Natural Organic Matter Enhances Natural Transformation of Extracellular Antibiotic Resistance Genes in Sunlit Water.

Antibiotic resistance genes (ARGs) as emerging environmental contaminants exacerbate the risk of spreading antibiotic resistance. Natural organic matter (NOM) is ubiquitous in aquatic environments and plays a crucial role in biogeochemical cycles. However, its impact on the dissemination of extracellular antibiotic resistance genes (eARGs) under sunlight exposure remains elusive. This study reveals that environmentally relevant levels of NOM (0.1-20 mg/L) can significantly enhance the natural transformation frequency of the model bacterium Acinetobacter baylyi ADP1 by up to 7.6-fold under simulated sunlight. Similarly, this enhancement was consistently observed in natural water and wastewater systems. Further mechanism analysis revealed that reactive oxygen species (ROS) generated by NOM under sunlight irradiation, primarily singlet oxygen and hydroxyl radicals, play a crucial role in this process. These ROS induce intracellular oxidative stress and elevated cellular membrane permeability, thereby indirectly boosting ATP production and enhancing cell competence of extracellular DNA uptake and integration. Our findings highlight a previously underestimated role of natural factors in the dissemination of eARGs within aquatic ecosystems and deepen our understanding of the complex interplay between NOM, sunlight, and microbes in environmental water bodies. This underscores the importance of developing comprehensive strategies to mitigate the spread of antibiotic resistance in aquatic environments.

A Meso Butterfly-Like Ce(III)-Containing Antimonotungstate with Catalytic Activity for Synthesizing Isoindolinones.

A unique meso Ce(III)-containing antimonotungstate, {Na(OAc)(H2O)2[Ce4(tar)(Htar)2(Sb2W21O72)2(H2O)7]}244- (Ce4tar3; H4tar = tartaric acid), consisting of two enantiomeric parts with a butterfly-like configuration, was successfully synthesized by a one-pot in situ method and characterized. The coordination of d- or l-tar ligands induced the formation of Dawson-like {Ce2Sb2W21} with right or left configurations, thereby determining the d/l configurations of {Na(OAc)(H2O)2[Ce4(tar)(Htar)2(Sb2W21O72)2(H2O)7]}22-. Carboxyl groups link these two enantiomeric parts with Ce(III) ions from each other around the symmetric center of the P1̅ space group. The three types of tar ligands exhibit distinct coordination modes, and all coordinate with at least one W(VI) atom using one carboxylate oxygen atom and one α-OH. Ce4tar3 represents the largest case among those meso-dl-tar-functionalized polyoxometalates. Furthermore, Ce4tar3 exhibits excellent catalytic activity for synthesizing isoindolinones via the three-component reaction of 2-acetylbenzoic acids, amines, and phosphine oxides.

Creating a bacterium that forms eukaryotic nucleosome core particles.

The nucleosome is one of the hallmarks of eukaryotes, a dynamic platform that supports many critical functions in eukaryotic cells. Here, we engineer the in vivo assembly of the nucleosome core in the model bacterium Escherichia coli. We show that bacterial chromosome DNA and eukaryotic histones can assemble in vivo to form nucleosome complexes with many features resembling those found in eukaryotes. The formation of nucleosomes in E. coli was visualized with atomic force microscopy and using tripartite split green fluorescent protein. Under a condition that moderate histones expression was induced at 1 µM IPTG, the nucleosome-forming bacterium is viable and has sustained growth for at least 110 divisions in longer-term growth experiments. It exhibits stable nucleosome formation, a consistent transcriptome across passages, and reduced growth fitness under stress conditions. In particular, the nucleosome arrays in E. coli genic regions have profiles resembling those in eukaryotic cells. The observed compatibility between the eukaryotic nucleosome and the bacterial chromosome machinery may reflect a prerequisite for bacteria-archaea union, providing insight into eukaryogenesis and the origin of the nucleosome.

C-FOS inhibition promotes pancreatic cancer cell ferroptosis by transcriptionally regulating the expression of SLC7A11.

Cellular proto-oncogene C-Fos forms the AP-1 transcription factor by dimerizing with proto-oncogene c-Jun; this factor upregulates the transcription of genes associated with different malignancies. However, its functions in pancreatic adenocarcinoma (PAAD) remain poorly understood. In this study, the c-Fos was increased in PAAD cells and tissues through bioinformatic analysis, RT-PCR, and WB. In two PAAD cell lines, PANC-1 and BxPC-3, we performed c-Fos knockdown studies using short hairpin RNA (shRNA). Functional analysis indicated that c-Fos depletion in PAAD cells inhibits cell proliferation and promotes ferroptosis. Chromatin Immunoprecipitation (ChIP) and Dual-luciferase experiments showed that c-Fos coupled to the promoter region of SLC7A11 stimulated its transcription, providing mechanistic insight into the process. Moreover, SLC7A11 blocked the decline of proliferation and ferroptosis by c-Fos knockdown in PAAD cells. Furthermore, a xenograft nude mouse model was established to study the impact of c-Fos on tumorigenesis in vivo. Depletion of c-Fos could suppress PC tumor growth and the expressions of SLC7A11, ki-67, and 4HNE, but overexpression of SLC7A11 reversed this process. In summary, our investigation has shown that c-Fos acts as a transcriptional regulator of SLC7A11, which may enhance tumour growth in pancreatic cancer by inhibiting ferroptosis. These results indicate that c-Fos might be a promising target for treating ferroptosis in PAAD.

[Risk Factors and a Prediction Model for Frequent Acute Exacerbations of Chronic Obstructive Pulmonary Disease].

Objective To identify the risk factors of patients with frequent acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and construct a prediction model based on the clinical data,providing a theoretical basis for the clinical prevention and treatment. Methods A total of 25 638 COPD patients admitted to the Department of Respiratory and Critical Care Medicine,the Third People's Hospital of Chengdu from January 1,2013 to May 1,2023 were selected.Among them,11 315 patients were included according to the inclusion and exclusion criteria,and their clinical characteristics were analyzed.Multivariate Logistic regression was carried out to identify the risk factors for frequent AECOPD.A nomogram model was utilized to quantify the risk of acute exacerbation,and the performance of the prediction model was assessed based on the area under the receiver operating characteristic (ROC) curve. Results In the patients with frequent AECOPD,male percentage (P<0.001),age (P<0.001),urban residence (P<0.001),smoking (P<0.001),length of stay (P<0.001),total cost (P<0.001),antibiotic cost (P<0.001),diabetes (P=0.003),respiratory failure (P<0.001),heart disease (P<0.001),application of systemic glucocorticoids (P<0.001),white blood cell count (P<0.001),neutrophil percentage (P<0.001),C-reactive protein (P<0.001),total cholesterol (P<0.001),and brain natriuretic peptide (BNP) (P<0.001) were all higher than those in the patients with infrequent AECOPD.Multivariate Logistic regression analysis revealed that age,urban residence,smoking,diabetes,heart disease,Pseudomonas aeruginosa infection,application of systemic glucocorticoids,antibiotics,respiratory failure,and elevated white blood cell count,total cholesterol,and BNP were independent risk factors for hospitalization due to frequent AECOPD.A nomogram model of hospitalization due to frequent AECOPD was constructed according to risk factors.The ROC curve was established to evaluate the performance of the model,which showed the area under the ROC curve of 0.899 (95%CI=0.892-0.905),the sensitivity of 85.30%,and the specificity of 79.80%. Conclusion Frequent AECOPD is associated with smoking,heart disease,application of systemic glucocorticoids,Pseudomonas aeruginosa infection,age,low body mass index,and elevated BNP.Predicting the risks of hospitalization due to frequent AECOPD by the established model can provide theoretical support for the treatment and risk factor management of the patients.

Differential roles of eosinophils in cardiovascular disease.

Eosinophils are essential innate immune cells in allergic responses. Accumulating evidence indicates that eosinophils also participate in the pathogenesis of cardiovascular diseases (CVDs). In clinical studies, high blood eosinophil counts and eosinophil cationic protein levels have been associated with an increased risk of CVD, including myocardial infarction (MI), cardiac hypertrophy, atrial fibrillation, abdominal aortic aneurysm (AAA) and atherosclerosis. However, low blood eosinophil counts have also been reported to be a risk factor for MI, heart failure, aortic dissection, AAA, deep vein thrombosis, pulmonary embolism and ischaemic stroke. Although these conflicting clinical observations remain unexplained, CVD status, timing of eosinophil data collection, and tissue eosinophil phenotypic and functional heterogeneities might account for these discrepancies. Preclinical studies suggest that eosinophils have protective actions in MI, cardiac hypertrophy, heart failure and AAA. By contrast, cationic proteins and platelet-activating factor from eosinophils have been shown to promote vascular smooth muscle cell proliferation, vascular calcification, thrombomodulin inactivation and platelet activation and aggregation, thereby exacerbating atherosclerosis, atrial fibrillation, thrombosis and associated complications. Therefore, eosinophils seem to promote calcification and thrombosis in chronic CVD but are protective in acute cardiovascular settings. In this Review, we summarize the available clinical and preclinical data on the different roles of eosinophils in CVD.

Impact of ginsenoside Rb1 on gut microbiome and associated changes in pharmacokinetics in rats.

Ginsenoside Rb1 exhibits a wide range of biological activities, and gut microbiota is considered the main metabolic site for Rb1. However, the impact of gut microbiota on the pharmacokinetics of Rb1 are still uncertain. In this study, we investigated the gut microbiome changes and the pharmacokinetics after a 30 d Rb1 intervention. Results reveal that the systemic exposure and metabolic clearance rate of Rb1 and Rd were substantially affected after orally supplementing Rb1 (60 mg/kg) to rats. Significant increase in the relative abundance of Bacteroides cellulosilyticus in gut microbiota and specific glycoside hydrolase (GH) families, such as GH2, GH92, and GH20 were observed based on microbiome and metagenomic analysis. Moreover, a robust association was identified between the pharmacokinetic parameters of Rb1 and the relative abundance of specific Bacteroides species, and glycoside hydrolase families. Our study demonstrates that Rb1 administration significantly affects the gut microbiome, revealing a complex relationship between B. cellulosilyticus, key GH families, and Rb1 pharmacokinetics.

Insights into the interactions of plant-associated bacteria and their role in the transfer of antibiotic resistance genes from soil to plant.

This study discussed the role of plant-associated microbiome in regulating ARG transfer in soil-plant systems. Results showed that target ARGs in plants were mainly derived from rhizosphere soil. Cooperative interactions among bacteria in rhizosphere soil, plant-roots, plant-shoots, and soil-roots-shoots systems occurred during ARG transfer. The number of modules and keystone taxa identified as positively correlated with ARG transfer in rhizosphere soil, roots, and shoots was 3 and 49, 3 and 41, 2 and 5, respectively. Among these modules, module 3 in roots was significantly positively correlated with module 3 in rhizosphere soils and module 2 in shoots, indicating that module 3 in roots played central hub roles in ARG transfer from rhizosphere soil to roost and shoots. This may be because module 3 in roots increased cell motility and xenobiotics biodegradation and metabolism. These keystone taxa mainly belonged to Proteobacteria that can carry ARGs to transfer in soil-plant systems, especially Clostridium-sensu_stricito and Pseudomonas in rhizosphere soil carried ARGs into the shoot. Additionally, they promoted ARG transfer by increasing plant biomass, net photosynthetic rate and water use efficiency. The findings helped reveal the mechanism of plant-associated bacterial interactions and provided understanding for potential risks of ARG transfer from soil to plants.

lncSNHG16 promotes hepatocellular carcinoma development by inhibiting autophagy.

OBJECTIVE: To investigate the expression of long non-coding RNA lncSNHG16 in hepatocellular carcinoma (HCC), associations between its expression and patient survival, and its potential role in regulating autophagy in the disease. METHODS: Expression of lncSNHG16 was measured using quantitative real-time PCR in HCC cells in culture and HCC tissues from patients. Effects of lncSNHG16 overexpression were examined in HCC cultures using assays of cell proliferation, wound healing, and migration or invasion in Transwell dishes. Effects of lncSNHG16 overexpression were also examined in subcutaneous tumor in mice. Relationships of lncSNHG16 expression to autophagy and apoptosis in HCC cultures were explored using western blotting and flow cytometry. RESULTS: Higher lncSNHG16 expression in HCC tissues was associated with significantly worse overall and recurrence-free survival of patients. Overexpressing lncSNHG16 in HCC cell culture promoted cell proliferation, migration, and invasion while suppressing apoptosis. lncSNHG16 was associated with upregulation of STAT3 as well as inhibition of autophagy and associated apoptosis. Overexpressing lncSNHG16 accelerated tumor growth and weight in mice. CONCLUSION: The non-coding RNA lncSNHG16 suppresses autophagy and associated apoptosis in HCC, making it a potential therapeutic target.

Programming Hydrogen Bonds for Reversible Elastic-Plastic Phase Transition in a Conductive Stretchable Hydrogel Actuator with Rapid Ultra-High-Density Energy Conversion and Multiple Sensory Properties.

Smart hydrogels have recently garnered significant attention in the fields of actuators, human-machine interaction, and soft robotics. However, when constructing large-scale actuated systems, they usually exhibit limited actuation forces (≈2 kPa) and actuation speeds. Drawing inspiration from hairspring energy conversion mechanism, an elasticity-plasticity-controllable composite hydrogel (PCTA) with robust contraction capabilities is developed. By precisely manipulating intermolecular and intramolecular hydrogen-bonding interactions, the material's elasticity and plasticity can be programmed to facilitate efficient energy storage and release. The proposed mechanism enables rapid generation of high contraction forces (900 kPa) at ultra-high working densities (0.96 MJ m-3). Molecular dynamics simulations reveal that modifications in the number and nature of hydrogen bonds lead to a distinct elastic-plastic transition in hydrogels. Furthermore, the conductive PCTA hydrogel exhibits multimodal sensing capabilities including stretchable strain sensing with a wide sensing range (1-200%), fast response time (180 ms), and excellent linearity of the output signal. Moreover, it demonstrates exceptional temperature and humidity sensing capabilities with high detection accuracy. The strong actuation power and real-time sensory feedback from the composite hydrogels are expected to inspire novel flexible driving materials and intelligent sensing systems.

Biological self-protection inspired engineering of nanomaterials to construct a robust bio-nano system for environmental applications.

Nanomaterials can empower microbial-based chemical production or pollutant removal, e.g., nano zero-valent iron (nZVI) as an electron source to enhance microbial reducing pollutants. Constructing bio-nano interfaces is critical for bio-nano system operation, but low interfacial compatibility due to nanotoxicity challenges the system performance. Inspired by microorganisms' resistance to nanotoxicity by secreting extracellular polymeric substances (EPS), which can act as electron shuttling media, we design a highly compatible bio-nano interface by modifying nZVI with EPS, markedly improving the performance of a bio-nano system consisting of nZVI and bacteria. EPS modification reduced membrane damage and oxidative stress induced by nZVI. Moreover, EPS alleviated nZVI agglomeration and probably reduced bacterial rejection of nZVI by wrapping camouflage, contributing to the bio-nano interface formation, thereby facilitating nZVI to provide electrons for bacterial reducing pollutant via membrane-anchoring cytochrome c. This work provides a strategy for designing a highly biocompatible interface to construct robust and efficient bio-nano systems for environmental implication.

Ganoderma lucidum polysaccharide promotes broiler health by regulating lipid metabolism, antioxidants, and intestinal microflora.

Ganoderma lucidum polysaccharides (GLP) are the primary bioactive macromolecular compounds of Ganoderma lucidum, possessing antioxidant and immunomodulatory effects. Hot water extract of Juncao-substrate Ganoderma Lucidum residue (HWE-JGLR) is abundant in GLP. There are few research reports on the application of HWE-JGLR in animal husbandry. Therefore, this study aims to investigate the effects of HWE-JGLR supplementation on growth performance, serum biochemistry, the antioxidant function of serum and liver, and the intestinal microbiota of yellow-feathered broilers. The control group was fed a corn-soybean meal basal diet, while the HJ I, II, and III groups received diets supplemented with 0.25 %, 0.5 %, and 1 % of HWE-JGLR, respectively. Results showed that HWE-JGLR increased the serum HDL-C content and decreased the TG content in broilers. Moreover, HWE-JGLR enhanced the antioxidant function by the Keap1-Nrf2/ARE signaling pathway and the antioxidative enzyme in broilers. In addition, the cecum of the metagenomic analysis of 16S rRNA showed that the relative abundance of no-rank Ruminococcacea was increased in the HJ I group. Our findings indicate that HWE-JGLR has strong potential for development as a green feed additive based on its functions of lipid-lowering, antioxidation, and the modulation of gut microbiota composition.

Effect of Purified Resveratrol Butyrate Ester Monomers against Hypertension after Maternal High-Fructose Intake in Adult Offspring.

BACKGROUND: Offspring hypertension arising from adverse maternal conditions can be mitigated through dietary nutritional supplementation, including resveratrol. Previously, we identified derivatives of resveratrol butyrate ester (RBE), specifically 3,4'-di-O-butanoylresveratrol (ED2) and 3-O-butanoylresveratrol (ED4), demonstrating their superior antioxidant capabilities compared to RBE itself. This study sought to assess the protective impact of maternal supplementation with ED2 or ED4 on offspring hypertension in a rat model subjected to a high-fructose (HF) diet during pregnancy and lactation. METHODS: Female Sprague-Dawley rats were distributed into distinct dietary groups throughout pregnancy and lactation: (1) standard chow; (2) HF diet (60%); (3) HF diet supplemented with ED2 (25 mg/L); and (4) HF diet supplemented with ED4 (25 mg/L). Male offspring were euthanized at the age of 12 weeks. RESULTS: The maternal HF diet induced hypertension in the offspring, which was mitigated by perinatal supplementation with either ED2 or ED4. These protective effects were attributed to the antioxidant properties of ED2 and ED4, resulting in an increased availability of nitric oxide (NO). Additionally, supplementation with ED2 was connected to an increased abundance of Bifidobacterium and Clostridium genera, which was accompanied by a decrease in Angelakisella and Christensenella. On the other hand, ED4 supplementation shielded rat offspring from hypertension by elevating concentrations of short-chain fatty acids (SCFAs) and their receptors while reducing trimethylamine-N-oxide (TMAO) levels. CONCLUSIONS: These findings highlight the potential of purified RBE monomers, ED2 and ED4, as preventive measures against hypertension resulting from a maternal high-fructose diet. Further research is warranted to explore their clinical applications based on these promising results.

Augmentation with prazosin for patients with depression and a history of trauma: A randomised, double-blind, placebo-controlled study.

INTRODUCTION: Depression with a history of trauma often responds poorly to conventional antidepressants and has a poor prognosis. Prazosin, an α1-adrenoceptor blocker, has shown promise in treating post-traumatic stress disorder symptoms, particularly nightmares. Its potential in treating depression with trauma history warrants investigation. AIMS OF THE STUDY: This randomised, double-blind, placebo-controlled study aimed to investigate the efficacy and tolerability of low-dose prazosin (0.5-1 mg/day) as an augmentation strategy in patients with depression and a history of trauma. We sought to determine if prazosin could provide rapid symptom improvement and enhance overall treatment response compared to placebo in this difficult-to-treat patient population. METHODS: This randomised, double-blind, placebo-controlled clinical study included 59 patients with first-episode or recurrent unipolar or bipolar depression. After basic antidepressant treatment, they were randomly assigned to a prazosin (0.5-1 mg/day) or placebo group for a 6-week double-blind controlled study. The Montgomery-Åsberg Depression Rating Scale, 17-item Hamilton Depression Scale (HAMD-17), and Hamilton Anxiety Scale (HAMA) were used to evaluate efficacy. RESULTS: There were no significant differences in the results of the demographic and clinical symptom assessment between the two groups (p > 0.05). The difference between the HAMD-17 and HAMA scores was statistically significant after 3 days of treatment (p < 0.05). The difference in response rate between the two groups was statistically significant after week 4 of treatment (end of week 4, 56.7% vs. 24.1%, p = 0.011; end of week 6, 80.0% vs. 48.3%, p = 0.011). The incidence of adverse reactions in the prazosin and placebo groups was 20.0% and 24.1%, respectively, with no statistically significant differences (p > 0.05); however, the prazosin group had a lower incidence of sleeplessness or nightmares (3.3% vs. 20.7%, p = 0.039) but a higher incidence of orthostatic hypotension (16.7% vs. 0%, p = 0.007). The severity of orthostatic hypotension was mild to moderate. CONCLUSION: Low-dose prazosin can effectively improve the emotional symptoms of patients with depression and a history of trauma, and the common adverse reaction is mild-to-moderate orthostatic hypotension. CLINICAL TRIAL REGISTRATION: ChiCTR2200063642.

Continuous evolution of Fermi arcs in a minimal ideal photonic Weyl medium.

Propagation properties of electromagnetic waves in an optical medium are mainly determined by the contour of equal-frequency states in k -space. In photonic Weyl media, the topological surface waves lead to a unique open arc of the equal-frequency contour, called the Fermi arc. However, for most realistic Weyl systems, the shape of Fermi arcs is fixed due to the constant impedance of the surrounding medium, making it difficult to manipulate the surface wave. Here we demonstrate that by adjusting the thickness of the air layer sandwiched between two photonic Weyl media, the shape of the Fermi arc can be continuously changed from convex to concave. Moreover, we show that the concave Fermi-arc waves can be used to achieve topologically protected electromagnetic pulling forces over a broad range of angles in the air layer. Our finding offers a generally applicable strategy to shape the Fermi arc in photonic Weyl media.

TIPE2 gene transfer ameliorates aging-associated osteoarthritis in a progeria mouse model by reducing inflammation and cellular senescence.

Osteoarthritis (OA) pain is often associated with the expression of tumor necrosis factor alpha (TNF-α), suggesting that TNF-α is one of the main contributing factors that cause inflammation, pain, and OA pathology. Thus, inhibition of TNF-α could potentially improve OA symptoms and slow disease progression. Anti-TNF-α treatments with antibodies, however, require multiple treatments and cannot entirely block TNF-α. TNF-α-induced protein 8-like 2 (TIPE2) was found to regulate the immune system's homeostasis and inflammation through different mechanisms from anti-TNF-α therapies. With a single treatment of adeno-associated virus (AAV)-TIPE2 gene delivery in the accelerated aging Zmpste24-/- (Z24-/-) mouse model, we found differences in Safranin O staining intensity within the articular cartilage (AC) region of the knee between TIPE2-treated mice and control mice. The glycosaminoglycan content (orange-red) was degraded in the Z24-/- cartilage while shown to be restored in the TIPE2-treated Z24-/- cartilage. We also observed that chondrocytes in Z24-/- mice exhibited a variety of senescent-associated phenotypes. Treatment with TIPE2 decreased TNF-α-positive cells, ß-galactosidase (ß-gal) activity, and p16 expression seen in Z24-/- mice. Our study demonstrated that AAV-TIPE2 gene delivery effectively blocked TNF-α-induced inflammation and senescence, resulting in the prevention or delay of knee OA in our accelerated aging Z24-/- mouse model.

Urolithin A attenuates hexavalent chromium-induced small intestinal injury by modulating PP2A/Hippo/YAP1 pathway.

Hexavalent chromium (Cr(VI)) exposure has been linked with gastrointestinal toxicity, whereas the molecular pathways and key targets remain elusive. Computational toxicology analysis predicted the correlation between protein phosphatase 2A (PP2A) and genes regarding Cr(VI)-induced intestinal injury. Here, we generated a mouse model with intestinal epithelium-specific knock out of Ppp2r1a (encoding PP2A Aα subunit) to investigate the mechanisms underlying Cr(VI)-induced small intestinal toxicity. Heterozygous (HE) mice and matched WT littermates were administrated with Cr(VI) at 0, 5, 20, and 80 mg/l for 28 successive days. Cr(VI) treatment led to crypt hyperplasia, epithelial cell apoptosis, and intestinal barrier dysfunction, accompanied by the decline of goblet cell counts and Occludin expression in WT mice. Notably, these effects were aggravated in HE mice, indicating that PP2A Aα deficiency conferred mice with susceptibility to Cr(VI)-induced intestinal injury. The combination of data analysis and biological experiments revealed Cr(VI) exposure could decrease YAP1 phosphorylation at Ser127 but increase protein expression and activity, together with elevated transcriptional coactivator with PDZ-binding motif protein driving epithelial crypt cells proliferation following damage, suggesting the involvement of Hippo/YAP1 signaling pathway in Cr(VI)-induced intestinal toxicity. Nevertheless, the enhanced phosphorylation of YAP1 in HE mice resulted in proliferation/repair defects in intestinal epithelium, thereby exacerbating Cr(VI)-induced gut barrier dysfunction. Notably, by molecular docking and further studies, we identified urolithin A, a microbial metabolite, attenuated Cr(VI)-induced disruption of intestinal barrier function, partly by modulating YAP1 expression and activity. Our findings reveal the novel molecular pathways participated in Cr(VI)-caused small intestinal injury and urolithin A could potentially protect against environmental hazards-induced intestinal diseases.

Flexible Single-Crystal Perovskite Photodetectors via Polymer-Controlled Transfer.

The large-sized perovskite single-crystal sheet (SCS) serves as the ideal research platform for perovskite photodetectors due to its outstanding carrier photophysics, pronounced geometric aspect ratio, and ultrahigh material utilization rate. However, its performance in flexible device applications is relatively lackluster due to the rigid and brittle nature of the three-dimensional cubic lattices. In this work, the indium tin oxide (ITO)-based multimillimeter-sized MAPbBr3 SCS is transformed into MAPbI3 SCS via ion exchange strategy. Significantly, we proposed and implemented a polymer-controlled transfer strategy─utilizing the dichloromethane (DCM) solution of poly(methyl methacrylate) (PMMA)─to nondestructively transfer the whole perovskite SCS off the ITO substrates and subsequently adhere it onto a flexible polyethylene terephthalate (PET) substrate of interdigital electrode, thereby fabricating a lateral-structured photodetector with a PMMA-SCS-Au-PET multilayer configuration. The tight self-encapsulation between the top PMMA membrane and the bottom PET substrate imparts excellent waterproof stability and concurrently excellent mechanical flexibility to these devices; additionally, the MAPbI3 device exhibits comprehensively superior performance to the MAPbBr3 one. This work represents a proactive attempt and exploration of the high-performance advancement of large-sized SCS photodetectors, undoubtedly introducing novel momentum and solutions to this domain.

CD8+ T-cell deficiency protects mice from abdominal aortic aneurysm formation in response to calcium chloride2.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is an aneurysm-like dilated and highly fatal cardiovascular disease. CD8+ T cells have been shown to be critical for vascular pathological processes, but the contribution of these lymphocytes to vascular diseases remains elusive. METHODS AND RESULTS: Eight-week-old male wildtype (CD8+/+) and Cd8a knockout (CD8-/-) mice were used in a calcium chloride2 (CaCl2)-induced experimental AAA model. At 6 weeks after surgery, CD8+ T-cell deletion prevented the formation of AAA, accompanied by reductions of the levels of inflammatory (interferon-γ [IFN-γ], interleukin-1ß, monocyte chemoattractant protein-1, intracellular adhesion molecule-1, vascular cell adhesion molecule-1, NOD-like receptor protein 3, caspase-1), oxidative stress [NADPH oxidase and gp91phox], and proteolysis (cathepsin S, cathepsin K, matrix metalloproteinase-2 [MMP-2] and MMP-9) proteins and/or genes in plasma and/or AAA tissues. Immunoreactivities of MMP-2 and MMP-9 were observed in macrophages. An injection of IFN-γ and adoptive transfer of CD8+ T cells of IFN-γ+/+ mice diminished CD8-/--mediated vasculoprotective actions in the AAA mice. In vitro, IFN-γ enhanced MMP-2 and MMP-9 gelatinolytic activities in macrophage and/or vascular smooth muscle cells. CONCLUSION: The vasculoprotective effects of CD8+ T-cell deletion in a mouse CaCl2-induced AAA model were likely attributable to, at least in part, the attenuation of IFN-γ-dependent inflammation action, oxidative stress production, and proteolysis, suggesting a novel therapeutic target for AAA formation by regulating CD8+ T-cell-derived IFN-γ secretion.

Insights into acrylamide and furanic compounds in coffee with a focus on roasting methods and additives.

Roasting is necessary for bringing out the aroma and flavor of coffee beans, making coffee one of the most consumed beverages. However, this process also generates a series of toxic compounds, including acrylamide and furanic compounds (5-hydroxymethylfurfural, furan, 2-methylfuran, 3-methylfuran, 2,3-dimethylfuran, and 2,5-dimethylfuran). Furthermore, not much is known about the formation of these compounds in emerging coffee formulations containing alcohol and sugars. Therefore, this study investigated the effect of roasting time and degree on levels of acrylamide and furanic compounds in arabica coffee using fast and slow roasting methods. The fast and slow roasting methods took 5.62 min and 9.65 min, respectively, and reached a maximum of 210 °C to achieve a light roast. For the very dark roast, the coffee beans were roasted for 10.5 min and the maximum temperature reached 245 °C. Our findings showed that the levels of acrylamide (375 ± 2.52 µg kg-1) and 5-HMF (194 ± 11.7 mg kg-1) in the slow-roasted coffee were 35.0 % and 17.4 % lower than in fast-roasted coffee. Furthermore, light roast coffee had significantly lower concentrations of acrylamide and 5-HMF than very dark roast, with values of 93.7 ± 7.51 µg kg-1 and 21.3 ± 10.3 mg kg-1, respectively. However, the levels of furan and alkylfurans increased with increasing roasting time and degree. In this study, we also examined the concentrations of these pollutants in new coffee formulations consisting of alcohol-, sugar-, and honey-infused coffee beans. Formulations with honey and sugar resulted in higher concentrations of 5-HMF, but no clear trend was observed for acrylamide. On the other hand, formulations with honey had higher concentrations of furan and alkylfurans. These results indicate that optimizing roasting time and temperature might not achieve the simultaneous reduction of all the pollutants. Additionally, sugar- and honey-infused coffee beans are bound to have higher furanic compounds, posing a higher health risk.