CCAR1 promotes DNA repair via alternative splicing.

DNA repair is directly performed by hundreds of core factors and indirectly regulated by thousands of others. We massively expanded a CRISPR inhibition and Cas9-editing screening system to discover factors indirectly modulating homology-directed repair (HDR) in the context of ∼18,000 individual gene knockdowns. We focused on CCAR1, a poorly understood gene that we found the depletion of reduced both HDR and interstrand crosslink repair, phenocopying the loss of the Fanconi anemia pathway. CCAR1 loss abrogated FANCA protein without substantial reduction in the level of its mRNA or that of other FA genes. We instead found that CCAR1 prevents inclusion of a poison exon in FANCA. Transcriptomic analysis revealed that the CCAR1 splicing modulatory activity is not limited to FANCA, and it instead regulates widespread changes in alternative splicing that would damage coding sequences in mouse and human cells. CCAR1 therefore has an unanticipated function as a splicing fidelity factor.

Correlation between motor function and health-related quality of life in early to mid-stage patients with Parkinson disease: a cross-sectional observational study.

Aim: To investigate the correlation between motor function and health-related quality of life (HrQOL) in early to mid-stage patients with Parkinson disease (PwP). Methods: This cross-sectional study recruited PwP from April 2020 to December 2023 at the outpatient clinic of Peking Union Medical College Hospital in Beijing, China. The motor symptoms were assessed using Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part 3. Balance function was evaluated using the Berg Balance Scale (BBS), and the risk of fall using Timed Up-and-Go test (TUG), and Five Times Sit-to-Stand test (FTSST). Freezing of gait questionnaire (FOGQ) was used to evaluate the severity of gait. The Intelligent Device for Energy Expenditure and Physical Activity (IDEEA) recorded gait cycle parameters, and the isokinetic dynamometer measured muscle strength. The Parkinson's Disease Questionnaire-39 (PDQ-39) was used to measure HrQOL. All assessments were tested during the on state. Spearman correlation was conducted to evaluate the correlation between motor function and HrQOL. Results: 243 patients with mean age of 69.33 years were enrolled. The PDQ-39 score was strongly correlated with FOG in H&Y stage III (r = 0.653, p < 0.001) and moderately correlated in H&Y stage I (r = 0.471, p < 0.001) and H&Y stage II (r = 0.386, p < 0.001). Furthermore, the FOG was strongly correlated with mobility domain at H&Y stage III (r = 0.694, p < 0.001) and moderately correlated at H&Y stage I (r = 0.431, p < 0.001) and H&Y stage II (r = 0.434, p < 0.001). All motor function scores were correlated with PDQ-39 scores at H&Y stage III (p < 0.05). Conclusion: Motor function correlated with HrQOL in early to mid-stage PwP, and FOG was the main factor, especially affecting mobility, activities of daily life and communication. HrQOL in patients at different disease stages were variously affected by motor function, and HrQOL and multiple dimensions was significantly associated with motor function in patients at H&Y stage III.

Sulfur vacancy-rich bismuth sulfide nanowire derived from CAU-17 for radioactive iodine capture in complex environments: Performance and intrinsic mechanisms.

Effective capture and immobilization of volatile radioiodine from the off-gas of post-treatment plants is crucial for nuclear safety and public health, considering its long half-life, high toxicity, and environmental mobility. Herein, sulfur vacancy-rich Vs-Bi2S3@C nanocomposites were systematically synthesized via a one-step solvothermal vulcanization of CAU-17 precursor. Batch adsorption experiments demonstrated that the as-synthesized materials exhibited superior iodine adsorption capacity (1505.8 mg g-1 at 200 °C), fast equilibrium time (60 min), and high chemisorption ratio (91.7%), which might benefit from the nanowire structure and abundant sulfur vacancies of Bi2S3. Furthermore, Vs-Bi2S3@C composites exhibited excellent iodine capture performance in complex environments (high temperatures, high humidity and radiation exposure). Mechanistic investigations revealed that the I2 capture by fabricated materials primarily involved the chemical adsorption between Bi2S3 and I2 to form BiI3, and the interaction of I2 with electrons provided by sulfur vacancies to form polyiodide anions (I3-). The post-adsorbed iodine samples were successfully immobilized into commercial glass fractions in a stable form (BixOyI), exhibiting a normalized iodine leaching rate of 3.81 × 10-5 g m-2 d-1. Overall, our work offers a novel strategy for the design of adsorbent materials tailed for efficient capture and immobilization of volatile radioiodine.

Development of a NiFe2O4 covalent organic framework based magnetic solid-phase extraction approach for specific capture of quinolones in animal innards prior to UHPLC-Q-Orbitrap HRMS detection.

This study aimed to present a selective and effective method for analyzing quinolones (QNs) in food matrix. Herein, a NiFe2O4-based magnetic sodium disulfonate covalent organic framework (NiFe2O4/COF) was prepared using a simple solvent-free grinding method, and was adopted as a selective adsorbent for magnetic solid phase extraction of QNs. Coupled with UHPLC-Q-Orbitrap HRMS, an efficient method for simultaneous detection of 18 kinds of QNs was established. The method exhibited good linearity (0.01-100 ng g-1), high sensitivity (LODs ranging from 0.0011 to 0.0652 ng g-1) and precision (RSDs below 9.5%). Successful extraction of QNs from liver and kidney samples was achieved with satisfactory recoveries ranging from 82.2% to 108.4%. The abundant sulfonate functional groups on NiFe2O4/COF facilitated strong affinity to QNs through electrostatic and hydrogen bonding interactions. The proposed method provides a new idea for the extraction of contaminants with target selectivity.

Appropriate induction of TOC1 ensures optimal MYB44 expression in ABA signaling and stress response in Arabidopsis.

Plants possess the remarkable ability to integrate the circadian clock with various signalling pathways, enabling them to quickly detect and react to both external and internal stress signals. However, the interplay between the circadian clock and biological processes in orchestrating responses to environmental stresses remains poorly understood. TOC1, a core component of the plant circadian clock, plays a vital role in maintaining circadian rhythmicity and participating in plant defences. Here, our study reveals a direct interaction between TOC1 and the promoter region of MYB44, a key gene involved in plant defence. TOC1 rhythmically represses MYB44 expression, thereby ensuring elevated MYB44 expression at dawn to help the plant in coping with lowest temperatures during diurnal cycles. Additionally, both TOC1 and MYB44 can be induced by cold stress in an Abscisic acid (ABA)-dependent and independent manner. TOC1 demonstrates a rapid induction in response to lower temperatures compared to ABA treatment, suggesting timely flexible regulation of TOC1-MYB44 regulatory module by the circadian clock in ensuring a proper response to diverse stresses and maintaining a balance between normal physiological processes and energy-consuming stress responses. Our study elucidates the role of TOC1 in effectively modulating expression of MYB44, providing insights into the regulatory network connecting the circadian clock, ABA signalling, and stress-responsive genes.

Acquired Multidrug Resistance in AML Is Caused by Low Apoptotic Priming in Relapsed Myeloblasts.

In many cancers, mortality is associated with the emergence of relapse with multidrug resistance (MDR). Thus far, the investigation of cancer relapse mechanisms has largely focused on acquired genetic mutations. Using acute myeloid leukemia (AML) patient-derived xenografts (PDX), we systematically elucidated a basis of MDR and identified drug sensitivity in relapsed AML. We derived pharmacologic sensitivity for 22 AML PDX models using dynamic BH3 profiling (DBP), together with genomics and transcriptomics. Using in vivo acquired resistant PDXs, we found that resistance to unrelated, narrowly targeted agents in distinct PDXs was accompanied by broad resistance to drugs with disparate mechanisms. Moreover, baseline mitochondrial apoptotic priming was consistently reduced regardless of the class of drug-inducing selection. By applying DBP, we identified drugs showing effective in vivo activity in resistant models. This study implies evasion of apoptosis drives drug resistance and demonstrates the feasibility of the DBP approach to identify active drugs for patients with relapsed AML. SIGNIFICANCE: Acquired resistance to targeted therapy remains challenging in AML. We found that reduction in mitochondrial priming and common transcriptomic signatures was a conserved mechanism of acquired resistance across different drug classes in vivo. Drugs active in vivo can be identified even in the multidrug resistant state by DBP.

N6-methyladenosine-modified CircPSMA7 enhances bladder cancer malignancy through the miR-128-3p/MAPK1 axis.

Several studies have indicated that circular RNAs (circRNAs) play vital roles in the progression of various diseases, including bladder cancer (BCa). However, the underlying mechanisms by which circRNAs drive BCa malignancy remain unclear. In this study, we identified a novel circRNA, circPSMA7 (circbaseID:has_circ_0003456), showing increased expression in BCa cell lines and tissues, by integrating the reported information with circRNA-seq and qRT-PCR. We revealed that circPSMA7 is associated with a higher tumor grade and stage in BCa. M6A modification was identified in circPSMA7, and IGF2BP3 recognized this modification and stabilized circPSMA7, subsequently increasing the circPSMA7 expression. In vitro and in vivo experiments showed that circPSMA7 promoted BCa proliferation and metastasis by regulating the cell cycle and EMT processes. CircPSMA7 acted as a sponge for miR-128-3p, which showed antitumor effects in BCa cell lines, increasing the expression of MAPK1. The tumor proliferation and metastasis suppression induced by silencing circPSMA7 could be partly reversed by miR-128-3p inhibition. Thus, the METTL3/IGF2BP3/circPSMA7/miR-128-3p/MAPK1 axis plays a critical role in BCa progression. Furthermore, circPSMA7 may be a potential diagnostic biomarker and novel therapeutic target for patients with BCa.

Association Between Atherogenic Index of Plasma and Risk of Incident Major Adverse Cardiovascular Events.

It is unclear whether the atherogenic index of plasma (AIP) is associated with major adverse cardiovascular events (MACEs) in the general population. A total of 361,644 participants (aged 56.19 ± 8.09 years; 44.79% male) free of a history of MACEs at baseline from the UK Biobank data were included in the analysis. The AIP was calculated using log (triglyceride/high-density lipoprotein-cholesterol). Over a mean follow-up of 12.19 ± 1.60 years, 16,683 participants developed MACEs. After adjustment for traditional risk factors, each 1 unit increase in AIP was associated with a 45.3% higher risk of incident MACEs (hazard ratio (HR), 1.453 [95% confidence interval (CI) 1.371-1.540], P < 0.001). Results were similar when individuals were categorized by the AIP quartiles (HR, 1.283 [95% CI 1.217-1.351]; comparing extreme quartiles). The subgroup analyses showed that the association between AIP and risk of incident MACEs was more obvious in female participants who are < 60 years old and free of hypertension or diabetes. Sensitivity analysis included participants without any lipid-lowering medication or excluded incident MACEs in the first 2 years of follow-up confirming the robustness of the findings. Elevated AIP is a risk factor of incident MACEs in the general population, independent of traditional risk factors.Dynamic monitoring of the AIP may help select the population at high risk of cardiovascular events and guide primary prevention.

Fabrication of a magnetic metal-organic framework/covalent organic framework composite for simultaneous magnetic solid-phase extraction of seventeen trace quinolones residues in meats.

Effective capture of quinolones (QNs) in animal-derived food is a vital procedure for food safety monitoring. However, the lack of adsorption specificity and difficult to recycle in complex substrate conditions have been major problems for most of the adsorbents. In this work, a magnetic Fe3O4/MOF/COF composite (named Fe3O4@NH2-MIL-125@TpPa-SO3H) was successfully synthesized with good magnetic responsiveness and conspicuous affinity towards QNs. The Fe3O4/MOF/COF composite was used as a magnetic solid-phase extraction (MSPE) adsorbent for pretreatment and determination of QNs in meat samples. Under optimal MSPE conditions in combination with high performance liquid chromatography-quadrupole orbitrap high resolution mass spectrometer (HPLC-Q-Orbitrap HRMS), the proposed method had good linearity (R2 ≥ 0.9978) from 0.01 to 100ng g-1, low limits of detection (0.0016 to 0.0940ng g-1), good precision with relative standard deviations lower than 5.8%. This method was effectively applied to the detection of 17 QNs in the spiked pork, chicken and beef samples with satisfactory recoveries from 83.9 to 106.2%. The separation selectivity mainly due to the π-π interaction, hydrogen bonding, and electrostatic attraction between QNs and the sulfonic acid and amino functional groups of the composite. After verification, the stability and reusability of the composite meet the requirements of complex matrix sample pretreatment. The developed MSPE method based on the magnetic Fe3O4/MOF/COF composite provided an ideal sample pretreatment alternative for determining trace QNs in complex matrixes with selectivity, simplicity, rapidity, and efficiency.

ANGPTL3 negatively regulates IL-1ß-induced NF-κB activation by inhibiting the IL1R1-associated signaling complex assembly.

Interleukin-1ß (IL-1ß)-induced signaling is one of the most important pathways in regulating inflammation and immunity. The assembly of the receptor complex, consisting of the ligand IL-1ß, the IL-1 receptor (IL-1R) type 1 (IL1R1), and the IL-1R accessory protein (IL1RAP), initiates this signaling. However, how the IL1R1-associated complex is regulated remains elusive. Angiopoietin like 3 (ANGPTL3), a key inhibitor of plasma triglyceride clearance, is mainly expressed in the liver and exists in both intracellular and extracellular secreted forms. Presently, ANGPTL3 has emerged as a highly promising drug target for hypertriglyceridemia and associated cardiovascular diseases. However, most studies have focused on the secreted form of ANGPTL3, while its intracellular role is still largely unknown. Here, we report that intracellular ANGPTL3 acts as a negative regulator of IL-1ß-triggered signaling. Overexpression of ANGPTL3 inhibited IL-1ß-induced NF-κB activation and the transcription of inflammatory genes in HepG2, THP1, and HEK293T cells, while knockdown or knockout of ANGPTL3 resulted in opposite effects. Mechanistically, ANGPTL3 interacted with IL1R1 and IL1RAP through its intracellular C-terminal fibrinogen-like domain (FLD) and disrupted the assembly of the IL1R1-associated complex. Taken together, our study reveals a novel role for ANGPTL3 in inflammation, whereby it inhibits the physiological interaction between IL1R1 and IL1RAP to maintain immune tolerance and homeostasis in the liver.

Do Types of Information in an Animated Video Intervention Affect University Students' Autism Knowledge and Openness Towards Peers on the Autism Spectrum?

This pre-test post-test control group design sought to compare the effectiveness of delivering different types of information ([1] factual information vs. [2] factual information + descriptive and explanatory information vs. [3] factual information + descriptive, explanatory + directive information) in an animated video intervention in increasing university students' autism knowledge and openness toward peers on the autism spectrum. The sample consisted of 92 undergraduates (27 males, 65 females; age range = 18-36) from various universities in Singapore. Participants were randomly assigned to one of the three experimental conditions/videos, where they completed a measure of their autism knowledge and openness scale, before viewing a 5-minute long animated video containing different types of information about autism. After which, participants completed the measure of autism knowledge and openness scale again, followed by a measure of their empathy level. Results indicated that participants' autism knowledge improved following the viewing of the animated video. However, the three different videos containing different types of information did not differ in influencing participants' openness toward peers on the autism spectrum. Nevertheless, qualitative responses proposed that the video containing factual information, with descriptive, explanatory, and directive information was useful in helping participants to know how to interact with their peers on the autism spectrum. The findings of this study provide preliminary support for the most effective method to educate and raise awareness about autism, among the general student population in order to foster a supportive and inclusive environment.

Distribution, sources, and ecological risk assessment of polycyclic aromatic hydrocarbons in sediments from Baiyang Lake, China.

The issue of polycyclic aromatic hydrocarbons (PAHs) has been an environmental focus worldwide. In this study, the contents, sources, and ecological risks of sixteen PAHs in the sediment of Baiyang Lake were estimated, and a list of priority pollutants was established. The total PAH contents ranged from 114 to 1010 ng·g-1. The composition of PAHs indicated that 4- to 6-ring PAHs predominated in the sediment samples. The diagnostic ratio analysis showed that combustion sources were predominant for PAHs in Baiyang Lake. Specifically, the positive matrix factorization model indicated that diesel engine emissions, gasoline engine emissions, wood combustion sources, and coal combustion sources contributed 22, 32, 24, and 22% of ∑PAHs, respectively. Based on the sediment quality guidelines, mean effects range median quotient, ecological risk quotient, and toxicity equivalent quotient methods, the comprehensive assessment results of PAHs in Baiyang Lake sediments indicated that the ecological risks were at medium and low levels. The priority pollutant list showed that benzo[b]fluoranthene and benzo[a]pyrene were the highest-priority pollutants and thus should be given more attention.

Structurally Diverse Sesquiterpenoids from the Genus of Ainsliaea.

The genus of Ainsliaea embraces approximately 70 recognized species, many of which have been used to treat various diseases in folklore medicines. As the main metabolites of Ainsliaea plants, Ainsliaea sesquiterpenoids have drawn considerable attention in related scientific communities due to their intriguing structures and a variety of bioactivities. In this review, we intend to provide a full-aspect coverage of sesquiterpenoids reported from the genus of Ainsliaea, including 145 monomeric sesquiterpenoids and 30 oligomeric ones. Multiple aspects will be summarized, including their classification, distributions, structures, bioactivities, and biomimetic syntheses. In addition, their possible biosynthetic pathway will be discussed in detail.

OsTOC1 plays dual roles in the regulation of plant circadian clock by functioning as a direct transcription activator or repressor.

Plant clock function relies on precise timing of gene expression through complex regulatory networks consisting of activators and repressors at the core of oscillators. Although TIMING OF CAB EXPRESSION 1 (TOC1) has been recognized as a repressor involved in shaping oscillations and regulating clock-driven processes, its potential to directly activate gene expression remains unclear. In this study, we find that OsTOC1 primarily acts as a transcriptional repressor for core clock components, including OsLHY and OsGI. Here, we show that OsTOC1 possesses the ability to directly activate the expression of circadian target genes. Through binding to the promoters of OsTGAL3a/b, transient activation of OsTOC1 induces the expression of OsTGAL3a/b, indicating its role as an activator contributing to pathogen resistance. Moreover, TOC1 participates in regulating multiple yield-related traits in rice. These findings suggest that TOC1's function as a transcriptional repressor is not inherent, providing flexibility to circadian regulations, particularly in outputs.

Machine learning analysis of humoral and cellular responses to SARS-CoV-2 infection in young adults.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces B and T cell responses, contributing to virus neutralization. In a cohort of 2,911 young adults, we identified 65 individuals who had an asymptomatic or mildly symptomatic SARS-CoV-2 infection and characterized their humoral and T cell responses to the Spike (S), Nucleocapsid (N) and Membrane (M) proteins. We found that previous infection induced CD4 T cells that vigorously responded to pools of peptides derived from the S and N proteins. By using statistical and machine learning models, we observed that the T cell response highly correlated with a compound titer of antibodies against the Receptor Binding Domain (RBD), S and N. However, while serum antibodies decayed over time, the cellular phenotype of these individuals remained stable over four months. Our computational analysis demonstrates that in young adults, asymptomatic and paucisymptomatic SARS-CoV-2 infections can induce robust and long-lasting CD4 T cell responses that exhibit slower decays than antibody titers. These observations imply that next-generation COVID-19 vaccines should be designed to induce stronger cellular responses to sustain the generation of potent neutralizing antibodies.

[Effects of Nitrogen and Phosphorus Addition on Soil Nutrient Content and Stoichiometry in Desert Grassland].

In order to discuss the response of soil nutrient content, stoichiometric ratio, and dynamic nutrient balance to the addition of multiple restrictive nutrients, the correlation between available nutrients and total nutrients in soil, as well as the indication of soil total and available stoichiometric characteristics, were studied in a desert grassland subjected to 4 years of nutrient addition treatments. The Ningxia desert grassland was used as the research object to carry out nitrogen (N) and phosphorus (P) addition experiments. The experiment included four treatments:control (CK), N addition[10 g·(m2·a)-1], P addition[10 g·(m2·a)-1], and NP co-addition (10 g·(m2·a)-1 N+10 g·(m2·a)-1 P). The results showed that:① in the fourth year of nutrient addition, soil total nitrogen (TN) content was significantly increased. The N:P ratio was significantly increased by N addition, and soil organic carbon (SOC) content was significantly increased by P addition and NP co-addition. In the third and fourth years of nutrient addition, the soil available N:P ratio (AN:AP) was significantly increased by N addition; N addition and NP co-addition significantly increased the content of ammonium nitrogen (NH4+-N) and nitrate nitrogen (NO3--N) but significantly reduced the soil available C:N ratio. P addition and NP co-addition significantly increased total phosphorus (TP) and soil available phosphorus (AP), whereas it significantly reduced the soil total and available C:P and N:P ratios. ② The interaction between N addition and P addition had a combined effect on NH4+-N, AP, available C:N, and AN:AP ratio of desert grassland. ③ The soil C:N ratio was relatively stable in desert grassland, soil N:P ratio was mainly limited by soil TP content, and the soil available C:P and AN:AP ratios were mainly limited by soil AP content. ④ There were cumulative effects of N and P additions on soil N, SOC, and inorganic nitrogen. N limitation in desert grassland was alleviated by N addition, whereas it was aggravated by P addition and NP co-addition. The variation coefficients of soil available stoichiometric characteristics were higher than that of soil total stoichiometric characteristics. Soil available stoichiometry was more sensitive to N and P addition than soil total stoichiometry in desert grassland, which could better reflect the effects of N and P addition on soil ecological stoichiometry and as a rapid indicator of soil nutrient status in desert grassland.

Identification of prognostic and therapeutic biomarkers in type 2 papillary renal cell carcinoma.

BACKGROUND: Papillary renal cell carcinoma (PRCC) can be divided into type 1 (PRCC1) and type 2 (PRCC2) and PRCC2 share a more invasive phenotype and worse prognosis. This study aims to identify potential prognostic and therapeutic biomarkers in PRCC2. METHODS: A cohort from The Cancer Genome Atlas and two datasets from Gene Expression Omnibus were examined. Common differentially expressed genes (DEGs) were screened and potential biomarkers were explored by using Kaplan-Meier method and cox regression analysis. Functional enrichment analysis was utilized to evaluate the potential biological functions. Tumor infiltrating immune cells were estimated by CIBERSORT algorithm. Ninety-two PRCC2 samples from Fudan University Shanghai Cancer Center were obtained, and immunostaining was performed to validate prognostic and therapeutic significance of the potential biomarker. RESULTS: PRCC2 has worse overall survival and shares distinct molecular characteristics from PRCC1. There was significant higher expression level of Targeting protein for Xklp2 (TPX2) in PRCC2 compared with normal tissues. Higher expression level of TPX2 was significantly associated with worse overall survival in PRCC2 and kinesin family genes expression were found significantly elevated in high risk PRCC2. Abundance of tumor infiltrating M1 macrophage was significantly higher in PRCC2 and it was also associated with worse overall survival. In the FUSCC cohort, higher TPX2 expression was significantly correlated with worse overall and progression-free survival. Retrospective analysis indicated that mTOR inhibitor (everolimus) had greater efficacy in the high-risk group than in the low-risk group (overall response rate: 28.6% vs. 16.7%) and that everolimus had greater efficacy than sunitinib in the high-risk group (overall response rate: 28.6% vs. 20%). CONCLUSIONS: TPX2 was a prognostic and therapeutic biomarker in PRCC2. Higher abundance of tumor infiltrating M1 macrophage was significantly associated with worse overall survival in PRCC2. mTOR inhibitors may have good efficacy in patients with high-risk PRCC2.

Facile synthesis of triazine-based microporous organic network for high-efficient adsorption of flumequine and nadifloxacin: A comprehensive study on adsorption mechanisms and practical application potentials.

Flumequine (FLU) and nadifloxacin (NAD), as emerging contaminants, have received extensive attention recently. In this study, a triazine-based microporous organic network (TMON) was synthetized and developed as an excellent adsorbent for FLU and NAD. The adsorption behavior and influence factors were investigated in both single and binary systems. Insight into the adsorption mechanisms were conducted through experiments, models, and computational studies, from macro and micro perspectives including functional groups, adsorption sites, adsorption energy and frontier molecular orbital. The results showed that the maximum adsorption capacities of TMON for FLU and NAD are 325.27 and 302.28 mg/g under 30 °C higher than records reported before. TMON exhibits the better adaptability and anti-interference ability for influence factors, leading to the preferable application effect in kinds of real water samples. TMON also shows the application potentials for the adsorption of other quinolone antibiotics and CO2 capture. Hydrogen-bonding interaction played the most critical role compared to π-π stacking effect, π-π electron-donor-acceptor interaction, CH-π interaction, and hydrophobic interaction during the adsorption. TMON could be regarded as a promising environmental adsorbent for its large surface area, stable physical and chemical properties, excellent recyclability, and wide range of applications.

Pharmacological agents for defatting livers by normothermic machine perfusion.

BACKGROUND: Ex-vivo normothermic machine perfusion (NMP) preserves the liver metabolism at 37°C and has rapidly developed as a promising approach for assessing the viability and improving the performance of organs from expanded criteria donors, including fatty liver grafts. NMP is an effective method for defatting fatty livers when combined with pharmaceutical therapies. Pharmacological agents have been shown to facilitate liver defatting by NMP. OBSERVATIONS: This systematic review summarizes available pharmacological therapies for liver defatting, with a particular emphasis on defatting agents that can be employed clinically as defatting components during liver NMP as an ex vivo translational paradigm. CONCLUSION: NMP provides an opportunity for organ treatment and can be used as a defatting platform in the future with defatting agents. Nagrath's cocktail is the most commonly used defatting cocktail in NMP; however, its carcinogenic components may limit its clinical application. Thus, the combination of a defatting cocktail with a new clinically applicable component, for example, a polyphenolic natural compound, may be a novel pharmacological option.

Screening and quantification of 146 veterinary drug residues in beef and chicken using QuEChERS combined with high performance liquid chromatography-quadrupole orbitrap mass spectrometry.

This work aimed to develop an integrated high-throughput screening and quantification for multi-class veterinary drug residues by HPLC-Q-Orbitrap mass spectrometry. A qualitative screening mass database of 171 veterinary drugs was created using full scanning mode, which improved the screening accuracy and scope. Beef and chicken samples were chosen to validate the quantification method at three spiked concentration levels. The quantification method of 146 veterinary drug residues was developed. After enzymatic hydrolysis, beef and chicken samples were treated using optimized QuEChERS. The calibration curves showed good linearities with correlation coefficients of 0.9921-0.9994. The recovery rates were within 52.1-138.2 % with relative standard deviations 0.4-17.7 %. The limits of detection and limits of quantification were in the range of 0.15-3.03 µg/kg and 0.5-10 µg/kg, respectively. The proposed method was demonstrated to be reliable for the simultaneous analysis of multi-class veterinary drugs. It is of significance to expand the screening scope and quantitative analysis efficiency.