidence of T2DM. Methods: The effects of CT (4-8°C) or room temperature (RT, 22-25°C) on T2DM mice were investigated. Mice blood and organ specimens were collected for fully automated biochemical testing, ELISA, HE staining, immunohistochemistry, and immunofluorescence. Glucose uptake was assessed using flow cytometry with 2-NBDG. Changes in potential signaling pathways such as protein kinase B (AKT), phosphorylated AKT (p-AKT), insulin receptor substrates 1 (IRS1), and phosphorylated IRS1 (p-IRS1) were evaluated by Western blot. Results: CT or CT mice plasma-derived extracellular vesicles (CT-EVs) remarkably reduced blood glucose levels and improved insulin sensitivity in T2DM mice. This treatment enhanced glucose metabolism, systemic insulin sensitivity, and insulin secretion function while promoting glycogen accumulation in the liver and muscle. Additionally, CT-EVs treatment protected against the streptozocin (STZ)-induced destruction of islets in T2DM mice by inhibiting ß-cell apoptosis. CT-EVs also shielded islets from destruction and increased the expression of p-IRS1 and p-AKT in adipocytes and hepatocytes. In vitro experiments further confirmed its pro-insulin sensitivity effect. Conclusion: Our data indicate that cold exposure may have a potentially beneficial effect on the development of T2DM, mainly through the anti-diabetic effect of plasma-derived EVs released during cold stimulation. This phenomenon could significantly contribute to understanding the lower prevalence of diabetes in colder regions.

Characterization of Potent Odorants Causing an Oily Odor in Rice-Made Baijiu by Comparative Aroma Extract Dilution Analysis, Quantitative Measurements, and Aroma Addition and Omission Studies.

The presence of an oily odor in rice-made Baijiu is a unique characteristic that has not been thoroughly studied. This study qualitatively and quantitatively identified important aroma-active compounds in samples with typical and atypical oily odors using aroma extract dilution analysis (AEDA). By comparing the differences between flavor dilution (FD) and odor activity values (OAVs), nine compounds showing significant differences were selected. By combining normal-phase silica gel column and sensory analysis, these nine potential oily odor compounds were isolated from the typical oily odor sample. Addition and omission experiments confirmed that hexanal, trans-2-heptenal, trans,trans-2,4-nonadienal, (2E)-2-decenal, trans,trans-2,4-decadienal, and γ-nonanolide are key contributors to the oily odor.

Cost-Effectiveness of Zanubrutinib Versus Bendamustine and Rituximab in Patients With Untreated Chronic Lymphocytic Leukemia.

PURPOSE: Zanubrutinib, a potent and specific irreversible Bruton's tyrosine kinase inhibitor, has proven to be effective in untreated chronic lymphocytic leukemia (CLL), whether used alone or in combination with other therapies. Here, we compared the cost-effectiveness of zanubrutinib with bendamustine-rituximab (R-bendamustine) to determine its effectiveness as the first-line treatment for Chinese patients with untreated CLL. METHODS: The evaluation utilized a partitioned survival model, constructed using TreeAge Pro 2011 software, incorporating data from SEQUOIA trial (NCT03336333). Transition probabilities were estimated from the reported survival probabilities in trials using parametric survival modeling. In this analysis, the quality-adjusted life years (QALYs), incremental cost-effectiveness ratio, and lifetime cost were calculated from the Chinese health care system perspective. Sensitivity analyses, including 1-way analysis and probabilistic sensitivity analysis, were carried out to explore the uncertainty of the modeling results. Additionally, several scenario analyses, including different zanubrutinib price calculation and 20-year time horizon, were evaluated. FINDINGS: The findings revealed that zanubrutinib had an incremental cost-effectiveness ratio of $58,258.18 per additional QALYs gained compared with bendamustine-rituximab, with zanubrutinib being cost-effective only if its price was reduced by more than 30%. Research indicated that zanubrutinib achieved at least a 3.70% probability of cost-effectiveness at the threshold of $38,223.34/QALY. One-way sensitivity analysis revealed that the results were sensitive to the utility of progressed disease. IMPLICATIONS: The study highlighted the importance of considering the cost-effectiveness of zanubrutinib at its current price point for patients with untreated CLL in China, emphasizing the need for further assessment and potential pricing adjustments to enhance its economic viability in clinical practice.

Clinical and laboratory features between anti-TIF1γ dermatomyositis with and without malignancy: 37 case series and a review.

We aimed to analyze the clinical profile and malignancy indicators in dermatomyositis (DM) with anti-transcriptional intermediary factor 1 antibody (anti-TIF1γ-Ab). A comparison was made between clinical information of anti-TIF1γ DM patients with and without malignancy. Additionally, a review of the literature on anti-TIF1γ DM and malignancy was conducted by searching PubMed and EMBASE databases. In our cohort of 37 patients, 27.0% (10/37) developed malignancy. The timeframe during which these 10 patients developed malignancy ranged from 21 months prior to the diagnosis of DM to 36 months following the diagnosis of DM. Specifically, one patient was diagnosed with breast cancer at the age of 36. Comparing the groups with and without malignancy, we found that age over 65 years (40% vs 7.4%, P = 0.035), a shorter duration from the onset of symptoms to the diagnosis of DM (2.5 vs 10 months, P = 0.003), and higher erythrocyte sedimentation rate (ESR) levels (23 vs 10 mm/h, P = 0.048) were found to be associated with an increased risk of malignancy. Conversely, the presence of Gottron's papules (63% vs 20%, P = 0.029) may suggest a lower likelihood of malignancy. The literature review revealed that the prevalence of myositis-associated malignancy was 40.7% (340/836), with variations ranging from 19% to 82.9% across different series. In summary, factors such as age over 65 years, a shorter duration between symptom onset and diagnosis of DM, and elevated ESR levels may indicate an increased risk of malignancy in anti-TIF1γ DM patients.

MiRNA-132/212 encapsulated by adipose tissue-derived exosomes worsen atherosclerosis progression.

BACKGROUND: Visceral adipose tissue in individuals with obesity is an independent cardiovascular risk indicator. However, it remains unclear whether adipose tissue influences common cardiovascular diseases, such as atherosclerosis, through its secreted exosomes. METHODS: The exosomes secreted by adipose tissue from diet-induced obesity mice were isolated to examine their impact on the progression of atherosclerosis and the associated mechanism. Endothelial apoptosis and the proliferation and migration of vascular smooth muscle cells (VSMCs) within the atherosclerotic plaque were evaluated. Statistical significance was analyzed using GraphPad Prism 9.0 with appropriate statistical tests. RESULTS: We demonstrate that adipose tissue-derived exosomes (AT-EX) exacerbate atherosclerosis progression by promoting endothelial apoptosis, proliferation, and migration of VSMCs within the plaque in vivo. MicroRNA-132/212 (miR-132/212) was detected within AT-EX cargo. Mechanistically, miR-132/212-enriched AT-EX exacerbates palmitate acid-induced endothelial apoptosis via targeting G protein subunit alpha 12 and enhances platelet-derived growth factor type BB-induced VSMC proliferation and migration by targeting phosphatase and tensin homolog in vitro. Importantly, melatonin decreases exosomal miR-132/212 levels, thereby mitigating the pro-atherosclerotic impact of AT-EX. CONCLUSION: These data uncover the pathological mechanism by which adipose tissue-derived exosomes regulate the progression of atherosclerosis and identify miR-132/212 as potential diagnostic and therapeutic targets for atherosclerosis.

Ammonia-induced lysosomal and mitochondrial damage causes cell death of effector CD8+ T cells.

Ammonia is thought to be a cytotoxin and its increase in the blood impairs cell function. However, whether and how this toxin triggers cell death under pathophysiological conditions remains unclear. Here we show that ammonia induces a distinct form of cell death in effector T cells. We found that rapidly proliferating T cells use glutaminolysis to release ammonia in the mitochondria, which is then translocated to and stored in the lysosomes. Excessive ammonia accumulation increases lysosomal pH and results in the termination of lysosomal ammonia storage and ammonia reflux into mitochondria, leading to mitochondrial damage and cell death, which is characterized by lysosomal alkalization, mitochondrial swelling and impaired autophagic flux. Inhibition of glutaminolysis or blocking lysosomal alkalization prevents ammonia-induced T cell death and improves T cell-based antitumour immunotherapy. These findings identify a distinct form of cell death that differs from previously known mechanisms.

Radical relay strategy for the construction of alkylsulfonated indolo[2,1-a]isoquinoline-6(5H)-ones via SO2 insertion/Smiles rearrangement.

A new radical relay approach for the efficient construction of alkylsulfonated indolo[2,1-a]isoquinoline-6(5H)-ones in moderate to good yields under mild conditions via SO2 insertion/Smiles rearrangement/intramolecular cyclization is developed. This approach utilizes 4-alkyl substituted Hantzsch esters as alkyl radical sources and further undergoes in situ SO2 insertion to obtain alkylsulfonyl radical species, which avoids the use of unstable alkyl sulfonyl chlorides and highly toxic sulfonyl hydrazides. Additionally, this method for the direct assembly of alkylsulfonated polycyclic molecule skeletons displays high chemical selectivity, broad substrate scope, and step-economy.

Radical Cascade Cyclization of N-(o-Cyanobiaryl)acrylamides with Sulfonium Salts via Synergetic Photoredox and Copper Catalysis.

As the magic methyl effect is well acknowledged in pharmaceutical molecules, the development of simple and efficient methods for the installment of methyl groups on complex molecules is highly coveted. Hence, we provide a general strategy for radical cascade cyclization of N-(o-cyanobiaryl)acrylamides by utilizing sulfonium salts as the sources of methyl radical and merging photoredox and copper catalysis. This novel protocol can access a wide variety of methylation or remote thioether-substituted benzo-fused N-heterocycle derivatives, which can be easily transformed into diverse highly valuable sulfone and sulfoximine compounds via late-stage diversification. Moreover, to further demonstrate the synthetic utility of this conversion, the methyl(phenyl)sulfide, which serves as both raw material and byproduct, can be recovered and reused in this transformation. The scale-up experiment for the one-pot two-step process directly offers the target product in good yield under the standard conditions.

Vascular wall microenvironment: Endothelial cells original exosomes mediated melatonin-suppressed vascular calcification and vascular ageing in a m6A methylation dependent manner.

Vascular calcification and vascular ageing are "silent" diseases but are highly prevalent in patients with end stage renal failure and type 2 diabetes, as well as in the ageing population. Melatonin (MT) has been shown to induce cardiovascular protection effects. However, the role of MT on vascular calcification and ageing has not been well-identified. In this study, the aortic transcriptional landscape revealed clues for MT related cell-to-cell communication between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in vascular calcification and vascular ageing. Furthermore, we elucidated that it was exosomes that participate in the information transportation from ECs to VSMCs. The exosomes secreted from melatonin-treated ECs (MT-ECs-Exos) inhibited calcification and senescence of VSMCs. Mechanistically, miR-302d-5p was highly enriched in MT-ECs-Exos, while depletion of miR-302d-5p blocked the ability of MT-ECs-Exos to suppress VSMC calcification and senescence. Notably, Wnt3 was a bona fide target of miR-302d-5p and modulated VSMC calcification and senescence. Furthermore, we found that maturation of endothelial derived exosomal miR-302d-5p was promoted by WTAP in an N6-methyladenosine (m6A)-dependent manner. Interestingly, MT alleviated vascular calcification and ageing in 5/6-nephrectomy (5/6 NTP) mice, a chronic kidney disease (CKD) induced vascular calcification and vascular ageing mouse model. MT-ECs-Exos was absorbed by VSMCs in vivo and effectively prevented vascular calcification and ageing in 5/6 NTP mice. ECs-derived miR-302d-5p mediated MT induced anti-calcification and anti-ageing effects in 5/6 NTP mice. Our study suggests that MT-ECs-Exos alleviate vascular calcification and ageing through the miR-302d-5p/Wnt3 signaling pathway, dependent on m6A methylation.

Functional Aptamers In Vitro Evolution for Intranuclear Blockage of RNA-Protein Interaction.

Over the last 30 years, despite considerable research and endeavors aimed at harnessing aptamers as pharmaceutical molecules, the progress in developing aptamer-based drugs has been falling short of expectations. Sequential steps of affinity molecule acquisition and functional screening are typically required for discovering affinity-based macromolecule therapeutics, which can be time-consuming and limiting in candidate selection. Additionally, aptamers often necessitate tedious postselection modifications to overcome pharmacokinetic limitations, which usually impede the binding affinity. Herein, we propose a novel in vitro screening platform termed Functional Aptamers in vitro Evolution (FAIVE), which integrates affinity molecule acquisition with functional screening and introduces chemical diversity during the process. This platform aims to rapidly generate functional aptamers capable of binding to target proteins and regulating their functions. Illustrated by targeting intranuclear RNA-protein interactions involving HIV-1 Tat protein and TAR RNA, FAIVE demonstrates a selection of functional aptamers with significant intracellular blocking effects. The study also explores lipid nanoparticle delivery systems to enhance intracellular delivery efficiency, expanding aptamer targeting potential to broader intracellular and intranuclear domains. This study emphasizes the potential of FAIVE to expedite the development of aptamer-based drugs and facilitate the creation of more versatile and effective therapeutics.

The metabolic activation of and platelet response to vicagrel vary with P-glycoprotein deficiency, rather than P-glycoprotein inhibition, in mice.

This study aimed to determine changes in the hydrolysis of vicagrel, a substrate drug of arylacetamide deacetylase (Aadac) and carboxylesterase 2 (Ces2), in P-glycoprotein (P-gp)-deficient or P-gp-inhibited mice and to elucidate the mechanisms involved.Male wild-type (WT) and P-gp knock-out (KO) mice were used to investigate the systemic exposure of vicagrel thiol active metabolite H4 and platelet response to vicagrel, and the mRNA and protein expression levels of intestinal Aadac and Ces2. Moreover, WT mice were administered vicagrel alone or in combination with elacridar (a potent P-gp inhibitor) to determine drug-drug interactions.Compared with WT mice, P-gp KO mice exhibited significant increases in the systemic exposure of H4, the protein expression levels of intestinal Aadac and Ces2, and inhibition of ADP-induced platelet aggregation by vicagrel. Further, the H4 exposure was positively correlated with intestinal Aadac protein expression levels but did not vary with short-term inhibition of P-gp efflux activity by elacridar.P-gp-deficient mice, rather than elacridar-treated mice, exhibited significant upregulation of intestinal Aadac and Ces2 and thus, enhanced metabolic activation of and platelet response to vicagrel, suggesting that the metabolic activation of vicagrel may vary with P-gp deficiency, not P-gp inhibition, in mice.

Conductive single-phase SrMoO3 epitaxial films synthesized in pure Ar ambience via plasma-assisted radio frequency sputtering.

The cubic perovskite SrMoO3 with a paramagnetic ground state and remarkably low room-temperature resistivity has been considered as a suitable candidate for the new-era oxide-based technology. However, the difficulty of preparing single-phase SrMoO3 thin films by hydrogen-free sputtering has hindered their practical use, especially due to the formation of thermodynamically favorable SrMoO4 impurity. In this work, we developed a radio frequency sputtering technology enabling the reduction reaction and achieved conductive epitaxial SrMoO3 films with pure phase from a SrMoO4 target in a hydrogen-free, pure argon environment. We demonstrated the significance of controlling the target-to-substrate distance (TSD) on the synthesis of SrMoO3; the film resistivity drastically changes from 1.46 × 105 µΩ·cm to 250 µΩ·cm by adjusting the TSD. Cross-sectional microstructural analyses demonstrated that films with the lowest resistivity, deposited for TSD = 2.5 cm, possess a single-phase SrMoO3 with an epitaxial perovskite structure. The formation mechanism of the conductive single-phase SrMoO3 films can be attributed to the plasma-assisted growth process by tuning the TSD. Temperature-dependent resistivity and Hall effect studies revealed metal-like conducting properties for low-resistive SrMoO3 films, while the high-resistive ones displayed semiconductor-like behavior. Our approach makes hydrogen-free, reliable and cost-efficient scalable deposition of SrMoO3 films possible, which may open up promising prospects for a wide range of future applications of oxide materials.

For the first time, we developed a plasma-assisted RF sputtering technology enabling the reduction reaction for the synthesis of single-phase conductive SrMoO₃ epitaxial films from insulating SrMoO₄ in pure-argon atmosphere.

Physical exercise on cortical brain activity in patients with mild cognitive impairment: A meta-analysis.

BACKGROUND: Physical exercise is recognized as a potential strategy to mitigate the cognitive decline associated with mild cognitive impairment (MCI). This systematic review aims to examine the specific effects of physical exercise on cortical brain activity in patients with MCI, an area that has not been thoroughly explored. METHODS: We conducted a search across 9 electronic databases for randomized controlled trials assessing the impact of physical exercise on the cortical activity of patients with MCI. The search covered the period from database inception to September 2023. Literature screening, data extraction, and quality assessments were carried out by 2 independent researchers. Meta-analyses were conducted using RevMan 5.3, and publication bias was evaluated using STATA 17.0. This study primarily assessed P300 latency and amplitude, alongside cognitive evaluations using the mini-mental state examination and Montreal Cognitive Assessment. RESULTS: Six high-quality randomized controlled trials, involving a total of 360 participants, were included. Compared to the control group, significant enhancements were observed in the amplitude of central midline electrode (mean difference [MD] = 1.64 [95% confidence interval [CI], 0.92-2.36]; P < .00001), frontal midline electrode (MD = 2.70 [95% CI, 2.02-3.38]; P < .00001), and parietal midline electrode (MD = 2.42 [95% CI, 0.44-4.41]; P = .02). Latency periods of the central midline electrode (MD = -32.40 [95% CI, -40.27 to -24.54]; P < .00001), frontal midline electrode (MD = -12.57 [95% CI, -30.83 to 5.69]; P = .18), and parietal midline electrode (MD = -12.57 [95% CI, -30.83 to 5.69]; P = .81) were also notably influenced. Moreover, overarching cognitive functions as measured by mini-mental state examination (MD = 1.02 [95% CI, 0.61-1.43]; P < .00001) and Montreal Cognitive Assessment (MD = 1.39 [95% CI, 0.67-2.12]; P = .0002) exhibited marked improvement. CONCLUSION: This meta-analysis suggests that physical exercise can augment the P300 amplitude, reduce the P300 latency period, and, overall, enhance cognitive functionality in individuals with MCI.

Differences and correlations between industrial experts and semi-trained assessors in the sensory evaluation of strong-aroma baijiu using rate-all-that-apply.

Baijiu has rich and complex sensory characteristics, and how to make the sensory analysis results given by baijiu industrial experts better understood by consumers has been attracting a lot of attention. In this study, 35 strong-aroma baijiu samples were evaluated by 12 industrial experts and 21 semi-trained assessors, respectively, using rate-all-that-apply (RATA) methods, which involved 2 groups of lexicons generated by the 2 panels. The results showed that the RATA method was suitable for analyzing and distinguishing different baijiu samples by both industrial experts and semi-trained assessors. Although the industrial experts and the semi-trained assessors selected very different lexicons to describe the same strong-aroma baijiu samples, most descriptors from the expert evaluators are either positively or negatively correlated with the semi-trained assessors, such as the attributes "aldehyde," "mud," "multi-grain," and "scorched," and these attributes are effective in distinguishing different strong-aroma baijiu samples. These correlations could enable the marketing promotion and consumer evaluation of baijiu products in the future. PRACTICAL APPLICATION: The result could help baijiu market, in particular the worldwide beverage market, better understand how different baijiu samples are described and evaluated by industrial experts, and further enable the marketing promotion and consumer evaluation of baijiu products in the future.

Multi-objective evolutionary optimization for hardware-aware neural network pruning.

Neural network pruning is a popular approach to reducing the computational complexity of deep neural networks. In recent years, as growing evidence shows that conventional network pruning methods employ inappropriate proxy metrics, and as new types of hardware become increasingly available, hardware-aware network pruning that incorporates hardware characteristics in the loop of network pruning has gained growing attention. Both network accuracy and hardware efficiency (latency, memory consumption, etc.) are critical objectives to the success of network pruning, but the conflict between the multiple objectives makes it impossible to find a single optimal solution. Previous studies mostly convert the hardware-aware network pruning to optimization problems with a single objective. In this paper, we propose to solve the hardware-aware network pruning problem with Multi-Objective Evolutionary Algorithms (MOEAs). Specifically, we formulate the problem as a multi-objective optimization problem, and propose a novel memetic MOEA, namely HAMP, that combines an efficient portfolio-based selection and a surrogate-assisted local search, to solve it. Empirical studies demonstrate the potential of MOEAs in providing simultaneously a set of alternative solutions and the superiority of HAMP compared to the state-of-the-art hardware-aware network pruning method.

Circulating tumor cells with increasing aneuploidy predict inferior prognosis and therapeutic resistance in small cell lung cancer.

AIMS: Treatment resistance commonly emerges in small cell lung cancer (SCLC), necessitating the development of novel and effective biomarkers to dynamically assess therapeutic efficacy. This study aims to evaluate the clinical utility of aneuploid circulating tumor cells (CTCs) for risk stratification and treatment response monitoring. METHODS: A total of 126 SCLC patients (two cohorts) from two independent cancer centers were recruited as the study subjects. Blood samples were collected from these patients and aneuploid CTCs were detected. Aneuploid CTC count (ACC) and aneuploid CTC score (ACS), were used to predict progression-free survival (PFS) and overall survival (OS). The performance of the ACC and the ACS was evaluated by calculating the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: Compared to ACC, ACS exhibited superior predictive power for PFS and OS in these 126 patients. Moreover, both univariate and multivariate analyses revealed that ACS was an independent prognostic factor. Dynamic ACS changes reflected treatment response, which is more precise than ACC changes. ACS can be used to assess chemotherapy resistance and is more sensitive than radiological examination (with a median lead time of 2.8 months; P < 0.001). When patients had high ACS levels (> 1.115) at baseline, the combination of immunotherapy and chemotherapy resulted in longer PFS (median PFS, 7.7 months; P = 0.007) and OS (median OS, 16.3 months; P = 0.033) than chemotherapy alone (median PFS, 4.9 months; median OS, 13.6 months). CONCLUSIONS: ACS could be used as a biomarker for risk stratification, treatment response monitoring, and individualized therapeutic intervention in SCLC patients.

H3K27ac acts as a molecular switch for doxorubicin-induced activation of cardiotoxic genes.

BACKGROUND: Doxorubicin (Dox) is an effective chemotherapeutic drug for various cancers, but its clinical application is limited by severe cardiotoxicity. Dox treatment can transcriptionally activate multiple cardiotoxicity-associated genes in cardiomyocytes, the mechanisms underlying this global gene activation remain poorly understood. METHODS AND RESULTS: Herein, we integrated data from animal models, CUT&Tag and RNA-seq after Dox treatment, and discovered that the level of H3K27ac (a histone modification associated with gene activation) significantly increased in cardiomyocytes following Dox treatment. C646, an inhibitor of histone acetyltransferase, reversed Dox-induced H3K27ac accumulation in cardiomyocytes, which subsequently prevented the increase of Dox-induced DNA damage and apoptosis. Furthermore, C646 alleviated cardiac dysfunction in Dox-treated mice by restoring ejection fraction and reversing fractional shortening percentages. Additionally, Dox treatment increased H3K27ac deposition at the promoters of multiple cardiotoxic genes including Bax, Fas and Bnip3, resulting in their up-regulation. Moreover, the deposition of H3K27ac at cardiotoxicity-related genes exhibited a broad feature across the genome. Based on the deposition of H3K27ac and mRNA expression levels, several potential genes that might contribute to Dox-induced cardiotoxicity were predicted. Finally, the up-regulation of H3K27ac-regulated cardiotoxic genes upon Dox treatment is conservative across species. CONCLUSIONS: Taken together, Dox-induced epigenetic modification, specifically H3K27ac, acts as a molecular switch for the activation of robust cardiotoxicity-related genes, leading to cardiomyocyte death and cardiac dysfunction. These findings provide new insights into the relationship between Dox-induced cardiotoxicity and epigenetic regulation, and identify H3K27ac as a potential target for the prevention and treatment of Dox-induced cardiotoxicity.

Erratum: Author correction to "Identification of the dietary supplement capsaicin as an inhibitor of Lassa virus entry" [Acta Pharmaceutica Sinica B 10 (2020) 789-798].

[This corrects the article DOI: 10.1016/j.apsb.2020.02.014.].