Surviving the Storm: The Role of Poly- and Depolyploidization in Tissues and Tumors.

Polyploidization and depolyploidization are critical processes in the normal development and tissue homeostasis of diploid organisms. Recent investigations have revealed that polyaneuploid cancer cells (PACCs) exploit this ploidy variation as a survival strategy against anticancer treatment and for the repopulation of tumors. Unscheduled polyploidization and chromosomal instability in PACCs enhance malignancy and treatment resistance. However, their inability to undergo mitosis causes catastrophic cellular death in most PACCs. Adaptive ploid reversal mechanisms, such as multipolar mitosis, centrosome clustering, meiosis-like division, and amitosis, counteract this lethal outcome and drive cancer relapse. The purpose of this work is to focus on PACCs induced by cytotoxic therapy, highlighting the latest discoveries in ploidy dynamics in physiological and pathological contexts. Specifically, by emphasizing the role of "poly-depolyploidization" in tumor progression, the aim is to identify novel therapeutic targets or paradigms for combating diseases associated with aberrant ploidies.

Chiral Supramolecular Nanofibers Regulated Tumor-Derived Exosomes Secretion for Constructing an Anti-Tumor Extracellular Microenvironment.

Tumor-derived exosomes (TDEs) induced extracellular microenvironment has recently been validated to be critical for tumor progression and metastasis, however, remodeling it for oncotherapy still remains a major challenge due to difficulty in regulation of TDEs secretion. Herein, the supramolecular chiral nanofibers, composed of L/D -phenylalanine derivates (L/D-Phe) and linear hyaluronic acid (HA), are successfully employed to construct TDEs induced anti-tumor extracellular microenvironment. The left-handed L-Phe @HA nanofibers significantly inhibit TDEs secretion into extracellular microenvironment, which results in suppression of tumor proliferation and metastasis in vitro and vivo. Biological assays and theoretical modeling reveal that these results are mainly attributed to strong adsorption of the key exosomes transporters (Ras-related protein Rab-27A and synaptosome-associated protein 23) on left-handed L-Phe @HA nanofibers via enhanced stereoselective interaction, leading to degradation and phosphorylated dropping of exosomes transporters. Subsequently, transfer function of exosomes transporters is limited, which causes remarkable inhibition of TDEs secretion. These findings provide a promising novel insight of chiral functional materials to establish an anti-tumor extracellular microenvironment via regulation of TDEs secretion.

Sulfidated nanoscale zero-valent iron derived from iron sludge for tetracycline removal: Role of sulfur and iron in reactivity and mechanisms.

Iron sludge, produced during the drinking water treatment process, can be recycled as potential iron resource to create environmental functional material. In this study, sulfur-iron composites derived from iron sludge (S-Fe composites) was synthesized through sulfidation and carbonization, and used for the tetracycline (TC) removal under aerobic and anoxic conditions. The reactivities of these as-prepared products were strongly depended on pyrolysis temperatures. In particular, sulfidated nanoscale zero-valent iron loaded on carbon (S-nFe0@CIS) carbonized at 800 °C exhibited the highest TC removal efficiency with 86.6% within 30 min at circumneutral pH compared with other S-Fe composites. The crystalline structure of α-Fe0, FeSx and S0 as main active sites in S-nFe0@CIS promoted the degradation of TC. Moreover, the Fe/S molar ratios significantly affected the TC removal rates, which reached the best value as the optimal S/Fe of 0.27. The results illustrated that the optimized extent of sulfidation could facilitate electron transfer from nFe0 towards contaminants and accelerate Fe(III)/Fe(II) cycle in reaction system compared to bared nFe0@CIS. We revealed that removal of TC by S-nFe0@CIS in the presence of dissolved oxygen (DO) is mainly attributed to oxidation, adsorption and reduction pathways. Their contribution to TC removal were 31.6%, 25.2% and 28.8%, respectively. Furthermore, this adsorption-oxygenation with the formation of S-nFe0@CIS-TC* complexes was a surface-mediated process, in which DO was transformed by the structural FeSx on complex surface to •OH with the generation of H2O2 intermediate. The intermediates of TC and toxicity analysis indicate that less toxicity products generated through degradation process. This study provides a new reclamation of iron sludge and offers a new insight into the TC removal by S-nFe0@CIS under aerobic conditions.

Leptin Reduction as a Required Component for Weight Loss.

Partial leptin reduction can induce significant weight loss, while weight loss contributes to partial leptin reduction. The cause-and-effect relationship between leptin reduction and weight loss remains to be further elucidated. Here, we show that FGF21 and the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide rapidly induced a reduction in leptin. This leptin reduction contributed to the beneficial effects of GLP-1R agonism in metabolic health, as transgenically maintaining leptin levels during treatment partially curtailed the beneficial effects seen with these agonists. Moreover, a higher degree of leptin reduction during treatment, induced by including a leptin neutralizing antibody with either FGF21 or liraglutide, synergistically induced greater weight loss and better glucose tolerance in diet-induced obese mice. Furthermore, upon cessation of either liraglutide or FGF21 treatment, the expected immediate weight regain was observed, associated with a rapid increase in circulating leptin levels. Prevention of this leptin surge with leptin neutralizing antibodies slowed down weight gain and preserved better glucose tolerance. Mechanistically, a significant reduction in leptin induced a higher degree of leptin sensitivity in hypothalamic neurons. Our observations support a model that postulates that a reduction of leptin levels is a necessary prerequisite for substantial weight loss, and partial leptin reduction is a viable strategy to treat obesity and its associated insulin resistance.

Characteristics of vitiligo patients with versus without associated autoimmune thyroid disease.

BACKGROUND: Clinical data are limited in patients with vitiligo with or without autoimmune thyroid disease. OBJECTIVES: The objective of the study was to investigate the clinical features and basic data of patients with vitiligo, especially those with autoimmune thyroid disease. METHODS: The study was a single-center retrospective study. A total of 1305 patients with vitiligo from June 2018 to May 2023 were included, and the clinical characteristics and basic information of the patients were recorded in detail. RESULTS: We identified an association between sex (odds ratio [OR]: 2.380; 95% confidence interval [CI]: 1.772-1.198), vitiligo duration (OR: 1.449; 95% CI: 1.076-1.952), skin involvement exceeding 5% of the body surface area (OR: 3.764; 95% CI: 2.134-6.640), negative emotions (OR: 3.076; 95% CI: 2.292-4.127), vitiligo type (OR: 1.974; 95% CI: 1.096-3.555), family history of AITD (OR: 4.979; 95% CI: 2.687-9.225), and family history of AD (OR: 2.418; 95% CI: 1.410-4.146) and patients with vitiligo. CONCLUSIONS: For patients with statistically significant associated risk factors, differential diagnosis and early intervention should be performed.

The Role of Regulatory Cell Death in Vitiligo.

Vitiligo is one of the common chronic autoimmune skin diseases in clinic, which is characterized by localized or generalized depigmentation and seriously affects the physical and mental health of patients. At present, the pathogenesis of vitiligo is not clear; mainly, heredity, autoimmunity, oxidative stress, melanocyte (MC) self-destruction, and the destruction, death, or dysfunction of MCs caused by various reasons are always the core of vitiligo. Regulatory cell death (RCD) is an active and orderly death mode of cells regulated by genes, which widely exists in various life activities, plays a pivotal role in maintaining the homeostasis of the organism, and is closely related to the occurrence and development of many diseases. With the deepening of the research and understanding of RCD, people gradually found that there are many different forms of RCD in the lesions and perilesional skin of vitiligo patients, such as apoptosis, autophagy, pyroptosis, ferroptosis, and so on. Different cell death modes have different mechanisms in vitiligo, and different RCDs can interact and regulate each other. In this article, the mechanism related to RCD in the pathogenesis of vitiligo is reviewed, which provides new ideas for exploring the pathogenesis and targeted treatment of vitiligo.

A comparative study on ctDNA and tumor DNA mutations in lung cancer and benign cases with a high number of CTCs and CTECs.

BACKGROUND: Liquid biopsy provides a non-invasive approach that enables detecting circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) using blood specimens and theoretically benefits early finding primary tumor or monitoring treatment response as well as tumor recurrence. Despite many studies on these novel biomarkers, their clinical relevance remains controversial. This study aims to investigate the correlation between ctDNA, CTCs, and circulating tumor-derived endothelial cells (CTECs)  while also evaluating whether mutation profiling in ctDNA is consistent with that in tumor tissue from lung cancer patients. These findings will help the evaluation and utilization of these approaches in clinical practice. METHODS: 104 participants (49 with lung cancer and 31 with benign lesions) underwent CTCs and CTECs detection using integrating subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) strategy. The circulating cell-free DNA (cfDNA) concentration was measured and the mutational profiles of ctDNA were examined by Roche AVENIO ctDNA Expanded Kit (targeted total of 77 genes) by next generation sequencing (NGS) in 28 patients (20 with lung cancer and 8 with benign lesions) with highest numbers of CTCs and CTECs. Mutation validation in matched tumor tissue DNA was then performed in 9 patients with ctDNA mutations using a customized xGen pan-solid tumor kit (targeted total of 474 genes) by NGS. RESULTS: The sensitivity and specificity of total number of CTCs and CTECs for the diagnosis of NSCLC were 67.3% and 77.6% [AUC (95%CI): 0.815 (0.722-0.907)], 83.9% and 77.4% [AUC (95%CI): 0.739 (0.618-0.860)]. The concentration of cfDNA in plasma was statistically correlated with the size of the primary tumor (r = 0.430, P = 0.022) and CYFRA 21-1 (r = 0.411, P = 0.041), but not with the numbers of CTCs and CTECs. In this study, mutations were found to be poorly consistent between ctDNA and tumor DNA (tDNA) in patients, even when numerous CTCs and CTECs were present. CONCLUSION: Detection of CTCs and CTECs could be the potential adjunct tool for the early finding of lung cancer. The cfDNA levels are associated with the tumor burden, rather than the CTCs or CTECs counts. Moreover, the poorly consistent mutations between ctDNA and tDNA require further exploration.

An ACE2 decamer viral trap as a durable intervention solution for current and future SARS-CoV.

The capacity of SARS-CoV-2 to evolve poses challenges to conventional prevention and treatment options such as vaccination and monoclonal antibodies, as they rely on viral receptor binding domain (RBD) sequences from previous strains. Additionally, animal CoVs, especially those of the SARS family, are now appreciated as a constant pandemic threat. We present here a new antiviral approach featuring inhalation delivery of a recombinant viral trap composed of ten copies of angiotensin-converting enzyme 2 (ACE2) fused to the IgM Fc. This ACE2 decamer viral trap is designed to inhibit SARS-CoV-2 entry function, regardless of viral RBD sequence variations as shown by its high neutralization potency against all known SARS-CoV-2 variants, including Omicron BQ.1, BQ.1.1, XBB.1 and XBB.1.5. In addition, it demonstrates potency against SARS-CoV-1, human NL63, as well as bat and pangolin CoVs. The multivalent trap is effective in both prophylactic and therapeutic settings since a single intranasal dosing confers protection in human ACE2 transgenic mice against viral challenges. Lastly, this molecule is stable at ambient temperature for more than twelve weeks and can sustain physical stress from aerosolization. These results demonstrate the potential of a decameric ACE2 viral trap as an inhalation solution for ACE2-dependent coronaviruses of current and future pandemic concerns.

Observing Discrete Blocking Events at a Polarized Micro- or Submicro-Liquid/Liquid Interface.

Single-entity collisional electrochemistry (SECE), a subfield of single-entity electrochemistry, enables directly characterizing entities and particles in the electrolyte solution at the single-entity resolution. Blockade SECE at the traditional solid ultramicroelectrode (UME)/electrolyte interface suffers from a limitation: only redox-inactive particles can be studied. The wide application of the classical Coulter counter is restricted by the rapid translocation of entities through the orifice, which results in a remarkable proportion of undetected signals. In response, the blocking effect of single charged conductive or insulating nanoparticles (NPs) at low concentrations for ion transfer (IT) at a miniaturized polarized liquid/liquid interface was successfully observed. Since the particles are adsorbed at the liquid/liquid interface, our method also solves the problem of the Coulter counter having a too-fast orifice translocation rate. The decreasing quantal staircase/step current transients are from landings (controlled by electromigration) of either conductive or insulating NPs onto the interface. This interfacial NP assembly shields the IT flux. The size of each NP can be calculated by the step height. The particle size measured by dynamic light scattering (DLS) is used for comparison with that calculated from electrochemical blocking events, which is in fairly good agreement. In short, the blocking effect of IT by single entities at micro- or submicro-liquid/liquid interface has been proven experimentally and is of great reference in single-entity detection.

imply: improving cell-type deconvolution accuracy using personalized reference profiles.

Real-world clinical samples are often admixtures of signal mosaics from multiple pure cell types. Using computational tools, bulk transcriptomics can be deconvoluted to solve for the abundance of constituent cell types. However, existing deconvolution methods are conditioned on the assumption that the whole study population is served by a single reference panel, which ignores person-to-person heterogeneity. Here we present imply, a novel algorithm to deconvolute cell type proportions using personalized reference panels. imply can borrow information across repeatedly measured samples for each subject, and obtain precise cell type proportion estimations. Simulation studies demonstrate reduced bias in cell type abundance estimation compared with existing methods. Real data analyses on large longitudinal consortia show more realistic deconvolution results that align with biological facts. Our results suggest that disparities in cell type proportions are associated with several disease phenotypes in type 1 diabetes and Parkinson's disease. Our proposed tool imply is available through the R/Bioconductor package ISLET at https://bioconductor.org/packages/ISLET/.

Enrichment of halotolerant hydrogen-oxidizing bacteria and production of high-value-added chemical hydroxyectoine using a hybrid biological-inorganic system.

Hybrid biological-inorganic (HBI) systems show great promise as CO2 conversion platforms combining CO2 fixation by hydrogen-oxidizing bacteria (HOB) with water splitting. Herein, halotolerant HOB were enriched using an HBI system with a high-ionic-strength medium containing 180 mM phosphate buffer to identify new biocatalysts. The reactors were inoculated with samples from saline environments and applied with a voltage of 2.0 V. Once an increase in biomass was observed with CO2 consumption, an aliquot of the medium was transferred to a new reactor. After two successive subcultures, Achromobacter xylosoxidans strain H1_3_1 and Mycolicibacterium mageritense strain H4_3_1 were isolated from the reactor media. Genome sequencing indicated the presence of genes for aerobic hydrogen-oxidizing chemolithoautotrophy and synthesis of the compatible solute hydroxyectoine in both strains. Furthermore, both strains produced hydroxyectoine in the reactors under the high-ionic-strength condition, suggesting the potential for new HBI systems using halotolerant HOB to produce high-value-added chemicals.

Microglial cGAS deletion protects against amyloid-ß induced Alzheimer's disease pathogenesis.

Innate immune activation plays a vital role in the development of Alzheimer's disease (AD) and related dementias (ADRD). Among which, the DNA sensing cyclic GMP-AMP synthase (cGAS)- STING pathway has been implicated in diverse aspects of AD progression. In the current study, we showed that the cGAS-STING signaling was up-regulated in AD and this elevation was mainly contributed by the microglial population other than non-microglial cell types in the brain. By establishing an inducible, microglia-specific cGAS knockout mouse model in 5xFAD background, we found that deleting microglial cGAS at the onset of amyloid-ß (Aß) pathology significantly limited plaque formation, and protected mice from Aß-induced cognitive impairment. Mechanistically, we found cGAS was necessary for plaque-associated microglial enrichment potentially driven by IRF8, and was indispensable for the development of disease-associated microglia (DAM) phenotype. Meanwhile, the loss of microglial cGAS reduced the levels of dystrophic neurites which led to preserved synaptic integrity and neuronal function. Our study provides new insights in understanding the effects of innate immune in AD via a cell-type specific manner, and lays the foundation for potential targeted intervention of the microglial cGAS-STING pathway toward the improvement of AD.

Adult-Onset CNS Sulfatide Deficiency Causes Sex-Dependent Metabolic Disruption in Aging.

The interconnection between obesity and central nervous system (CNS) neurological dysfunction has been widely appreciated. Accumulating evidence demonstrates that obesity is a risk factor for CNS neuroinflammation and cognitive impairment. However, the extent to which CNS disruption influences peripheral metabolism remains to be elucidated. We previously reported that myelin-enriched sulfatide loss leads to CNS neuroinflammation and cognitive decline. In this study, we further investigated the impact of CNS sulfatide deficiency on peripheral metabolism while considering sex- and age-specific effects. We found that female sulfatide-deficient mice gained significantly more body weight, exhibited higher basal glucose levels, and were glucose-intolerant during glucose-tolerance test (GTT) compared to age-matched controls under a normal diet, whereas male sulfatide-deficient mice only displayed glucose intolerance at a much older age compared to female sulfatide-deficient mice. Mechanistically, we found that increased body weight was associated with increased food intake and elevated neuroinflammation, especially in the hypothalamus, in a sex-specific manner. Our results suggest that CNS sulfatide deficiency leads to sex-specific alterations in energy homeostasis via dysregulated hypothalamic control of food intake.

Outcomes after HSCT for mucolipidosis II (I-cell disease) caused by novel compound heterozygous GNPTAB mutations.

Background: Mucolipidosis type II (MLII), or I-cell disease, is a rare lysosomal storage disease (LSD) caused by variants in the GNPTAB gene. MLII patients exhibit clinical phenotypes in the prenatal or neonatal stage, such as marked dysmorphic features, cardiac involvement, respiratory symptoms, dysostosis multiplex, severe growth abnormalities, and mental and motor developmental abnormalities. The median age at diagnosis for MLII is 0.7 years, the median survival is 5.0 years, and the median age at death is 1.8 years. No cure for MLII exists. Methods: Sanger sequencing of the GNPTAB gene identified the compound heterozygous mutations c.673C > T in exon 7 and c.1090C > T in exon 9, which were novel double heterozygous mutations first reported in China. For the first time, we describe our experience in the use of HSCT for MLII. Our patient underwent HSCT with cells from a 9/10 human leukocyte antigen (HLA)-matched unrelated donor at 12 months of age. Myeloid neutrophil and platelet engraftment occurred on Days 10 and 11, respectively. Results: The patient's limb muscle tension was significantly reduced, and his gross and fine motor skills were improved four months after transplantation. DST(Developmental Screen Test) results showed that the patient's fine motor skills and mental development were improved compared with before HSCT. Conclusion: MLII is a very severe lysosomal storage disease, to date, only 3 cases have been reported on the use of HSCT to treat MLII. Our data show that HSCT is a potential way to prolong the life of patients and improve their quality of life. Due to the lack of comparable data and time, the exact benefit remains unclear in MLII patients. Longer-term follow-up and in-depth prospective studies are indispensable.

Chiral Supramolecular Assemblies: Controllable Construction and Biological Activity.

Chiral supramolecular assemblies with helical structures (e. g., proteins with α-helix, DNA with double helix, collagen with triple-helix) as the central structure motifs in biological systems play a crucial role in various physiological activities of living organisms. Variations in chiral structure can cause many abnormal physiological activities. To gain insight into the construction, structural transition, and related physiological functions of these complex helix in natural systems, it is necessary to fabricate artificial supramolecular assemblies with controllable helix orientation as research platform. This review discusses recent advances in chiral supramolecular assembly, including the precise construction and regulation of assembled chiral nanostructures with tunable chirality. Chiral structure-dependent biological activities, including cell proliferation, cell differentiation, antibacterial activity and tissue regeneration, are also discussed. This review not only contributes to further understanding of the importance of chirality in the physiological environment, but also plays an important role in the development of chiral biomedical materials for the treatment of diseases (e. g., tissue engineering regeneration, stem cell transplantation therapy).

Central nervous system sulfatide deficiency as a causal factor for bladder disorder in Alzheimer's disease.

BACKGROUND: Despite being a brain disorder, Alzheimer's disease (AD) is often accompanied by peripheral organ dysregulations (e.g., loss of bladder control in late-stage AD), which highly rely on spinal cord coordination. However, the causal factor(s) for peripheral organ dysregulation in AD remain elusive. METHODS: The central nervous system (CNS) is enriched in lipids. We applied quantitative shotgun lipidomics to determine lipid profiles of human AD spinal cord tissues. Additionally, a CNS sulfatide (ST)-deficient mouse model was used to study the lipidome, transcriptome and peripheral organ phenotypes of ST loss. RESULTS: We observed marked myelin lipid reduction in the spinal cord of AD subjects versus cognitively normal individuals. Among which, levels of ST, a myelin-enriched lipid class, were strongly and negatively associated with the severity of AD. A CNS myelin-specific ST-deficient mouse model was used to further identify the causes and consequences of spinal cord lipidome changes. Interestingly, ST deficiency led to spinal cord lipidome and transcriptome profiles highly resembling those observed in AD, characterized by decline of multiple myelin-enriched lipid classes and enhanced inflammatory responses, respectively. These changes significantly disrupted spinal cord function and led to substantial enlargement of urinary bladder in ST-deficient mice. CONCLUSIONS: Our study identified CNS ST deficiency as a causal factor for AD-like lipid dysregulation, inflammation response and ultimately the development of bladder disorders. Targeting to maintain ST levels may serve as a promising strategy for the prevention and treatment of AD-related peripheral disorders.

The unfolding story of dying tumor cells during cancer treatment.

Generally, the demise of cancer cells in different ways enables the body to clear these harmful cells. However, cancer cells obtain unlimited replication and immortality from successful circumvention of cell death via various mechanisms. Some evidence suggests that treatment-induced dying tumor cells even promote cancer progression. Notably, therapeutic interventions to harness the immune system against tumor cells have shown complicated influences in clinics. Herein, there is an urgent need to clarify the underlying mechanisms that influence the outcome and regulation of the immune system during cancer treatment. In this review, we provide an account on the cell death modes and the relationship between dying tumor cells with tumor immune microenvironment during cancer treatment, focusing on immunotherapy, from mechanistic standpoint to emerging limitations and future directions.

Enrichment of hydrogen-oxidizing bacteria using a hybrid biological-inorganic system.

Hybrid biological-inorganic (HBI) systems comprising inorganic water-splitting catalysts and aerobic hydrogen-oxidizing bacteria (HOB) have previously been used for CO2 conversion. In order to identify new biocatalysts for CO2 conversion, the present study used an HBI system to enrich HOB directly from environmental samples. Three sediment samples (from a brackish water pond, a beach, and a tide pool) and two activated sludge samples (from two separate sewage plants) were inoculated into HBI systems using a cobalt phosphorus (Co-P) alloy and cobalt phosphate (CoPi) as inorganic catalysts with a fixed voltage of 2.0 V. The gas composition of the reactor headspaces and electric current were monitored. An aliquot of the reactor medium was transferred to a new reactor when significant consumption of H2 and CO2 was detected. This process was repeated twice (with three reactors in operation for each sample) to enrich HOB. Increased biomass concomitant with increased H2 and CO2 consumption was observed in the third reactor, indicating enrichment of HOB. 16S rRNA gene amplicon sequencing demonstrated enrichment of sequences related to HOB (including bacteria from Mycobacterium, Hydrogenophaga, and Xanthobacter genera) over successive sub-cultures. Finally, four different HOB belonging to the Mycobacterium, Hydrogenophaga, Xanthobacter, and Acidovorax genera were isolated from reactor media, representing potential candidates as HBI system biocatalysts.

Cancer Cells Enter an Adaptive Persistence to Survive Radiotherapy and Repopulate Tumor.

Repopulation of residual tumor cells impedes curative radiotherapy, yet the mechanism is not fully understood. It is recently appreciated that cancer cells adopt a transient persistence to survive the stress of chemo- or targeted therapy and facilitate eventual relapse. Here, it is shown that cancer cells likewise enter a "radiation-tolerant persister" (RTP) state to evade radiation pressure in vitro and in vivo. RTP cells are characterized by enlarged cell size with complex karyotype, activated type I interferon pathway and two gene patterns represented by CST3 and SNCG. RTP cells have the potential to regenerate progenies via viral budding-like division, and type I interferon-mediated antiviral signaling impaired progeny production. Depleting CST3 or SNCG does not attenuate the formation of RTP cells, but can suppress RTP cells budding with impaired tumor repopulation. Interestingly, progeny cells produced by RTP cells actively lose their aberrant chromosomal fragments and gradually recover back to a chromosomal constitution similar to their unirradiated parental cells. Collectively, this study reveals a novel mechanism of tumor repopulation, i.e., cancer cell populations employ a reversible radiation-persistence by poly- and de-polyploidization to survive radiotherapy and repopulate the tumor, providing a new therapeutic concept to improve outcome of patients receiving radiotherapy.

Assembly of Helical Nanostructures: Solvent-Induced Morphology Transition and Its Effect on Cell Adhesion.

Being able to precisely manipulate both the morphology and chiroptical signals of supramolecular assemblies will help to better understand the natural biological self-assembly mechanism. Two simple l/d-phenylalanine-based derivatives (L/DPFM) have been designed, and their solvent-dependent morphology evolutions are illustrated. It was found that, as the content of H2 O in aqueous ethanol solutions was increased, LPFM self-assembles first into right-handed nanofibers, then flat fibrous structures, and finally inversed left-handed nanofibers. Assemblies in ethanol and H2 O exhibit opposite conformations and circular dichroism (CD) signals even though they are constructed from the same molecules. Thus, the morphology-dependent cell adhesion and proliferation behaviors are further characterized. Left-handed nanofibers are found to be more favorable for cell adhesion than right-handed nanostructures. Quantitative AFM analysis showed that the L929 cell adhesion force on left-handed LPFM fibers is much higher than that on structures with inversed handedness. Moreover, the value of cell Young's modulus is lower for left-handed nanofibrous films, which indicates better flexibility. The difference in cell-substrate interactions might lead to different effects on cell behavior.