Bulk and single cells transcriptomes with experimental validation identify USP18 as a novel glioma prognosis and proliferation indicator.

The mechanism by which ubiquitin-specific protease 18 (USP18) (enzyme commission: 3.4.19.12) inhibition in cancer promotes cell pyroptosis via the induction of interferon (IFN)-stimulated genes has been recently demonstrated. It is also known that USP18 influences the epithelial-mesenchymal transition of glioma cells. In the present study, the upregulation of USP18 in glioma was revealed through bulk transcriptome analysis, which was associated with poor prognosis in patients with glioma. Furthermore, USP18 levels affected the response to immunotherapy in patients with glioma. Single-cell transcriptome and enrichment analyses demonstrated that USP18 was associated with type 1 IFN responses in glioma T cells. To demonstrate the effect of USP18 expression levels on glioma cells, USP18 expression was knocked down in U251 and U87MG ATCC cell lines. A subsequent Cell Counting Kit-8 assay revealed that glioma cell viability was significantly decreased 4 days after USP18 knockdown. In addition, the knockdown of USP18 expression significantly inhibited the clonogenicity of U251 and U87MG ATCC cells. In conclusion, the present study demonstrated that knockdown of USP18 expression inhibited the proliferation of glioma cells, which may be mediated by the effect of USP18 on the IFN-I response.

DTX2 promotes glioma development via regulation of HLTF.

BACKGROUND: Human Deltex 2 (DTX2) is a ubiquitin E3 ligase that functions as an oncogene and has been shown to participate in many human cancers. However, the role of DTX2 in glioma progression has remained obscure. In this study, we explore the mechanism underlying the function of DTX2 in glioma progression. METHODS: The associations between DTX2 expression and clinical characteristics of glioma were determined by bioinformatic analysis of data from The Cancer Genome Atlas and Human Protein Atlas. The expression of DTX2 in glioma tissues was detected using immunohistochemistry and western blotting. Lentivirus-mediated gene knockdown and overexpression were used to determine the effects of DTX2 and helicase-like transcription element (HLTF) on glioma cell proliferation and migration with CCK-8, cell colony formation, transwell, and wound healing assays; flow cytometry in vitro; and animal models in vivo. The interaction of the DTX2 and HLTF proteins was verified by immunoprecipitation assay and confocal microscopy. RESULTS: DTX2 was highly expressed in glioma samples, and this was correlated with worse overall survival. Silencing of DTX2 suppressed glioma cell viability, colony formation, and migration and induced cell apoptosis. In vitro ubiquitination assays confirmed that DTX2 could downregulate HLTF protein levels by increasing ubiquitination of the HLTF protein. We also observed that HLTF inhibited proliferation and migration of glioma cells. Subcutaneous xenografts with DTX2-overexpressing U87 cells showed significantly increased tumor volumes and weights. CONCLUSIONS: We have identified DTX2/HLTF as a new axis in the development of glioma that could serve as a prognostic or therapeutic marker.

Polystyrene microplastics induce kidney injury via gut barrier dysfunction and C5a/C5aR pathway activation.

Microplastic is an emerging environmental pollutant with potential health risks. Recent studies have shown that microplastic could impair gut homeostasis in mammals. Although it has been widely demonstrated that gut dyshomeostasis could impact renal health through the gut-kidney axis, the effects of microplastic-induced gut dyshomeostasis on renal health and underlying mechanisms are still largely unknown. In the current work, we found that polystyrene microplastics (PS-MPs) treatment impaired the gut barrier, increased urinary complement-activated product C5a levels and renal C5aR expression, leading to chronic kidney disease-related symptoms in mice. Restoring the gut barrier using an antibiotic mixture effectively alleviated PS-MPs-induced kidney injury, indicating the involvement of the gut-kidney axis in PS-MPs-induced renal injury. Moreover, it also mitigated PS-MPs-induced alterations in urinary C5a levels and renal C5aR expression, suggesting that the renal C5a/C5aR pathway might be involved in PS-MPs' impacts on the gut-kidney axis. Further experiments using a C5aR inhibitor, PMX53, verified the vital role of renal C5a/C5aR pathway activation in the development of kidney injury induced by PS-MPs. Collectively, our results suggest that PS-MPs induce kidney injury in mice by impairing the gut barrier, increasing C5a levels, and ultimately activating the renal C5a/C5aR pathway, highlighting the crucial role of the gut-kidney axis in PS-MPs-induced kidney injury.

Psychrophilic phage phiGM22-3 efficiently controls Pseudomonas fluorescens contamination in cold-stored milk.

Pseudomonas fluorescens is a common spoilage causing microbe found in milk. Antibiotic preservatives may cause emergence of multidrug resistance, posing food safety related risks to public health. Phage treatment may be used as an alternative to antibiotics in controlling P. fluorescens contaminations. Here we reported that P. fluorescens phage phiGM22-3 reproduced rapidly over a broad temperature range of 4 through 30°C, and the optimum growth of phiGM22-3 occurred at 10°C, indicating that it was a psychrophilic virus. Genome analysis revealed that phiGM22-3 has a genome of 42,662 bp with an identical terminal direct repeat sequence of 328 bp and encodes 58 predicted proteins. Evidence revealed that phiGM22-3 recognized lipopolysaccharides (LPS) as receptor for infection. Additionally, two phage mutants phiMX2 and phiMX8 with different host ranges were identified in the phiGM22-3 population. Phage killing efficiency of P. fluorescens cells artificially inoculated in milk was evaluated. Phage phiGM22-3 and the cocktails containing phiMX2 and phiMX8 can lyse almost 100% bacterial cells at 4°C within 24 h. Taken together, our data indicated that the psychrophilic virus phiGM22-3 and its two mutants can efficiently inhibit bacteria growth at 4°C, showing a great potential to be used as alternatives to conventional antibiotics against P. fluorescens in refrigerated foods.

Decision-theoretic rough set model and spatial analysis-based waste-to-energy incineration plant site selection: a case study in first-tier cities of China.

Selecting a sustainable waste-to-energy (WTE) incineration plant site is important for handling huge challenges created by on-going municipal solid waste. However, many studies with WTE incineration plant site problems fail to determine alternative evaluation criteria and cities beforehand, which may increase decision costs and evaluation risks. This paper proposes a novel methodology based on decision-theoretic rough set model and suitable analysis for selecting the optimal WTE incineration plant site. Firstly, from the features of cities, alternative evaluation criteria are determined by three-phase method. Considering different geographical features, a geographical index system is established. Secondly, subjective and objective criteria weights are determined by an improved DEMATEL (Decision Making Trial and Evaluation Laboratory) method and TOPSIS (Technique for Order of Preference by Similarity to Ideal Solution) method-based linear programming model under the hesitant fuzzy linguistic context, respectively. Subjective and objective criteria weights are combined to form the final criteria weights by building an optimization model. Thirdly, the decision-theoretic rough set model is utilized to select alternative WTE incineration plant sites. We utilize spatial analysis adopting Geographic Information System technology to rank all alternative cities to build facilities. Finally, a numerical case is performed to illustrate the feasibility of the proposed methodology. The sensitivity analysis with the parameter [Formula: see text] ranking from 0 to 1 is performed, the result confirms that the proposed methodology has better robustness. Compared with the multi-criteria decision-making methods, the effectiveness and superiority of the proposed methodology are demonstrated.

The role of vasoactive intestinal peptide in pulmonary diseases.

Vasoactive intestinal peptide (VIP) is an abundant neurotransmitter in the lungs and other organs. Its discovery dates back to 1970. And VIP gains attention again due to the potential application in COVID-19 after a research wave in the 1980s and 1990s. The diverse biological impacts of VIP extend beyond its usage in COVID-19 treatment, encompassing its involvement in various pulmonary and systemic disorders. This review centers on the function of VIP in various lung diseases, such as pulmonary arterial hypertension, chronic obstructive pulmonary disease, asthma, cystic fibrosis, acute lung injury/acute respiratory distress syndrome, pulmonary fibrosis, and lung tumors. This review also outlines two main limitations of VIP as a potential medication and gathers information on extended-release formulations and VIP analogues.

Maternal polysorbate 80 exposure causes intestinal ILCs and CD4+ T cell developmental abnormalities in mouse offspring.

This study aimed to investigate the transgenerational impacts of maternal intake of polysorbate 80 (P80), an emulsifier widely used in modern society, on the development of offspring immunity. Our results revealed that maternal P80 treatment led to impaired differentiation of innate lymphoid cells (ILCs) and CD4+ T cells in the small intestinal lamina propria (SiLP), resulting in intestinal dyshomeostasis in female offspring. Furthermore, we found that SiLP ILCs abundances were significantly altered in 0-day-old fetuses from P80-treated mothers, indicating a prenatal impact of P80-treated mothers on offspring immunity. Additionally, cesarean section and foster-nursing studies demonstrated that P80-induced altered SiLP ILCs in 0-day-old fetuses could further induce dysregulation of ILCs and CD4+ T cells in the SiLP, thus promoting intestinal dysregulation in offspring later in life. Overall, our findings suggest that maternal P80 intake could prenatally program the development of offspring immunity, exerting a significant and long-lasting impact.

Variants of a putative baseplate wedge protein extend the host range of Pseudomonas phage K8.

BACKGROUND: Narrow host range is a major limitation for phage applications, but phages can evolve expanded host range through adaptations in the receptor-binding proteins. RESULTS: Here, we report that Pseudomonas phage K8 can evolve broader host range and higher killing efficiency at the cost of virion stability. Phage K8 host range mutant K8-T239A carries a mutant version of the putative baseplate wedge protein GP075, termed GP075m. While phage K8 adsorbs to hosts via the O-specific antigen of bacterial LPS, phage K8-T239A uses GP075m to also bind the bacterial core oligosaccharide, enabling infection of bacterial strains resistant to K8 infection due to modified O-specific antigens. This mutation in GP075 also alters inter-protein interactions among phage proteins, and reduces the stability of phage particles to environmental stressors like heat, acidity, and alkalinity. We find that a variety of mutations in gp075 are widespread in K8 populations, and that the gp075-like genes are widely distributed among the domains of life. CONCLUSION: Our data show that a typical life history tradeoff occurs between the stability and the host range in the evolution of phage K8. Reservoirs of viral gene variants may be widely present in phage communities, allowing phages to rapidly adapt to any emerging environmental stressors. Video Abstract.

Democratizing Pathological Image Segmentation with Lay Annotators via Molecular-empowered Learning.

Multi-class cell segmentation in high-resolution Giga-pixel whole slide images (WSI) is critical for various clinical applications. Training such an AI model typically requires labor-intensive pixel-wise manual annotation from experienced domain experts (e.g., pathologists). Moreover, such annotation is error-prone when differentiating fine-grained cell types (e.g., podocyte and mesangial cells) via the naked human eye. In this study, we assess the feasibility of democratizing pathological AI deployment by only using lay annotators (annotators without medical domain knowledge). The contribution of this paper is threefold: (1) We proposed a molecular-empowered learning scheme for multi-class cell segmentation using partial labels from lay annotators; (2) The proposed method integrated Giga-pixel level molecular-morphology cross-modality registration, molecular-informed annotation, and molecular-oriented segmentation model, so as to achieve significantly superior performance via 3 lay annotators as compared with 2 experienced pathologists; (3) A deep corrective learning (learning with imperfect label) method is proposed to further improve the segmentation performance using partially annotated noisy data. From the experimental results, our learning method achieved F1 = 0.8496 using molecular-informed annotations from lay annotators, which is better than conventional morphology-based annotations (F1 = 0.7015) from experienced pathologists. Our method democratizes the development of a pathological segmentation deep model to the lay annotator level, which consequently scales up the learning process similar to a non-medical computer vision task. The official implementation and cell annotations are publicly available at https://github.com/hrlblab/MolecularEL.

An End-to-end Pipeline for 3D Slide-wise Multi-stain Renal Pathology Registration.

Tissue examination and quantification in a 3D context on serial section whole slide images (WSIs) were labor-intensive and time-consuming tasks. Our previous study proposed a novel registration-based method (Map3D) to automatically align WSIs to the same physical space, reducing the human efforts of screening serial sections from WSIs. However, the registration performance of our Map3D method was only evaluated on single-stain WSIs with large-scale kidney tissue samples. In this paper, we provide a Docker for an end-to-end 3D slide-wise registration pipeline on needle biopsy serial sections in a multi-stain paradigm. The contribution of this study is three-fold: (1) We release a containerized Docker for an end-to-end multi-stain WSI registration. (2) We prove that the Map3D pipeline is capable of sectional registration from multi-stain WSI. (3) We verify that the Map3D pipeline can also be applied to needle biopsy tissue samples. The source code and the Docker have been made publicly available at https://github.com/hrlblab/Map3D.

Phage phiZ98: A novel tri-segmented dsRNA cystovirus for controlling Pseudomonas strains with defective lipopolysaccharides in foods.

Many Pseudomonas phages recognize lipopolysaccharides (LPS) as the receptor for infection. LPS defective mutants are often recovered from phage treatments, possibly causing the failure of phage applications. In this work, we isolated a lytic Pseudomonas phage, phiZ98, that can specifically lyse LPS defective strains of the genus Pseudomonas. Transmission electron microscopy (TEM) showed that phiZ98 particles were enveloped in a layer of membrane-like structure. Genomic analysis revealed that the phage has a genome of tri-segmented double-stranded RNA molecules of 6627 bp, 3769 bp, and 3075 bp, respectively. The results indicated that phage phiZ98 was the nineth member of the genus Cystovirus. The phiZ98 genome encoded 12 putative proteins with predicted functions and 15 hypothetical proteins. Mass spectrum analysis further identified 11 proteins present in the virions. Antibacterial activity assays showed that phage phiZ98 significantly inhibited cell growth, reduced biofilm formation, and removed mature biofilm. Moreover, phage phiZ98 can significantly control the growth of the host bacterial cells in sterilized milk or canned corned beef. In combination with phage K8 which used LPS as the receptor, phiZ98 can significantly reduce the phage-resistant mutants generated from the K8 treatment in milk. Taken together, the dsRNA phage phiZ98 could be an effective scavenger in removing phage-resistant mutants with defective LPS in cocktail applications.

Precision Seeding Compensation and Positioning Based on Multisensors.

The current multi-row planter always leads to uneven seeding spacing between rows while seeding in curve paths, which causes uneven growth, a cost increase of production and management, and reduced yield. With the development of smart farming technology, a curve seeding compensation and precise positioning model is proposed in the paper to calculate the real-time speed and position of each seeding unit based on the information from multisensors, such as GNSS and IMU, and to predict the next seeding position to achieve uniform seeding on the curve and improve the unit yield of crops. MATLAB Simulink simulation experiments show that the seeding pass rate of the model is 99.97% when the positioning accuracy is ±0.01 m and the traction speed is 1 m/s, and the seeding pass rate of the five-row seeder is as high as 99.81% when the traction speed is 3 m/s, which verifies the effectiveness and practicality of the model.

A microbiome abundant environment remodels the intestinal microbiota and improves resistance to obesity induced by chlorpyrifos in mice.

There is a growing consensus that the appropriate microbiome abundant environment actuates microbiota changes to influence human health. Whether living environment reacts on the threat of contaminants and the underlying mechanism remain largely unknown. Therefore, we constructed microbiome abundant environment models, focusing on their regulatory effects on the obesity induced by the exogenous chemical chlorpyrifos (CPF) and the related mechanisms. The results uncovered that the constructed farm and woodland microbiome abundant environment could protect mice against CPF-induced obesity effectively. The microbiome abundant environment regulated CPF-induced microbiota imbalance, characterized by an increase in Lactobacillus abundance. These altered microbiotas modified the intestinal immune system by increasing the expression of Foxp3 and IL-10, and mitigated intestinal barrier injury by upregulating the expression of IL-22 and intestinal tight junction proteins. Fecal microbiota transplantation could receive similar phenotypes on alleviating CPF-induced obesity development. Our results demonstrate that the microbiome abundant environment attenuates exogenous chemical-induced health risks by remodeling the intestinal microbiota, improving the intestinal ecosystem, and preventing intestinal epithelial leakage.

Studies on irritable bowel syndrome associated with anxiety or depression in the last 20 years: A bibliometric analysis.

Irritable bowel syndrome (IBS) associated with anxiety or depression is ubiquitous in clinical practice, and multiple related articles have been published. However, studies that utilize bibliometric analyses to address this topic are rare. In our study, we aimed to reveal research trends in IBS with anxiety or depression. Publications on IBS in relation to anxiety or depression in the last 20 years were obtained from the Web of Science Core Collection (WoSCC). CiteSpace software (5.8.R3) and GraphPad Prism 8 were used to perform bibliometric analysis of authors, countries, institutions, journals, keywords, and references involved in this topic. A total of 2,562 publications from 716 academic journals were included in this study. The majority of publications (n = 833, 32.51%) were from the USA, and the University of California, Los Angeles, contributed the most publications (n = 97, 3.79%). Active cooperations among countries and institutions were observed. Neurogastroenterology and Motility [impact factor (IF) 2020 = 3.598] published the most papers (170 publications, 6.64%), followed by Alimentary Pharmacology Therapeutics (IF 2020 = 8.171; 88 publications; 3.44%). The literatures related to IBS and anxiety or depression were primarily published in journals related to medicine/medical/clinical, neurology/sports/ophthalmology, and molecular/biology/immunology. Cryan JF and Drossman DA, with the largest number of articles (84 publications) and citations (917 citations), respectively, were considered as the most influential authors in this field. A total of 336 co-cited references were divided into 17 clusters, and #1 fecal microbiota transplantation contained most of the documents published in recent years. Moreover, the keyword "psychosocial factor" had the largest burst strength of 13.52, followed by the keyword "gut microbiota" with a burst strength of 11.71. This study shows the research performance of IBS related to anxiety or depression from 2002 to 2021 and helps researchers master the trend in this field, which should receive more attention.

Metabolomic profiling to assess the effects of chlordanes and its bioaccumulation characteristics in chicken embryo.

Although chlordane-related compounds (CHLs) have been regulated, a variety of CHLs are still identified and detected in wild birds and eggs. Embryo is one of fragile periods and is very susceptible to toxic effects of pollutants. In this study, the fate of CHLs during embryo development and degradation of CHLs in neonatal chick were investigated. During embryo development, CHLs were mainly distributed to the liver and muscle, in which trans-nonachlor and an octachlorochlordane (MC5) were hardly metabolized and showed the high persistence, implying a greater risk to birds' offspring. CHLs with the lower Kow were found to be higher uptake efficiency in embryo, implying contaminants with the lower lipophilicity may contribute to their transport to embryo. Furthermore, the effects of CHLs on the metabolome of neonatal chicks was evaluated. The ether lipid metabolism and glycerophospholipid metabolism were found to be significantly affected, which may disturb the angiogenesis and endothelial cell migration in embryogenesis. Taken together, the lipophilicity of contaminants might be a main factor influencing their transport to embryo, and metabolomics results improve understanding of the effects of CHLs on embryo.

Knowledge Mapping of Acupuncture for Fibromyalgia from 1990 to 2022: A Bibliometric Analysis.

Background: Fibromyalgia is a rheumatic disease with no specific laboratory markers and is insensitive to hormonal drugs and nonsteroidal anti-inflammatory drugs commonly used to treat rheumatism. Guidelines recommend that non-pharmacological therapy should be the first-line treatment for fibromyalgia. Since the publication of the first diagnostic criteria for fibromyalgia in 1990, studies on acupuncture for fibromyalgia have been reported periodically. This study aims to explore the intellectual landscape of acupuncture for fibromyalgia since 1990, and to identify research trends and fronts in this field. Methods: The Web of Science Core Collection Database was searched for publications on acupuncture for fibromyalgia from 1990 to 2022. VOSviewer and CiteSpace were used to analyze the annual publication, countries, institutions, authors and cited authors, journals and cited journals, references and keywords. Results: A total of 280 publications were retrieved, and the number of publications showed an overall upward trend. The United States was the most productive country. China Medical University was the institution with the most publications. Lin Yi-wen was the most prolific author, while Wolfe was the most cited author. Evidence-Based Complementary and Alternative Medicine was the journal in which most of the research was published, while Pain was the most cited journal. An article by Wolfe (1990) had the most citations, but an article by Crofford (2001) had the highest centrality. The four most frequently used keywords in the included articles were mechanism, spinal cord, activation and sensitivity. Conclusion: Acupuncture can effectively relieve pain in patients with fibromyalgia and improve accompanying symptoms such as anxiety and depression. However, the design of clinical trials still needs to be optimized to better verify the efficacy of acupuncture on various clinical symptoms of fibromyalgia. Exploring the central analgesic mechanism of acupuncture on fibromyalgia is also the focus research direction now and future.

Herbicidal activity and differential metabolism of lactofen in rat and loach on an enantiomeric level.

Enantioselectivity of chiral compounds is receiving growing concern. Lactofen, a chiral herbicide widely used in field crops and vegetables to control broadleaf weeds, is still sold as racemate. In this work, the herbicidal activity and metabolism behavior of lactofen were investigated on an enantiomeric level. Two common broadleaf weeds (Eclipta prostrata L. and Portulaca oleracea L.) were used to evaluate the herbicidal activity of rac-/R- and S-lactofen, and their metabolism behavior in loach and rat liver microsomes was explored. Higher herbicidal activity of S-lactofen was observed, with the 20d-EC50 values being 1.9-3.4 times lower than R-lactofen. Both loach and rat liver microsomes had ability to metabolize rac-lactofen, with half-lives of 1.93 and 1.28 h, respectively. Enantioselective metabolism behaviors were observed in loach and rat liver microsomes and the direction of enantioselectivity were different. R-lactofen was preferentially metabolized in loach liver microsome, while S-lactofen was preferentially metabolized in rat liver microsome. No interconversion of R- and S-lactofen was found. Besides, the main metabolic pathways of R- and S-lactofen were found to be significantly different. R-lactofen was metabolized to R-desethyl lactofen in both loach and rat liver microsomes without further metabolism. However, S-lactofen was metabolized to both S-desethyl lactofen and acifluorfene in rat liver microsome, which was mainly metabolized to acifluorfene in loach liver microsome. This study indicated enantioselectivity and metabolites should be taken into consideration when overall evaluating the environmental behavior of lactofen.

Gut microbiome alterations induced by tributyltin exposure are associated with increased body weight, impaired glucose and insulin homeostasis and endocrine disruption in mice.

Tributyltin (TBT), an organotin compound once widely used in agriculture and industry, has been reported to induce obesity and endocrine disruption. Gut microbiota has a strong connection with the host's physiology. Nevertheless, the influences of TBT exposure on gut microbiota and whether TBT-influenced gut microbiota is related to TBT-induced toxicity remain unclear. To fill these gaps, ICR (CD-1) mice were respectively exposed to TBT at NOEL (L-TBT) and tenfold NOEL (H-TBT) daily by gavage for 8 weeks in the current study. The results showed that TBT exposure significantly increased body weight as well as epididymal fat, and led to adipocyte hypertrophy, dyslipidemia and impaired glucose and insulin homeostasis in mice. Additionally, TBT exposure significantly decreased the levels of T4, T3 and testosterone in serum. Also of note, TBT exposure changed gut microbiota composition mainly by decreasing Bacteroidetes and increasing Firmicutes proportions. To confirm the role of gut microbiota in TBT-induced overweight and hormonal disorders, fecal microbiota transplantation was performed and the mice receiving gut microbiota from H-TBT mice had similar phenotypes with their donor mice including significant body weight and epididymal fat gain, glucose and insulin dysbiosis and hormonal disorders. These results suggested that gut microbiome altered by TBT exposure was involved in the TBT-induced increased body weight, impaired glucose and insulin homeostasis and endocrine disruption in mice, providing significant evidence and a novel perspective for better understanding the mechanism by which TBT induces toxicity.

Toxicity risk assessment of pyriproxyfen and metabolites in the rat liver: A vitro study.

Pyriproxyfen (PYR) is a type of aromatic juvenile hormone analog and a hygienic insecticide used in agriculture to control insect species. Therefore, assessing the metabolic behavior and toxic effects of PYR in mammals is the best means of evaluating its risks to human health. Previous studies have reported conflicting results regarding the toxicity risks of PYR and its metabolites in rat hepatocytes. We used ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to perform a chiral analysis of PYR and its metabolites investigating the enantioselective metabolism of PYR in rat liver microsomes. Our results concluded that the recoveries of PYR, metabolites A and B ranged from 81.13%-111.54 %, with RSD values of 0.01 %-6.52 %. The method limits of detection (LODs) and limits of quantification (LOQs) for PYR, metabolites A and B were in accordance with the analysis requirements. Previous studies have demonstrated the enantioselective metabolism of PYR and the generation of metabolites. Measurements of cell proliferation toxicity to rat hepatocytes, apoptosis and DNA damage induced by PYR and its metabolites in rat hepatocytes indicated that the metabolites reflected higher toxicity potential than PYR in rat hepatocytes. More studies about the molecular mechanism of PYR-induced toxicity are urgently needed in future work.

Low-Cost Ru/C-Catalyzed Depolymerization of the Polymeric Proanthocyanidin-Rich Fraction from Bark To Produce Oligomeric Proanthocyanidins with Antioxidant Activity.

A new method has been developed for the high-value utilization of larch bark, which is regarded as a low-value byproduct of the logging industry. Polymeric proanthocyanidins (PPCs) were extracted from the Larix gmelinii bark and depolymerized by catalytic hydrogenolysis, using ruthenium/carbon (Ru/C) as the catalyst. The method has been found that although the molecular weight of the depolymerized product was significantly lower, the basic structural units were not destroyed, and the product retained a condensed flavanol polyphenol structure; the depolymerized product contains very little Ru metal and thus complies with food safety standards; the antioxidant properties of both the depolymerized products and PPCs were better than those of the commonly used antioxidant 2,6-di-tert-butyl-4-methylphenol. The relative molecular weight and steric hindrance of the depolymerized products were lower than those of the PPCs, leading to better antioxidant performance. A new technical route for the depolymerization of PPCs from the L. gmelinii bark is provided. The route offers practical and commercial advantages, and the product could have many applications as an antioxidant.