High-Efficiency Effect-Directed Analysis Leveraging Five High Level Advancements: A Critical Review.

Organic contaminants are ubiquitous in the environment, with mounting evidence unequivocally connecting them to aquatic toxicity, illness, and increased mortality, underscoring their substantial impacts on ecological security and environmental health. The intricate composition of sample mixtures and uncertain physicochemical features of potential toxic substances pose challenges to identify key toxicants in environmental samples. Effect-directed analysis (EDA), establishing a connection between key toxicants found in environmental samples and associated hazards, enables the identification of toxicants that can streamline research efforts and inform management action. Nevertheless, the advancement of EDA is constrained by the following factors: inadequate extraction and fractionation of environmental samples, limited bioassay endpoints and unknown linkage to higher order impacts, limited coverage of chemical analysis (i.e., high-resolution mass spectrometry, HRMS), and lacking effective linkage between bioassays and chemical analysis. This review proposes five key advancements to enhance the efficiency of EDA in addressing these challenges: (1) multiple adsorbents for comprehensive coverage of chemical extraction, (2) high-resolution microfractionation and multidimensional fractionation for refined fractionation, (3) robust in vivo/vitro bioassays and omics, (4) high-performance configurations for HRMS analysis, and (5) chemical-, data-, and knowledge-driven approaches for streamlined toxicant identification and validation. We envision that future EDA will integrate big data and artificial intelligence based on the development of quantitative omics, cutting-edge multidimensional microfractionation, and ultraperformance MS to identify environmental hazard factors, serving for broader environmental governance.

Mechanism of interaction between ascorbic acid and soil iron-containing minerals for peroxydisulfate activation and organophosphorus flame retardant degradation.

Soil constituents may play an important role in peroxydisulfate (PDS)-based oxidation of organic contaminants in soil. Iron-containing minerals (Fe-minerals) have been found to promote PDS activation for organics degradation. Our study found that ascorbic acid (H2A) could enhance PDS activation by soil Fe-minerals for triphenyl phosphate (TPHP) degradation. Determination and characterization analyses of Fe fractions showed that H2A could induce the reductive dissolution of solid Fe-minerals and the increasing of oxygen vacancies/hydroxyl groups content on Fe-minerals surface. The increasing of divalent Fe (Fe(II)) accelerated PDS activation to generate reactive oxygen species (ROS). Electron paramagnetic resonance (EPR) and quenching studies showed that sulfate radicals (SO4•-) and hydroxyl radicals (HO•) contributed significantly to TPHP degradation. The composition and content of Fe-minerals and soil organic matter (SOM) markedly influenced ROS transformations. Surface-bond and structural Fe played the main role in the production of Fe(II) in reaction system. The high-concentration SOM could result in ROS consumption and degradation inhibition. Density functional theory (DFT) studies revealed that H2A is preferentially adsorbed at α-Fe2O3(012) surface through Fe-O-C bridges rather than hydrogen bonds. After absorption, H atoms on H2A may further be migrated to adjacent O atoms on the α-Fe2O3(012) surface. With the transformation of H atoms to the α-Fe2O3(012) surface, the Fe-O-C bridge is broken and one electron is transferred from the O to Fe atom, inducing the reduction of trivalent Fe (Fe(III)) atom. MS/MS2 analysis, HPLC analysis, and toxicity assessment demonstrated that TPHP was transformed to less toxic 4-hydroxyphenyl diphenyl phosphate (OH-TPHP), diphenyl hydrogen phosphate (DPHP), and phenyl phosphate (PHP) through phenol-cleavage and hydroxylation processes, and even be mineralized in reaction system.

Meta-analysis comparing different ultrasound detection methods to accurately assess wound healing and scar formation after caesarean section.

The accurate assessment of wound healing post-caesarean section, especially in twin pregnancies, remains a pivotal concern in obstetrics, given its implications for maternal health and recovery. Traditional methods, including conventional abdominal ultrasonography (CU), have been challenged by the advent of transvaginal ultrasonography (TU), offering potentially enhanced sensitivity and specificity. This meta-analysis directly compares the efficacy of TU and CU in evaluating wound healing and scar formation, crucial for optimizing postoperative care. Results indicate that TU is associated with significantly better outcomes in wound healing, demonstrated by lower REEDA scores (SMD = -20.56, 95% CI: [-27.34.20, -13.77], p < 0.01), and in scar formation reduction, evidenced by lower Manchester Scar Scale scores (SMD = -25.18, 95% CI: [-29.98, -20.39], p < 0.01). These findings underscore the potential of integrating TU into routine post-caesarean evaluation protocols to enhance care quality and patient recovery.

SWATH-F: A Novel Nontarget Strategy Based on the SWATH-MS Deconvolution Method Assisting in Annotating PFAS Homologues in Multisample Studies.

In order to identify emerging per- and polyfluoroalkyl substances (PFASs) and their alternatives in the environment or population, we need to perform extensive profiling of PFASs to determine their distribution in samples. The sequential window acquisition of all theoretical fragment-ion spectra (SWATH mode) is capable of obtaining a wide range of MS2 spectra but is difficult for direct identification of PFASs due to its complex MS2 spectra, and the nontarget screening method is difficult to identify due to its lack of a priori information. In this study, we demonstrated the great potential of SWATH-F, a nontarget fragment-based homologue screening method in combination with the SWATH-MS deconvolution, for detecting PFASs. We evaluated the application of SWATH-F to gradient spiked samples and real population serum samples, compared it with nontarget homologue screening in the information-dependent acquisition mode (IDA mode), and obtained better results for SWATH-F with 276% improvement (IDA:17 PFASs, SWATH-F: 64 PFASs) in identification. In addition, we automated the screening and identification process of SWATH-F to facilitate its use by researchers. SWATH-F is freely available on GitHub (https://github.com/njuIrene/SWATH-F) under an MIT license.

Diversity and correlation analysis of endophytes and metabolites of Panax quinquefolius L. in various tissues.

BACKGROUND: Panax quinquefolius L. (American ginseng) is widely used in medicine due to its wealth of diverse pharmacological effects. Endophytes colonize within P. quinquefolius in multiple tissue types. However, the relationship between endophytes and the production of their active ingredients in different parts of the plant is not clear. RESULTS: In this study, the relationship of endophytic diversity and the metabolites produced in different plant tissues of P. quinquefolius were analyzed using metagenomic and metabolomic approaches. The results showed relatively similar endophyte composition in roots and fibrils, but obvious differences between endophyte populations in stems and leaves. Species abundance analysis showed that at the phylum level, the dominant bacterial phylum was Cyanobacteria for roots, fibrils, stems and leaves, Ascomycota forroots and fibrils roots, and Basidiomycota for stems and leaves. LC-MS/MS technology was used to quantitatively analyze the metabolites in different tissues of P. quinquefolius. A total of 398 metabolites and 294 differential metaboliteswere identified, mainly organic acids, sugars, amino acids, polyphenols, and saponins. Most of the differential metabolites were enriched in metabolic pathways such as phenylpropane biosynthesis, flavonoid biosynthesis, citric acid cycle, and amino acid biosynthesis. Correlation analysis showed a positive and negative correlation between the endophytes and the differential metabolites. Conexibacter significantly enriched in root and fibril was significantly positively correlated with saponin differential metabolites, while cyberlindnera significantly enriched in stem and leaf was significantly negatively correlated with differential metabolites (p < 0.05). CONCLUSION: The endophytic communities diversity were relatively similar in the roots and fibrils of P. quinquefolius, while there were greater differences between the stems and leaves. There was significant difference in metabolite content between different tissues of P. quinquefolius. Correlation analysis methods demonstrated a correlation between endophytes and differential metabolism.

Nontarget Discovery of Antimicrobial Transformation Products in Wastewater Based on Molecular Networks.

Antimicrobial transformation products (ATPs) in the environment have raised extensive concerns in recent years due to their potential health risks. However, only a few ATPs have been investigated, and most of the transformation pathways of antimicrobials have not been completely elucidated. In this study, we developed a nontarget screening strategy based on molecular networks to detect and identify ATPs in pharmaceutical wastewater. We identified 52 antimicrobials and 49 transformation products (TPs) with a confidence level of three or above. Thirty of the TPs had not been previously reported in the environment. We assessed whether TPs could be classified as persistent, mobile, and toxic (PMT) substances based on recent European criteria for industrial substances. Owing to poor experimental data, definitive PMT classifications could not be established for novel ATPs. PMT assessment based on structurally predictive physicochemical properties revealed that 47 TPs were potential PMT substances. These results provide evidence that novel ATPs should be the focus of future research.

Methodology for Effect-Based Identification of Bioconcentratable Endocrine Disrupting Chemicals (EDCs) in Water: Establishment, Validation, and Application.

Since the wide occurrence of endocrine disrupting chemicals (EDCs) in water is associated with various adverse effects in aquatic organisms, it is urgent to identify key bioconcentratable EDCs. Currently, bioconcentration is generally ignored during the identification of key EDCs. Thus, a methodology for effect-based identification of bioconcentratable EDCs was established in Microcosm, validated in the field, and applied to typical surface water in Taihu Lake. In Microcosm, an inverted U-shaped relationship between logBCFs and logKows was observed for typical EDCs, with medium hydrophobic EDCs (3 ≤ logKow ≤ 7) exhibiting the greatest bioconcentration potentials. On this basis, enrichment methods for bioconcentratable EDCs were established using POM and LDPE, which better fitted the bioconcentration characteristics and enabled the enrichment of 71 ± 8% and 69 ± 6% bioconcentratable compounds. The enrichment methods were validated in the field, where LDPE exhibited a more significant correlation with the bioconcentration characteristics than POM, with mean correlation coefficients of 0.36 and 0.15, respectively, which was selected for further application. By application of the new methodology in Taihu Lake, 7 EDCs were prioritized from 79 identified EDCs as key bioconcentratable EDCs on consideration of their great abundance, bioconcentration potentials, and anti-androgenic potencies. The established methodology could support the evaluation and identification of bioconcentratable contaminants.

Are New Phthalate Ester Substitutes Safer than Traditional DBP and DiBP? Comparative Endocrine-Disrupting Analyses on Zebrafish Using In Vivo, Transcriptome, and In Silico Approaches.

Although previous studies have confirmed the association between phthalate esters (PAEs) exposure and endocrine disorders in humans, few studies to date have systematically assessed the threats of new PAE alternatives to endocrine disruptions. Herein, zebrafish embryos were continuously exposed to two PAEs [di-n-butyl phthalate (DBP) and diisobutyl phthalate (DiBP)], two structurally related alternatives [diiononyl phthalate (DINP) and diisononyl hexahydrophthalate (DINCH)], and two non-PAE substitutes [dipropylene glycol dibenzoate (DGD) and glyceryl triacetate (GTA)], and the endocrine-disrupting effects were investigated during the early stages (8-48 hpf). For five endogenous hormones, including progesterone, testosterone, 17ß-estradiol, triiodothyronine (T3), and cortisol, the tested chemicals disturbed the contents of at least one hormone at environmentally relevant concentrations (≤3.9 µM), except DINCH and GTA. Then, the concentration-dependent reduced zebrafish transcriptome analysis was performed. Thyroid hormone (TH)- and androgen/estrogen-regulated adverse outcome pathways (AOPs) were the two types of biological pathways most sensitive to PAE exposure. Notably, six compounds disrupted four TH-mediated AOPs, from the inhibition of deiodinases (molecular initiating event, MIE), a decrease in T3 levels (key event, KE), to mortality (adverse outcome, AO) with the quantitatively linear relationships between MIE-KE (|r| = 0.96, p = 0.002), KE-AO (|r| = 0.88, p = 0.02), and MIE-AO (|r| = 0.89, p = 0.02). Multiple structural analyses showed that benzoic acid is the critical toxicogenic fragment. Our data will facilitate the screening and development of green alternatives.

An efficient isolation and purification of broad partition coefficient range ginsenosides from roots of Panax quinquefolium L. by linear gradient counter-current chromatography coupled with preparative high-performance liquid chromatography.

As a famous health food, roots of Panax quinquefolium L. possessed immune regulation and enhancement of the central nervous system, in which ginsenosides are the main active component with different numbers and positions of sugars, causing different chemical polarities with a challenge for the separation and isolation. In this study, a fast and effective bilinear gradient counter-current chromatography was proposed for preparative isolation ginsenosides with a broad partition coefficient range from roots of Panax quinquefolium L. In terms of the established method, the mobile phases comprising n-butanol and ethyl acetate were achieved by adjusting the proportion. Coupled with the preparative HPLC, eleven main ginsenosides were successfully separated, including ginsenoside Rg1 (1), Re (2), acetyl ginsenoside Rg1 (3), Rb1 (4), Rc (5), Rg2 (6), Rb3 (7), quinquefolium R1 (8), Rd (9), gypenoside X VII (10) and notoginsenoside Fd (11), with purities exceeding 95% according to the HPLC results. Tandem mass spectrometry and electrospray ionization mass spectrometry were adopted for recognizing the isolated compound architectures. Our study suggests that linear gradient counter-current chromatography effectively separates the broad partition coefficient range of ginsenosides compounds from the roots of Panax quinquefolium L. In addition, it can apply to active compound isolation from other complicated natural products.

LC-MS Analysis of Ginsenosides in Different Parts of Panax quinquefolius and Their Potential for Coronary Disease Improvement.

Seven main ginsenosides, including ginsenoside Re, ginsenoside Rb1, pseudoginsenoside F11, ginsenoside Rb2, ginsenoside Rb3, ginsenoside Rd, and ginsenoside F2, were identified by LC-QTOF MS/MS from root, leaf and flower extracts of Panax quinquefolius. These extracts promoted intersegmental vessel growth in a zebrafish model, indicating their potential cardiovascular health benefits. Network pharmacology analysis was then conducted to reveal the potential mechanisms of ginsenoside activity in the treatment of coronary artery disease. GO and KEGG enrichment analyses elucidated that G protein-coupled receptors played a critical role in VEGF-mediated signal transduction and that the molecular pathways associated with ginsenoside activity are involved in neuroactive ligand-receptor interaction, cholesterol metabolism, the cGMP-PKG signaling pathway, etc. Moreover, VEGF, FGF2, and STAT3 were confirmed as the major targets inducing proliferation of endothelial cells and driving the pro-angiogenic process. Overall, ginsenosides could be potent nutraceutical agents that act to reduce the risks of cardiovascular disease. Our findings will provide a basis to utilize the whole P. quinquefolius plant in drugs and functional foods.

Icariin Ameliorates Alzheimer's Disease Pathology by Alleviating Myelin Injury in 3 × Tg-AD Mice.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by excessive deposition of ß amyloid (Aß), hyperphosphorylation of tau protein, and neuronal cell death. Recent studies have shown that myelin cell damage, which leads to cognitive dysfunction, occurs before AD-related pathological changes. Here, we examine the effect of icariin (ICA), a prenylated flavonol glycoside, in improving cognitive function in AD model mice. ICA has been reported to exhibit cardiovascular protective functions and antiaging effects. In this study, we used 3 × Tg-AD mice as an AD model. The Morris water maze and Y maze tests were performed to assess the learning and memory of the mice. Immunofluorescence analysis of Aß1-42 deposition and myelin basic protein (MBP) expression in the mouse hippocampus was performed. Tau protein phosphorylation and MBP protein expression in the hippocampus were further analyzed by Western blotting. Myelin damage in the mouse optic nerve was evaluated by electron microscopy, and LFB staining was performed to assess myelin morphology in the mouse corpus callosum. MBP, Mpp5, and Egr2 transcript levels were quantified by qPCR. We observed that ICA treatment improved the learning and memory of 3 × Tg-AD mice and reduced Aß deposition and tau protein phosphorylation in the hippocampus. Moreover, this treatment protocol increased myelin-related gene expression and reduced myelin damage.

Improved in situ analysis of lead isotopes in low-Pb melt inclusions using laser ablation-multi-collector-inductively coupled plasma-mass spectrometry.

RATIONALE: In situ Pb isotope analyses of tiny melt inclusions using laser ablation-multi-collector-inductively coupled plasma-mass spectrometry (LA-MC-ICP-MS) are crucial for exploring the origins of mafic lavas. However, quantitative use of this technique with low-Pb (<10 ppm) melt inclusions is difficult due to their low 204 Pb content and 204 Hg interference. METHODS: Pb isotopic ratios of various reference glasses and olivine-hosted melt inclusions were determined using LA-MC-ICP-MS. Multiple ion counters were used to simultaneously determine signal intensities of all Pb isotopes and 202 Hg. An Hg signal-removal smoothing device reduced its signal in the gas blank by >80%. Instrumental mass bias was corrected using the standard-sample bracketing method. RESULTS: With 24-90 µm diameter laser spots, 2-4 Hz repetition rates, and 2.5-4 J cm-2 energy fluence, the analytical precisions of 20x Pb/204 Pb ratios (x = 6, 7, 8) for standards BHVO-2G, ML3B-G, NIST 614, NKT-1G, T1-G, GOR132-G, and StHs6/80-G were <1.0% (2RSD) when 208 Pb signals >100 000 cps. The Wangjiadashan melt inclusions have 206 Pb/204 Pb = 17.14-18.44, 207 Pb/204 Pb = 15.28-15.66, and 208 Pb/204 Pb = 37.12-38.68. CONCLUSIONS: The described method improves the precision and accuracy of in situ Pb isotope analysis in low-Pb melt inclusions using LA-MC-ICP-MS. The Pb isotopic compositions of the Wangjiadashan melt inclusions indicate the coexistence of LoMu and EMII+young HIMU components in the mantle source of weakly alkaline basalts.

Toxicological Mechanism of Individual Susceptibility to Formaldehyde-Induced Respiratory Effects.

Understanding the mechanisms of individual susceptibility to exposure to environmental pollutants has been a challenge in health risk assessment. Here, an integrated approach combining a CRISPR screen in human cells and epidemiological analysis was developed to identify the individual susceptibility to the adverse health effects of air pollutants by taking formaldehyde (FA) and the associated chronic obstructive pulmonary disease (COPD) as a case study. Among the primary hits of CRISPR screening of FA in human A549 cells, HTR4 was the only gene genetically associated with COPD susceptibility in global populations. However, the association between HTR4 and FA-induced respiratory toxicity is unknown in the literature. Adverse outcome pathway (AOP) network analysis of CRISPR screen hits provided a potential mechanistic link between activation of HTR4 (molecular initiating event) and FA-induced lung injury (adverse outcome). Systematic toxicology tests (in vitro and animal experiments) were conducted to reveal the HTR4-involved biological mechanisms underlying the susceptibility to adverse health effects of FA. Functionality and enhanced expression of HTR4 were required for susceptibility to FA-induced lung injury, and FA-induced epigenetic changes could result in enhanced expression of HTR4. Specific epigenetic and genetic characteristics of HTR4 were associated with the progression and prevalence of COPD, respectively, and these genetic risk factors for COPD could be potential biomarkers of individual susceptibility to adverse respiratory effects of FA. These biomarkers could be of great significance for defining subpopulations susceptible to exposure to FA and reducing uncertainty in the next-generation health risk assessment of air pollutants. Our study delineated a novel toxicological pathway mediated by HTR4 in FA-induced lung injury, which could provide a mechanistic understanding of the potential biomarkers of individual susceptibility to adverse respiratory effects of FA.

Development, Validation, and Application of a Human Reproductive Toxicity Prediction Model Based on Adverse Outcome Pathway.

A growing number of environmental contaminants have been proved to have reproductive toxicity to males and females. However, the unclear toxicological mechanism of reproductive toxicants limits the development of virtual screening methods. By consolidating androgen (AR)-/estrogen receptors (ERs)-mediated adverse outcome pathways (AOPs) with more than 8000 chemical substances, we uncovered relationships between chemical features, a series of pathway-related effects, and reproductive apical outcomes─changes in sex organ weights. An AOP-based computational model named RepTox was developed and evaluated to predict and characterize chemicals' reproductive toxicity for males and females. Results showed that RepTox has three outstanding advantages. (I) Compared with the traditional models (37 and 81% accuracy, respectively), AOP significantly improved the predictive robustness of RepTox (96.3% accuracy). (II) Compared with the application domain (AD) of models based on small in vivo datasets, AOP expanded the ADs of RepTox by 1.65-fold for male and 3.77-fold for female, respectively. (III) RepTox implied that hydrophobicity, cyclopentanol substructure, and several topological indices (e.g., hydrogen-bond acceptors) were important, unbiased features associated with reproductive toxicants. Finally, RepTox was applied to the inventory of existing chemical substances of China and identified 2100 and 7281 potential toxicants to the male and female reproductive systems, respectively.

Comprehensive Exposure Studies of Per- and Polyfluoroalkyl Substances in the General Population: Target, Nontarget Screening, and Toxicity Prediction.

Novel per- and polyfluoroalkyl substances (PFASs) in the environment and populations have received extensive attention; however, their distribution and potential toxic effects in the general population remain unclear. Here, a comprehensive study on PFAS screening was carried out in serum samples of 202 individuals from the general population in four cities in China. A total of 165 suspected PFASs were identified using target and nontarget analysis, including seven identified PFAS homolog series, of which 16 PFASs were validated against standards, and seven PFASs [4:2 chlorinated polyfluorinated ether sulfonate (4:2 Cl-PFESA), 7:2 chlorinated polyfluorinated ether sulfonate (7:2 Cl-PFESA), hydrosubstituted perfluoroheptanoate (H-PFHpA), chlorine-substituted perfluorooctanoate (Cl-PFOA), chlorine-substituted perfluorononanate (Cl-PFNA), chlorine-substituted perfluorodecanoate (Cl-PFDA), and perfluorodecanedioic acid (PFLDCA n = 8)] were reported for the first time in human serum. The Tox21-GCN model (a graph convolutional neural network model based on the Tox21 database) was established to predict the toxicity of the discovered PFASs, revealing that PFASs containing sulfonic acid groups exhibited multiple potential toxic effects, such as estrogenic effects and stress responses. Our study indicated that the general population was exposed to various PFASs, and the toxicity prediction results of individual PFASs suggested potential health risks that could not be ignored.

Effect-Directed Analysis Based on the Reduced Human Transcriptome (RHT) to Identify Organic Contaminants in Source and Tap Waters along the Yangtze River.

Since a large number of contaminants are detected in source waters (SWs) and tap waters (TWs), it is important to perform a comprehensive effect evaluation and key contributor identification. A reduced human transcriptome (RHT)-based effect-directed analysis, which consisted of a concentration-dependent RHT to reveal the comprehensive effects and noteworthy pathways and systematic identification of key contributors based on the interactions between compounds and pathway effects, was developed and applied to typical SWs and TWs along the Yangtze River. By RHT, 42% more differentially expressed genes and 33% more pathways were identified in the middle and lower reaches, indicating heavier pollution. Hormone and immune pathways were prioritized based on the detection frequency, sensitivity, and removal efficiency, among which the estrogen receptor pathway was the most noteworthy. Consistent with RHT, estrogenic effects were widespread along the Yangtze River based on in vitro evaluations. Furthermore, 38 of 100 targets, 39 pathway-related suspects, and 16 estrogenic nontargets were systematically identified. Among them, diethylstilbestrol was the dominant contributor, with the estradiol equivalent (EEQ) significantly correlated with EEQwater. In addition, zearalenone and niclosamide explained up to 54% of the EEQwater. The RHT-based EDA method could support the effect evaluation, contributor identification, and risk management of micropolluted waters.

One-step hydrothermal synthesis of WS2 quantum dots as fluorescent sensor for sensitive and selective recognition of hemoglobin and cardiac biomarker myoglobin.

Transition metal dichalcogenide (TMD) dots exhibit excellent photoluminescence performance due to the quantum confinement effect and edge effect, and are extensively applied in electronic and optical devices, sensors, catalysis, and bioimaging. In this work, WS2 quantum dots (WS2 QDs) were prepared under a simple one-step hydrothermal method by optimizing the reaction conditions, and a quantum yield of 11.23% was achieved. The as-prepared WS2 QDs possess good photo-bleaching resistance, salt tolerance, and pH stability. The fluorescence investigations showed that the WS2 QDs acted as a highly efficient fluorescent sensor to detect hemoglobin (Hb) and cardiac biomarker myoglobin (Myo). The linear range was 1-600 µg/mL for Hb and 0.01-120 µg/mL for Myo, with detection limits as low as 260 and 7.6 ng/mL, respectively. Importantly, the WS2 QDs were used to determine the Hb/Myo content in human blood/serum samples, with satisfactory results, indicating that this technique holds promise for application in clinical diagnosis associated with Hb/Myo levels. To the best of our knowledge, this is the first example of TMD QDs without any modification as a fluorescent sensor for detecting Hb and Myo simultaneously.

Experiences of bowel symptoms in patients with rectal cancer after sphincter-preserving surgery: a qualitative meta-synthesis.

PURPOSE: This study is to identify and synthesize the available evidence of bowel symptom experiences of patients with rectal cancer after sphincter-preserving surgery (SPS). METHODS: This qualitative meta-synthesis was conducted following the Joanna Briggs Institute (JBI) qualitative systematic review methodology and reported following the Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) guidelines. Seven databases were searched on 22 December 2021. The selected studies were reviewed by two independent reviewers, and disagreements were resolved by discussion or with a third reviewer. RESULTS: Seven qualitative articles were included in the meta-synthesis with 192 total rectal cancer patients. The review summarized 53 qualitative findings into three synthesized findings: (a) Patients experienced bowel symptoms and triggered additional physiological problems, and they underestimated bowel symptoms; (b) patients had many negative emotions, and their daily life and social interaction were disturbed; and (c) patients adopted strategies to adapt or control their bowel symptoms. According to the ConQual evidence grading approach, the confidence of the synthesized findings was rated as moderate to low. CONCLUSIONS: The bowel symptoms of patients with rectal cancer after SPS have troubled their lives. Timely acquisition of symptom-related knowledge and enhancement of their coping abilities are important for the control and management of bowel symptoms. Healthcare professionals should clearly understand the bowel symptoms that patients may experience after SPS and provide supportive care for patients to improve patients' self-management abilities and quality of life. TRIAL REGISTRATION: PROSPERO: CRD42021242610.

CRISPR screen identified that UGT1A9 was required for bisphenols-induced mitochondria dyshomeostasis.

Exposure to bisphenols chemicals could cause various adverse health effects, including non-alcoholic fatty liver disease (NAFLD), which have been associated with cellular mitochondria stress. However, the biological mechanism underlying the mitochondria stress-mediated cell death by bisphenols was poorly understood. Here, CRISPR screens were performed to identify the critical genes which were involved in cell death caused by exposure to four bisphenols (BPA, BPB, BPE and BPS). Results of CRISPR screens showed that UGT1A9 was the primary genetic factor facilitating cell death induced by all of the four bisphenols. Systematic toxicological tests demonstrated that UGT1A9 was required for BPA-induced mitochondria dyshomeostasis in vitro and in vivo, and UGT1A9-mediated mitochondria dyshomeostasis was an important cause of facilitating cell death. Liver injury caused by exposure to BPA in wild-type mice was accompanied with suppression of mitophagy and increased expression of C-Caspase 3, but UGT1A9 knockout attenuated these adverse effects induced by BPA. Finally, molecular epidemiology analysis suggested that the five genetic variants of UGT1A9 could be potential genetic risk factors of NAFLD when people were exposed to BPA. The biological mechanism uncovered here provided mechanistic evidence for identification of susceptible populations of liver injury associated with exposure to BPA.

The inhibitory effect of rBCG on EB virus-positive tumours using an EB virus fusion gene.

At present, studies have found that latent Epstein-Barr virus (EBV) infection is associated with a variety of human tumours, and a vaccine is not available in this field. In this research, RT-PCR was used to obtain BZLF1 (immediately expressed early antigen Z) and LMP2 (latent membrane protein 2) cDNA from EBV. A ZLP2 fusion gene containing a linker sequence that encoded the polypeptide (Gly4Ser)3 was obtained using the sequence splicing overlap extension method. Then, ZLP2 was inserted into pMV261 cells, and the recombinant plasmid pMV-ZLP2 was transformed into BCG competent cells. After EB virus-positive tumour cell (NPRC18) cancer models were established with C57BL/6 J mice, tumour weight, tumour formation time and mouse survival conditions were analyzed, and flow cytometry was used to analyze the quantities of CD8 + and CD4 + T cells. HE staining was used to detect and analyze lymphocyte infiltration, and statistical analysis was used to analyze the immunological effect of recombinant BCG (rBCG). Compared with the control group, rBCG could significantly prolong the survival time of mice, slow tumour growth and delay tumour formation time. Recombinant BCG exhibits an obvious immune effect in mice and an inhibitory effect on EBV-positive cancer.Key points• AZLP2 fusion gene with BZLF1 and LMP2 of EB virus was constructed.• ZLP2 fusion gene was expressed with rBCG.• rBCG with ZLP2 has an obvious effect on EBV-positive cancer.