Understanding the Coupling Mechanism of Intercalation and Conversion Hybrid Storage in Lithium-Graphite Anode.

Anodes with high capacity and long lifespan play an important role in the advanced batteries. However, none of the existing anodes can meet these two requirements simultaneously. Lithium (Li)-graphite composite anode presents great potential in balancing these two requirements. Herein, the working mechanism of Li-graphite composite anode is comprehensively investigated. The capacity decay features of the composite anode are different from those of Li ion intercalation in Li ion batteries and Li metal deposition in Li metal batteries. An intercalation and conversion hybrid storage mechanism are proposed by analyzing the capacity decay ratios in the composite anode with different initial specific capacities. The capacity decay models can be divided into four stages including Capacity Retention Stage, Relatively Independent Operation Stage, Intercalation & Conversion Coupling Stage, Pure Li Intercalation Stage. When the specific capacity is between 340 and 450 mAh g-1, its capacity decay ratio is between that of pure intercalation and conversion model. These results intensify the comprehensive understandings on the working principles in Li-graphite composite anode and present novel insights in the design of high-capacity and long-lifespan anode materials for the next-generation batteries.

Inubritantrimers A-D: Trimerized Sesquiterpenoid [4 + 2] Adducts Featuring a Distinctive Spiro-Polycyclic Scaffold from Inula britannica.

Inubritantrimer A (1), a trace trimerized sesquiterpenoid [4 + 2] adduct featuring an unusual exo-exo type spiro-polycyclic scaffold, together with three new endo-exo [4 + 2] adducts, inubritantrimers B-D (2-4), were discovered from the flowers of Inula britannica. Their structures were elucidated using 1D/2D NMR, X-ray diffraction, and ECD approaches. 1 is characterized as a novel exo-exo trimer, synthesized biogenetically from three sesquiterpenoid monomers, featuring a unique linkage of C-11/C-1', C-13/C-3' and C-13'/C-3″, C-11'/C-1″ through a two-step exo [4 + 2] cycloaddition process. Compounds 1-4 exhibited modest cytotoxicity against breast cancer cells with IC50 values in the range of 5.84-12.01 µM.

Simulations of a PKA RIα homodimer reveal cAMP-coupled conformational dynamics of each protomer and the dimer interface with functional implications.

Protein kinase A (PKA) is a ubiquitous cAMP-dependent enzyme in mammalian tissues. The inactive PKA holoenzyme disassociates into a homodimer of regulatory (R) subunits and two active catalytic (C) subunits upon cAMP binding to two tandem domains (termed CBD-A and CBD-B) in R subunits. The release of cAMP facilitates reassociation of R and C subunits, resetting PKA to its basal state. The cAMP-mediated structural changes in the activation-termination cycle remain partially understood. The multimeric states of PKA complicate the issue and are particularly less studied. Therefore, we computationally investigated the conformational dynamics of the PKA RIα homodimer in different cAMP-bound states. The absence of cAMP in two CBDs differently affects the conformational dynamics of protomers. Moreover, such disparate responses are extended to the dimer interface constituted by the N-terminal helical sub-domains termed N3A motifs. The removal of cAMP from CBD-A induces large-scale structural changes of individual R subunits towards the holoenzyme state, consistent with previous simulations of a single R subunit. Meanwhile it keeps the structural heterogeneity of the N3A-N3A' dimer interface observed in the fully bound state. By contrast, the removal of cAMP from CBD-B does not affect individual R subunits but alters the conformational space of the N3A-N3A' dimer interface. The cAMP-coupled structural changes of each protomer and conserved conformational space of the N3A-N3A' dimer interface are essential for the transition between the fully cAMP-bound R2 homodimer and the R2C2 holoenzyme as suggested by their crystal structures. Our work provides structural insights into the regulatory mechanism of cAMP in PKA signaling.

In vivo proximity proteomics uncovers palmdelphin (PALMD) as a Z-disc-associated mitigator of isoproterenol-induced cardiac injury.

Z-discs are core ultrastructural organizers of cardiomyocytes that modulate many facets of cardiac pathogenesis. Yet a comprehensive proteomic atlas of Z-disc-associated components remain incomplete. Here, we established an adeno-associated virus (AAV)-delivered, cardiomyocyte-specific, proximity-labeling approach to characterize the Z-disc proteome in vivo. We found palmdelphin (PALMD) as a novel Z-disc-associated protein in both adult murine cardiomyocytes and human pluripotent stem cell-derived cardiomyocytes. Germline and cardiomyocyte-specific Palmd knockout mice were grossly normal at baseline but exhibited compromised cardiac hypertrophy and aggravated cardiac injury upon long-term isoproterenol treatment. By contrast, cardiomyocyte-specific PALMD overexpression was sufficient to mitigate isoproterenol-induced cardiac injury. PALMD ablation perturbed the transverse tubule (T-tubule)-sarcoplasmic reticulum (SR) ultrastructures, which formed the Z-disc-associated junctional membrane complex (JMC) essential for calcium handling and cardiac function. These phenotypes were associated with the reduction of nexilin (NEXN), a crucial Z-disc-associated protein that is essential for both Z-disc and JMC structures and functions. PALMD interacted with NEXN and enhanced its protein stability while the Nexn mRNA level was not affected. AAV-based NEXN addback rescued the exacerbated cardiac injury in isoproterenol-treated PALMD-depleted mice. Together, this study discovered PALMD as a potential target for myocardial protection and highlighted in vivo proximity proteomics as a powerful approach to nominate novel players regulating cardiac pathogenesis.

[Study on the mesoscopic dynamic effects of tumor treating fields on cell tubulin].

Tumor treatment fields (TTFields) can effectively inhibit the proliferation of tumor cells, but its mechanism remains exclusive. The destruction of cellular microtubule structure caused by TTFields through electric field force is considered to be the main reason for inhibiting tumor cell proliferation. However, the validity of this hypothesis still lacks exploration at the mesoscopic level. Therefore, in this study, we built force models for tubulins subjected to TTFields, based on the physical and electrical properties of tubulin molecules. We theoretically analyzed and simulated the dynamic effects of electric field force and torque on tubulin monomer polymerization, as well as the alignment and orientation of α/ß tubulin heterodimer, respectively. Research results indicate that the interference of electric field force induced by TTFields on tubulin monomer is notably weaker than the inherent electrostatic binding force among tubulin monomers. Additionally, the electric field torque generated by the TTFileds on α/ß tubulin dimers is also difficult to affect their random alignment. Therefore, at the mesoscale, our study affirms that TTFields are improbable to destabilize cellular microtubule structures via electric field dynamics effects. These results challenge the traditional view that TTFields destroy the microtubule structure of cells through TTFields electric field force, and proposes a new approach that should pay more attention to the "non-mechanical" effects of TTFields in the study of TTFields mechanism. This study can provide reliable theoretical basis and inspire new research directions for revealing the mesoscopic bioelectrical mechanism of TTFields.

Thermally Activated Delayed Fluorescence (TADF)-active Coinage-metal Sulfide Clusters for High-resolution X-ray Imaging.

The study of facile-synthesis and low-cost X-ray scintillators with high light yield, low detection limit and high X-ray imaging resolution plays a vital role in medical and industrial imaging fields. However, the optimal balance between X-ray absorption, decay lifetime and excitonic utilization efficiency of scintillators to achieve high-resolution imaging is extremely difficult due to the inherent contradiction. Here two thermally activated delayed fluorescence (TADF)-actived coinage-metal clusters M6 S6 L6 (M=Ag or Cu) were synthesized by simple solvothermal reaction, where the cooperation of heavy atom-rich character and TADF mechanism supports strong X-ray absorption and rapid luminescent collection of excitons. Excitingly, Ag6 S6 L6 (SC-Ag) displays a high photoluminescence quantum yield of 91.6 % and scintillating light yield of 17420 photons MeV-1 , as well as a low detection limit of 208.65 nGy s-1 that is 26 times lower than the medical standard (5.5 µGy s-1 ). More importantly, a high X-ray imaging resolution of 16 lp/mm based on SC-Ag screen is demonstrated. Besides, rigid core skeleton reinforced by metallophilicity endows clusters M6 S6 L6 strong resistance to humidity and radiation. This work provides a new view for the design of efficient scintillators and opens the research door for silver clusters in scintillation application.

[Identification of Q-markers for Schisandrae Sphenantherae Fructus in treating drug-induced liver injury based on network pharmacology, fingerprint and quantitative analysis].

This study aims to establish the ultra-performance liquid chromatography(UPLC) fingerprint and multi-indicator quantitative analysis method for Schisandrae Sphenantherae Fructus(SSF) and to screen out the potential quality markers(Q-markers) of hepatoprotection based on network pharmacology. The similarity analysis was performed using the Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System, which showed that the similarity of the fingerprints of 15 samples from different regions ranged from 0.981 to 0.998. Eighteen common components were identified, from which 3 differential components were selected by cluster analysis and principal component analysis. The "component-target-pathway" network was built to predict the core components related to the hepatoprotective effects. Fourteen core components were screened by network pharmacology. They acted on the targets such as AKT1, CCND1, CYP1A1, CYP3A4, MAPK1, MAPK3, NOS2, NQO1, and PTGS2 to regulate the signaling pathways of lipid metabolism and atherosclerosis, hepatitis B, interleukin-17, and tumor necrosis factor. Considering the chemical measurability, characteristics, and validity, schisantherin A, anwulignan, and schisandrin A were identified as the Q-markers. The content of schisantherin A, anwulignan, and schisandrin A in the test samples were 0.20%-0.57%, 0.13%-0.33%, and 0.42%-0.70%, respectively. Combining the fingerprint, network pharmacology, and content determination, this study predicted that schisantherin A, anwulignan, and schisandrin A were the Q-markers for the hepatoprotective effect of SSF. The results can provide reference for improving the quality evaluation standard and exploring the hepatoprotective mechanism of SSF.

KNCFS: Feature selection for high-dimensional datasets based on improved random multi-subspace learning.

Feature selection has long been a focal point of research in various fields.Recent studies have focused on the application of random multi-subspaces methods to extract more information from raw samples.However,this approach inadequately addresses the adverse effects that may arise due to feature collinearity in high-dimensional datasets.To further address the limited ability of traditional algorithms to extract useful information from raw samples while considering the challenge of feature collinearity during the random subspaces learning process, we employ a clustering approach based on correlation measures to group features.Subsequently, we construct subspaces with lower inter-feature correlations.When integrating feature weights obtained from all feature spaces,we introduce a weighting factor to better handle the contributions from different feature spaces.We comprehensively evaluate our proposed algorithm on ten real datasets and four synthetic datasets,comparing it with six other feature selection algorithms.Experimental results demonstrate that our algorithm,denoted as KNCFS,effectively identifies relevant features,exhibiting robust feature selection performance,particularly suited for addressing feature selection challenges in practice.

Diagnostic value of contrast-enhanced ultrasound in judging the survival of graft after heteroautoplasty for secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is one of the common complications of end-stage renal disease-uremia, and is mainly manifested as parathyroid hyperplasia and abnormal secretion of parathyroid hormone (PTH). OBJECTIVE: To investigate the value and advantages of contrast-enhanced ultrasound (CEUS) in evaluating the survival of autografts after parathyroidectomy + parathyroid autotransplantation. METHODS: In this study, 125 patients with renal failure due to polycystic kidney disease, chronic nephritis, diabetic nephropathy, lupus nephritis, and atherosclerotic nephropathy were enrolled as the participants and each of them had 4 secondary hyperactive parathyroid glands and underwent parathyroid autotransplantation. One parathyroid gland was taken from each patient and equally divided into 4 parts and placed in the subcutaneous fat of one forearm for transplantation. CEUS was performed 14 days after the transplantation to observe the micro blood supply of the graft and assess the survival and secretory function of the transplanted parathyroid. The grafts were divided into the partial survival group and the total survival group based on the enhancement characteristics. The survival of the grafts was determined by comparing the parathyroid hormone level in bilateral elbow cephalic veins 1 month after surgery. RESULTS: Among the 125 patients, 112 had linear or punctate enhancement of 2-4 parathyroid glands 14 days after surgery, and 13 patients had linear or punctate enhancement of 0-1 parathyroid gland. There were statistically significant differences in the perfusion pattern, enhancement uniformity, and parathyroid hormone levels in the cephalic veins at the elbow on both the graft and non-graft sides among all groups (P< 0.05). CONCLUSION: Compared to the detection of the difference in the parathyroid hormone level in the cephalic vein of bilateral elbows 1 month after surgery, CEUS can reflect the parathyroid survival after transplantation more quickly and accurately 2 weeks later, and provide a more rapid and agile non-invasive clinical diagnosis method.

Oral peptide therapeutics for diabetes treatment: State-of-the-art and future perspectives.

Diabetes, characterized by hyperglycemia, is a major cause of death and disability worldwide. Peptides, such as insulin and glucagon-like peptide-1 (GLP-1) analogs, have shown promise as treatments for diabetes due to their ability to mimic or enhance insulin's actions in the body. Compared to subcutaneous injection, oral administration of anti-diabetic peptides is a preferred approach. However, biological barriers significantly reduce the efficacy of oral peptide therapeutics. Recent advancements in drug delivery systems and formulation techniques have greatly improved the oral delivery of peptide therapeutics and their efficacy in treating diabetes. This review will highlight (1) the benefits of oral anti-diabetic peptide therapeutics; (2) the biological barriers for oral peptide delivery, including pH and enzyme degradation, intestinal mucosa barrier, and biodistribution barrier; (3) the delivery platforms to overcome these biological barriers. Additionally, the review will discuss the prospects in this field. The information provided in this review will serve as a valuable guide for future developments in oral anti-diabetic peptide therapeutics.

Optimal time to initiate early oral feeding in postoperative patients with upper gastrointestinal malignancy: A network meta-analysis.

BACKGROUND: With the development of enhanced recovery after surgery, early oral feeding is likely to become the preferred mode of nutrition after surgery for upper gastrointestinal tract malignancies. However, the optimal time to initiate early oral feeding remains unknown. OBJECTIVE: We aimed to compare the effects of different introduction times of early oral feeding in patients with upper gastrointestinal malignancies in terms of safety, tolerance, and effectiveness and to identify the optimal time for early oral feeding after surgery. METHODS: A random-effects meta-analysis was performed to identify evidence from relevant randomized controlled trials. Ten electronic databases were searched for randomized controlled trials from their earliest records to May 2023. Data were analyzed using the Stata 16.0 software. RESULTS: A total of 22 randomized controlled trials including 2510 patients and seven time points for oral feeding after surgery were considered. Regarding safety, oral feeding initiated on postoperative day 3 may be the safest (high-quality evidence) compared with other times. Regarding tolerance, oral feeding initiated on postoperative day 5 may be the most well-tolerated (moderate-quality evidence) compared with other times. Regarding effectiveness, oral feeding initiated on postoperative day 3 may be the most effective (moderate-quality evidence) compared with other times. CONCLUSIONS: Early oral feeding is safe, tolerable, and effective in postoperative patients with upper gastrointestinal malignancies. The optimal time to initiate early oral feeding after surgery was most likely postoperative day 3. The results of this meta-analysis provide evidence-based guidelines for clinical decision-making.

Dual-functional mediators of high-entropy Prussian blue analogues for lithiophilicity and sulfiphilicity in Li-S batteries.

Lithium-sulfur (Li-S) batteries are considered promising next-generation energy storage systems due to their high energy density (2600 W h kg-1) and cost-effectiveness. However, the shuttle effect of lithium polysulfides in sulfur cathodes and uncontrollable Li dendrite growth in Li metal anodes significantly impede the practical application of Li-S batteries. In this study, we address these challenges by employing a high-entropy Prussian blue analogue Mn0.4Co0.4Ni0.4Cu0.4Zn0.4[Fe(CN)6]2 (HE-PBA) composite containing multiple metal ions as a dual-functional mediator for Li-S batteries. Specifically, the HE-PBA composite provides abundant metal active sites that efficiently chemisorb lithium polysulfides (LiPSs) to facilitate fast redox conversion kinetics of LiPSs. In Li metal anodes, the exceptional lithiophilicity of the HE-PBA ensures a homogeneous Li ion flux, resulting in uniform Li deposition while mitigating the growth of Li dendrites. As a result, our work demonstrates outstanding long-term cycling performance with a decay rate of only 0.05% per cycle over 1000 cycles at 2.0 C. The HE-PBA@Cu/Li anode maintains a stable overpotential even after 600 h at 0.5 mA cm-2 under the total areal capacity of 1.0 mA h cm-2. This study showcases the application potential of the HE-PBA in Li-S batteries and encourages further exploration of prospective high-entropy materials used to engineer next-generation batteries.

Nickel-catalyzed γ-alkylation of cyclopropyl ketones with unactivated primary alkyl chlorides: balancing reactivity and selectivity via halide exchange.

A novel method was developed for synthesizing γ-alkyl ketones via nickel-catalyzed cross-electrophile coupling of cyclopropyl ketones and non-activated primary alkyl chlorides. High reactivity and selectivity can be achieved with sodium iodide as a crucial cocatalyst that generates a low concentration of alkyl iodide via halide exchange, thus avoiding the formation of alkyl dimers. This reaction possessed excellent regioselectivity and high step economy circumventing in situ or pregenerated organometallics.

Organocatalytic enantioselective decarboxylative protonation of α-alkyl-α-aryl malonate monoesters.

In contrast to the well-established enzymatic enantioselective decarboxylative protonation (EDP), the corresponding chemocatalytic reactions of acyclic malonic acid derivatives remain challenging. Herein, we developed a biomimetic EDP of α-alkyl-α-aryl malonate monoesters using a chiral 1,2-trans-diaminocyclohexane-based N-sulfonamide as an organocatalyst. The method demonstrates excellent chemical yields, good enantioselectivity, mild reaction conditions, and the generation of only CO2 as waste.

Correction: Nickel-catalyzed γ-alkylation of cyclopropyl ketones with unactivated primary alkyl chlorides: balancing reactivity and selectivity via halide exchange.

[This corrects the article DOI: 10.1039/D4RA02616K.].

Comparative transcriptome and metabolome analysis revealed diversity in the response of resistant and susceptible rose (Rosa hybrida) varieties to Marssonina rosae.

Rose black spot disease caused by Marssonina rosae is among the most destructive diseases that affects the outdoor cultivation and production of roses; however, the molecular mechanisms underlying the defensive response of roses to M. rosae have not been clarified. To investigate the diversity of response to M. rosae in resistant and susceptible rose varieties, we performed transcriptome and metabolome analyses of resistant (KT) and susceptible (FG) rose varieties and identified differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) in response to M. rosae at different time points. In response to M. rosae, DEGs and DAMs were mainly upregulated compared to the control and transcription factors were concentrated in the WRKY and AP2/ERF families. Gene Ontology analysis showed that the DEGs of FG were mainly enriched in biological processes, such as the abscisic acid-activated signaling pathway, cell wall, and defense response, whereas the DEGs of KT were mainly enriched in Golgi-mediated vesicle transport processes. Kyoto Encyclopedia of Genes and Genomes analysis showed that the DEGs of both varieties were concentrated in plant-pathogen interactions, plant hormone signal transduction, and mitogen-activated protein kinase signaling pathways, with the greatest number of DEGs associated with brassinosteroid (BR) in the plant hormone signal transduction pathway. The reliability of the transcriptome results was verified by qRT-PCR. DAMs of KT were significantly enriched in the butanoate metabolism pathway, whereas DAMs of FG were significantly enriched in BR biosynthesis, glucosinolate biosynthesis, and tryptophan metabolism. Moreover, the DAMs in these pathways were significantly positively correlated with the DEGs. Disease symptoms were aggravated when FG leaves were inoculated with M. rosae after 24-epibrassinolide treatment, indicating that the response of FG to M. rosae involves the BR signaling pathway. Our results provide new insights into the molecular mechanisms underlying rose response to M. rosae and lay a theoretical foundation for formulating rose black spot prevention and control strategies and cultivating resistant varieties.

Lineage-specific gene duplication and expansion of DUF1216 gene family in Brassicaceae.

Proteins containing domain of unknown function (DUF) are prevalent in eukaryotic genome. The DUF1216 proteins possess a conserved DUF1216 domain resembling to the mediator protein of Arabidopsis RNA polymerase II transcriptional subunit-like protein. The DUF1216 family are specifically existed in Brassicaceae, however, no comprehensive evolutionary analysis of DUF1216 genes have been performed. We performed a first comprehensive genome-wide analysis of DUF1216 proteins in Brassicaceae. Totally 284 DUF1216 genes were identified in 27 Brassicaceae species and classified into four subfamilies on the basis of phylogenetic analysis. The analysis of gene structure and conserved motifs revealed that DUF1216 genes within the same subfamily exhibited similar intron/exon patterns and motif composition. The majority members of DUF1216 genes contain a signal peptide in the N-terminal, and the ninth position of the signal peptide in most DUF1216 is cysteine. Synteny analysis revealed that segmental duplication is a major mechanism for expanding of DUF1216 genes in Brassica oleracea, Brassica juncea, Brassica napus, Lepidium meyneii, and Brassica carinata, while in Arabidopsis thaliana and Capsella rubella, tandem duplication plays a major role in the expansion of the DUF1216 gene family. The analysis of Ka/Ks (non-synonymous substitution rate/synonymous substitution rate) ratios for DUF1216 paralogous indicated that most of gene pairs underwent purifying selection. DUF1216 genes displayed a specifically high expression in reproductive tissues in most Brassicaceae species, while its expression in Brassica juncea was specifically high in root. Our studies offered new insights into the phylogenetic relationships, gene structures and expressional patterns of DUF1216 members in Brassicaceae, which provides a foundation for future functional analysis.

Complex causal association between genetically predicted 731 immunocyte phenotype and osteonecrosis: a bidirectional two-sample Mendelian randomization analysis.

PURPOSE: Previous studies have explored the role of immune cells on osteonecrosis. This Mendelian randomization (MR) study further assessed 731 immunocyte phenotypes on osteonecrosis, whether a causal relationship exists, and provides some evidence of causality. METHODS: The 731 immunocyte phenotypes and osteonecrosis data used in this study were obtained from their respective genome-wide association studies (GWAS). The authors used inverse variable weighting (IVW) as the primary analysis method. In addition, the authors simultaneously employed multiple analytical methods, including MR-Egger, weighted mode, simple mode, and weighted median, to strengthen the final results. Finally, sensitivity analyses were conducted to verify the stability and feasibility of the data. RESULTS: The results of the IVW method of MR analysis showed that 8 immunocyte phenotypes were positively associated with osteonecrosis [ P <0.05, odds ratio (OR) > 1]; 18 immunocyte phenotypes were negatively associated with osteonecrosis ( P <0.05, OR<1), none of which were heterogeneous or horizontally pleiotropic ( P > 0.05) or reverse causality. In addition to this, in reverse MR, osteonecrosis was positively associated with 10 additional immunocyte phenotypes ( P <0.05, OR > 1) and negatively associated with 14 immunocyte phenotypes ( P <0.05, OR<1). And none of them had heterogeneity and horizontal pleiotropy ( P > 0.05) or reverse causality. CONCLUSIONS: The authors demonstrated a complex causal relationship between multiple immune phenotypes and osteonecrosis through a comprehensive two-way, two-sample MR analysis, highlighting the complex pattern of interactions between the immune system and osteonecrosis.

Dimerized sesquiterpenoid [4 + 2] adducts with ferroptosis-promoting activity from Inula britannica Linn.

Inubritanolides C and D (1 and 2), two exo sesquiterpenoid [4 + 2] adducts with unprecedented interconverting conformations of twist-chair and chair, together with two previously undescribed endo [4 + 2] dimers (3 and 4) were discovered from Inula britannica flowers. Dimers 1 and 2 have an undescribed carbon skeleton comprising of eudesmanolide and guaianolide units with the linkage mode of C-11/C-1' and C-13/C-3' via a Diels-Alder cycloaddition reaction. Their structures were elucidated using 1D/2D NMR, X-ray diffraction, ECD, and variable-temperature NMR experiments. Dimer 2 displayed a strong inhibitory effect on breast cancer cells by promoting lipid ROS production, showing its potential as ferroptosis inducer.

Elucidating the reversible and irreversible self-assembly mechanisms of low-complexity aromatic-rich kinked peptides and steric zipper peptides.

Many RNA-binding proteins such as fused-in sarcoma (FUS) can self-assemble into reversible liquid droplets and fibrils through the self-association of their low-complexity (LC) domains. Recent experiments have revealed that SYG-rich segments in the FUS LC domains play critical roles in the reversible self-assembly behaviors of FUS. These FUS LC segments alone can self-assemble into reversible kinked fibrils, which are markedly different from the canonical irreversible steric zipper ß-sheet fibrils. However, the molecular determinants underlying the reversible and irreversible self-assembly are poorly understood. Herein we conducted extensive all-atom and coarse-grained molecular dynamics simulations of four representative hexapeptides: two low-complexity aromatic-rich kinked peptides from the amyotrophic lateral sclerosis-related FUS protein, FUS37-42 (SYSGYS) and FUS54-59 (SYSSYG); and two steric zipper peptides from Alzheimer's-associated Aß and Tau proteins, Aß16-21 (KLVFFA) and Tau306-311 (VQIVYK). We dissected their reversible and irreversible self-assembly dynamics, predicted their phase separation behaviors, and elucidated the underpinning molecular interactions. Our simulations showed that alternating stickers (Tyr) and spacers (Gly and Ser) in FUS37-42 and FUS54-59 facilitate the formation of highly dynamic coil-rich oligomers and lead to reversible self-assembly, while consecutive hydrophobic residues of LVFF in Aß16-21 and IVY in Tau306-311 act as hydrophobic patches, favoring the formation of stable ß-sheet-rich oligomers and driving the irreversible self-assembly. Intriguingly, we found that FUS37-42 and FUS54-59 peptides, possessing the same amino acid composition and the same number of sticker and spacer residues, display differential self-assembly propensities. This finding suggests that the self-assembly behaviors of FUS peptides are fine-tuned by the site-specific patterning of spacer residues (Ser and Gly). This study provides significant mechanistic insights into reversible and irreversible peptide self-assembly, which would be helpful for understanding the molecular mechanisms underlying the formation of biological liquid condensates and pathological solid amyloid fibrils.