Fragmentation characteristics-based nontargeted screening method of exogenous chemical residues in animal-derived foods using reversed-phase and hydrophilic interaction liquid chromatography-high-resolution mass spectrometry.

Fragmentation characteristics are crucial for nontargeted screening to discover and identify unknown exogenous chemical residues in animal-derived foods. In this study, first, fragmentation characteristics of 51 classes of exogenous chemical residues were summarized based on experimental mass spectra of standards in reversed-phase and hydrophilic interaction liquid chromatography-high-resolution mass spectrometry (MS) and mass spectra from the MassBank of North America (MoNA) library. According to the proportion of fragmentation characteristics to the total number of chemical residues in each class, four screening levels were defined to classify 51 classes of chemical residues. Then, a nontargeted screening method was developed based on the fragmentation characteristics. The evaluation results of 82 standards indicated that more than 90 % of the chemical residues with MS/MS spectra can be identified at concentrations of 100 and 500 µg/kg, and about 80 % can be identified at 10 µg/kg. Finally, the nontargeted screening method was applied to 16 meat samples and 21 egg samples as examples. As a result, eight chemical residues and transformation products (TPs) of 5 classes in the exemplary samples were found and identified, in which 3 TPs of azithromycin were identified by fragmentation characteristics-assisted structure interpretation. The results demonstrated the practicability of the nontargeted screening method for routine risk screening of food safety.

Integrated analysis of metabolome, transcriptome, and bioclimatic factors of Acer truncatum seeds reveals key candidate genes related to unsaturated fatty acid biosynthesis, and potentially optimal production area.

BACKGROUND: Lipids found in plant seeds are essential for controlling seed dormancy, dispersal, and defenses against biotic and abiotic stress. Additionally, these lipids provide nutrition and energy and are therefore important to the human diet as edible oils. Acer truncatum, which belongs to the Aceaceae family, is widely cultivated around the world for its ornamental value. Further because its seed oil is rich in unsaturated fatty acids (UFAs)- i.e. α-linolenic acid (ALA) and nervonic acid (NA)- and because it has been validated as a new food resource in China, the importance of A. truncatum has greatly risen. However, it remains unknown how UFAs are biosynthesized during the growth season, to what extent environmental factors impact their content, and what areas are potentially optimal for their production. RESULTS: In this study, transcriptome and metabolome of A. truncatum seeds at three representative developmental stages was used to find the accumulation patterns of all major FAs. Cumulatively, 966 metabolites and 87,343 unigenes were detected; the differential expressed unigenes and metabolites were compared between stages as follows: stage 1 vs. 2, stage 1 vs. 3, and stage 2 vs. 3 seeds, respectively. Moreover, 13 fatty acid desaturases (FADs) and 20 ß-ketoacyl-CoA synthases (KCSs) were identified, among which the expression level of FAD3 (Cluster-7222.41455) and KCS20 (Cluster-7222.40643) were consistent with the metabolic results of ALA and NA, respectively. Upon analysis of the geographical origin-affected diversity from 17 various locations, we found significant variation in phenotypes and UFA content. Notably, in this study we found that 7 bioclimatic variables showed considerable influence on FAs contents in A. truncatum seeds oil, suggesting their significance as critical environmental parameters. Ultimately, we developed a model for potentially ecological suitable regions in China. CONCLUSION: This study provides a comprehensive understanding of the relationship between metabolome and transcriptome in A. truncatum at various developmental stages of seeds and a new strategy to enhance seed FA content, especially ALA and NA. This is particularly significant in meeting the increasing demands for high-quality edible oil for human consumption. The study offers a scientific basis for A. truncatum's novel utilization as a woody vegetable oil rather than an ornamental plant, potentially expanding its cultivation worldwide.

Detoxification of tetracycline and synthetic dyes by a newly characterized Lentinula edodes laccase, and safety assessment using proteomic analysis.

Fungal laccase has strong ability in detoxification of many environmental contaminants. A putative laccase gene, LeLac12, from Lentinula edodes was screened by secretome approach. LeLac12 was heterogeneously expressed and purified to characterize its enzymatic properties to evaluate its potential use in bioremediation. This study showed that the extracellular fungal laccase from L. edodes could effectively degrade tetracycline (TET) and the synthetic dye Acid Green 25 (AG). The growth inhibition of Escherichia coli and Bacillus subtilis by TET revealed that the antimicrobial activity was significantly reduced after treatment with the laccase-HBT system. 16 transformation products of TET were identified by UPLC-MS-TOF during the laccase-HBT oxidation process. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that LeLac12 could completely mineralize ring-cleavage products. LeLac12 completely catalyzed 50 mg/L TET within 4 h by adding AG (200 mg/L), while the degradation of AG was above 96% even in the co-contamination system. Proteomic analysis revealed that central carbon metabolism, energy metabolism, and DNA replication/repair were affected by TET treatment and the latter system could contribute to the formation of multidrug-resistant strains. The results demonstrate that LeLac12 is an efficient and environmentally method for the removal of antibiotics and dyes in the complex polluted wastewater.

An exposome atlas of serum reveals the risk of chronic diseases in the Chinese population.

Although adverse environmental exposures are considered a major cause of chronic diseases, current studies provide limited information on real-world chemical exposures and related risks. For this study, we collected serum samples from 5696 healthy people and patients, including those with 12 chronic diseases, in China and completed serum biomonitoring including 267 chemicals via gas and liquid chromatography-tandem mass spectrometry. Seventy-four highly frequently detected exposures were used for exposure characterization and risk analysis. The results show that region is the most critical factor influencing human exposure levels, followed by age. Organochlorine pesticides and perfluoroalkyl substances are associated with multiple chronic diseases, and some of them exceed safe ranges. Multi-exposure models reveal significant risk effects of exposure on hyperlipidemia, metabolic syndrome and hyperuricemia. Overall, this study provides a comprehensive human serum exposome atlas and disease risk information, which can guide subsequent in-depth cause-and-effect studies between environmental exposures and human health.

The silent threat: Nanopolystyrene and chrysene pollutants disrupt the intestinal mucosal barrier, new insights from juvenile Siniperca chuatsi.

The intestinal mucosal barrier-comprising microbial, mechanical, chemical, and immunological barriers-is critical to protection against pathogens and maintenance of host health; however, it remains unclear whether it is affected by environmental contaminants. Therefore, the present study assessed whether exposure to ambient concentrations of nanopolystyrene (NP) and chrysene (CHR)-two ubiquitous environmental pollutants in the aquatic environment-affect the intestinal mucosal barrier in juvenile Siniperca chuatsi. After exposure for 21 days, S. chuatsi exhibited intestinal oxidative stress and imbalance of intestinal microbial homeostasis. NP and/or CHR exposure also disrupted the intestinal mechanical barrier, as evidenced by the altered intestinal epithelial cell morphology, disrupted structure of intercellular tight junctions, and decreased expression of tight junction proteins. Damage to the intestinal chemical barrier manifested as thinning of the mucus layer owing to the loss and damage of goblet cells. Furthermore, the intestinal immunological barrier was impaired as indicated by the loss of intestinal intraepithelial lymphocytes and increase in pro-inflammatory cytokines, chemokines, and immunoglobulins. These findings collectively suggest that the intestinal mucosal barrier was damaged. This study is, to the best of our knowledge, the first to report that exposure to NP and/or CHR at environmentally relevant concentrations disrupts the intestinal mucosal barrier in organisms and highlight the significance of nanoplastic/CHR pollution for intestinal health.

Genome-wide identification of SWEET genes reveals their roles during seed development in peanuts.

Sugar Will Eventually be Exported Transporter (SWEET) proteins are highly conserved in various organisms and play crucial roles in sugar transport processes. However, SWEET proteins in peanuts, an essential leguminous crop worldwide, remain lacking in systematic characterization. Here, we identified 94 SWEET genes encoding the conservative MtN3/saliva domains in three peanut species, including 47 in Arachis hypogea, 23 in Arachis duranensis, and 24 in Arachis ipaensis. We observed significant variations in the exon-intron structure of these genes, while the motifs and domain structures remained highly conserved. Phylogenetic analysis enabled us to categorize the predicted 286 SWEET proteins from eleven species into seven distinct groups. Whole genome duplication/segment duplication and tandem duplication were the primary mechanisms contributing to the expansion of the total number of SWEET genes. In addition, an investigation of cis-elements in the potential promoter regions and expression profiles across 22 samples uncovered the diverse expression patterns of AhSWEET genes in peanuts. AhSWEET24, with the highest expression level in seeds from A. hypogaea Tifrunner, was observed to be localized on both the plasma membrane and endoplasmic reticulum membrane. Moreover, qRT-PCR results suggested that twelve seed-expressed AhSWEET genes were important in the regulation of seed development across four different peanut varieties. Together, our results provide a foundational basis for future investigations into the functions of SWEET genes in peanuts, especially in the process of seed development.

Carbon monoxide-releasing nanomotors based on endogenous biochemical reactions for tumor therapy.

The lack of selective release ability in the tumor microenvironment and the limited efficacy of monotherapy are important factors that limit the current use of carbon monoxide (CO) donors for tumor therapy. Herein, inspired by endogenous biochemical reactions in vivo, one kind of CO-releasing nanomotor was designed for the multimodal synergistic treatment of tumor. Specifically, glucose oxidase (GOx) and 5-aminolevulinic acid (5-ALA) were co-modified onto metal-organic framework material (MIL-101) to obtain MIL-GOx-ALA nanomotors (M-G-A NMs), which exhibit excellent biocompatibility and degradation ability in tumor microenvironment. Subsequently, the released 5-ALA generates CO in the tumor microenvironment through an endogenous reaction and further acts on mitochondria to release large amounts of reactive oxygen species (ROS), which directly kill tumor cells. Furthermore, the produced ROS and the degradation products of M-G-A NMs can also provide the reaction substrate for the Fenton reaction, thereby enhancing chemodynamic therapy (CDT) and inducing apoptosis of tumor cells. Both in vitro and in vivo experimental data confirm the successful occurrence of the above process, and the combination of CO gas therapy/enhanced CDT can effectively inhibit tumor growth. This CDT-enhancing agent designed based on endogenous biochemical reactions has good prospects for tumor treatment application.

Leveraging Unidentified Metabolic Features for Key Pathway Discovery: Chemical Classification-driven Network Analysis in Untargeted Metabolomics.

Untargeted metabolomics using liquid chromatography-electrospray ionization-high-resolution tandem mass spectrometry (UPLC-ESI-MS/MS) provides comprehensive insights into the dynamic changes of metabolites in biological systems. However, numerous unidentified metabolic features limit its utilization. In this study, a novel approach, the Chemical Classification-driven Molecular Network (CCMN), was proposed to unveil key metabolic pathways by leveraging hidden information within unidentified metabolic features. The method was demonstrated by using the herbivore-induced metabolic response in corn silk as a case study. Untargeted metabolomics analysis using UPLC-MS/MS was performed on wild corn silk and two genetically modified lines (pre- and postinsect treatment). Global annotation initially identified 256 (ESI-) and 327 (ESI+) metabolites. MS/MS-based classifications predicted 1939 (ESI-) and 1985 (ESI+) metabolic features into the chemical classes. CCMNs were then constructed using metabolic features shared classes, which facilitated the structure- or class annotation for completely unknown metabolic features. Next, 844/713 significantly decreased and 1593/1378 increased metabolites in ESI-/ESI+ modes were defined in response to insect herbivory, respectively. Method validation on a spiked maize sample demonstrated an overall class prediction accuracy rate of 95.7%. Potential key pathways were prescreened by a hypergeometric test using both structure- and class-annotated differential metabolites. Subsequently, CCMN was used to deeply amend and uncover the pathway metabolites deeply. Finally, 8 key pathways were defined, including phenylpropanoid (C6-C3), flavonoid, octadecanoid, diterpenoid, lignan, steroid, amino acid/small peptide, and monoterpenoid. This study highlights the effectiveness of leveraging unidentified metabolic features. CCMN-based key pathway analysis reduced the bias in conventional pathway enrichment analysis. It provides valuable insights into complex biological processes.

Crystal structure of HPPD inhibitor sensitive protein from Oryza sativa.

4-hydroxyphenylpyruvate dioxygenase (HPPD) Inhibitor Sensitive 1 (HIS1) is an endogenous gene of rice, conferring broad-spectrum resistance to ß-triketone herbicides. Similar genes, known as HIS1-like genes (HSLs), exhibit analogous functions and can complement the herbicide-resistant characteristics endowed by HIS1. The identification of HIS1 and HSLs represents a valuable asset, as the intentional pairing of herbicides with resistance genes emerges as an effective strategy for crop breeding. Encoded by HIS1 is a Fe(II)/2-oxoglutarate-dependent oxygenase responsible for detoxifying ß-triketone herbicides through hydroxylation. However, the precise structure supporting this function remains unclear. This work, which determined the crystal structure of HIS1, reveals a conserved core motif of Fe(II)/2-oxoglutarate-dependent oxygenase and pinpoints the crucial residue dictating substrate preference between HIS1 and HSL.

Nanoplastics and chrysene pollution: Potential new triggers for nonalcoholic fatty liver disease and hepatitis, insights from juvenile Siniperca chuatsi.

Nanopolystyrene (NP) and chrysene (CHR) are ubiquitous contaminants in the natural environment; however, research on their hepatotoxicity and associated adverse effects remains relatively inadequate. The present study aimed to investigate the hepatotoxic effects of NP and/or CHR at environmentally relevant concentrations, as well as the underlying molecular mechanisms, in juvenile Siniperca chuatsi (mandarin fish). After a 21-day exposure period, the livers of exposed S. chuatsi exhibited macrostructural and microstructural damage accompanied by oxidative stress. Importantly, our study provides the first evidence that NP exposure leads to the development of nonalcoholic fatty liver disease (NAFLD) and hepatitis in S. chuatsi. Similarly, CHR exposure has also been found, for the first time, to cause hepatic sinusoidal dilatation (HSD) and hepatitis. Exposure to the combination of NP and CHR alleviated the symptoms of NAFLD, HSD, and hepatitis. Furthermore, our comprehensive multi-omic analysis revealed that the pathogenesis of NP-induced NAFLD was mainly due to induction of the triglyceride synthesis pathway and inhibition of the very-low-density lipoprotein secretion process. CHR induced HSD primarily through a reduction in vasoprotective ability and smooth muscle contractility. Hepatitis was induced by activation of the JAK-STAT/NF-kappa B signaling pathways, which upregulated the expression of inflammation-specific genes. Collectively, results of this study offer novel insight into the multiple hepatotoxicity endpoints of NP and/or CHR exposure at environmentally relevant concentrations in organisms, and highlight the importance of nanoplastic/CHR pollution for liver health.

Fine-Scale Characterization of Plant Diterpene Glycosides Using Energy-Resolved Untargeted LC-MS/MS Metabolomics Analysis.

Plant diterpene glycosides are essential for diverse physiological processes. Comprehensive structural characterization proved to be a challenge due to variations in glycosylation patterns, diverse aglycone structures, and the absence of comprehensive reference databases. In this study, a method for fine-scale characterization was proposed based on energy-resolved (ER) untargeted LC-MS/MS metabolomics analysis using steviol glycosides as a demonstration. Energy-dependent fragmentation patterns were unveiled by a series of model compounds. Distinct glycosylation sites were discerned by leveraging varying fragmentation energies for the precursor ions. The sugar moiety linkage at C19OOH (R1) exhibited facile and intact cleavage at low collision energies, while the sugar moiety at C13-OH (R2) demonstrated consecutive cleavage with increasing energy. Aglycone ions exhibited a higher relative intensity at NCE 50, with relative intensities ranging from 95% to 100%. Subsequently, aglycone candidates, R1 sugar composition, and R2 sugar sequence were deduced through ER-MS/MS analysis. The developed method was applied to Stevia rebaudiana leaves. A total of 91 diterpene glycosides were unambiguously identified, including 16 steviol glycosides with novel acetylglycosylation patterns. This method offers a rapid alternative for glycan analysis and the structural differentiation of isomers. The developed method enhances the understanding of diterpene glycosides in plants, providing a reliable tool for the in-depth characterization of complex metabolite profiles.

Rational Electrochemical Design of Cuprous Oxide Hierarchical Microarchitectures and Their Derivatives for SERS Sensing Applications.

Rational morphology control of inorganic microarchitectures is important in diverse fields, requiring precise regulation of nucleation and growth processes. While wet chemical methods have achieved success regarding the shape-controlled synthesis of micro/nanostructures, accurately controlling the growth behavior in real time remains challenging. Comparatively, the electrodeposition technique can immediately control the growth behavior by tuning the overpotential, whereas it is rarely used to design complex microarchitectures. Here, the electrochemical design of complex Cu2 O microarchitectures step-by-step by precisely controlling the growth behavior is demonstrated. The growth modes can be switched between the thermodynamic and kinetic modes by varying the overpotential. Cl- ions preferably adhered to {100} facets to modulate growth rates of these facets is proved. The discovered growth modes to prepare Cu2 O microarchitectures composed of multiple building units inaccessible with existing methods are employed. Polyvinyl alcohol (PVA) additives can guarantee all pre-electrodeposits simultaneously evolve into uniform microarchitectures, instead of forming undesired microstructures on bare electrode surfaces in following electrodeposition processes is discovered. The designed Cu2 O microarchitectures can be converted into noble metal microstructures with shapes unchanged, which can be used as surface-enhanced Raman scattering substrates. An electrochemical avenue toward rational design of complex inorganic microarchitectures is opened up.

The Ruminococcus bromii amylosome protein Sas6 binds single and double helical α-glucan structures in starch.

Resistant starch is a prebiotic accessed by gut bacteria with specialized amylases and starch-binding proteins. The human gut symbiont Ruminococcus bromii expresses Sas6 (Starch Adherence System member 6), which consists of two starch-specific carbohydrate-binding modules from family 26 (RbCBM26) and family 74 (RbCBM74). Here, we present the crystal structures of Sas6 and of RbCBM74 bound with a double helical dimer of maltodecaose. The RbCBM74 starch-binding groove complements the double helical α-glucan geometry of amylopectin, suggesting that this module selects this feature in starch granules. Isothermal titration calorimetry and native mass spectrometry demonstrate that RbCBM74 recognizes longer single and double helical α-glucans, while RbCBM26 binds short maltooligosaccharides. Bioinformatic analysis supports the conservation of the amylopectin-targeting platform in CBM74s from resistant-starch degrading bacteria. Our results suggest that RbCBM74 and RbCBM26 within Sas6 recognize discrete aspects of the starch granule, providing molecular insight into how this structure is accommodated by gut bacteria.

Label-free and highly sensitive detection of microRNA from cancer cells via target-induced cascade amplification generation of lighting-up RNA aptamers.

The abnormal expression levels of miRNAs have been proven to be highly related to the generation of various diseases and are also closely associated with the stages and types of disease development. The novel RNA aptamers-based homogenous fluorescent methods were simple, with low background signal and high signal-to-noise ratio, but lacked effective signal amplification technology to achieve sensitive detection of trace miRNA markers. There is an urgent need for combining effective nucleic acid amplification technology with RNA aptamer to achieve highly sensitive and accurate detection of miRNA. For this purpose, a new DNA multi-arm nanostructure-based dual rolling circle transcription machinery for the generation of lighting-up MG RNA aptamers is constructed for label-free and highly sensitive sensing of miRNA-21. In this system, the target miRNA-21 induces a structural transformation of the DNA multi-arm nanostructure probe to recycle miRNA-21 and trigger two independent rolling circle transcription reactions to generate two long RNAs, which can partially hybridize with each other to generate large amounts of complete MG RNA aptamers. These RNA aptamers can associate with organic MG dye to produce significantly enhanced fluorescence signals to accomplish ultrasensitive miRNA-21 detection down to 0.9 fM. In addition, this method exhibits high selectivity to distinguish miRNA-21 even with single nucleotide mismatch, and also has potential application capability to monitor different expression levels of miRNA-21 from different cancer cells. The effective collaboration between MG RNA aptamer and rolling circle transcription reaction makes this fluorescent method show the significant advantages of low background signal, high signal-to-noise ratio and high detection sensitivity. It has great potential to be a promising means to achieve label-free and highly sensitive monitoring of other trace biological markers via a simple change of target sequence.

Strategy for Comprehensive Detection and Annotation of Gut Microbiota-Related Metabolites Based on Liquid Chromatography-High-Resolution Mass Spectrometry.

Gut microbiota, widely populating the mammalian gastrointestinal tract, plays an important role in regulating diverse pathophysiological processes by producing bioactive molecules. Extensive detection of these molecules contributes to probing microbiota function but is limited by insufficient identification of existing analytical methods. In this study, a systematic strategy was proposed to detect and annotate gut microbiota-related metabolites on a large scale. A pentafluorophenyl (PFP) column-based liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method was first developed for high-coverage analysis of gut microbiota-related metabolites, which was verified to be stable and robust with a wide linearity range, high sensitivity, satisfactory recovery, and repeatability. Then, an informative database integrating 968 knowledge-based microbiota-related metabolites and 282 sample-sourced ones defined by germ-free (GF)/antibiotic-treated (ABX) models was constructed and subsequently used for targeted extraction and annotation in biological samples. Using pooled feces, plasma, and urine of mice for demonstration application, 672 microbiota-related metabolites were annotated, including 21% neglected by routine nontargeted peak detection. This strategy serves as a useful tool for the comprehensive capture of the intestinal flora metabolome, contributing to our deeper understanding of microbe-host interactions.

Screening and identification of unknown chemical contaminants in food based on liquid chromatography-high-resolution mass spectrometry and machine learning.

Unknown or unexpected chemical contaminants and/or their transformation products in food that may be harmful to humans need to be discovered for comprehensive safety evaluation. Liquid chromatography-high-resolution mass spectrometry (LC-HRMS) is a powerful tool for detecting chemical contaminants in food samples. However, identifying all of peaks in LC-HRMS is not possible, but if class information is known in advance, further identification will become easier. In this work, a novel MS2 spectra classification-driven screening strategy was constructed based on LC-HRMS and machine learning. First, the classification model was developed based on machine learning algorithm using class information and experimental MS2 data of chemical contaminants and other non-contaminants. By using the developed artificial neural network classification model, in total 32 classes of pesticides, veterinary drugs and mycotoxins were classified with good prediction accuracy and low false-positive rate. Based on the classification model, a screening procedure was developed in which the classes of unknown features in LC-HRMS were first predicted through the classification model, and then their structures were identified under the guidance of class information. Finally, the developed strategy was tentatively applied to the analysis of pork and aquatic products, and 8 chemical contaminants and 11 transformation products belonging to 8 classes were found. This strategy enables screening of unknown chemical contaminants and transformation products in complex food matrices.

Cobalt-Catalyzed Enantioselective Reductive Amination of Ketones with Hydrazides.

An efficient cobalt-catalyzed asymmetric reductive amination of ketones with hydrazides has been realized, directly producing valuable chiral hydrazines in high yields and enantioselectivities (up to 98% enantiomeric excess).

Histopathological, physiological, and multi-omics insights into the hepatotoxicity mechanism of nanopolystyrene and/or diclofenac in Mylopharyngodon piceus.

Nanopolystyrene (NP) and diclofenac (DCF) are common environmental contaminants in the aquatic ecosystem; therefore, the present study aimed to investigate the hepatotoxicity of NP and/or DCF exposure on aquatic organisms and the underlying mechanisms. Juvenile Mylopharyngodon piceus were used as a model organism to study the effects of NP and/or DCF exposure at environmentally relevant concentrations for 21 days. Subchronic exposure to NP and/or DCF resulted in liver histological damage. In the NP group, the presence of large lipid droplets was observed, whereas the DCF group exhibited marked hepatic sinusoidal dilatation accompanied by inflammation. Additionally, this exposure induced liver oxidative stress, as evidenced by the changes in several physiological parameters, including catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), reactive oxygen species (ROS), and malondialdehyde (MDA). Integrated transcriptomic and metabolomic analysis was performed to further investigate the molecular mechanism underlying hepatotoxicity. Multi-omics analysis demonstrated, for the first time to our knowledge, that NP induced hepatic steatosis mainly through activating the glycerol-3-phosphate pathway and inhibiting VLDL assembly by targeting several key enzyme genes including GPAT, DGAT, ACSL, APOB, and MTTP. Furthermore, NP exposure disrupted arachidonic acid metabolism, which induced the release of inflammatory factors and inhibited the release of anti-inflammatory factors, ultimately causing liver inflammation in M. piceus. In contrast, DCF induced interleukin production and downregulated KLF2, causing hepatic sinusoidal dilatation with inflammation in juvenile M. piceus, which is consistent with the finding of JAK-STAT signaling pathway activation. In addition, the upregulated AMPK signaling pathway in the DCF group suggested perturbation of energy metabolism. Collectively, these findings provide novel insights into the molecular mechanism of the multiple hepatotoxicity endpoints of NP and/or DCF exposure in aquatic organisms.

Physically cross-linked chitosan gel with tunable mechanics and biodegradability for tissue engineering scaffold.

Chitosan, a cationic polysaccharide, exhibits promising potential for tissue engineering applications. However, the poor mechanical properties and rapid biodegradation have been the major limitations for its applications. In this work, an effective strategy was proposed to optimize the mechanical performance and degradation rate of chitosan gel scaffolds by regulating the water content. Physical chitosan hydrogel (HG, with 93.57 % water) was prepared by temperature-controlled cross-linking, followed by dehydration to obtain xerogel (XG, with 2.84 % water) and rehydration to produce wet gel (WG, with 56.06 % water). During this process, changes of water content significantly influenced the water existence state, hydrogen bonding, and the chain entanglements of chitosan in the gel network. The mechanical compression results showed that the chitosan gel scaffolds exhibited tunable compressive strength (0.3128-139 MPa) and compressive modulus (0.2408-1094 MPa). XG could support weights exceeding 65,000 times its own mass while maintaining structural stability. Furthermore, in vitro and in vivo experiments demonstrated that XG and WG exhibited better biocompatibility and resistance to biodegradation compared with HG. Overall, this work contributes to the design and optimization of chitosan scaffolds without additional chemical crosslinkers, which has potential in tissue engineering and further clinical translation.

Statistical Insight into China's Indigenous Diagnosis-Related-Group System Evolution.

The use of Diagnosis-Related Groups (DRG) is a prevalent payment system employed to control hospitalization costs and improve medical efficiency. China has developed an indigenized DRG payment system including Single Disease Payment (SDP), DRGs, and Big Data Diagnosis-Intervention Packet (DIP). In this study, we took cholecystitis as an example, drawing on both primary and secondary data to verify the effectiveness of China's indigenized DRG system and to introduce the evolution of DRGs in China. Primary data were gathered from Qilu Hospital in 2019-2021. Secondary data were collected from published literature from 2004-2016. Only studies with both pre-SDP/DRG and post-SDP/DRG groups were included. Among the studies included, 92.9% (13/14) reported a significant reduction in hospitalization costs after the implementation of SDP while other studies identified length of stay (LOS) and age as the most significant influential factors in SDP. Furthermore, we elaborated the efficiency of DRGs using data from 2738 inpatients in Qilu hospital. Moreover, 60% (6/10) of the studies from the databases also showed the efficiency of DRGs in different regions. SDP is efficient in saving hospitalization costs, but its implementation is limited. DRGs have a broader scope of application, but their effectiveness remains to be validated. DIP is a brand new concept in China, and more data are needed to assess its efficiency.