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Wood-based solar steam evaporators have been attracting increasing interest due to their great potential for addressing water scarcity by utilizing sustainable materials and energy. However, engineering a 3D porous structure within the wood lumens and its effect on solar vapor evaporation have not yet been well explored. Here, a natural wood-based solar evaporator with hierarchical pores is fabricated by assembling polyvinyl alcohol within the lumens through an ice-templating approach. The polyvinyl alcohol porous network is engineered from vertically aligned microchannels to dendritically bridged pores with a narrowed size of a few micrometers and significantly increased surface area. Although the formation of plenty of microscopic channels increases the capillary force in comparison to the native wood lumen, the morphology change induces a high tortuosity factor of the porous structure, resulting in a reduced water transportation rate as well as an increased contact angle. On the other hand, the high surface area of the engineered wood lumens and the good hydrophilicity of the filled polyvinyl alcohol improve the ratio of the formed intermediate water, contributing to reduced vaporization enthalpy. Consequently, by using polydopamine as the photothermal material, the hierarchically structured polyvinyl alcohol-wood solar evaporator exhibits an evaporation rate of 1.6 kg m

Pyrrolizidine alkaloids (PAs) are phytotoxins widely present in various natural products and foodstuffs. The present study aims to investigate the effects of fasting on PA-induced hepatotoxicity and the underlying biochemical mechanisms. The results of hepatotoxic study showed that 15-h overnight fasting significantly exacerbated the hepatotoxicity of retrorsine (RTS, a representative toxic PA) in fasted rats compared to fed rats, as indicated by remarkably elevated plasma ALT and bilirubin levels and obvious liver histological changes. Further toxicokinetic studies revealed that fasting significantly enhanced cytochromes P450 enzymes (CYPs)-mediated metabolic activation of RTS leading to increased formation of pyrrole-protein adducts and thus decreased the in vivo exposure and excretion of both parent RTS and its N-oxide metabolite. Metabolic studies demonstrated that fasting induced enzyme activities of CYP1A2, CYP2B6 and CYP2E1 that participated in catalyzing RTS to its reactive pyrrolic metabolites. Moreover, fasting also dramatically decreased hepatic glutathione (GSH) content, which restricted the detoxification of GSH by neutralizing the reactive pyrrolic metabolite of RTS, further contributing to the enhanced hepatotoxicity. The present findings may have an impact on future PA toxicity tests with different dietary styles and/or risk assessment of metabolite-mediated toxins by considering the profound effects of fasting.

Pyrrolizidine alkaloids (PAs) have been found in over 6000 plants worldwide and represent the most common hepatotoxic phytotoxins. Currently, a definitive diagnostic method for PA-induced liver injury (PA-ILI) is lacking. In the present study, using a newly developed analytical method, we identified four pyrrole-amino acid adducts (PAAAs), namely pyrrole-7-cysteine, pyrrole-9-cysteine, pyrrole-9-histidine, and pyrrole-7-acetylcysteine, which are generated from reactive pyrrolic metabolites of PAs, in the urine of PA-treated male Sprague Dawley rats and PA-ILI patients. The elimination profiles, abundance, and persistence of PAAAs were systematically investigated first in PA-treated rat models via oral administration of retrorsine at a single dose of 40 mg/kg and multiple doses of 5 mg/kg/day for 14 consecutive days, confirming that these urinary excreted PAAAs were derived specifically from PA exposure. Moreover, we determined that these PAAAs were detected in ~ 82% (129/158) of urine samples collected from ~ 91% (58/64) of PA-ILI patients with pyrrole-7-cysteine and pyrrole-9-histidine detectable in urine samples collected at 3 months or longer times after hospital admission, indicating adequate persistence time for use as a clinical test. As direct evidence of PA exposure, we propose that PAAAs can be used as a biomarker of PA exposure and the measurement of urinary PAAAs could be used as a non-invasive test assisting the definitive diagnosis of PA-ILI in patients. Supplementary Information The online version contains supplementary material available at 10.1007/s00204-021-03129-6.

Birefringence has been attracting broad attention due to its strong potential for applications in biomedicine and optics, such as biomedical diagnosis, colorimetric sensing, retardant, and polarization encoding. However, engineering architectures with precisely controllable birefringence remains a challenge due to the lack of effective modulation of the localized orientation. Here, by taking advantage of the inherently one-dimensional (1D) anisotropic structure of cellulose nanocrystals (CNCs), we demonstrate an approach to tune the alignment of CNCs with a well-controllable orientation at localized preciseness, which is in contrast to the previously reported unidirectional/radical orientation of CNC-based birefringent structures. The localized modulation of CNC orientation is facilitated by directing the 1D nanocrystals to align along the template periphery and the migrated three-phase contact line during the evaporation. The resultant CNC films exhibit birefringent extinction patterns under polarized light, in which versatile pattern designs can be obtained by employing templates with different shapes and template arrays with varied layouts. Due to the locally modulated orientation of CNCs, the films indicate "kaleidoscope-like" dynamically transformable designs of the birefringent patterns depending on the polarized angle, which has barely been observed previously. Furthermore, an N-nary encoding system for abundant information storage is demonstrated based on the sunlight-transparent CNC films, but with visible extinction patterns under polarized light, which is promising for encryptions, anticounterfeiting, and imaging, enriching the attractive research area of bio-based photonics.

Pyrrolizidine alkaloids (PAs) and PA N-oxides are common phytotoxins produced by over 6000 plant species. Humans are frequently exposed to PAs via ingestion of PA-containing herbal products or PA-contaminated foods. PAs require metabolic activation to form pyrrole-protein adducts and pyrrole-DNA adducts which lead to cytotoxicity and genotoxicity. Individual PAs differ in their metabolic activation patterns, which may cause significant difference in toxic potency of different PAs. This review discusses the current knowledge and recent advances of metabolic pathways of different PAs, especially the metabolic activation and metabolism-mediated cytotoxicity and genotoxicity, and the risk evaluation methods of PA exposure. In addition, this review provides perspectives of precision toxicity assessment strategies and biomarker development for the risk control and translational investigations of human intoxication by PAs.

Pyrrolizidine alkaloids (PAs) are naturally occurring hepatotoxins widely present in hundreds of plant species and also known to contaminate many foodstuffs, such as grain, honey, and tea. The formation of pyrrole–protein adducts via metabolic activation of PAs has been suggested as a primary trigger initiating hepatotoxicity. The present study for the first time tested the suitability of pyrrole–hemoglobin adducts as a novel and specific biomarker of PA exposure in humans. The level and elimination kinetics of pyrrole–hemoglobin adducts were systematically investigated in the blood samples of 43 PA-induced liver injury (PA-ILI) patients. The results revealed significantly higher concentrations (84.50 ± 78.38 nM) and longer persistence (~ 4 months) of pyrrole–hemoglobin adducts than that (concentration: 9.53 ± 10.72 nM; persistence: ~ 2 months) of pyrrole–plasma protein adducts, our previously developed PA exposure biomarker. Our findings confirmed that pyrrole–hemoglobin adducts with higher level and longer persistence should serve as a more applicable PA exposure biomarker for future clinical diagnosis of PA-ILI in drug/herb-induced liver injury patients.

The hepatotoxic pyrrolizidine alkaloids (PAs) are metabolically activated in the liver to form reactive dehydro-PAs, which generate pyrrole-protein adducts leading to hepatotoxicity. Monocrotaline, but not other PAs, is also pneumotoxic, supposedly due to the migration of the liver-generated corresponding dehydro-PA into the lung to form pyrrole-protein adducts to induce pneumotoxicity. The present study investigated whether other PAs are also pneumotoxic. Metabolic activation of four representative hepatotoxic PAs, monocrotaline, retrorsine, riddelliine and clivorine, was investigated using rat liver or lung S9 incubation. All PAs produced pyrrole-protein adducts significantly in rat liver S9 but negligible in lung S9 fraction, revealing that liver is the key organ responsible for metabolic activation generating dehydro-PAs. Furthermore, these four PAs and another two PAs present in the alkaloid extract of Gynura segetum, a widely used PA-producing herb responsible for human PA poisonings in China, were orally administered to rats using the same hepatotoxic dose of 0.2 mmol/kg. All six PAs induced pneumotoxicity in rats within 48 h. The results demonstrated that pneumotoxicity could be a common phenomenon of PAs and the liver-derived dehydro-PAs might move to the lung and form pyrrole-protein adducts, leading to pulmonary toxicity.

Tunable and reconfigurable materials with autonomic shape transformation in response to the environment have emerged as one of the most promising approaches for a variety of biomedical applications, such as tissue engineering, biosensing, and in vivo biomedical devices. Currently, it is still quite challenging to fabricate soft, microscaled 3D shape-reconfigurable structures due to either complicated microfabrication or limited microscale photopolymerization-based printing approaches to enable adaptive shape transformation. Here, a one-step photo-cross-linking approach has been demonstrated to obtain a 3D-to-3D morphological transformable microhelix from a self-rolled hydrogel microsheet, resulting in chirality conversion. It was enabled by a custom-designed "hard" stripe/"soft" groove topography on the microsheets for introducing, which introduced both in-planar and out-of-planar anisotropies. Both experiment and simulation confirmed that a stripe/groove geometry can effectively control the 3D transformation by activating in-planar or/and out-of-planar mismatch stress within the microsheets, resulting in switching of the rolling direction between perpendicular/parallel to the length of the stripe. Furthermore, versatile 3D microconstructs with the ability to transform between two distinct 3D configurations have been achieved based on controlled rolling of microhelices, demonstrated as "windmill"-to-"T-cross" and "cylinder"-to-"scroll" transformations and dynamic blossoming of biomimetic orchids. In contrast to conventional 2D-to-3D micro-origami, we have successfully demonstrated an approach for fabricating microscale, all-soft-material-based constructs with autonomic 3D-to-3D structural transformation, which presents an opportunity for designing more complex hydrogel-based microrobotics.

Pyrrolizidine alkaloids (PAs) and PA N-oxides are hepatotoxic natural products, produced by over 6000 plant species worldwide. However, an unmet need remains for confirmative measurement of PAs in routine clinical tests. Here, we develop a visual, easy-to-use, and economic mesoporous silica-electrochemiluminescence (MPS-ECL) sensor for point-of-care (POC) testing of PAs, utilizing MPS's amplification effect on positive ions. The relationship between PAs' different structures and corresponding Ru(bpy)

Background: Controversy exists as towards the association of excessive fruits intake and certain disease risks. Longan is an edible fruit rich in high levels of fructose, glucose and sucrose. The aim of this study was to provide direct evidence on the effect of the sugar rich longan fruit on the development of non-alcoholic fatty liver disease (NAFLD). Chemical profiling of longan fruit was conducted using LC-HRMS and HPLC-ELSD.Results: Longan extracts at the doses of 4.0 g/kg, 8.0 and 16.0 g/kg were orally administered for 4 weeks to healthy C57BL/6J mice or to C57BL/6J mice fed with a HFD diet. Fecal microbiome was analyzed by 16S rRNA sequencing. The amounts of short chain fatty acids (SCFAs) in colonic contents were determined by GC-MS. Colon and liver tissues were used for histopathological examination after H&E, Masson’s trichrome, and Oil-red O staining. ELISA method was used for biochemical analysis in serum. In mice fed a normal diet, repeated longan intake for 4 weeks at excess doses (8 or 16 g/kg), but not the normal dose (4 g/kg), promoted inflammation and gut dysbiosis-like status and reduced short-chain fatty acids (SCFAs) production. In high-fat diet (HFD)-fed mice, longan intake at 4 g/kg hardly influenced the NAFLD development. In contrast, excess longan intake (8 or 16 g/kg) promoted NAFLD pathogenesis, including increased abnormality in hepatic indices, elevated inflammation, and gut permeability associated with more severe liver steatosis and fibrosis. Moreover, the exacerbated pathogenic markers were positively correlated with increased blood sugar, aggravated HFD-associated microbial dysbiosis. Conclusions: Effects mediated by excess longan intake resembled that of equivalent free sugars supplementation, suggesting that high level of free sugars in fruits contributed to the promotion of NAFLD development as demonstrated in case of excessive longan intake.

Pyrrolizidine alkaloids (PAs) are the most common plant-derived toxins with emerging evidence to contaminate soil, water, nearby plants and derived food products. Outbreaks of human poisoning cases, due to the ingestion of PA-contaminated food, have been reported in various countries including Ethiopia. This study first investigated the contamination of PAs in retail honey in Ethiopia. A striking 77% of honey samples (27/30) were found to contain PAs with the content ranging over 1.5–323.4 μg/kg. Notably, these PAs were also found as contaminants in mead, an alcoholic beverage made from local honey, indicating the transfer of PAs from the primarily contaminated honey into mead. Further toxicological examinations revealed that long-term PA exposure caused vasculature damage, fibrosis, and steatosis in mouse livers, and co-exposure to dietary alcohol exacerbated the PA-induced chronic hepatotoxicity. Furthermore, the study revealed that moderate alcohol intake did not affect the initiation mechanism (hepatic cytochrome P450-mediated bioactivation) of PA-induced hepatotoxicity but significantly disturbed hepatic glutathione homeostasis, thereby increasing oxidative stress in mouse liver and enhancing PA-induced hepatotoxicity. Our findings exemplify the carry-over of PA contamination through the food chain. Precautionary interventions are warranted on the hazardous effects of dietary exposure to PAs, particularly with concomitant alcohol consumption.

Pyrrolizidine alkaloids (PAs) are the most common phytotoxins with documented human hepatotoxicity. PAs require metabolic activation by cytochromes P450 to generate toxic intermediates which bind to proteins and form protein adducts, thereby causing cytotoxicity. This study investigated the role of the gut–liver axis in PA intoxication and the underlying mechanisms. We exposed mice to retrorsine (RTS), a representative PA, and for the first time found RTS-induced intestinal epithelium damage and disruption to intestinal barrier function. Using mice with tissue-selective ablation of P450 activity, we found that hepatic P450s, but not intestinal P450s, were essential for PA bioactivation. Besides, in RTS-exposed, bile duct-cannulated rats, we found the liver-derived reactive PA metabolites were transported by bile into the intestine to exert enterotoxicity. The impact of gut-derived pathogenic factors in RTS-induced hepatotoxicity was further studied in mice with dextran sulfate sodium (DSS)-induced chronic colitis. DSS treatment increased the hepatic endotoxin level and depleted hepatic reduced glutathione, thereby suppressing the PA detoxification pathway. Compared to RTS-exposed normal mice, the colitic mice displayed more severe RTS-induced hepatic vasculature damage, fibrosis, and steatosis. Overall, our findings provide the first mode-of-action evidence of PA-induced enterotoxicity and highlight the importance of gut barrier function in PA-induced liver injury., Graphical abstract Pyrrolizidine alkaloids (PAs) are common phytotoxins. We provide the first mode-of-action evidence of PA-induced enterotoxicity. A disrupted gut barrier in turn exacerbates PA-induced liver injury via depleting the hepatic glutathione.Image 1

In this work, we present FFB6D, a Full Flow Bidirectional fusion network designed for 6D pose estimation from a single RGBD image. Our key insight is that appearance information in the RGB image and geometry information from the depth image are two complementary data sources, and it still remains unknown how to fully leverage them. Towards this end, we propose FFB6D, which learns to combine appearance and geometry information for representation learning as well as output representation selection. Specifically, at the representation learning stage, we build bidirectional fusion modules in the full flow of the two networks, where fusion is applied to each encoding and decoding layer. In this way, the two networks can leverage local and global complementary information from the other one to obtain better representations. Moreover, at the output representation stage, we designed a simple but effective 3D keypoints selection algorithm considering the texture and geometry information of objects, which simplifies keypoint localization for precise pose estimation. Experimental results show that our method outperforms the state-of-the-art by large margins on several benchmarks. Code and video are available at \url{https://github.com/ethnhe/FFB6D.git}., Accepted to CVPR2021

Misusage of pyrrolizidine alkaloid (PA)-containing plants or unaware intake of PA-contaminated foodstuffs causes thousands of PA poisoning cases in humans. PA intoxication is accompanied by oxidative stress and subsequent extensive hepatocellular damage. Our previous study has demonstrated that 18β-glycyrrhetinic acid (GA), a bioactive constituent of liquorice, prevented PA-induced hepatotoxicity in rats, however the underlying mechanisms remain unclear.This study aims to explore the mechanisms underlying the hepato-protective effect of GA in combating retrorsine (RTS, a representative toxic PA)-induced liver injury.Histological and biochemical assessments were employed to evaluate the protective effect of GA on RTS-induced hepatotoxicity in rats. Sulforhodamine B assay, real-time PCR, western blotting, and immunostaining were used to explore the underlying mechanisms in human hepatocytes and rats.Our findings demonstrated that GA alleviated RTS-induced elevation of serum ALT and bilirubin levels, as well as hepatocytes necrosis and sinusoidal endothelial cells (SECs) damage in rats. GA also enhanced the activities and expressions of several antioxidant enzymes through upregulating nuclear factor-erythroid 2-related factor2 (Nrf2). Moreover, inhibition of Nrf2 blocked the hepatoprotective effect of GA against RTS intoxication. Mechanistically, GA increased the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and enhanced glycogen synthase kinase 3 beta (GSK3β) inhibitory phosphorylation at serine 9, thus promoting the nuclear accumulation of Nrf2 and activating its downstream targets.This study for the first time demonstrated that GA exerted protective effects against RTS-induced liver injury by potentiating the Nrf2-mediated antioxidant system through PI3K/Akt/GSK3β pathway. The findings indicated that GA may serve as a potential candidate drug for the treatment of PA intoxication.

Background: Longan is the fruit of Dimocarpus longan Lour. and the longan arillus has long been used in traditional Chinese medicine possessing various health benefits. However, the excessive intake of longan is found in daily life to cause “shanghuo” syndrome. “Shanghuo” has been linked to increased disease susceptibility. The present study thus aimed to investigate the toxicological outcomes after excessive longan treatment.Methods: Longan extract at a normal dosage of 4 g/kg and two excess dosages of 8 and 16 g/kg was orally administered to normal C57BL/6J mice for two weeks or to C57BL/6J mice with DSS-induced colitis. Mouse gut microbiome were analyzed by 16S rRNA sequencing. Short chain fatty acid (SCFA) contents in colonic contents were measured by GC-MS. Colon tissue was used for histopathological observation after H and E staining, detection of protein expression by western blot, analysis of gene expression by qPCR, and detection of apoptotic cells by TUNEL assay. ELISA was used for biochemical analysis in serum.Results: In normal mice, repeated longan intake at excess doses, but not the normal dose, increased infiltration of inflammatory cells, elevated serum levels of TNF-α and IL-6 and reduced production of SCFAs. In DSS-induced colitic mice, longan intake at 4 g/kg did not promote colitis in mice, while excessive longan (8 or 16 g/kg) aggravated colitis in mice, showing increased inflammation, more serious histological abnormalities, increased gut permeability, and increased epithelia injury when compared to DSS alone. Excessive longan induced a significant reduction of microbial diversity in colitic mice, accompanied with aggravated alterations of DSS-associated bacteria including the increase of Proteobacteria phylum and genera of Bacteroides, Akkermansia, Turicibacter and Escherchia-Shigella, and the decrease of norank_f__Muribaculaceae. The changed microbial compositions were accompanied with decreased SCFAs when longan was supplemented with DSS. The aggravated colon injury by excessive intake of longan in colitic mice was tightly correlated with the altered microbial communities and decreased SCFAs production.Conclusion: Excessive longan intake disturbs gut homeostasis and aggravates colitis via promoting inflammation and altering gut microbe compositions and associated metabolism in mice. Our findings warrant rational longan arillus consumption as a dietary supplement or herbal medicine.

Background and aims Mutational signature analyses are an effective tool in identifying cancer etiology. Humans are frequently exposed to pyrrolizidine alkaloids (PAs), the most common carcinogenic phytotoxins widely distributed in herbal remedies and foods. However, due to the lack of human epidemiological data, PAs are classified as group II hepatocarcinogens by the World Health Organization. This study identified a PA mutational signature as the biomarker to investigate the association of PA exposure with human liver cancer. Approach and results Pyrrole-protein adducts (PPAs), the PA exposure biomarker, were measured and found in 32% of surgically resected specimens from 34 patients with liver cancer in Hong Kong. Next, we delineated the mode of mutagenic and tumorigenic actions of retrorsine, a representative PA, in mice and human hepatocytes (HepaRG). Retrorsine induced DNA adduction, DNA damage, and activation of tumorigenic hepatic progenitor cells, which initiated hepatocarcinogenesis. PA mutational signature, as the unique molecular fingerprint of PA-induced mutation, was derived from exome mutations in retrorsine-exposed mice and HepaRG cells. Notably, PA mutational signature was validated in genomes of patients with PPA-positive liver cancer but not patients with PPA-negative liver cancer, confirming the specificity of this biomarker in revealing PA-associated liver cancers. Furthermore, we examined the established PA mutational signature in 1,513 liver cancer genomes and found that PA-associated liver cancers were potentially prevalent in Asia (Mainland China [48%], Hong Kong [44%], Japan [22%], South Korea [6%], Southeast Asia [25%]) but minor in Western countries (North America [3%] and Europe [5%]). Conclusions This study provides a clinical indication of PA-associated liver cancer. We discovered an unexpectedly extensive implication of PA exposure in patients with liver cancer, laying the scientific basis for precautionary approaches and prevention of PA-associated human liver cancers.

Pyrrolizidine alkaloids (PAs) are naturally occurring hepatotoxins widely present in hundreds of plant species and also known to contaminate many foodstuffs, such as grain, honey, and tea. The formation of pyrrole-protein adducts via metabolic activation of PAs has been suggested as a primary trigger initiating hepatotoxicity. The present study for the first time tested the suitability of pyrrole-hemoglobin adducts as a novel and specific biomarker of PA exposure in humans. The level and elimination kinetics of pyrrole-hemoglobin adducts were systematically investigated in the blood samples of 43 PA-induced liver injury (PA-ILI) patients. The results revealed significantly higher concentrations (84.50 ± 78.38 nM) and longer persistence (~ 4 months) of pyrrole-hemoglobin adducts than that (concentration: 9.53 ± 10.72 nM; persistence: ~ 2 months) of pyrrole-plasma protein adducts, our previously developed PA exposure biomarker. Our findings confirmed that pyrrole-hemoglobin adducts with higher level and longer persistence should serve as a more applicable PA exposure biomarker for future clinical diagnosis of PA-ILI in drug/herb-induced liver injury patients.

In this work, we present a novel data-driven method for robust 6DoF object pose estimation from a single RGBD image. Unlike previous methods that directly regressing pose parameters, we tackle this challenging task with a keypoint-based approach. Specifically, we propose a deep Hough voting network to detect 3D keypoints of objects and then estimate the 6D pose parameters within a least-squares fitting manner. Our method is a natural extension of 2D-keypoint approaches that successfully work on RGB based 6DoF estimation. It allows us to fully utilize the geometric constraint of rigid objects with the extra depth information and is easy for a network to learn and optimize. Extensive experiments were conducted to demonstrate the effectiveness of 3D-keypoint detection in the 6D pose estimation task. Experimental results also show our method outperforms the state-of-the-art methods by large margins on several benchmarks. Code and video are available at https://github.com/ethnhe/PVN3D.git., Comment: Accepted to Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition, 2020. (CVPR 2020)