Polystyrene nanoplastics exacerbate aflatoxin B1-induced hepatic injuries by modulating the gut-liver axis.

Dietary pollution of Aflatoxin B1 (AFB1) poses a great threat to global food safety, which can result in serious hepatic injuries. Following the widespread use of plastic tableware, co-exposure to microplastics and AFB1 has dramatically increased. However, whether microplastics could exert synergistic effects with AFB1 and amplify its hepatotoxicity, and the underlying mechanisms are still unelucidated. Here, mice were orally exposed to 100 nm polystyrene nanoplastics (NPs) and AFB1 to investigate the influences of NPs on AFB1-induced hepatic injuries. We found that exposure to only NPs or AFB1 resulted in colonic inflammation and the impairment of the intestinal barrier, which was exacerbated by combined exposure to NPs and AFB1. Meanwhile, co-exposure to NPs exacerbated AFB1-induced dysbiosis of gut microbiota and remodeling of the fecal metabolome. Moreover, NPs and AFB1 co-exposure exhibited higher levels of systemic inflammatory factors compared to AFB1 exposure. Additionally, NPs co-exposure further exacerbated AFB1-induced hepatic fibrosis and inflammation, which could be associated with the overactivation of the TLR4/MyD88/NF-κB pathway. Notably, Spearman's correlation analysis revealed that the exacerbation of NPs co-exposure was closely associated with microbial dysbiosis. Furthermore, microbiota from NPs-exposed mice (NPsFMT) partly reproduced the exacerbation of NPs on AFB1-induced systemic and hepatic inflammation, but not fibrosis. In summary, our findings indicate that gut microbiota could be involved in the exacerbation of NPs on AFB1-induced hepatic injuries, highlighting the health risks of NPs.

Depositional Model and Controlling Factors of High-Quality Shales of the Wufeng and Longmaxi Formations in Western Chongqing, Sichuan Basin, China.

The enrichment of organic matter is the foundation for a high-quality shale deposition. It is generally believed that high productivity and persistent anoxic conditions facilitate the preservation and enrichment of organic matter. However, there is a lack of investigation into how the dynamic combination of productivity and anoxia affects organic matter enrichment. Here, the black shales of the Wufeng Formation and Longmaxi Formation in the western Chongqing area were selected, where oceanic anoxia and high productivity evolved as a function of the water depth. The main findings were as follows: (1) the distribution of high-quality shales in the Upper Ordovician Wufeng Formation and the Lower Silurian Longmaxi Formation is closely related to the oxygen minimum zone (OMZ), indicating that the physicochemical conditions within the OMZ zone facilitated the development of high-quality shale; (2) in the late period of the Wufeng Formation, intense ocean upwelling in the middle shelf and outer shelf regions caused high productivity where thick-bedded high-quality shales were deposited; and (3) in the early period of the Longmaxi Formation, ocean upwelling weakened, accompanied by the expansion of the OMZ to shallow water regions, and high-quality shales were widely distributed. Based on the above findings, two depositional models were proposed to account for the formation of high-quality shales, and it is suggested that intense ocean upwelling during the late period of the Wufeng Formation and OMZ expansion during the early period of the Longmaxi Formation played crucial roles in facilitating the formation of high-quality shales. These two models present the spatial and temporal variability of high-quality shale development for the first time and can guide shale gas exploration and development strategies.

Polyethylene Terephthalate Hydrolases in Human Gut Microbiota and Their Implications for Human Health.

Polyethylene terephthalate (PET), primarily utilized for food and beverage packaging, consistently finds its way into the human gut, thereby exerting adverse effects on human health. PET hydrolases, critical for the degradation of PET, have been predominantly sourced from environmental microbial communities. Given the fact that the human gut harbors a vast and intricate consortium of microorganisms, inquiry into the presence of potential PET hydrolases within the human gut microbiota becomes imperative. In this investigation, we meticulously screened 22,156 homologous sequences that could potentially encode PET hydrolases using the hidden Markov model (HMM) paradigm, drawing from 4984 cultivated genomes of healthy human gut bacteria. Subsequently, we methodically validated the hydrolytic efficacy of five selected candidate PET hydrolases on both PET films and powders composed of micro-plastics (MPs). Notably, our study also unveiled the influence of both diverse PET MP powders and their resultant hydrolysates on the modulation of cytokine expression in macrophages. In summary, our research underscores the ubiquitous prevalence and considerable potential of the human gut microbiota in PET hydrolysis. Furthermore, our study significantly contributes to the holistic evaluation of the potential health hazards posed by PET MPs to human well-being.

Unexpected Noremestrin with a Sulfur-Bearing 15-Membered Macrocyclic Lactone from Emericella sp. 1454.

Two previous unreported epipolythiodioxopiperazines of the emestrin family, namely, noremestrin A (1) and secoemestrin E (2), were successfully isolated from the fungal source Emericella sp. 1454. Employing comprehensive spectroscopic techniques, such as high-resolution electrospray ionization mass spectrometry, infrared, and nuclear magnetic resonance (NMR), along with NMR and electronic circular dichroism calculations, the chemical structures of compounds 1 and 2 were elucidated. Particularly noteworthy is the distinctive nature of noremestrin A, representing the inaugural instance of a noremestrin variant incorporating a sulfur-bearing 15-membered macrocyclic lactone moiety. Compounds 1 and 2 exhibited weak cytotoxic activities against the human chronic myelocytic leukemia cell lines MEG-01 and K562.

Three new isocoumarin analogues from an endolichenic fungus Aspergillus flavus CPCC 400810.

Five isocoumarin derivatives including three new compounds, aspermarolides A-C (1-3), and two known analogues, 8-methoxyldiaporthin (4) and diaporthin (5) were obtained from the culture extract of Aspergillus flavus CPCC 400810. The structures of these compounds were elucidated by spectroscopic methods. The double bond geometry of 1 and 2 were assigned by the coupling constants. The absolute configuration of 3 was determined by electronic circular dichroism experiment. All compounds showed no cytotoxic activities against the two human cancer cells HepG2 and Hela.

Dietary exposure to nTiO2 reduces byssus performance of mussels under ocean warming.

Nano­titanium dioxide (nTiO2) is a widely used nanomaterial posing potential ecological risk for marine ecosystems that might be enhanced by elevated temperatures such as expected during climate change. nTiO2 may affect benthic filter feeders like mussels through waterborne exposures and via food chain due to the adsorption on/in algae. Mussel byssus are proteinaceous fibers secreted by byssal glands of the mussels for attachment. Byssus production and mechanical properties are sensitive to environmental stressors but the combined effects of warming and nTiO2 on byssus performance of mussels are unclear hampering our understanding of the predation and dislodgement risk of mussels under the multiple stressor scenarios. We explored the effects of a short-term (14-day) single and combined exposures to warming (28 °C) and 100 µg L-1 nTiO2 (including food co-exposure) on the byssus performance of the thick shell mussel Mytilus coruscus. The mechanical strength (measured as the breaking force) of the byssal threads was impaired by warming and nTiO2 (including food co-exposure), but the number and length of the byssal threads were increased. The mRNA expression levels of mussel foot proteins (mfp-3, mfp-5) and pre-collagens (preCOL-D, preCOL-P, preCOL-NG) were up-regulated to varying degrees, with the strongest effects induced by warming. This indicates that the physiological and molecular mechanisms of byssus secretion are plastic. However, downregulation of the mRNA expression of preCOL-D and preCOL-P under the combined warming and nTiO2 exposures indicate the limits of these plasticity mechanisms and suggest that the attachment ability and survival of the mussels may be impaired if the pollution or temperature conditions further deteriorate.

Combined toxic effects of nanoplastics and norfloxacin on mussel: Leveraging biochemical parameters and gut microbiota.

Antibiotics and nanoplastics (NPs) are among the two most concerned and studied marine emerging contaminants in recent years. Given the large number of different types of antibiotics and NPs, there is a need to apply efficient tools to evaluate their combined toxic effects. Using the thick-shelled mussel (Mytilus coruscus) as a marine ecotoxicological model, we applied a battery of fast enzymatic activity assays and 16S rRNA sequencing to investigate the biochemical and gut microbial response of mussels exposed to antibiotic norfloxacin (NOR) and NPs (80 nm polystyrene beads) alone and in combination at environmentally relevant concentrations. After 15 days of exposure, NPs alone significantly inhibited superoxide dismutase (SOD) and amylase (AMS) activities, while catalase (CAT) was affected by both NOR and NPs. The changes in lysozyme (LZM) and lipase (LPS) were increased over time during the treatments. Co-exposure to NPs and NOR significantly affected glutathione (GSH) and trypsin (Typ), which might be explained by the increased bioavailable NOR carried by NPs. The richness and diversity of the gut microbiota of mussels were both decreased by exposures to NOR and NPs, and the top functions of gut microbiota that were affected by the exposures were predicted. The data fast generated by enzymatic test and 16S sequencing allowed further variance and correlation analysis to understand the plausible driving factors and toxicity mechanisms. Despite the toxic effects of only one type of antibiotics and NPs being evaluated, the validated assays on mussels are readily applicable to other antibiotics, NPs, and their mixture.

Moldavica acid A, a new salicylic acid derivative from Dracocephalum moldavica.

In this paper, we present the discovery of a novel salicylic acid derivative, moldavica acid A (1), and a new natural dibenzo[b,f]oxepin, moldavica acid B (2), together with four known phenylpropionic acids (3-6) and protocatechuic acid (7) that were isolated from Dracocephalum moldavica L. Their structures were elucidated by comprehensive spectroscopic methods, including infrared and nuclear magnetic resonance. Compound 1 is the first example of salicylic acid linking a carboxylated α-pyrone via an ethyl bridge. Beyond expanding the knowledge of the chemical diversity of D. moldavica, both compounds 1 and 2 were shown to upregulate the expression of Kruppel-like factor 2, which could serve as a prospective therapeutic target for the treatment of atherosclerosis.

Analysis of Golgi Morphology Using Immunofluorescence and CellProfiler Software.

The architecture of the Golgi apparatus in mammalian cells changes dynamically in response to internal and external cues and may be permanently altered in disease states. Here, we present a method to quantify changes in Golgi morphology using immunofluorescence and confocal microscopy followed by CellProfiler software analysis. This method will assist researchers in evaluating alterations in the Golgi complex morphology of cultured cells under a variety of different experimental conditions.

Trichostatin D as a Novel KLF2 Activator Attenuates TNFα-Induced Endothelial Inflammation.

Krüppel-like factor 2 (KLF2) is an atherosclerotic protective transcription factor that maintains endothelial cell homeostasis through its anti-inflammatory, anti-oxidant, and antithrombotic properties. The aim of this study was to discover KLF2 activators from microbial secondary metabolites and explore their potential molecular mechanisms. By using a high-throughput screening model based on a KLF2 promoter luciferase reporter assay, column chromatography, electrospray ionization mass spectrometry (ESI-MS), and nuclear magnetic resonance (NMR) spectra, trichostatin D (TSD) was isolated from the rice fermentation of Streptomyces sp. CPCC203909 and identified as a novel KLF2 activator. Real-time-quantitative polymerase chain reaction (RT-qPCR) results showed that TSD upregulated the mRNA level of KLF2 in endothelial cells. Functional assays showed that TSD attenuated monocyte adhesion to endothelial cells, decreased vascular cell adhesion protein 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) expression, and exhibited an anti-inflammatory effect in tumor necrosis factor alpha (TNFα)-induced endothelial cells. We further demonstrated through siRNA and western blot assays that the effects of TSD on monocyte adhesion and inflammation in endothelial cells were partly dependent on upregulating KLF2 expression and then inhibiting the NOD-like receptor protein 3 (NLRP3)/Caspase-1/interleukin-1beta (IL-1ß) signaling pathway. Furthermore, histone deacetylase (HDAC) overexpression and molecular docking analysis results showed that TSD upregulated KLF2 expression by inhibiting HDAC 4, 5, and 7 activities. Taken together, TSD was isolated from the fermentation of Streptomyces sp. CPCC203909 and first reported as a potential activator of KLF2 in this study. Furthermore, TSD upregulated KLF2 expression by inhibiting HDAC 4, 5, and 7 and attenuated endothelial inflammation via regulation of the KLF2/NLRP3/Caspase-1/IL-1ß signaling pathway.

A Real-World Study on Ge Gen Tang in Combination with Herbal Medicines for Relieving Common Cold-Associated Symptoms.

Purpose: Real-world evidence refers to patient data derived from the healthcare process. In this study, we used National Health Insurance Research Database (NHIRD) assessments and clinical studies of Ge Gen Tang (GGT, ) in patients with common cold to establish a real-world study model of Traditional Chinese Medicine formulae. GGT is widely prescribed for the treatment of common cold in Taiwan, generally in combination with other medicines. The aim of this study was to determine whether a correlation exists between GGT combined with other medicines and an improvement in cold symptoms. We also established a GGT prescription compatibility system by analyzing Taiwan's NHIRD records for GGT prescription patterns in patients with different types of common cold. Materials and Methods: We extracted and analyzed records from the NHIRD for the period 2000-2015 to determine the most common clinical applications of GGT. GGT and GGT with Chuan Xiung Cha Tiao San were most commonly prescribed for common cold, as per NHIRD recommendations. Records for adults aged 20-65 years who were prescribed GGT for the treatment of common cold (Diagnosis Code ICD-9-460) were included in this study. We assessed the following indicators of the common cold, before and after treatment with GGT: nasal congestion, cough, runny nose, sneezing, sore throat, hoarseness, stiff shoulder, headache, and general physical condition. Results: The cold symptom scores before and after taking the GGT prescriptions significantly differed in the 29 volunteers. The 29 volunteers reported a significantly lower headache severity score after medication than before medication (p < 0.004). Furthermore, patient scores for general physical condition decreased significantly (p < 0.01) after medication.

Prenylemestrins A and B: Two Unexpected Epipolythiodioxopiperazines with a Thioethanothio Bridge from Emericella sp. Isolated by Genomic Analysis.

Prenylemestrins A and B (1 and 2, respectively), two unusual epipolythiodioxopiperazines featuring a thioethanothio bridge instead of a polysulfide bridge, were isolated from the fungus Emericella sp. CPCC 400858 guided by genomic analysis. Their structures were determined by extensive spectroscopic data, NMR and ECD calculations, and X-ray diffraction analysis. A plausible biosynthetic pathway for 1 and 2 was proposed on the basis of gene cluster analysis. Prenylemestrins A and B exhibited cytotoxicities against human chronic myelocytic leukemia cell lines K562 and MEG-01.

TXN inhibitor impedes radioresistance of colorectal cancer cells with decreased ALDH1L2 expression via TXN/NF-κB signaling pathway.

BACKGROUND: Colorectal cancer (CRC) is prevalent worldwide and is often challenged by treatment failure and recurrence due to resistance to radiotherapy. Here, we aimed to identify the elusive underlying molecular mechanisms of radioresistance in CRC. METHODS: Weighted gene co-expression network analysis was used to identify potential radiation-related genes. Colony formation and comet assays and multi-target single-hit survival and xenograft animal models were used to validate the results obtained from the bioinformatic analysis. Immunohistochemistry was performed to examine the clinical characteristics of ALDH1L2. Co-immunoprecipitation, immunofluorescence and flow cytometry were used to understand the molecular mechanisms underlying radioresistance. RESULTS: Bioinformatic analysis, in vitro, and in vivo experiments revealed that ALDH1L2 is a radiation-related gene, and a decrease in its expression induces radioresistance in CRC cells by inhibiting ROS-mediated apoptosis. Patients with low ALDH1L2 expression exhibit resistance to radiotherapy. Mechanistically, ALDH1L2 interacts with thioredoxin (TXN) and regulates the downstream NF-κB signaling pathway. PX-12, the TXN inhibitor, overcomes radioresistance due to decreased ALDH1L2. CONCLUSIONS: Our results provide valuable insights into the potential role of ALDH1L2 in CRC radiotherapy. We propose that the simultaneous application of TXN inhibitors and radiotherapy would significantly ameliorate the clinical outcomes of patients with CRC having low ALDH1L2.

Cytotoxic hexadepsipeptides and anti-coronaviral 4-hydroxy-2-pyridones from an endophytic Fusarium sp.

Three new hexadepsipeptides (1-3), along with beauvericin (4), beauvericin D (5), and four 4-hydroxy-2-pyridone derivatives (6-9) were isolated from the endophytic fungus Fusarium sp. CPCC 400857 that derived from the stem of tea plant. Their structures were determined by extensive 1D and 2D NMR, and HRESIMS analyses. The absolute configuration of hexadepsipeptides were elucidated by the advanced Marfey's method and chiral HPLC analysis. Compounds 4, and 7-9 displayed the cytotoxicity against human pancreatic cancer cell line, AsPC-1 with IC50 values ranging from 3.45 to 29.69 µM, and 7 and 8 also showed the antiviral activity against the coronavirus (HCoV-OC43) with IC50 values of 13.33 and 6.65 µM, respectively.

High-Entropy Atomic Layers of Transition-Metal Carbides (MXenes).

High-entropy materials (HEMs) have great potential for energy storage and conversion due to their diverse compositions, and unexpected physical and chemical features. However, high-entropy atomic layers with fully exposed active sites are difficult to synthesize since their phases are easily segregated. Here, it is demonstrated that high-entropy atomic layers of transition-metal carbide (HE-MXene) can be produced via the selective etching of novel high-entropy MAX (also termed Mn +1 AXn (n = 1, 2, 3), where M represents an early transition-metal element, A is an element mainly from groups 13-16, and X stands for C and/or N) phase (HE-MAX) (Ti1/5 V1/5 Zr1/5 Nb1/5 Ta1/5 )2 AlC, in which the five transition-metal species are homogeneously dispersed into one MX slab due to their solid-solution feature, giving rise to a stable transition-metal carbide in the atomic layers owing to the high molar configurational entropy and correspondingly low Gibbs free energy. Additionally, the resultant high-entropy MXene with distinct lattice distortions leads to high mechanical strain into the atomic layers. Moreover, the mechanical strain can efficiently guide the nucleation and uniform growth of dendrite-free lithium on HE-MXene, achieving a long cycling stability of up to 1200 h and good deep stripping-plating levels of up to 20 mAh cm-2 .

Cerium-Based Metal-Organic Framework Nanocrystals Interconnected by Carbon Nanotubes for Boosting Electrochemical Capacitor Performance.

In this study, nanocrystals of a cerium-based metal-organic framework (Ce-MOF), Ce-MOF-808, are directly grown on the surface of carboxylic acid-functionalized carbon nanotubes (CNTs) by a facile one-step solvothermal synthesis method. Ce-MOF-CNT nanocomposites with various Ce-MOF-to-CNT ratios are synthesized, and their crystallinity, morphology, porosity, and electrical conductivity are examined. The redox-hopping and electrochemical behaviors of the pristine Ce-MOF in aqueous electrolytes are investigated, suggesting that the pristine Ce-MOF is electrochemically active but possesses a limited charge-transport behavior. As a demonstration, all the Ce-MOF, CNT, and nanocomposites are used as active materials for application in aqueous-based supercapacitors. The capacitive performance of the CNT can be significantly boosted with the help of redox-active Ce-MOF-808 nanocrystals.

Construction of intracellular asymmetry and asymmetric division in Escherichia coli.

The design principle of establishing an intracellular protein gradient for asymmetric cell division is a long-standing fundamental question. While the major molecular players and their interactions have been elucidated via genetic approaches, the diversity and redundancy of natural systems complicate the extraction of critical underlying features. Here, we take a synthetic cell biology approach to construct intracellular asymmetry and asymmetric division in Escherichia coli, in which division is normally symmetric. We demonstrate that the oligomeric PopZ from Caulobacter crescentus can serve as a robust polarized scaffold to functionalize RNA polymerase. Furthermore, by using another oligomeric pole-targeting DivIVA from Bacillus subtilis, the newly synthesized protein can be constrained to further establish intracellular asymmetry, leading to asymmetric division and differentiation. Our findings suggest that the coupled oligomerization and restriction in diffusion may be a strategy for generating a spatial gradient for asymmetric cell division.

Selective Formation of Polyaniline Confined in the Nanopores of a Metal-Organic Framework for Supercapacitors.

In this study, a strategy that can result in the polyaniline (PANI) solely confined within the nanopores of a metal-organic framework (MOF) without forming obvious bulk PANI between MOF crystals is developed. A water-stable zirconium-based MOF, UiO-66-NH2 , is selected as the MOF material. The polymerization of aniline is initiated in the acidic suspension of UiO-66-NH2 nanocrystals in the presence of excess poly(sodium 4-styrenesulfonate) (PSS). Since the pore size of UiO-66-NH2 is too small to enable the insertion of the bulky PSS, the quick formation of pore-confined solid PANI and the slower formation of well dispersed PANI:PSS occur within the MOF crystals and in the bulk solution, respectively. By taking advantage of the resulting homogeneous PANI:PSS polymer solution, the bulk PANI:PSS can be removed from the PANI/UiO-66-NH2 solid by successive washing the sample with fresh acidic solutions through centrifugation. As this is the first time reporting the PANI solely confined in the pores of a MOF, as a demonstration, the obtained PANI/UiO-66-NH2 composite material is applied as the electrode material for supercapacitors. The PANI/UiO-66-NH2 thin films exhibit a pseudocapacitive electrochemical characteristic, and their resulting electrochemical activity and charge-storage capacities are remarkably higher than those of the bulk PANI thin films.

Identification of immune landscape signatures associated with clinical and prognostic features of hepatocellular carcinoma.

While cancer immunotherapy has been remarkably successful in some malignancies, some cancers derive limited benefit from current immunotherapies. Here, we combined immune landscape signatures with hepatocellular carcinoma clinical and prognostic features to classify them into distinct subtypes. The immunogenomic profiles, stromal cell features and immune cell composition of the subtypes were then systematically analyzed. Two independent prognostic indexes were established based on 6 immune-related genes and 17 differentially expressed genes associated with stromal cell content. These indexes were significantly correlated with tumor mutation burden, deficient DNA mismatch repair and microsatellite instability. In addition, tumor-infiltrating lymphocytes, including activated NK cells, resting memory CD4 T-cells, eosinophils, and activated mast cells were significantly correlated with hepatocellular carcinoma survival. In conclusion, we have comprehensively described the immune landscape signatures and identified prognostic immune-associated biomarkers of hepatocellular carcinoma. Our findings highlight potential novel avenues for improving responses to immunotherapy.

Polyoxometalate adsorbed in a metal-organic framework for electrocatalytic dopamine oxidation.

A redox-active vanadium-based polyoxometalate, V10O28, was post-synthetically immobilized into a water-stable zirconium-based metal-organic framework, NU-902. The adsorbed V10O28 in NU-902 renders charge hopping in the framework in aqueous electrolytes, and the obtained V10O28@NU-902 can be used as a heterogeneous electrocatalyst for electrochemical dopamine sensors.