Understanding Emergent Complexity from a Single-Molecule Perspective.

Molecules, with structural, scaling, and interaction diversities, are crucial for the emergence of complex behaviors. Interactions are essential prerequisites for complex systems to exhibit emergent properties that surpass the sum of individual component characteristics. Tracing the origin of complex molecular behaviors from interactions is critical to understanding ensemble emergence, and requires insights at the single-molecule level. Electrical signals from single-molecule junctions enable the observation of individual molecular behaviors, as well as intramolecular and intermolecular interactions. This technique provides a foundation for bottom-up explorations of emergent complexity. This Perspective highlights investigations of various interactions via single-molecule junctions, including intramolecular orbital and weak intermolecular interactions and interactions in chemical reactions. It also provides potential directions for future single-molecule junctions in complex system research.

The Natural Product Secoemestrin C Inhibits Colorectal Cancer Stem Cells via p38-S100A8 Feed-Forward Regulatory Loop.

Cancer stem cells (CSCs) are closely associated with tumor initiation, metastasis, chemoresistance, and recurrence, which represent some of the primary obstacles to cancer treatment. Targeting CSCs has become an important therapeutic approach to cancer care. Secoemestrin C (Sec C) is a natural compound with strong anti-tumor activity and low toxicity. Here, we report that Sec C effectively inhibited colorectal CSCs and non-CSCs concurrently, mainly by inhibiting proliferation, self-renewal, metastasis, and drug resistance. Mechanistically, RNA-seq analysis showed that the pro-inflammation pathway of the IL17 axis was enriched, and its effector S100A8 was dramatically decreased in Sec C-treated cells, whose roles in the stemness of CSCs have not been fully clarified. We found that the overexpression of S100A8 hindered the anti-CSCs effect of Sec C, and S100A8 deficiency attenuated the stemness traits of CSCs to enhance the Sec C killing activity on them. Meanwhile, the p38 signal pathway, belonging to the IL17 downstream axis, can also mediate CSCs and counter with Sec C. Notably, we found that S100A8 upregulation increased the p38 protein level, and p38, in turn, promoted S100A8 expression. This indicated that p38 may have a mutual feedback loop with S100A8. Our study discovered that Sec C was a powerful anti-colorectal CSC agent, and that the positive feedback loop of p38-S100A8 mediated Sec C activity. This showed that Sec C could act as a promising clinical candidate in colorectal cancer treatment, and S100A8 could be a prospective drug target.

Deciphering thyroid function and CIMT: a Mendelian randomization study of the U-shaped influence mediated by apolipoproteins.

Background: Carotid Intima-Media Thickness (CIMT) is a key marker for atherosclerosis, with its modulation being crucial for cardiovascular disease (CVD) risk assessment. While thyroid function's impact on cardiovascular health is recognized, the causal relationship and underlying mechanisms influencing CIMT remain to be elucidated. Methods: In this study, Mendelian Randomization (MR) was employed to assess the causal relationship between thyroid function and CIMT. Thyroid hormone data were sourced from the Thyroidomics Consortium, while lipid traits and CIMT measurements were obtained from the UK Biobank. The primary analysis method was a two-sample MR using multiplicative random effects inverse variance weighting (IVW-MRE). Additionally, the study explored the influence of thyroid hormones on lipid profiles and assessed their potential mediating role in the thyroid function-CIMT relationship through multivariate MR analysis. Results: The study revealed that lower levels of Free Thyroxine (FT4) within the normal range are significantly associated with increased CIMT. This association was not observed with free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), or TPOAb. Additionally, mediation analysis suggested that apolipoprotein A-I and B are involved in the relationship between thyroid function and CIMT. The findings indicate a potential U-shaped curve relationship between FT4 levels and CIMT, with thyroid hormone supplementation in hypothyroid patients showing benefits in reducing CIMT. Conclusion: This research establishes a causal link between thyroid function and CIMT using MR methods, underscoring the importance of monitoring thyroid function for early cardiovascular risk assessment. The results advocate for the consideration of thyroid hormone supplementation in hypothyroid patients as a strategy to mitigate the risk of carotid atherosclerosis. These insights pave the way for more targeted approaches in managing patients with thyroid dysfunction to prevent cardiovascular complications.

From genomic insights to clinical hope: Targeting NEU1 in IgA nephropathy.

BACKGROUND: IgA Nephropathy (IgAN), the primary form of glomerulonephritis, presents significant clinical challenges due to its obscure pathogenesis and lack of targeted treatments. We conducted a proteome-wide Mendelian randomization (MR) study to identify therapeutic targets for IgAN. METHODS: Utilizing a plasma proteome dataset comprising 4907 blood plasma proteins as the exposure variable, and renal biopsy-confirmed IgAN cases as the outcome, this study employed MR to pinpoint proteins potentially pathogenic to IgAN. The robustness of our findings was affirmed through external dataset validation, reverse causation testing, and Bayesian colocalization analysis. Additionally, we conducted phenotypic scanning and analyzed downstream metabolites to investigate candidate proteins's biological function. RESULTS: In our study, a significant association was identified between an increase in neuraminidase 1 (NEU1) expression and the risk of IgAN. Specifically, a one standard deviation increase in NEU1 expression was associated with an odds ratio of 11.80 for the development of IgAN (95% confidence interval: 4.03-34.54). This association was substantiated across various statistical models and external validations. Colocalization analysis indicated a shared causal variant between NEU1 expression and IgAN. Furthermore, an increased influenza risk associated with NEU1 was observed, supporting the therapeutic potential of NEU1 inhibitors for IgAN. However, our study found no significant role for neuraminic acid-related metabolites in IgAN's development, suggesting an independent pathway for NEU1's influence. CONCLUSION: This study identifies NEU1 as a promising therapeutic target for IgAN, backed by robust genetic evidence. Future research should explore NEU1's therapeutic potential in diverse populations and clinical scenarios, further establishing its role in IgAN.

Fortified Dual-Spectral Overlap with Enhanced Colorimetric/Fluorescence Dual-Response Immunochromatography for On-Site Bimodal-Type Gentamicin Monitoring.

Immunochromatography (ICA) remains untapped toward enhanced sensitivity and applicability for fulfilling the nuts and bolts of on-site food safety surveillance. Herein, we report a fortified dual-spectral overlap with enhanced colorimetric/fluorescence dual-response ICA for on-site bimodal-type gentamicin (Gen) monitoring by employing polydopamine (PDA)-coated AuNPs (APDA) simultaneously serving as a colorimetric reporter and a fluorescence quencher. Availing of the enhanced colorimetric response that originated from the PDA layer, the resultant APDA exhibits less required antibody and immunoprobes in a single immunoassay, which facilitates improved antibody utilization efficiency and immuno-recognition in APDA-ICA. Further integrated with the advantageous features of fortified excitation and emission dual-spectral overlap for the Arg/ATT-AuNCs, this APDA-ICA with a "turn on/off" pattern achieves the visual limits of detection of 1.0 and 0.5 ng mL-1 for colorimetric and fluorescence patterns (25- and 50-fold lower than standard AuNPs-ICA). Moreover, the excellent self-calibration and satisfactory recovery of 79.03-118.04% were shown in the on-site visual colorimetric-fluorescence analysis for Gen in real environmental media (including real river water, an urban aquaculture water body, an aquatic product, and an animal byproduct). This work provides the feasibility of exploiting fortified dual-spectral overlap with an enhanced colorimetric/fluorescence dual response for safeguarding food safety and public health.

Hybrid Interface Chemistry Enabling Mixed Conducting via Ultrafast Microwave Polarization Toward Dendrite-Free Zn Anodes.

Zn metal anodes in aqueous electrolytes suffer from interface issues including uncontrolled dendrite growth and undesired side reactions, resulting in their limited application in terms of short circuits and cell failure. Herein, a hybrid interface chemistry strategy is developed through ultrafast microwave polarization at the skin region of bare Zn. Owing to efficient Joule heating directed by abundant local hot spots at electron valleys, the rapid establishment of a dense interfacial layer can be realized within a minute. Stabilized Zn with suppressed side reactions or surface corrosion is therefore achieved due to the interfacial protection. Importantly, hybrid zincophilic sites involving laterally/vertically interconnected Cu-Zn intermetallic compound and Zn2+ -conductive oxide species ensure mixed charge conducting (denoted as CuHL@Zn), featuring uniformly distributed electric field and boosted Zn2+ diffusion kinetics. As a consequence, CuHL@Zn in symmetric cells affords lifespans of 2800 and 3200 h with ultra-low polarization voltages (≈19 and 56 mV) at a plating capacity of 1.0 mAh cm-2 for 1 and 5 mA cm-2 , respectively. The CuHL@Zn||MnO2 full cell further exhibits cycling stability with a capacity retention of over 80% for 500 cycles at 2 A g-1 .

Unveiling the Properties of Sulfhydryl Groups in a Single-Molecule Junction.

The metal-thiol interface is ubiquitous in nanotechnology and surface chemistry. It is not only used to construct nanocomposites but also plays a decisive role in the properties of these materials. When organothiol molecules bind to the gold surface, there is still controversy over whether sulfhydryl groups can form disulfide bonds and whether these disulfide bonds can remain stable on the gold surface. Here, we investigate the intrinsic properties of sulfhydryl groups on the gold surface at the single-molecule level using a scanning tunneling microscope break junction technique. Our findings indicate that sulfhydryl groups can react with each other to form disulfide bonds on the gold surface, and the electric field can promote the sulfhydryl coupling reaction. In addition to these findings, ultraviolet irradiation is used to effectively regulate the coupling between sulfhydryl groups, leading to the formation and cleavage of disulfide bonds. These results unveil the intrinsic properties of sulfhydryl groups on the gold surface, therefore facilitating the accurate construction of broad nanocomposites with the desired functionalities.

AI-assisted mass spectrometry imaging with in situ image segmentation for subcellular metabolomics analysis.

Subcellular metabolomics analysis is crucial for understanding intracellular heterogeneity and accurate drug-cell interactions. Unfortunately, the ultra-small size and complex microenvironment inside the cell pose a great challenge to achieving this goal. To address this challenge, we propose an artificial intelligence-assisted subcellular mass spectrometry imaging (AI-SMSI) strategy with in situ image segmentation. Based on the nanometer-resolution MSI technique, the protonated guanine and threonine ions were respectively employed as the nucleus and cytoplasmic markers to complete image segmentation at the subcellular level, avoiding mutual interference of signals from various compartments in the cell. With advanced AI models, the metabolites within the different regions could be further integrated and profiled. Through this method, we decrypted the distinct action mechanism of isomeric drugs, doxorubicin (DOX) and epirubicin (EPI), only with a stereochemical inversion at C-4'. Within the cytoplasmic region, fifteen specific metabolites were discovered as biomarkers for distinguishing the drug action difference between DOX and EPI. Moreover, we identified that the downregulations of glutamate and aspartate in the malate-aspartate shuttle pathway may contribute to the higher paratoxicity of DOX. Our current AI-SMSI approach has promising applications for subcellular metabolomics analysis and thus opens new opportunities to further explore drug-cell specific interactions for the long-term pursuit of precision medicine.

Precise Spectral Overlap-Based Donor-Acceptor Pair for a Sensitive Traffic Light-Typed Bimodal Multiplexed Lateral Flow Immunoassay.

Bimodal-type multiplexed immunoassays with complementary mode-based correlation analysis are gaining increasing attention for enhancing the practicability of the lateral flow immunoassay (LFIA). Nonetheless, the restriction in visually indistinguishable multitargets induced by a single fluorescent color and difficulty in single acceptor ineffectual fluorescence quenching due to the various spectra of multiple different donors impede the further execution of colorimetric-fluorescence bimodal-type multiplexed LFIAs. Herein, the precise spectral overlap-based donor-acceptor pair construction strategy is proposed by regulating the size of the nanocore, coating it with an appropriate nanoshell, and selecting a suitable fluorescence donor with distinct colors. By in situ coating Prussian blue nanoparticles (PBNPs) on AuNPs with a tunable size and absorption spectrum, the resultant APNPs demonstrate efficient fluorescence quenching ability, higher colloidal stability, remarkable colorimetric intensity, and an enhanced antibody coupling efficiency, all of which facilitate highly sensitive bimodal-type LFIA analysis. Following integration with competitive-type immunoreaction, this precise spectral overlap-supported spatial separation traffic light-typed colorimetric-fluorescence dual-response assay (coined as the STCFD assay) with the limits of detection of 0.013 and 0.152 ng mL-1 for ractopamine and clenbuterol, respectively, was proposed. This work illustrates the superiority of the rational design of a precise spectral overlap-based donor-acceptor pair, hinting at the enormous potential of the STCFD assay in the point-of-care field.

Myofibrillogenesis Regulator-1 Regulates the Ubiquitin Lysosomal Pathway of Notch3 Intracellular Domain Through E3 Ubiquitin-Protein Ligase Itchy Homolog in the Metastasis of Non-Small Cell Lung Cancer.

Myofibrillogenesis regulator-1 (MR-1) is a multifunctional protein involved in the development of various human tumors. The study is the first to report the promoting effect of MR-1 on the development and metastasis of non-small cell lung cancer (NSCLC). MR-1 is upregulated in NSCLC and positively associated with poor prognosis. The overexpression of MR-1 promotes the metastasis of NSCLC cells by stabilizing the expression of Notch3-ICD (NICD3) in the cytoplasm through enrichment analysis, in vitro and in vivo experimental researches. And Notch3 signaling can upregulate many genes related to metastasis. The stabilizing effect of MR-1 on NICD3 is achieved through the mono-ubiquitin lysosomal pathway and the specific E3 ubiquitin ligase is Itchy homolog (ITCH). There is a certain interaction between MR-1 and NICD3. Elevated MR-1 can affect the level of ITCH phosphorylation, reduce its E3 enzyme activity, and thus lead to reduce the ubiquitination and degradation of NICD3. Interference with the interaction between MR-1 and NICD3 can increase the degradation of NICD3 and impair the metastatic ability of NSCLC cells, which is a previously overlooked treatment option in NSCLC. In summary, interference with the interaction between MR-1 and NICD3 in the progression of lung cancer may be a promising therapeutic target.

An Optical Fiber-Based Nanomotion Sensor for Rapid Antibiotic and Antifungal Susceptibility Tests.

The emergence of antibiotic and antifungal resistant microorganisms represents nowadays a major public health issue that might push humanity into a post-antibiotic/antifungal era. One of the approaches to avoid such a catastrophe is to advance rapid antibiotic and antifungal susceptibility tests. In this study, we present a compact, optical fiber-based nanomotion sensor to achieve this goal by monitoring the dynamic nanoscale oscillation of a cantilever related to microorganism viability. High detection sensitivity was achieved that was attributed to the flexible two-photon polymerized cantilever with a spring constant of 0.3 N/m. This nanomotion device showed an excellent performance in the susceptibility tests of Escherichia coli and Candida albicans with a fast response in a time frame of minutes. As a proof-of-concept, with the simplicity of use and the potential of parallelization, our innovative sensor is anticipated to be an interesting candidate for future rapid antibiotic and antifungal susceptibility tests and other biomedical applications.

An actor-critic framework based on deep reinforcement learning for addressing flexible job shop scheduling problems.

With the rise of Industry 4.0, manufacturing is shifting towards customization and flexibility, presenting new challenges to meet rapidly evolving market and customer needs. To address these challenges, this paper suggests a novel approach to address flexible job shop scheduling problems (FJSPs) through reinforcement learning (RL). This method utilizes an actor-critic architecture that merges value-based and policy-based approaches. The actor generates deterministic policies, while the critic evaluates policies and guides the actor to achieve the most optimal policy. To construct the Markov decision process, a comprehensive feature set was utilized to accurately represent the system's state, and eight sets of actions were designed, inspired by traditional scheduling rules. The formulation of rewards indirectly measures the effectiveness of actions, promoting strategies that minimize job completion times and enhance adherence to scheduling constraints. The experimental evaluation conducted a thorough assessment of the proposed reinforcement learning framework through simulations on standard FJSP benchmarks, comparing the proposed method against several well-known heuristic scheduling rules, related RL algorithms and intelligent algorithms. The results indicate that the proposed method consistently outperforms traditional approaches and exhibits exceptional adaptability and efficiency, particularly in large-scale datasets.

Relationship between Serum Indoxyl Sulfate and Klotho Protein and Vascular Calcification in Patients with Chronic Kidney Disease Stages 3-5.

Objective: This study aims to explore the relationships between serum indoxyl sulfate (IS) and Klotho protein levels with vascular calcification in patients with chronic kidney disease (CKD) stages 3-5. Methods: From December 2021 to January 2023, a total of 108 CKD patients in stages 3-5 were enrolled in this cross-sectional investigation. Demographic information and routine clinical biochemistry test results were gathered. Serum levels of IS and Klotho were quantified through enzyme-linked immunosorbent assays. Furthermore, multislice spiral computed tomography was employed to evaluate vascular calcification. The association between serum IS or Klotho levels and abdominal aorta calcification was assessed using univariate analysis and logistic regression analyses. Results: With the progression of CKD stages, serum creatinine, phosphorus, intact parathyroid hormone (iPTH), serum IS, and abdominal aortic calcification exhibited incremental trends, while serum calcium and Klotho protein levels showed a diminishing trend, with statistically significant differences (P < 0.05). Significant differences were observed in age, blood phosphorus, calcium, total parathyroid hormone, serum IS, and Klotho protein levels between patients with and without aortic calcification (P < 0.05). Logistic regression analysis demonstrated that advanced age, high IS level, and low Klotho protein level were independent risk factors for abdominal aortic calcification in CKD patients (P < 0.05). Conclusion: This study indicates elevated serum IS levels and decreased Klotho protein levels in CKD patients. High IS level and low Klotho level were independent risk factors for abdominal aortic calcification.

Correlation between gout and dry eye disease.

BACKGROUND: Gout is a common form of inflammatory arthritis that can cause a number of serious complications. Complications are common in patients with gout and complicate their management and disease outcome. The recent literature has reported that an increasing number of gout patients are presenting with dry eye symptoms. However, until now, the link between gout and dry eye disease has not been clearly defined. (It is unclear whether the two conditions simply co-exist, whether there are common risk factors, or whether dry eye disease is a complication of gout.) METHODS: A thorough literature search was conducted in the PubMed database to summarize the most recent information on the correlation between gout and dry eye disease and to explore the potential relationship between the pathogenesis of the two. (Objective: Therefore, in this paper, we review the recent literature on the correlation between gout and dry eye disease and explore the potential association between the pathogenesis of both.) RESULTS: Studies in the last five years have shown a correlation between gout and dry eye, i.e., gout is associated with an increased risk of dry eye. The NLRP3-IL-1ß signaling pathway may be a potential mechanism for the combination of gout and dry eye disease; factors such as high blood uric acid and xanthine oxidase activation in gout patients may aggravate the development of dry eye disease; reducing the use of visual display terminals; reducing or abstaining from alcohol consumption; and moderate coffee intake may effectively prevent gout and dry eye disease. CONCLUSIONS: It is an undisputed fact that many gout patients present with dry eye manifestations that seriously affect the quality of life of gout patients, and early detection and treatment of dry eye in gout patients are crucial.

Selective Access to Functional Fluoroenones via Palladium-Catalyzed Selenofluoroalkylacylation of Terminal Alkynes.

The trifluoromethylacyl group (-COCF3) is an important motif and widely studied in catalysis, medicinal chemistry, and materials science. Herein, a novel palladium-catalyzed selenofluoroalkylacylation of terminal alkynes with commercially available fluoroalkyl anhydride and diorganyl diselenides to afford ß-seleno and aryl/alkyl disubstituted enones under mild conditions is disclosed. In addition, selenodifluoroacetylations and selenoperfluoroacetylations are also suitable for this reaction. Mechanistic studies reveal that this reaction proceeds via an oxidative radical-polar crossover process.

Insights into the Mechanism of Nitrobenzene Reduction to Aniline by Phosphomolybdic Acid Supported TM1 Single-Atom Catalysts.

Catalytic hydrogenation of nitrobenzene (Ph-NO2) to aniline (Ph-NH2) is a model reaction in the field of catalysis, in which the development of efficient catalysts remains a great challenge due to the lack of strategies to solve activity and selectivity problems. In this work, the mechanism of Ph-NO2 hydrogenation over Pt1 supported on phosphomolybdic acid (α-PMA) was proposed by density functional theory (DFT) calculations. The results show that the dissociation of the first and second N-O bonds is triggered by single H-induced and double H-induced mechanisms, respectively. The limiting potential of the reaction process is -0.19 V, which is the smallest potential in the field of Ph-NO2 reduction reaction to date. In the whole reaction process, the catalytic active site is the Pt atom, and polyoxometalate plays the role of an electronic sponge in the reaction. Additionally, based on experimentally confirmed Pt1/Na3PMA, the reduction capacity of Pd1/Na3PMA toward Ph-NO2 was predicted by DFT calculation. The distinctive adsorption patterns of Ph-NO2 on Pt1/Na3PMA and Pd1/Na3PMA were elucidated using the DOS diagram and fragment molecular orbital analysis. We anticipate that our theoretical calculations can provide novel perspectives for experimental researchers.

Wet Film Leveling for Promoting the Uniformity and Conductivity of Silver Nanowire Transparent Electrode.

Wet film leveling can greatly promote film uniformity. However, in the field of metal nanowire, wet film leveling is rarely mentioned. For low-viscosity inks like metal nanowire ink, how to realize wet film leveling is still unclear. Herein, we study the wet film leveling of silver nanowire ink and systematically investigate the relationship between leveling effect and influence factors: (1) there is a uniformity-promotion limit for traditional methods, while wet film leveling can break through this limit and further promote the film uniformity; (2) for wet film leveling, lowering ink's surface tension has no effect, and eliminating surface tension gradient by high-surface-tension leveling agent is the main task; (3) leveling process includes wet film destruction process and ink reflow process; (4) in the destruction process, the leveling-agent solubility and quantity dominate the leveling effect, while the influence of surface tension is little; (5) for solubility and quantity, there is a suitable range to realize optimum leveling effect, and the leveling effect exhibits a contrary relationship with the solubility in a suitable range (2-11%); (6) in the reflow process, the main influence factor is ink viscosity, and the leveling effect exhibits a contrary relationship with ink viscosity. After being leveled by 1.5% n-pentanol, the sheet resistance and sheet-resistance variation coefficient of film decrease from 38.3 Ω/sq/3.83% to 25.7 Ω/sq/1.88%. Further study reveals that the film improvement is not from the ink wettability and drying. Above theoretical results possess certain universality for film preparation by a wet process and can be used by the science and industry field.

Modeling the potential distribution of the energy tree species Triadica sebifera in response to climate change in China.

As an important woody oilseed species in China, Triadica sebifera is not only concerned with the substitution of traditional energy sources, but also plays a considerable role in coping with energy shortages. Accurately predicting the potential geographic distribution of Triadica sebifera in China and understanding its ecological needs are crucial for alleviating the energy crisis and effectively implementing energy substitution strategies. In this study, the potential geographic distribution of Triadica sebifera in China at contemporary and future periods was predicted based on the distribution data of Triadica sebifera in China and the environmental factor variables by Maxent model and ArcGIS software. The combination of important factors governing the potential geographic distribution of Triadica sebifera was assessed by the contribution of environmental factor variables. The accuracy of Maxent model's predictions was assessed by AUC values, TSS values and Kappa statistics. The results show that: High AUC and TSS values indicate high accuracy and performance of the model. The crucial environmental factors limiting the potential geographic distribution of Triadica sebifera are the temperature factor (mean air temperature of the driest quarter), precipitation factor (precipitation of the coldest quarter, precipitation of the wettest month), and the intensity of human activities (hf). The total suitable area for Triadica sebifera is 233.64 × 104 km2, primarily located in Yunnan, Sichuan, Hubei, Guizhou, Jiangxi, Guangdong province and Guangxi Zhuang Autonomous Region; its high suitability area is 30.89 × 104 km2, accounting for 13.22% of the total suitable area, mainly distributed in Jiangxi, Sichuan and Hunan provinces in the shape of a cake. Under the four typical greenhouse gas emission concentration patterns in the 2050s and 2070s, the areas of high and medium suitable areas for Triadica sebifera will increase, while the area of its low suitable area will decrease. However, the total suitable area will remain relatively unchanged. Its potential suitable habitats show a trend of shifting towards lower latitudes and southeast regions. The study predicted the pattern of Triadica sebifera under different climate change conditions, which can provide guidance for future cultivation of Triadica sebifera as well as for biofuel development and utilization.

Multi-Stage Asynchronous Federated Learning With Adaptive Differential Privacy.

The fusion of federated learning and differential privacy can provide more comprehensive and rigorous privacy protection, thus attracting extensive interests from both academia and industry. However, facing the system-level challenge of device heterogeneity, most current synchronous FL paradigms exhibit low efficiency due to the straggler effect, which can be significantly reduced by Asynchronous FL (AFL). However, AFL has never been comprehensively studied, which imposes a major challenge in the utility optimization of DP-enhanced AFL. Here, theoretically motivated multi-stage adaptive private algorithms are proposed to improve the trade-off between model utility and privacy for DP-enhanced AFL. In particular, we first build two DP-enhanced AFL frameworks with consideration of universal factors for different adversary models. Then, we give a solid analysis on the model convergence of AFL, based on which, DP can be adaptively achieved with high utility. Through extensive experiments on different training models and benchmark datasets, we demonstrate that the proposed algorithms achieve the overall best performances and improve up to 24% test accuracy with the same privacy loss and have faster convergence compared with the state-of-the-art algorithms. Our frameworks provide an analytical way for private AFL and adapt to more complex FL application scenarios.