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Recent advances in high-throughput chromosome conformation capture (Hi-C) techniques have allowed us to map genome-wide chromatin interactions and uncover higher-order chromatin structures, thereby shedding light on the principles of genome architecture and functions. However, statistical methods for detecting changes in large-scale chromatin organization such as topologically associating domains (TADs) are still lacking. Here, we proposed a new statistical method, DiffGR, for detecting differentially interacting genomic regions at the TAD level between Hi-C contact maps. We utilized the stratum-adjusted correlation coefficient to measure similarity of local TAD regions. We then developed a nonparametric approach to identify statistically significant changes of genomic interacting regions. Through simulation studies, we demonstrated that DiffGR can robustly and effectively discover differential genomic regions under various conditions. Furthermore, we successfully revealed cell type-specific changes in genomic interacting regions in both human and mouse Hi-C datasets, and illustrated that DiffGR yielded consistent and advantageous results compared with state-of-the-art differential TAD detection methods. The DiffGR R package is published under the GNU General Public License (GPL) ≥ 2 license and is publicly available at https://github.com/wmalab/DiffGR.

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The aim of this study was to establish and validate the precision of a novel radiomics approach that integrates 18Fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-computed tomography (CT) scan data with clinical information to improve the prognostication of survival rates in patients diagnosed with stage III Non-Small Cell Lung Cancer (NSCLC) who are not candidates for surgery. We evaluated pretreatment 18F-FDG PET-CT scans from 156 individuals diagnosed with stage III inoperable NSCLC at Shandong Cancer Hospital. These individuals were divided into two groups: a training set comprising 110 patients and an internal validation set consisting of 46 patients. By employing random forest classifier and cox proportional hazards model , we identified and utilized relevant features to create predictive models and a nomogram. The effectiveness of these models was assessed through the use of the receiver operating characteristics(ROC) curves, Kaplan-Meier (KM) curves, and the application of the nomogram. Our findings showed that the combined model, which integrates both clinical and radiomic data, outperformed those based solely on clinical or radiomic features in predicting 3-year overall survival(OS). Furthermore, calibration plots revealed a high level of agreement between predicted and actual survival times. The research successfully established a predictive radiomics model that integrates 18F-FDG PET/CT imaging with clinical indicators to enhance survival predictions for patients with stage III inoperable NSCLC.

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Background: Intestinal barrier defect is an essential inflammatory bowel disease (IBD) pathogenesis. Mitochondrial dysfunction results in energy deficiency and oxidative stress, which contribute to the pathogenesis of IBD. ß-arrestin1 (ARRB1) is a negative regulator that promotes G protein-coupled receptors desensitization, endocytosis, and degradation. However, its role in maintaining the intestinal barrier remains unclear. Methods: Dextran sulfate sodium-induced colitis was performed in ARRB1 knockout and wild-type mice. Intestinal permeability and tight junction proteins were measured to evaluate the intestinal barrier. Mitochondria function and mitophagic flux in mice and cell lines were detected. Finally, the interaction between ARRB1 and mitofusin 2 was investigated by co-immunoprecipitation and dual luciferase assay. Results: We identified that ARRB1 protected the intestinal tight junction barrier against experimental colitis in vivo. ARRB1 deficiency was accompanied by abnormal mitochondrial morphology, lower adenosine triphosphate (ATP) production, and severe oxidative stress. In vitro, the knockdown of ARRB1 reduced ATP levels and mitochondrial membrane potential while increasing reactive oxygen species levels and oxidative stress. Upon ARRB1 ablation, mitophagy was inhibited, accompanied by decreased LC3BII, phosphatase and tension homologue-induced protein kinase1 (PINK1), and parkin, but increased p62 expression. Mitophagy inhibition via PINK1 siRNA or mitochondrial division inhibitor 1 impaired ARRB1-mediated tight junction protection. The interaction of ARRB1 with E2F1 activated mitophagy by enhancing the transcription of mitofusin 2. Conclusions: Our results suggest that ARRB1 is critical to maintaining the intestinal tight junction barrier by promoting mitophagy. These results reveal a novel link between ARRB1 and the intestinal tight junction barrier, which provides theoretical support for colitis treatment.

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BACKGROUND: The complexity of cancer is intricately linked to its multifaceted biological processes, including the roles of the tumor microenvironment (TME) as well as genetic and metabolic regulation. Histone lactylation has recently emerged as a novel epigenetic modification mechanism that plays a pivotal role in regulating cancer initiation, proliferation, invasion, and metastasis. OBJECTIVE: This review aims to elucidate the role of histone lactylation in modulating various aspects of tumor biology, including DNA repair mechanisms, glycolytic metabolic abnormalities, functions of non-tumor cells in the TME, and the promotion of tumor inflammatory responses and immune escape. Additionally, the review explores potential therapeutic strategies targeting histone lactylation. METHODS: A comprehensive literature review was performed, analyzing recent findings on histone lactylation and its impact on cancer biology. This involved a systematic examination of studies focusing on biochemical pathways, cellular interactions, and clinical implications related to histone lactylation. RESULTS: Histone lactylation was identified as a critical regulator of tumor cell DNA repair mechanisms and glycolytic metabolic abnormalities. It also significantly influences the functions of non-tumor cells within the TME, promoting tumor inflammatory responses and immune escape. Moreover, histone lactylation acts as a multifunctional biological signaling molecule impacting immune responses within the TME. Various cell types within the TME, including T cells and macrophages, were found to regulate tumor growth and immune escape mechanisms through lactylation. CONCLUSION: Histone lactylation offers a novel perspective on tumor metabolism and its role in cancer development. It presents promising opportunities for the development of innovative cancer therapies. This review underscores the potential of histone lactylation as a therapeutic target, paving the way for new strategies in cancer treatment.

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BACKGROUND: Chlorinated paraffins (CPs) are industrial chemicals categorised as persistent organic pollutants because of their toxicity, persistency and tendency to long-range transport, bioaccumulation and biomagnification. Despite having been the subject of environmental attention for decades, analytical methods for CPs still struggle reaching a sufficient degree of accuracy. Among the issues negatively impacting the quantification of CPs, the unavailability of well-characterised standards, both as pure substances and as matrix (certified) reference materials (CRMs), has played a major role. The focus of this study was to provide a matrix CRM as quality control tool to improve the comparability of CPs measurement results. RESULTS: We present the process of certification of ERM®-CE100, the first fish reference material assigned with certified values for the mass fraction of short-chain and medium-chain chlorinated paraffins (SCCPs and MCCPs, respectively). The certification was performed in accordance with ISO 17034:2016 and ISO Guide 35:2017, with the value assignment step carried out via an intercomparison of laboratories of demonstrated competence in CPs analysis and applying procedures based on different analytical principles. After confirmation of the homogeneity and stability of the CRM, two certified values were assigned for SCCPs, depending on the calibrants used: 31 ± 9 µg kg-1 and 23 ± 7 µg kg-1. The MCCPs certified value was established as 44 ± 17 µg kg-1. All assigned values are relative to wet weight in the CRM that was produced as a fish paste to enhance similarity to routine biota samples. SIGNIFICANCE AND NOVELTY: The fish tissue ERM-CE100 is the first matrix CRM commercially available for the analysis of CPs, enabling analytical laboratories to improve the accuracy and the metrological traceability of their measurements. The certified CPs values are based on results obtained by both gas and liquid chromatography coupled with various mass spectrometric techniques, offering thus a broad validity to laboratories employing different analytical methods and equipment.

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Dibutyl phthalate (DBP) as a plasticizer has been widely used in the processing of plastic products. Nevertheless, these DBP additives have the potential to be released into the environment throughout the entire life cycle of plastic products. Herein, the leaching behavior of DBP from PVC microplastics (MPs) in freshwater and seawater and its potential risks were investigated. The results show that the plasticizer content, UV irradiation, and hydrochemical conditions have a great influence on the leaching of DBP from the MPs. The release of DBP into the environment increases proportionally with higher concentrations of additive DBP in MPs, particularly when it exceeds 15 %. The surface of MPs undergoes accelerated oxidation and increased hydrophilicity under UV radiation, thereby facilitating the leaching of DBP. Through 30 continuous leaching experiments, the leaching of DBP from MPs in freshwater and seawater can reach up to 12.28 and 5.42 mg g-1, respectively, indicating that MPs are a continuous source of DBP pollution in the aquatic environment. Moreover, phthalate pollution index (PPI) indicates that MPs can significantly increase DBP pollution in marine environment through land and sea transport processes. Therefore, we advocate that the management of MPs waste containing DBP be prioritized in coastal sustainable development.

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Electrocatalytic reduction of biomass-derived furan compounds provides a green and sustainable approach to produce value-added fuels and chemicals. Despite the achievements in unimolecular transformation, C-C coupling which holds great promise to yield precursors for high-density fuels has not received extensive attention. Herein, we report a Cu2O-derived nanowire array material with switchable selectivity to electrocatalytic reduction of furfural depending on the electrolyte pH. Besides a high selectivity of 98.4% to furfuryl alcohol via hydrogenation at pH 9.5, the Cu2O-derived array structure also exhibits a high selectivity of 83.5% to hydrofuroin via C-C coupling at pH 14. Upon control experiments and detailed characterization of the electrodes, the array architecture is proposed to decrease the diffusion of ketyl radicals which are the key intermediates for C-C coupling. The confined diffusion results in a high local concentration of the radicals in the array and facilitates their collision for enhancing the formation of hydrofuroin.

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Tri (2-chloropropyl) phosphate (TCPP) was an emerging contaminant of global concern because of its frequent occurrence, potential toxic effects, and persistence in the environment. Microbial degradation might be an efficient and safe removal method, but limited information was available. In this study, Providencia rettgeri was isolated from contaminated sediment and showed it could use TCPP as unique phosphorus source to promote growth, and decompose 34.7% of TCPP (1 mg/L) within 5 days. The microbial inoculation and the initial concentration of TCPP could affect the biodegradation efficient. Further study results indicated that TCPP decomposition by Providencia rettgeri was mainly via phosphoester bond hydrolysis, evidenced by the production of bis (2-chloropropyl) phosphate (C6H13Cl2PO4) and mono-chloropropyl phosphate (C3H8ClPO4). Both intracellular and extracellular enzymes could degrade TCPP, but intracellular degradation was dominant in the later reaction stage, and the presence of Cu2+ ions had a promoting effect. These findings developed novel insights into the potential mechanism of TCPP microbial degradation.

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The present study investigates the chemical composition variances among Pinelliae Rhizoma, a widely used Chinese herbal medicine, and its common adulterants including Typhonium flagelliforme, Arisaema erubescens, and Pinellia pedatisecta. Utilizing the non-targeted metabolomics technique of employing UHPLC-Q-Orbitrap HRMS, this research aims to comprehensively delineate the metabolic profiles of Pinelliae Rhizoma and its adulterants. Multivariate statistical methods including PCA and OPLS-DA are employed for the identification of differential metabolites. Volcano plot analysis is utilized to discern upregulated and downregulated compounds. KEGG pathway analysis is conducted to elucidate the differences in metabolic pathways associated with these compounds, and significant pathway enrichment analysis is performed. A total of 769 compounds are identified through metabolomics analysis, with alkaloids being predominant, followed by lipids and lipid molecules. Significant differential metabolites were screened out based on VIP > 1 and p-value < 0.05 criteria, followed by KEGG enrichment analysis of these differential metabolites. Differential metabolites between Pinelliae Rhizoma and Typhonium flagelliforme, as well as between Pinelliae Rhizoma and Pinellia pedatisecta, are significantly enriched in the biosynthesis of amino acids and protein digestion and absorption pathways. Differential metabolites between Pinelliae Rhizoma and Arisaema erubescens are mainly enriched in tyrosine metabolism and phenylalanine metabolism pathways. These findings aim to provide valuable data support and theoretical references for further research on the pharmacological substances, resource development and utilization, and quality control of Pinelliae Rhizoma.

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Depression, a common mental illness, seriously affects the health of individuals and has deleterious effects on society. The prevention and treatment of depression has drawn the attention of many researchers and has become an important social issue. The treatment strategies for depression include drugs, psychotherapy, and physiotherapy. Drug therapy is ineffective in some patients and psychotherapy has treatment limitations. As a reliable adjuvant therapy, physiotherapy compensates for the shortcomings of drug and psychotherapy and effectively reduces the disease recurrence rate. Physiotherapy is more scientific and rigorous, its methods are diverse, and to a certain extent, provides more choices for the treatment of depression. Physiotherapy can relieve symptoms in many ways, such as by improving the levels of neurobiochemical molecules, inhibiting the inflammatory response, regulating the neuroendocrine system, and increasing neuroplasticity. Physiotherapy has biological effects similar to those of antidepressants and may produce a superimposed impact when combined with other treatments. This article summarizes the findings on the use of physiotherapy to treat patients with depression over the past five years. It also discusses several methods of physiotherapy for treating depression from the aspects of clinical effect, mechanism of action, and disadvantages, thereby serving as a reference for the in-depth development of physiotherapy research.

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The published grant number was "OFJH2021008", while the correct should read "DFJH2021008". Reference: Yinghong Wu, Huiling Liu, Minghao Zhong, Xiyi Chen, Zhiqiong Ba, Guibin Qiao, Jiejie Feng, Xiuqun Zeng: Enhanced Patient Comfort and Satisfaction with Early Oral Feeding after Thoracoscopic Lung Cancer Resection. Med Sci Monit, 2023; 29: e941577. DOI: 10.12659/MSM.941577.

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Large bone defects cause significant clinical challenges due to the lack of optimal grafts for effective regeneration. The tissue engineering way that requires the combination of biomaterials scaffold, stem cells and proper bioactive factors is a prospective method for large bone repair. Here, we synthesized a three-arm host-guest supramolecule (HGSM) to covalently crosslinking with the naturally derived polymer methacrylated silk fibroin (SFMA). The combination of HGSM and SFMA can form a high strength double-crosslinked hydrogel HGSFMA, that serve as the hydrogel scaffold for bone marrow mesenchymal stem cells (BMSCs) growing. Icariin (ICA) loaded in the HGSFMA hydrogel can promote the osteogenesis efficiency of BMSCs and inhibit the osteoclasts differentiation. Our findings demonstrated that the HGSFMA/ICA hydrogel effectively promoted the in vitro adhesion, proliferation, and osteogenic differentiation of BMSCs. Rat femoral defects model show that this hydrogel can completely repair femoral damage within 4 weeks and significantly promote the secretion of osteogenesis-related proteins. In summary, we have prepared an effective biomimetic bone carrier, offering a novel strategy for bone regeneration and the treatment of large-scale bone defects.

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Primary Biliary Cholangitis (PBC) and Autoimmune Hepatitis (AIH) are autoimmune diseases that target hepatocytes and bile duct cells, respectively. Despite their shared autoimmune nature, the differences in immunologic characteristics between them remain largely unexplored. This study seeks to elucidate the unique immunological profiles of PBC and AIH, and to identify key differences. We comprehensively analyzed various T-cell subsets and their receptor expression in a cohort of 45 patients, including 27 PBC and 18 AIH cases. Both diseases exhibited T cell exhaustion and senescence along with a surge in inflammatory cytokines. Significantly increased CD38+HLA-DR+CD8+T cell populations were observed in both diseases. AIH was characterized by an upregulation of CD8+TEMRA, CD4+TEM, and CD4+TEMRA cells, and a concurrent reduction in Treg cells. In contrast, PBC displayed a pronounced presence of Tfh cells and a contraction of CD4-CD8-T cell populations. Correlation analysis revealed that NKP46+NK frequency was closely tied to ALT and AST levels, and TIGIT expression on T cells was associated with GLB level in AIH. In PBC, there is a significant correlation between Tfh cells and ALP levels. Moreover, the identified immune landscapes in both diseases strongly related to disease severity. Through logistic regression analysis, γδ T, TIGIT+Vδ2 T, and Tfh1 cell frequencies emerged as distinct markers capable of differentiating PBC from AIH. In conclusion, our analyses reveal that PBC and AIH share similarities and differences regarding to immune profiles. And γδ T, TIGIT+Vδ2 T, and Tfh1 cell frequencies are potential noninvasive immunological markers that can differentiate PBC from AIH.

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Noninvasive differentiation between the squamous cell carcinoma (SCC) and adenocarcinoma (ADC) subtypes of non-small cell lung cancer (NSCLC) could benefit patients who are unsuitable for invasive diagnostic procedures. Therefore, this study evaluates the predictive performance of a PET/CT-based radiomics model. It aims to distinguish between the histological subtypes of lung adenocarcinoma and squamous cell carcinoma, employing four different machine learning techniques. A total of 255 Non-Small Cell Lung Cancer (NSCLC) patients were retrospectively analyzed and randomly divided into the training (n = 177) and validation (n = 78) sets, respectively. Radiomics features were extracted, and the Least Absolute Shrinkage and Selection Operator (LASSO) method was employed for feature selection. Subsequently, models were constructed using four distinct machine learning techniques, with the top-performing algorithm determined by evaluating metrics such as accuracy, sensitivity, specificity, and the area under the curve (AUC). The efficacy of the various models was appraised and compared using the DeLong test. A nomogram was developed based on the model with the best predictive efficiency and clinical utility, and it was validated using calibration curves. Results indicated that the logistic regression classifier had better predictive power in the validation cohort of the radiomic model. The combined model (AUC 0.870) exhibited superior predictive power compared to the clinical model (AUC 0.848) and the radiomics model (AUC 0.774). In this study, we discovered that the combined model, refined by the logistic regression classifier, exhibited the most effective performance in classifying the histological subtypes of NSCLC.

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Rationally modulating the binding strength of reaction intermediates on surface sites of copper-based catalysts could facilitate C-C coupling to generate multicarbon products in an electrochemical CO2 reduction reaction. Herein, theoretical calculations reveal that cascade Ag-Cu dual sites could synergistically increase local CO coverage and lower the kinetic barrier for CO protonation, leading to enhanced asymmetric C-C coupling to generate C2H4. As a proof of concept, the Cu3N-Ag nanocubes (NCs) with Ag located in partial Cu sites and a Cu3N unit center are successfully synthesized. The Faraday efficiency and partial current density of C2H4 over Cu3N-Ag NCs are 7.8 and 9.0 times those of Cu3N NCs, respectively. In situ spectroscopies combined with theoretical calculations confirm that Ag sites produce CO and Cu sites promote asymmetric C-C coupling to *COCHO, significantly enhancing the generation of C2H4. Our work provides new insights into the cascade catalysis strategy at the atomic scale for boosting CO2 to multicarbon products.

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Acoustically actuated magnetoelectric (ME) antennas utilize acoustic wave resonance to complete the process of receiving and transmitting signals, which promotes the development of antenna miniaturization technology. This paper presents a bilayer magnetostrictive/AlN ME laminated antenna. The proposed laminated antenna uses the FeGa/FeGaB bilayer materials as magnetostrictive materials, which combine the advantages of soft magnetic properties of FeGa and the low loss of FeGaB. First, multiphysics modeling and analysis are performed for the proposed ME laminated antenna by finite element method (FEM). The positive/inverse ME effects and the influences of the volume ratio of the FeGa/FeGaB bilayer on the antenna performance are studied. The results show that the output voltage and ME coefficient of the FeGa/FeGaB bilayer magnetostrictive material with a volume ratio of 1:1 are 3.97 times and 195.8% higher than that of the single FeGaB layer, respectively. The eddy current loss is 52.08% lower than that of single-layer FeGa. According to the surface equivalence principle, the far-field radiation process is simulated. The results show that the gain of the ME antenna is 15 dB larger than that of the same-size micro-loop antenna, and the gain of the ME antenna is about -44.9 dB. The improved performance and magnetic tunability of the proposed bilayer magnetostrictive materials make ME antennas excellent candidates for portable devices and implantable medical devices.

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BACKGROUND: Renal fibrosis is a common pathway that drives the advancement of numerous kidney maladies towards end-stage kidney disease (ESKD). Suppressing renal fibrosis holds paramount clinical importance in forestalling or retarding the transition of chronic kidney diseases (CKD) to renal failure. Schisandrin A (Sch A) possesses renoprotective effect in acute kidney injury (AKI), but its effects on renal fibrosis and underlying mechanism(s) have not been studied. STUDY DESIGN: Serum biochemical analysis, histological staining, and expression levels of related proteins were used to assess the effect of PKCß knockdown on renal fibrosis progression. Untargeted metabolomics was used to assess the effect of PKCß knockdown on serum metabolites. Unilateral Ureteral Obstruction (UUO) model and TGF-ß induced HK-2 cells and NIH-3T3 cells were used to evaluate the effect of Schisandrin A (Sch A) on renal fibrosis. PKCß overexpressed NIH-3T3 cells were used to verify the possible mechanism of Sch A. RESULTS: PKCß was upregulated in the UUO model. Knockdown of PKCß mitigated the progression of renal fibrosis by ameliorating perturbations in serum metabolites and curbing oxidative stress. Sch A alleviated renal fibrosis by downregulating the expression of PKCß in kidney. Treatment with Sch A significantly attenuated the upregulated proteins levels of FN, COL-I, PKCß, Vimentin and α-SMA in UUO mice. Moreover, Sch A exhibited a beneficial impact on markers associated with oxidative stress, including MDA, SOD, and GSH-Px. Overexpression of PKCß was found to counteract the renoprotective efficacy of Sch A in vitro. CONCLUSION: Sch A alleviates renal fibrosis by inhibiting PKCß and attenuating oxidative stress.

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Gentamicin mycelium residues (GMRs) abundant in organic substances were generated during the production of gentamicin. Inappropriate handling techniques not only waste valuable resources, they could also result in residual gentamicin into the natural environment, leading to the generation of antibiotic resistance genes (ARGs), which would cause a significant threat to ecological system and human health. In the present work, the effects of thermal treatment on the removal of residual gentamicin in GMRs, as well as the changes of associated ARGs abundance, antimicrobial activity and bioresources properties were investigated. The results indicated that the hazards of GMRs was significantly reduced through thermal treatment. The degradation rate of residual gentamicin in GMRs reached 100 %, the total abundance of gentamicin resistance genes declined from 8.20 to 1.14 × 10-5 and the antibacterial activity of the decomposition products of GMRs on Vibrio fischeri was markedly reduced at 200 °C for 120 min. Additionally, the thermal treatment remarkably influenced the bioresource properties of GMRs-decomposition products. The release of soluble organic matters including soluble carbohydrates and soluble proteins have been enhanced in GMRs, while excessively high temperatures could lead to a reduction of nutrient substances. Generally, thermal treatment technology was a promising strategy for synergistic reducing hazards and utilizing bioresources of GMRs.

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The construction of structural complexity and diversity of natural products is crucial for drug discovery and development. To overcome high dark toxicity and poor photostability of natural photosensitizer perylenequinones (PQs) for photodynamic therapy, herein, we aim to introduce the structural complexity and diversity to biosynthesize the desired unnatural PQs in fungus Cercospora through synthetic biology-based strategy. Thus, we first elucidate the intricate biosynthetic pathways of class B PQs and reveal how the branching enzymes create their structural complexity and diversity from a common ancestor. This enables the rational reprogramming of cercosporin biosynthetic pathway in Cercospora to generate diverse unnatural PQs without chemical modification. Among them, unnatural cercosporin A displays remarkably low dark toxicity and high photostability with retention of great photodynamic anticancer and antimicrobial activities. Moreover, it is found that, unlike cercosporin, unnatural cercosporin A could be selectively accumulated in cancer cells, providing potential targets for drug development. Therefore, this work provides a comprehensive foundation for preparing unnatural products with customized functions through synthetic biology-based strategies, thus facilitating drug discovery pipelines from nature.

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