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The study of quantum geometry effects in materials has been one of the most important research directions in recent decades. The quantum geometry of a material is characterized by the quantum geometric tensor of the Bloch states. The imaginary part of the quantum geometry tensor gives rise to the Berry curvature while the real part gives rise to the quantum metric. While Berry curvature has been well studied in the past decades, the experimental investigation on the quantum metric effects is only at its infancy stage. In this work, we measure the nonlinear transport of bulk MnBi2Te4, which is a topological anti-ferromagnet. We found that the second order nonlinear responses are negligible as required by inversion symmetry, the third-order nonlinear responses are finite. The measured third-harmonic longitudinal ( V x x 3 ω ) and transverse ( V x y 3 ω ) voltages with frequency 3 ω , driven by an a.c. current with frequency ω , show an intimate connection with magnetic transitions of MnBi2Te4 flakes. Their magnitudes change abruptly as MnBi2Te4 flakes go through magnetic transitions from an antiferromagnetic state to a canted antiferromagnetic state and to a ferromagnetic state. In addition, the measured V x x 3 ω is an even function of the applied magnetic field B while V x y 3 ω is odd in B. Amazingly, the field dependence of the third-order responses as a function of the magnetic field suggests that V x x 3 ω is induced by the quantum metric quadrupole and V x y 3 ω is induced by the Berry curvature quadrupole. Therefore, the quadrupoles of both the real and the imaginary part of the quantum geometry tensor of bulk MnBi2Te4 are revealed through the third order nonlinear transport measurements. This work greatly advanced our understanding on the connections between the higher order moments of quantum geometry and nonlinear transport.

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We have developed a cryogen-free, low-temperature terahertz scanning tunneling microscope (THz-STM). This system utilizes a continuous-flow cryogen-free cooler to achieve low temperatures of ∼25 K. Meanwhile, an ultra-small ultra-high vacuum chamber results in the reduction of the distance from sample to viewport to only 4 cm. NA = 0.6 can be achieved while placing the entire optical component, including a large parabolic mirror, outside the vacuum chamber. Thus, the convenience of optical coupling is much improved without compromising the performance of STM. Based on this, we introduced THz pulses into the tunnel junction and constructed the THz-STM, achieving atomic-level spatial resolution in THz-driven current imaging and sub-picosecond (sub-ps) time resolution in autocorrelation signals during pump-probe measurements. Experimental data from various representative samples are presented to showcase the performance of the instrument, establishing it as an ideal platform for studying non-equilibrium dynamic processes at nanoscale.

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In vitro embryonic technology is crucial for improving farm animal reproduction but is hampered by the poor quality of oocytes and insufficient development potential. This study investigated the relationships among changes in the gut microbiota and metabolism, serum features, and the follicular fluid metabolome atlas. Correlation network maps were constructed to reveal how the metabolites affect follicular development by regulating gene expression in granulosa cells. The superovulation synchronization results showed that the number of follicle diameters from 4 to 8 mm, qualified oocyte number, cleavage, and blastocyst rates were improved in the dairy heifers (DH) compared with the non-lactating multiparous dairy cows (NDC) groups. The gut microbiota was decreased in Rikenellaceae_RC9_gut_group, Alistipes, and Bifidobacterium, but increased in Firmicutes, Cyanobacteria, Fibrobacterota, Desulfobacterota, and Verrucomicrobiota in the NDC group, which was highly associated with phospholipid-related metabolites of gut microbiota and serum. Metabolomic profiling of the gut microbiota, serum, and follicular fluid further demonstrated that the co-metabolites were phosphocholine and linoleic acid. Moreover, the expression of genes related to arachidonic acid metabolism in granulosa cells was significantly correlated with phosphocholine and linoleic acid. The results in granulosa cells showed that the levels of PLCB1 and COX2, participating in arachidonic acid metabolism, were increased in the DH group, which improved the concentrations of PGD2 and PGF2α in the follicular fluid. Finally, the expression levels of apoptosis-related proteins, cytokines, and steroidogenesis-related genes in granulosa cells and the concentrations of steroid hormones in follicular fluid were determinants of follicular development. According to our results, gut microbiota-related phosphocholine and linoleic acid participate in arachidonic acid metabolism in granulosa cells through the gut-follicle axis, which regulates follicular development. These findings hold promise for enhancing follicular development and optimizing oocyte quality in subfertile dairy cows.

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PURPOSE: The epidemiologic data of metabolic associated fatty liver disease (MAFLD) in breast cancer (BC) patients remains limited. We aimed to investigate the prevalence and clinicopathological characteristics of hepatic steatosis (HS) and MAFLD in Chinese BC women at initial diagnosis. METHODS: 3217 non-metastatic primary BC women with MAFLD evaluation indexes at initial diagnosis and 32,170 age-matched (in a 1:10 ratio) contemporaneous health check-up women were enrolled. RESULTS: The prevalence of HS (21.5% vs. 19.7%, p = 0.013) and MAFLD (20.8% vs. 18.6%, p = 0.002) were significantly higher in BC women than in health check-ups, respectively. Meanwhile, the prevalence of HS/MAFLD among elderly BC women (≥ 60 years) was significantly higher than the health check-ups (38.7%/37.6% vs 31.9%/30.8%), respectively. In BC women with HS/MAFLD, the prevalence of overweight/obesity was up to 85.7%/88.6%, dyslipidemia and elevated blood pressure were 63.2%/63.7% and 59.7%/61.7%, respectively. No statistical significance of the expressions of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER-2) and Ki67 were found between BC women with HS/MAFLD and BC women without HS/MAFLD. After adjustment, BC women with HS showed significantly higher risk of lymph node metastasis than BC women without HS. Subjects with HS/MAFLD had higher risks of overweight/obesity, dyslipidemia, elevated blood pressure, hyperuricemia, and elevated enzymes than those without HS/MAFLD. CONCLUSIONS: Compared with health check-ups, BC patients have higher prevalence of HS/MAFLD. HS/MAFLD coexist with high prevalence of metabolic complications, and the risk of lymph node metastasis was significantly higher in BC women with HS than in BC women without HS.

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DPP4 was considered a canonical receptor for merbecoviruses until the recent discovery of African bat-borne MERS-related coronaviruses using ACE2. The extent and diversity with which merbecoviruses engage ACE2 and their receptor species tropism remain unknown. Here, we reveal that HKU5 enters host cells utilizing Pipistrellus abramus (P.abr) and several non-bat mammalian ACE2s through a binding mode distinct from that of any other known ACE2-using coronaviruses. These results show that several merbecovirus clades independently evolved ACE2 utilization, which appears to be a broadly shared property among these pathogens, through an extraordinary diversity of ACE2 recognition modes. We show that MERS-CoV and HKU5 have markedly distinct antigenicity, due to extensive genetic divergence, and identified several HKU5 inhibitors, including two clinical compounds. Our findings profoundly alter our understanding of coronavirus evolution and pave the way for developing countermeasures against viruses poised for human emergence.

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The ruby lattice is one of the tight-binding models which hosts a flat band in its electronic structure and has potential applications in future spintronics and quantum devices. However, the experimental realization of a ruby lattice in realistic materials remains elusive. Here, we have experimentally realized an atomic ruby lattice by fabricating monolayer CuCl1+x on a Au(111) substrate. Scanning tunneling microscopy/spectra (STM/STS) measurements combined with density-functional theory (DFT) calculations reveal that the Cu atoms are arranged in a ruby lattice in this monolayer. Moreover, a significant density of states (DOS) peak corresponding to the characteristic of a ruby system is observed, consistent with both the tight-binding model and first-principles calculations on the band structure. Our work provides a promising platform to explore the physics of the ruby model.

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Gossypol, a yellow polyphenolic compound found in the Gossypium genus, is toxic to animals that ingest cotton-derived feed materials. However, ruminants display a notable tolerance to gossypol, attributed to the pivotal role of ruminal microorganisms in its degradation. The mechanisms of how rumen microorganisms degrade and tolerate gossypol remain unclear. Therefore, in this study, Enterobacter sp. GD5 was isolated from rumen fluid, and the effects of gossypol on its metabolism and gene expression were investigated using liquid chromatography-mass spectrometry (LC-MS) and RNA analyses. The LC-MS results revealed that gossypol significantly altered the metabolic profiles of 15 metabolites (eight upregulated and seven downregulated). The Kyoto Encyclopedia of Genes and Genomes analysis results showed that significantly different metabolites were associated with glutathione metabolism in both positive and negative ion modes, where gossypol significantly affected the biosynthesis of amino acids in the negative ion mode. Transcriptomic analysis indicated that gossypol significantly affected 132 genes (104 upregulated and 28 downregulated), with significant changes observed in the expression of catalase peroxidase, glutaredoxin-1, glutathione reductase, thioredoxin 2, thioredoxin reductase, and alkyl hydroperoxide reductase subunit F, which are related to antioxidative stress. Furthermore, Gene Ontology analysis revealed significant changes in homeostatic processes following gossypol supplementation. Overall, these results indicate that gossypol induces oxidative stress, resulting in the increased expression of antioxidative stress-related genes in Enterobacter sp. GD5, which may partially explain its tolerance to gossypol.

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Hyperuricemia is with growing incidence and of high risk to develop into gout and other metabolic diseases. The key enzyme catalyzing uric acid synthesis, xanthine oxidoreductase (XOR) is a vital target for anti-hyperuricemic drugs, while XOR inhibitors characterized as both potent and safe are currently in urgent need. In this study, a novel small molecule compound, CC15009, was identified as a specific XOR inhibitor. CC15009 exerted strongest in vitro XOR inhibitory activity among current XOR inhibitors. It also showed favorable dose-dependent uric acid-lowering effects in two different XOR substrate-induced hyperuricemic mouse models, which was significantly superior than the current first-line drug, allopurinol. Mechanically, the direct binding of CC15009 against XOR was confirmed by molecular docking and SPR analysis. The inhibition mode was competitive and reversible. Besides, the potential antioxidant activity of CC15009 was indicated by its strong inhibitory activity against the oxidized isoform of XOR, which reduced ROS generation as the byproduct. Regarding the safety concerns of current XOR inhibitors, especially in cardiovascular risks, the safety of CC15009 was comprehensively evaluated. No significant abnormality was observed in the acute, subacute toxicity tests and mini-AMES test. Notably, there was no obvious inhibition of CC15009 against cardiac ion channels, including hERG, Nav1.5, Cav1.2 at the concentration of 30 µM, indicating its lower cardiovascular risk. Taken together, our results supported CC15009 as a candidate of high efficacy and safety profile to treat hyperuricemia through direct XOR inhibition.

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Agonists of the secretin receptor have potential applications for diseases of the cardiovascular, gastrointestinal, and metabolic systems, yet no clinically-active non-peptidyl agonists of this receptor have yet been developed. In the current work, we have identified a new small molecule lead compound with this pharmacological profile. We have prepared and characterized a systematic structure-activity series around this thiadiazole scaffold to better understand the molecular determinants of its activity. We were able to enhance the in vitro activity and to maintain the specificity of the parent compound. We found the most active candidate to be quite stable in plasma, although it was metabolized by hepatic microsomes. This chemical probe should be useful for in vitro studies and needs to be tested for in vivo pharmacological activity. This could be an important lead toward the development of a first-in-class orally active agonist of the secretin receptor, which could be useful for multiple disease states.

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Although therapeutic targets for colorectal cancer (CRC) treatment have been developed, the treatment outcomes are not ideal and survival rates for CRC patients remain low. It is critical to identify a specific target and develop an effective CRC treatment system. The ZNF334 gene is a newly identified member of Zinc-finger proteins (ZNFs), which is essential for key biological processes associated with tumorigenesis. Abnormal epigenetic reprogramming of the ZNF334 gene promoter region decreases its expression in CRC and further induces the occurrence of CRC. Here, we clarified that P300 in CRC can regulate the H3K9/27 ac in the ZNF334 promoter. Furthermore, histone acetylation of the ZNF334 promoter region was increased by dCas9-P300 to normalize the deficiency of ZNF334 expression, thereby inhibiting the growth of CRC. Collectively, our findings enable a facile way to affect gene expression using CRISPR/Cas9-based epigenome editing and further determine the causal link between histone acetylation and gene activation, providing a promising gene therapy strategy for the CRC treatment.

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Drought dramatically affects plant growth and yield. A previous study indicated that endophytic fungus Phomopsis liquidambaris can improve the drought resistance of peanuts, which is related with the root arbuscular mycorrhizal fungi (AMF) community; however, how root endophytes mediate AMF assembly to affect plant drought resistance remains unclear. Here, we explored the mechanism by which endophytic fungus recruits AMF symbiotic partners via rhizodeposits to improve host drought resistance. The results showed that Ph. liquidambaris enhanced peanut drought resistance by enriching the AMF genus Claroideoglomus of the rhizosphere. Furthermore, metabolomic analysis indicated that Ph. liquidambaris significantly promoted isoformononetin and salicylic acid (SA) synthesis in rhizodeposits, which were correlated with the increase in Claroideoglomus abundance following Ph. liquidambaris inoculation. Coinoculation experiments confirmed that isoformononetin and SA could enrich Claroideoglomus etunicatum in the rhizosphere, thereby improving the drought resistance. This study highlights the crucial role of fungal consortia in plant stress resistance.

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The rare physical property of negative thermal expansion (NTE) is intriguing because materials with a large NTE over a wide temperature range can serve as high-performance thermal expansion compensators. However, the applications of NTE are hindered by the fact that most of the available NTE materials show small magnitudes of NTE, and/or NTE occurs only in a narrow temperature range. Herein, for the first time, we investigated the effect of anion substitution instead of general Pb/Ti-site substitutions on the thermal expansion properties of a typical ferroelectric NTE material, PbTiO3. Intriguingly, the substitution of S for O in PbTiO3 further increases the tetragonality of PbTiO3. Consequently, an unusually enhanced NTE with an average volumetric coefficient of thermal expansion of V = -2.50 × 10-5 K-1 was achieved over a wide temperature range (300-790 K), which is in contrast to that of pristine PbTiO3 (V = -1.99 × 10-5 K-1, RT-763 K). The intensified NTE is attributed to the enhanced hybridization between Pb/Ti and O/S atoms by the substitution of S, as evidenced by our theoretical investigations. We therefore demonstrate a new technique for introducing mixed anions to achieve a large NTE over a wide temperature range in PbTiO3-based ferroelectrics.

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The quality of Japanese forensic experts has been widely recognized around the world, which cannot be separated from the "ripple effect" caused by the rapid rise of the modern forensic education in Japan. By continuously adopting foreign forensic education resources and teaching experience, it has finally formed a forensic professional talent training model with a clear hierarchy of basic education and professional training, as well as classroom teaching and case studies complementing each other; and it continuously improves the comprehensive quality of practitioners through domestic training and international exchange and cooperation, providing talented professionals for the development of the Japanese forensic industry. In this context, this article takes the development history of Japanese forensic medicine as the starting point to study how it gradually formed the embryonic form of forensic education in modern times. Based on this, it analyzes the characteristics of Japan's modern forensic medicine talent training model, summarizes excellent experiences for localized transformation, such as emphasizing the role of practical teaching, exerting the effectiveness of vocational skills training, and promoting international exchange and cooperation, to provide reference and inspiration for the training of relevant professional talents in China.

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Methamphetamine (METH) is the second abused drug which affects abusers' health and induces social crimes, developing novel methods with high sensitivity and selectivity for METH detecting is still challenging. In this paper, a colorimetric and fluorescent dual-channel sensor for METH has been constructed. We combine the enzyme-mimic catalytic activity of gold nanoparticles (GNPs) with high target specificity of METH aptamer to create a nanosensor (Apt-GNP), in the presence of METH, the absorption of 3,3',5,5'-tetramethylbenzidine (OxTMB) at 650 nm enhanced with METH concentration increasing, while the absorption characteristic peak of GNPs at 530 nm remained almost unchanged. The ratio of A650nm/A530nm and METH concentration had a good linear relationship when METH concentration was in the range of 5-50 µM, and the corresponding linear equation is A650nm/A530nm = 0.00727CMETH (µM) + 0.783 with R2 = 0.997 and LOD = 0.40 µM (LOD = 3σ/s, n = 11). Interestingly, the fluorescence emission of Rhodamine B (RB) overlaps with the absorption spectrum of OxTMB which represents the content of METH and the fluorescence signal of RB can be quenched through internal filtering effect (IEF). Hence, when RB was doped to the detection system, the decay of RB fluorescence can reflect the concentrations change of METH. Accordingly, the linear equation is F/FR = -0.00751CMETH (µM) + 0.895 with R2 = 0.993 and LOD = 0.40 µM, where F was the fluorescence of the analytical solution at 580 nm with METH and FR was fluorescence of RB control solution. The dual-channel sensor can measure METH in serum and artificial urine successfully which is potential to be applied in drug-using crime sites and provide direct evidence to law enforcement officials.

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BACKGROUND: The correlation between breast cancer and hepatitis B virus (HBV) remains inconclusive. This study aims to explore the serological status of HBV infection and past infection in different age groups of female breast cancer patients, patients with benign breast diseases, and individuals undergoing routine physical examinations. METHODS: Serum data on HBV serological markers were collected and analyzed from 6072 female breast cancer patients first diagnosed from September 2012 to July 2020 at the First Affiliated Hospital of Chongqing Medical University, along with 4019 women with benign breast diseases and 54,740 healthy females undergoing routine physical examinations in the same period. The data were stratified by age for comparison between groups. RESULTS: The prevalence of HBV infection and past infection in the breast cancer group (7.9%, 55.1%) was higher than that in the benign breast disease group (6.5%, 39.1%) and the healthy females group(5.0%, 17.6%);the rate of only HBV surface antibody positivity (HBsAb ( +)) in the breast cancer group (10.3%) was lower than that in the benign breast disease group (26.9%) and the healthy females group (49.2%), with significant differences between the three groups (p < 0.05). Stratified by age, the prevalence of HBV infection in the breast cancer group (8%, 8.9%) and benign breast disease group (7.75%, 8.1%)was higher than that in the healthy females group (4.5%, 6.3%) in the 30-39 and 40-49 age group, respectively. The past infection rate of HBV in the breast cancer group (24.8%, 45.0%) was higher than that in the benign breast disease group (16.1%, 35.4%) in the ≤ 29 and 30-39 age group, respectively.. The past infection rate of HBV in the breast cancer group was higher than that in the healthy females group in all age groups, while the rate of only HBsAb ( +) in the breast cancer group was lower than that in the benign breast disease group and the routine physical examination group in all age groups. CONCLUSIONS: Breast cancer women and women with benign breast diseases have higher rates of hepatitis B virus infection and previous infections, with more significant differences among middle-aged women. Breast cancer women and women with benign breast diseases have lower rates of only HBsAb ( +) for HBV.

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Due to the low permeability characteristics of the deep gas-containing coal seam, the conventional prevention and control measures that cannot solve the problems of gas outbursts are unsatisfactory for the prevention and control of the coal and gas outbursts disaster. Therefore, in this study, a strain of methane-oxidizing bacteria M07 with high-pressure resistance, strong resistance, and high methane degradation rate was selected from coal mines. The growth and degradation abilities of M07 in chelating wetting agent solutions to assess its adaptability and find the optimal agent-to-M07 ratio. It provides a new method for integrating the reduction of impact tendency and gas pressure in deep coal mines. The experimental results show that M07 is a Gram-positive bacterium of the genus Bacillus, which has strong resistance and adaptability to high-pressure water injection. By degrading 70 mol of methane, M07 produces 1 mol of carbon dioxide, which can reduce gas pressure and reduce the risk of gas outbursts in coal mines. As the experiment proves, the best effect was achieved when the M07 concentration of the chelating wetting agent was 0.05%. The methane-oxidizing bacteria based on the chelating wetting agent as carriers prove a new prevention and control method for the integrated prevention and control of coal and gas outbursts in coal mines and also provide a new idea for microbial application in coal mine disaster control.

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PURPOSE: Opioids remain the mainstay of analgesia for critically ill patients, but its exposure is associated with negative effects including persistent use after discharge. Nonsteroidal anti-inflammatory drugs (NSAIDs) may be an effective alternative to opioids with fewer adverse effects. We aimed to describe beliefs and attitudes towards the use of NSAIDs in adult intensive care units (ICUs). METHODS: Our survey of Canadian ICU physicians was conducted using a web-based platform and distributed through the Canadian Critical Care Society (CCCS) email distribution list. We used previously described survey development methodology including question generation and reduction, pretesting, and clinical sensibility and pilot testing. RESULTS: We received 115 completed surveys from 321 CCCS members (36%). Nonsteroidal anti-inflammatory drugs use was most described as "rarely" (59 respondents, 51%) with the primary concern being adverse events (acute kidney injury [108 respondents, 94%] and gastrointestinal bleeding [92 respondents, 80%]). The primary preferred analgesic was acetaminophen (75 respondents, 65%) followed by opioids (40 respondents, 35%). Most respondents (91 respondents, 80%) would be willing to participate in a randomized controlled trial examining NSAID use in critical care. CONCLUSIONS: In our survey, Canadian critical care physicians did not mention commonly using NSAIDs primarily because of concerns about adverse events. Nevertheless, respondents were interested in further studying ketorolac, a commonly used NSAID outside of the ICU, in critically ill patients.

RéSUMé: OBJECTIF: Les opioïdes restent le pilier de l'analgésie pour les patient·es gravement malades, mais l'exposition à ces agents est associée à des effets négatifs, notamment à leur utilisation persistante après le congé de l'hôpital. Les anti-inflammatoires non stéroïdiens (AINS) pourraient constituer une alternative efficace aux opioïdes avec moins d'effets indésirables. Nous avons cherché à décrire les croyances et les attitudes à l'égard de l'utilisation des AINS dans les unités de soins intensifs (USI) pour adultes. MéTHODE: Notre sondage auprès des médecins intensivistes au Canada a été mené à l'aide d'une plateforme Web et distribué aux personnes sur la liste de distribution électronique de la Société canadienne de soins intensifs (SCSI). Nous avons utilisé une méthodologie d'élaboration d'enquêtes décrite précédemment, y compris la génération et la réduction de questions, les tests préalables, la sensibilité clinique et les tests pilotes. RéSULTATS: Nous avons reçu 115 sondages remplis par 321 membres de la SCSI (36 %). L'utilisation d'anti-inflammatoires non stéroïdiens a été décrite comme « rare ¼ (59 répondant·es, 51 %), la principale préoccupation étant les événements indésirables (insuffisance rénale aiguë [108 répondant·es, 94 %] et saignements gastro-intestinaux [92 répondant·es, 80 %]). Le principal analgésique préféré était l'acétaminophène (75 répondant·es, 65 %), suivi des opioïdes (40 répondant·es, 35 %). La plupart des répondant·es (91 répondant·es, 80 %) seraient prêt·es à participer à une étude randomisée contrôlée examinant l'utilisation des AINS en soins intensifs. CONCLUSION: Dans notre sondage, les médecins intensivistes au Canada n'ont pas mentionné l'utilisation courante d'AINS, principalement en raison de préoccupations concernant leurs effets indésirables. Néanmoins, les répondant·es étaient intéressé·es à étudier plus avant le kétorolac, un AINS couramment utilisé en dehors des soins intensifs, chez les patient·es gravement malades.

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Estimating the impact of pesticide residue bioaccessibility in fruits on dietary exposure is a complex task in human health risk assessment. This research investigated the bioaccessibility of ten commonly used and detected pesticides in bananas and mangoes, as well as the factors influencing it, using an in vitro model. The highest bioaccessibility was observed at pH levels of 2.5 and 6.5 in the gastric and intestinal stages, respectively. Bioaccessibility decreased significantly with increasing solid/liquid ratios for most pesticides. The consumption of protein and four dietary components (carbohydrates, protein, lipids, and dietary fiber) could significantly reduce pesticide bioaccessibility by 9.89-48.32% (p < 0.05). Bioaccessibility in oral and gastric stages among four populations followed the order of adults/the elderly > children > infants, due to decreasing concentrations of α-amylase and pepsin. Pesticides in bananas generally exhibited a higher bioaccessibility (18.65-82.97%) compared to that in mangoes (11.68-87.57%). Bioaccessibility showed a negative correlation with the Log P values of the target pesticide, while no clear relationship was found between bioaccessibility and initial pesticide concentrations. Incorporating bioaccessible pesticide concentrations into risk assessments could lower dietary risk estimates by 11.85-79.57%. Assessing human exposure to pesticides based on bioaccessibility would greatly improve the accuracy of the risk assessment.

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We developed a new transient directing group, N-(2-benzoyl-4-chlorophenyl)-1,1,1-trifluoromethanesulfonamide, which can facilitate the γ-monoarylation of free amines containing symmetric γ-C-H bonds. A variety of amines containing symmetric and identical γ-C(sp3)-H and γ-C(sp2)-H reacted with a diverse range of aryl and heteroaryl iodides to provide γ-monoarylated products exclusively.