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As an emerging environmental contaminant, antibiotic resistance genes (ARGs) in tap water have attracted great attention. Although studies have provided ARG profiles in tap water, research on their abundance levels, composition characteristics, and potential threat is still insufficient. Here, 9 household tap water samples were collected from the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) in China. Additionally, 75 sets of environmental sample data (9 types) were downloaded from the public database. Metagenomics was then performed to explore the differences in the abundance and composition of ARGs. 221 ARG subtypes consisting of 17 types were detected in tap water. Although the ARG abundance in tap water was not significantly different from that found in drinking water plants and reservoirs, their composition varied. In tap water samples, the three most abundant classes of resistance genes were multidrug, fosfomycin and MLS (macrolide-lincosamide-streptogramin) ARGs, and their corresponding subtypes ompR, fosX and macB were also the most abundant ARG subtypes. Regarding the potential mobility, vanS had the highest abundance on plasmids and viruses, but the absence of key genes rendered resistance to vancomycin ineffective. Generally, the majority of ARGs present in tap water were those that have not been assessed and are currently not listed as high-threat level ARG families based on the World Health Organization Guideline. Although the current potential threat to human health posed by ARGs in tap water is limited, with persistent transfer and accumulation, especially in pathogens, the potential danger to human health posed by ARGs should not be ignored.
Subject(s)
Drinking Water , Drug Resistance, Microbial , Metagenomics , Drug Resistance, Microbial/genetics , Drinking Water/microbiology , China , Environmental Monitoring , Anti-Bacterial Agents/pharmacology , Water MicrobiologyABSTRACT
Tick-borne encephalitis virus (TBEV) is a pathogen that causes febrile infectious diseases and neurological damage to humans. TBEVs are prevalent from Europe to Far Eastern Asia, including Northeastern China. The understanding of TBEV phylogeny in China has been limited owing to insufficient genomic data on Chinese TBEV strains. Here, six TBEV strains were isolated from ticks collected in Inner Mongolia. The transmission electron microscopy revealed spherical particles with an enveloped structure of 50-60 nm in diameter. Phylogenetic analysis showed that, two strains were classified as the Siberian subtype, while the remaining four were identified as the Far Eastern subtype. Migration analyses based on TBEV ORF and envelope (E) protein sequences revealed that Chinese TBEV strains were migrated from Russia and/or Kazakhstan into China. Hulun Buir and Mudanjiang, the northeastern region of China, are considered hotspots with multiple import and export routes of Chinese TBEV strains. These results promote the understanding of TBEV genetic variations and phylogeny in China and suggest the importance of improving investigation of TBEV prevalence, which would instrumental for vaccine design strategies and better preparation for controlling TBEV infection in humans.
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Purpose: This study aimed to establish and evaluate the value of integrated models involving 18F-FDG PET/CT-based radiomics and clinicopathological information in the prediction of pathological complete response (pCR) to neoadjuvant therapy (NAT) for non-small cell lung cancer (NSCLC). Methods: A total of 106 eligible NSCLC patients were included in the study. After volume of interest (VOI) segmentation, 2,016 PET-based and 2,016 CT-based radiomic features were extracted. To select an optimal machine learning model, a total of 25 models were constructed based on five sets of machine learning classifiers combined with five sets of predictive feature resources, including PET-based alone radiomics, CT-based alone radiomics, PET/CT-based radiomics, clinicopathological features, and PET/CT-based radiomics integrated with clinicopathological features. Area under the curves (AUCs) of receiver operator characteristic (ROC) curves were used as the main outcome to assess the model performance. Results: The hybrid PET/CT-derived radiomic model outperformed PET-alone and CT-alone radiomic models in the prediction of pCR to NAT. Moreover, addition of clinicopathological information further enhanced the predictive performance of PET/CT-derived radiomic model. Ultimately, the support vector machine (SVM)-based PET/CT radiomics combined clinicopathological information presented an optimal predictive efficacy with an AUC of 0.925 (95% CI 0.869-0.981) in the training cohort and an AUC of 0.863 (95% CI 0.740-0.985) in the test cohort. The developed nomogram involving radiomics and pathological type was suggested as a convenient tool to enable clinical application. Conclusions: The 18F-FDG PET/CT-based SVM radiomics integrated with clinicopathological information was an optimal model to non-invasively predict pCR to NAC for NSCLC.
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The buried interface tens of nanometers beneath the solid-liquid junction is crucial for photocarrier extraction, influencing the overall efficiency of photoelectrochemical devices. Precise characterization of the interfacial properties is essential for device optimization but remains challenging. Here, we directly probe the in situ transformation of a CuxO interlayer at the NiO/n-Si interface by hard X-ray photoelectron spectroscopy. It is found that Cu(I) in the CuxO interlayer gradually transforms to Cu(II) with air exposure, forming an energetically more favorable interface and improving photoanode's efficiency. Based on this finding, a reactive e-beam evaporation process is developed for the direct deposition of a CuO interlayer, achieving a half-cell solar-to-hydrogen efficiency of 4.56% for the optimized NiO/CuO/n-Si heterojunction photoanode. Our results highlight the importance of precision characterization of interfacial properties with advanced hard X-ray photoelectron spectroscopy in guiding the design of efficient solar water-splitting devices.
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The high prevalence of cancer and detrimental side effects associated with many cancer treatments necessitate the search for effective alternative therapies. Natural products are increasingly being recognized and investigated for their potential therapeutic benefits. Scutellaria barbata D. Don (SBD), a plant with potent antitumor properties, has attracted significant interest from oncology researchers. Its primary flavonoid components-scutellarin and luteolin-which have limited oral bioavailability due to poor absorption. This hinders its application for cancer treatment. The gut microbiota, which is considered a metabolic organ, can modulate the biotransformation of compounds, thereby altering their bioavailability and efficacy. In this study, we employed liquid chromatography tandem mass spectrometry (LC-MS/MS 8060) and ion trap-time of flight (LC-MSn-IT-TOF) analysis to investigate the ex vivo metabolism of scutellarin and luteolin by the gut microbiota. Five metabolites and one potential metabolite were identified. We summarized previous studies on their antitumor effects and performed in vitro tumor cell line studies to prove their antitumor activities. The possible key pathway of gut microbiota metabolism in vitro was validated using molecular docking and pure enzyme metabolic experiments. In addition, we explored the antitumor mechanisms of the two components of SBD through network pharmacology, providing a basis for subsequent target identification. These findings expand our understanding of the antitumor mechanisms of SBD. Notably, this study contributes to the existing body of knowledge regarding flavonoid biotransformation by the gut microbiota, highlighting the therapeutic potential of SBD in cancer treatment. Moreover, our results provide a theoretical basis for future in vivo pharmacokinetic studies, aiming to optimize the clinical efficacy of SBD in oncological applications.
Subject(s)
Apigenin , Gastrointestinal Microbiome , Glucuronates , Luteolin , Scutellaria , Tandem Mass Spectrometry , Gastrointestinal Microbiome/drug effects , Luteolin/pharmacology , Luteolin/metabolism , Luteolin/pharmacokinetics , Scutellaria/chemistry , Apigenin/pharmacology , Glucuronates/metabolism , Humans , Tandem Mass Spectrometry/methods , Cell Line, Tumor , Animals , Molecular Docking Simulation , Plant Extracts/pharmacology , Chromatography, Liquid/methods , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/pharmacokinetics , Biological Availability , Male , Biotransformation , Antineoplastic Agents/pharmacology , Antineoplastic Agents/pharmacokineticsABSTRACT
The primary aim of this study was to conduct a methodical examination and assessment of the prognostic efficacy exhibited by magnetic resonance imaging (MRI)-derived radiomic models concerning the preoperative prediction of lymph-vascular space infiltration (LVSI) in cervical cancer cases. A comprehensive and thorough exploration of pertinent academic literature was undertaken by two investigators, employing the resources of the Embase, PubMed, Web of Science, and Cochrane Library databases. The scope of this research was bounded by a publication cutoff date of May 15, 2023. The inclusion criteria encompassed studies that utilized radiomic models based on MRI to prognosticate the accuracy of preoperative LVSI estimation in instances of cervical cancer. The Diagnostic Accuracy Studies-2 framework and the Radiomic Quality Score metric were employed. This investigation included nine distinct research studies, enrolling a total of 1,406 patients. The diagnostic performance metrics of MRI-based radiomic models in the prediction of preoperative LVSI among cervical cancer patients were determined as follows: sensitivity of 83% (95% confidence interval [CI]=77%-87%), specificity of 74% (95% CI=69%-79%), and a corresponding AUC of summary receiver operating characteristic measuring 0.86 (95% CI=0.82-0.88). The results of the synthesized meta-analysis did not reveal substantial heterogeneity.This meta-analysis suggests the robust diagnostic proficiency of the MRI-based radiomic model in the prognostication of preoperative LVSI within the cohort of cervical cancer patients. In the future, radiomics holds the potential to emerge as a widely applicable noninvasive modality for the early detection of LVSI in the context of cervical cancer.
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BACKGROUND: The management of locally recurrent gynecological carcinoma remains a challenge due to the limited availability of data. This study aims to share our institutional experience in using definitive radiotherapy (RT) for the treatment of locally recurrent cervical and endometrial carcinoma. METHODS: The study retrospectively reviewed 20 patients in our hospital completing salvage 3D image-based HDR brachytherapy, with or without EBRT, for locally recurrent cervical and endometrial carcinoma after surgery. The Kaplan-Meier method was applied to estimate the disease-free survival (DFS) and overall survival (OS). The toxicities were assessed by CTCAEv5. RESULTS: During a median observation period of 21 months, the study reported a tumor objective response rate of 95%. The 3-year DFS and OS rates were 89.4% and 90.9%, respectively. The EBRT combined with brachytherapy achieved a median cumulative dose of 88 Gy to CTV D90. 14 patients received concurrent and/or systemic chemotherapy. Two patients suffered locoregional recurrence after salvage treatment, one of whom only received salvage brachytherapy for prior RT history. The analysis identified significant predictors for DFS, including tumor histology and FIGO stage. 5 patients observed acute grade 1-2 rectal (15%) or genitourinary (10%) toxicities. Late toxicities including grade 1-2 rectal bleeding (10%) and grade 2 pelvic fracture (5%) were seen in 3 patients. CONCLUSIONS: 3D image-guided brachytherapy combined with EBRT shows effective tumor control and acceptable toxicity profile for women with locally recurrent gynecologic cancer. The success in managing vaginal recurrence is notably influenced by histologic subtype and FIGO staging.
Subject(s)
Brachytherapy , Endometrial Neoplasms , Neoplasm Recurrence, Local , Salvage Therapy , Uterine Cervical Neoplasms , Humans , Female , Endometrial Neoplasms/radiotherapy , Endometrial Neoplasms/pathology , Salvage Therapy/methods , Middle Aged , Neoplasm Recurrence, Local/radiotherapy , Aged , Uterine Cervical Neoplasms/radiotherapy , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/mortality , Retrospective Studies , Brachytherapy/methods , Brachytherapy/adverse effects , Adult , Treatment OutcomeABSTRACT
BACKGROUND: Previous studies have shown a correlation between depression and obesity, as well as between depression and the Atherogenic Index of Plasma (AIP). However, there is limited research on the association between visceral obesity and depression, as well as the potential mediating role of AIP in this relationship. METHODS: This study included 13,123 participants from the 2005-2018 National Health and Nutrition Examination Survey. Visceral obesity was measured with the Body Roundness Index (BRI), while depression was evaluated with the Patient Health Questionnaire-9. The AIP served as a marker for lipid disorders. To investigate the association between the BRI and depression, multivariate logistic regressions, restricted cubic spline models, subgroup analyses, and interaction tests were used. Additionally, a mediation analysis was conducted to explore the role of AIP in mediating the effect of BRI on depression. RESULTS: There was a positive linear correlation between the BRI and depression. After controlling for all covariates, individuals in the highest BRI (Q4) group had an OR of 1.42 for depression (95% CI: 1.12-1.82) in comparison with individuals in the lowest BRI (Q1) group. Moreover, the AIP partially mediated the association between the BRI and depression, accounting for approximately 8.64% (95% CI: 2.04-16.00%) of the total effect. CONCLUSION: The BRI was positively associated with depression, with the AIP playing a mediating role. This study provides a novel perspective on the mechanism that connects visceral obesity to depression. Managing visceral fat and monitoring AIP levels may contribute to alleviating depression.
Subject(s)
Atherosclerosis , Depression , Nutrition Surveys , Obesity, Abdominal , Humans , Depression/blood , Female , Male , Middle Aged , Adult , Atherosclerosis/blood , Obesity, Abdominal/blood , Body Mass Index , Logistic Models , Aged , Biomarkers/bloodABSTRACT
Liquiritigenin is a natural medicine. However, its inhibitory effect and its potential mechanism on bladder cancer (BCa) remain to be explored. It was found that it could be visualized that the transplanted tumours in the low-dose liquiritigenin -treated group and the high-dose liquiritigenin -treated group were smaller than those in the model group. Liquiritigenin treatment led to alterations in Lachnoclostridium, Escherichia-Shigella, Alistipes and Akkermansia. Non-targeted metabolomics analysis showed that a total of multiple differential metabolites were identified between the model group and the high-dose liquiritigenin-treated group. This provides a new direction and rationale for the antitumour effects of liquiritigenin.
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p-Benzoquinones are important organic intermediates in the synthesis of biopharmaceuticals and fine chemicals. In this study, two crystalline 3D polyoxovanadate-based metal-organic frameworks, H[Cu(tpi)2]{Cu2V7O21}·H2O (1, tpi = C18N5H13) and [Co(Htpi)2]{V4O12} (2, Htpi = C18N5H14), were synthesized, which as heterogeneous catalysts showed excellent catalytic activities for the synthesis of p-benzoquinones. Both compounds were characterized by IR, UV-vis diffuse reflectance spectroscopy, TG, XPS, X-ray diffraction, etc. In 1, {Cu2V7} clusters are connected together by copper cations and 1D Cu-organic coordination chains to yield a 3D polyoxometalate-based metal-organic framework (POMOF); in 2, adjacent 2D bimetallic oxide layers, constructed from 1D polyoxovanadate chains and cobalt ions, are further connected by 1D Co-organic coordination chains to form a 3D POMOF. Noteworthily, in the synthesis of trimethyl-p-benzoquinone, the key intermediate of vitamin E, using 2,3,6-trimethylphenol as the model substrate, the turnover frequency values for compounds 1 and 2 can, respectively, reach 607 and 380 h-1 in 8 min. Furthermore, both compounds demonstrated excellent recyclability and structural stability, characterized by PXRD and IR. The catalytic mechanism reveals that both the homolytic radical mechanism and heterolytic oxygen atom transfer mechanism are involved.
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BACKGROUND: The Atherogenic Index of Plasma (AIP) is a novel metric linked to several diseases. However, there is inadequate evidence to investigate the relationship between AIP and depression. Therefore, we aim to elucidate the non-linear association between AIP and depression. METHODS: 12,453 participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2018 were included. The AIP was calculated as log10 (triglycerides/high-density lipoprotein cholesterol). The Patient Health Questionnaire (PHQ-9) was used to identify depression (PHQ-9 ≥ 10). Weighted multivariate logistic regression, restricted cubic splines (RCS) models, subgroup analysis, and interaction tests were employed to reveal the relationship between AIP and depression. RESULTS: AIP was found to be significantly correlated with depression. In the fully adjusted model, elevated AIP levels were associated with higher odds of depression (odds ratio [OR] = 1.50; 95 % CI: 1.06-2.12). The RCS analysis indicated an L-shaped pattern in the relationship between depression and AIP, with inflection points at -0.289. Beyond this inflection point, individuals with elevated AIP levels were associated with higher odds of depression (OR = 2.25; 95 % CI: 1.49-3.39). Notably, the association was particularly pronounced among individuals with diabetes. LIMITATION: This cross-sectional study is unable to establish causal relationships. CONCLUSION: There was an L-shaped association between AIP and depression among US adults. AIP has the potential value as a biological marker for depression, and maintaining AIP values below a certain threshold may help in managing depression.
Subject(s)
Atherosclerosis , Cholesterol, HDL , Depression , Nutrition Surveys , Triglycerides , Humans , Female , Male , Middle Aged , Atherosclerosis/blood , Atherosclerosis/epidemiology , Adult , Depression/epidemiology , Depression/blood , Cholesterol, HDL/blood , Triglycerides/blood , Cross-Sectional Studies , Aged , United States/epidemiologyABSTRACT
The deleterious impact of pollution point sources on the surrounding environment and human has long been a focal point of environmental research. When considering the local atmospheric dispersion of semi-volatile organic compounds (SVOCs) around the emission sites, it is essential to account the dynamic process for the gas/particle (G/P) partitioning, which involves the transition from an initial state to a steady state. In this study, we have developed a model that enables the prediction of the dynamic process for G/P partitioning of SVOCs, particularly considering the influence from emission. It is important to note that the dynamic processes of the concentrations of SVOCs in particle phase (CP) and in gas phase (CG) differ significantly. These differences arise due to the influence of two critical factors: particulate proportion of SVOCs in the emissions (Ï0) and octanol-air partitioning coefficient (KOA). The validity of our model was assessed by comparing its predictions of the extremum value of the G/P partitioning quotient (KP) with the results obtained from the steady-state model. Remarkably, the characteristic time (tC), used to evaluate the timescale required for SVOCs to reach steady state, demonstrated different variations with KOA for CP and CG. Additionally, the values of tC were quite different for CP and CG, which were markedly influenced by Ï0. For some SVOCs with high KOA values, it took approximately 35 h to reach steady state. Furthermore, it was found that the time to achieve 95 % of steady state (t95 ≈ 3tC) could reach approximately 105 h. This duration is sufficient for chemicals to disperse from their emission site to the surrounding areas. Therefore, it is crucial to consider the dynamic process of G/P partitioning in local atmospheric transport studies. Moreover, the influence of Ï0 should be incorporated into future investigations examining the dynamic process of G/P partitioning.
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The droplet-based nanogenerator (DNG) is a highly promising technology for harvesting high-entropy water energy in the era of the Internet of Things. Yet, despite the exciting progress made in recent years, challenges have emerged unexpectedly for the AC-type DNG-based energy system as it transitions from laboratory demonstrations to real-world applications. In this work, we propose a high-performance DNG system based on the total-current nanogenerator concept to address these challenges. This system utilizes the water-charge-shuttle architecture for easy scale-up, employs the field effect to boost charge density of the triboelectric layer, adopts an on-solar-panel design to improve compatibility with solar energy, and is equipped with a novel DC-DC buck converter as power management circuit. These features allow the proposed system to overcome the existing bottlenecks of DNG and empower the system with superior performances compared with previous ones. Notably, with the core architecture measuring only 15 cm × 12.5 cm × 0.3 cm in physical dimensions, this system reaches a record-high open-circuit voltage of 4200 V, capable of illuminating 1440 LEDs, and can charge a 4.7 mF capacitor to 4.5 V in less than 24 min. In addition, the practical potential of the proposed DNG system is further demonstrated through a self-powered, smart greenhouse application scenario. These demonstrations include the continuous operation of a thermohygrometer, the operation of a Bluetooth plant monitor, and the all-weather energy harvesting capability. This work will provide valuable inspiration and guidance for the systematic design of next-generation DNG to unlock the sustainable potential of distributed water energy for real-world applications.
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BACKGROUND: Provoked anger is associated with an increased risk of cardiovascular disease events. The underlying mechanism linking provoked anger as well as other core negative emotions including anxiety and sadness to cardiovascular disease remain unknown. The study objective was to examine the acute effects of provoked anger, and secondarily, anxiety and sadness on endothelial cell health. METHODS AND RESULTS: Apparently healthy adult participants (n=280) were randomized to an 8-minute anger recall task, a depressed mood recall task, an anxiety recall task, or an emotionally neutral condition. Pre-/post-assessments of endothelial health including endothelium-dependent vasodilation (reactive hyperemia index), circulating endothelial cell-derived microparticles (CD62E+, CD31+/CD42-, and CD31+/Annexin V+) and circulating bone marrow-derived endothelial progenitor cells (CD34+/CD133+/kinase insert domain receptor+ endothelial progenitor cells and CD34+/kinase insert domain receptor+ endothelial progenitor cells) were measured. There was a group×time interaction for the anger versus neutral condition on the change in reactive hyperemia index score from baseline to 40 minutes (P=0.007) with a mean±SD change in reactive hyperemia index score of 0.20±0.67 and 0.50±0.60 in the anger and neutral conditions, respectively. For the change in reactive hyperemia index score, the anxiety versus neutral condition group by time interaction approached but did not reach statistical significance (P=0.054), and the sadness versus neutral condition group by time interaction was not statistically significant (P=0.160). There were no consistent statistically significant group×time interactions for the anger, anxiety, and sadness versus neutral condition on endothelial cell-derived microparticles and endothelial progenitor cells from baseline to 40 minutes. CONCLUSIONS: In this randomized controlled experimental study, a brief provocation of anger adversely affected endothelial cell health by impairing endothelium-dependent vasodilation.
Subject(s)
Anger , Anxiety , Endothelium, Vascular , Vasodilation , Humans , Male , Female , Adult , Endothelium, Vascular/physiopathology , Anxiety/psychology , Endothelial Progenitor Cells/metabolism , Middle Aged , Sadness , Cell-Derived Microparticles/metabolism , Hyperemia/physiopathology , Emotions , Young Adult , Time Factors , Endothelial CellsABSTRACT
Polycyclic aromatic hydrocarbons (PAHs) have the capability for solar radiation absorption related to climate forcing. Herein, pollution characteristics and absorption spectra of size-resolved PAHs in atmospheric particles in a cold megacity were comprehensively investigated. The mean concentrations of Σ18PAHs in all the 11 particle size ranges were 3.95 ± 4.77 × 104 pg/m3 and 2.17 ± 1.54 × 103 pg/m3 in heating period (HP) and non-heating period (NHP), respectively. Except for most PAHs with 2 and 3 benzene rings in NHP, most other PAHs showed a unimodal distribution pattern with the peak at 0.56-1.0 µm in both periods, which was caused by PAH emission sources. The PAH-related climate forcing was mainly caused by the solar radiation absorptions at â¼325 (â¼330) nm and â¼365 nm. In general, the absorption intensities were higher in HP than NHP. The absorption intensity in the particle size range of 0.56-1.0 µm was the highest, and benzo[e]pyrene was the dominant contributor. In colder periods in HP, higher PAH concentrations caused more intensive PAH-related climate forcing. This study provided new insights for pollution characteristics and absorption spectra of size-resolved PAHs in atmospheric particles, which will be useful for better understanding PAH-related climate forcing.
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Catalysts for zinc-air batteries (ZABs) must be stable over long-term charging-discharging cycles and exhibit bifunctional catalytic activity. In this study, by doping nitrogen-doped carbon (NC) materials with three metal atoms (Fe, Ni, and Cu), a single-atom-distributed FeNiCu-NC bifunctional catalyst is prepared. The catalyst includes Fe(Ni-doped)-N4 for the oxygen evolution reaction (OER), Fe(Cu-doped)-N4 for the oxygen reduction reaction (ORR), and the NiCu-NC catalytic structure for the oxygen reduction reaction (ORR) in the nitrogen-doped carbon nanoparticles. This single-atom distribution catalyst structure enhances the bifunctional catalytic activity. If a trimetallic single-atom catalyst is designed, it will surpass the typical bimetallic single-atom catcalyst. FeNiCu-NC exhibits outstanding performance as an electrocatalyst, with a half-wave potential (E1/2) of 0.876 V versus RHE, overpotential (Ej = 10) of 253 mV versus RHE at 10 mA cm-2, and a small potential gap (ΔE = 0.61 V). As the anode in a ZAB, FeNiCu-NC can undergo continuous charge-discharged cycles for 575 h without significant attenuation. This study presents a new method for achieving high-performance, low-cost ZABs via trimetallic single-atom doping.
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Single-cell chromatin accessibility sequencing (scATAC-seq) reconstructs developmental trajectory by phenotypic similarity. However, inferring the exact developmental trajectory is challenging. Previous studies showed age-associated DNA methylation (DNAm) changes in specific genomic regions, termed clock-like differential methylation loci (ClockDML). Age-associated DNAm could either result from or result in chromatin accessibility changes at ClockDML. As cells undergo mitosis, the heterogeneity of chromatin accessibility on clock-like loci is reduced, providing a measure of mitotic age. In this study, we developed a method, called EpiTrace, that counts the fraction of opened clock-like loci from scATAC-seq data to determine cell age and perform lineage tracing in various cell lineages and animal species. It shows concordance with known developmental hierarchies, correlates well with DNAm-based clocks and is complementary with mutation-based lineage tracing, RNA velocity and stemness predictions. Applying EpiTrace to scATAC-seq data reveals biological insights with clinically relevant implications, ranging from hematopoiesis, organ development, tumor biology and immunity to cortical gyrification.
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Isatropolone C from Streptomyces sp. CPCC 204095 features a fused cyclopentadienone-tropolone-oxacyclohexadiene tricyclic moiety in its structure. Herein, we report an isatropolone C dimer derivative, di-isatropolone C, formed spontaneously from isatropolone C in methanol. Notably, the structure of di-isatropolone C resolved by NMR reveals a newly formed cyclopentane ring to associate the two isatropolone C monomers. The configurations of four chiral carbons, including a ketal one, in the cyclopentane ring are assigned using quantum NMR calculations and DP4+ probability. The plausible molecular mechanism for di-isatropolone C formation is proposed, in which complex dehydrogenative C-C bond coupling may have happened to connect the two isatropolone C monomers. Like isatropolone C, di-isatropolone C shows the biological activity of inducing autophagy in HepG2 cells.