Oxygen Vacancy Defect Enhanced NIR-II Photothermal Performance of BiOxCl Nanosheets for Combined Phototherapy of Cancer Guided by Multimodal Imaging.

Narrow photo-absorption range and low carrier utilization are significant barriers that restrict the antitumor efficiency of 2D bismuth oxyhalide (BiOX, X = Cl, Br, I) nanosheets (NSs). Introducing oxygen vacancy (OV) defects can expand the absorption range and improve carrier utilization, which are crucial but also challenging. In this study, a series of BiOxCl NSs with different OV defect concentrations (x = 1, 0.7, 0.5) is developed, which shows full spectrum absorption and strong absorption in the second near-infrared region (NIR-II). Density functional theory calculations are utilized to calculate the crystal structure and density states of BiOxCl, which confirm that part of the carriers is separated by OV enhanced internal electric field to improve carrier utilization. The carriers without redox reaction can be trapped in the OV, leading to great majority of photo-generated carriers promoting the photothermal performance. Triggered by single NIR-II (1064 nm), BiOxCl NSs' bidirectional efficient utilization of carriers achieves synchronously combined phototherapy, leading to enhanced tumor ablation and multimodal diagnostic in vitro and vivo. It is thus believed that this work provides an innovative strategy to design and construct nanoplatforms of indirect band gap semiconductors for clinical phototheranostics.

Janus mesoporous organosilica/platinum nanomotors for active treatment of suppurative otitis media.

We report a Janus mesoporous organosilica/platinum (MOS/Pt) nanomotor for active targeted treatment of suppurative otitis media, as a new type of multi-functional ear drop. The efficient propulsion of MOS/Pt nanomotors in hydrogen peroxide ear-cleaning drops significantly improves their binding efficiency with Staphylococcus aureus and enhances their antibacterial efficacy.

Enhanced CT combined with texture analysis for differential diagnosis of pleomorphic adenoma and adenolymphoma.

OBJECTIVE: This study sought to evaluate the worth of the general characteristics of enhanced CT images and the histogram parameters of each stage in distinguishing pleomorphic adenoma (PA) and adenolymphoma (AL). METHODS: The imaging features and histogram parameters of preoperative enhanced CT images in 20 patients with PA and 29 patients with AL were analyzed. Tumor morphology and histogram parameters of PA and AL were compared. Area under the curve (AUC), sensitivity, and subject operational feature specificity (ROC) analysis were used to determine the differential diagnostic effect of single-stage or multi-stage parameter combinations. RESULTS: The difference in CT value and net enhancement value of arterial phase (AP) were significant (p < 0.05); Flat sweep phase (FSP), AP mean, percentiles, 10th, 50th, 90th, 99th and arterial period variance and venous phase (VP) kurtosis in the nine histogram parameters of each period (p < 0.05). An analysis of the ROC curve revealed a maximum area beneath the curve (AUC) in the 90th percentile of FSP for a single-parameter differential diagnosis to be 0.870. The diagnostic efficacy of the mean value of FSP + The 90th percentile of AP + Kurtosis of VP was the best in multi-parameter combination diagnosis, with an AUC of 0.925, and the sensitivity and specificity of 0.900 and 0.850, respectively. CONCLUSION: The histogram analysis of enhanced CT images is valuable for the differentiation of PA and AL. Moreover, the combination of single-stage parameters or multi-stage parameters can improve the differential diagnosis efficiency.

Bismuth-based two-dimensional nanomaterials for cancer diagnosis and treatment.

The intrinsic high X-ray attenuation and insignificant biological toxicity of Bi-based nanomaterials make them a category of advanced materials in oncology. Bi-based two-dimensional nanomaterials have gained rapid development in cancer diagnosis and treatment owing to their adjustable bandgap structure, high specific surface area and strong NIR absorption. In addition to the single functional cancer diagnosis and treatment modalities, Bi-based two-dimensional nanomaterials have been certified for accomplishing multi-imaging guided multifunctional synergistic cancer therapies. In this review, we summarize the recent progress including controllable synthesis, defect engineering and surface modifications of Bi-based two-dimensional nanomaterials for cancer diagnosis and treatment in the past ten years. Their medical applications in cancer imaging and therapies are also presented. Finally, we discuss the potential challenges and future research priorities of Bi-based two-dimensional nanomaterials.

Sequential targeting biomimetic nano platform for enhanced mild photothermal therapy and chemotherapy of tumor.

Tumor targeting drug delivery is of significant importance for the treatment of triple negative breast cancer (TNBC) considering the presence of appreciable amount of tumor matrix and the absence of effective targets on the tumor cells. Hence in this study, a new therapeutic multifunctional nanoplatform with improved TNBC targeting ability and efficacy was constructed and used for therapy of TNBC. Specifically, curcumin loaded mesoporous polydopamine (mPDA/Cur) nanoparticles were synthesized. Thereafter, manganese dioxide (MnO2) and a hybrid of cancer-associated fibroblasts (CAFs) membranes as well as cancer cell membranes were sequentially coated on the surface of mPDA/Cur to obtain mPDA/Cur@M/CM. It was found that two distinct kinds of cell membranes were able to endow the nano platform with homologous targeting ability, thereby achieving accurate delivery of drugs. Nanoparticles gathered in the tumor matrix can loosen the tumor matrix via the photothermal effect mediated by mPDA to rupture the physical barrier of tumor, which is conducive to the penetration and targeting of drugs to tumor cells in the deep tissues. Moreover, the existence of curcumin, MnO2 and mPDA was able to promote the apoptosis of cancer cells by promoting increased cytotoxicity, enhanced Fenton-like reaction, and thermal damage, respectively. Overall, both in vitro and in vivo results showed that the designed biomimetic nanoplatform could significantly inhibit the tumor growth and thus provide an efficient novel therapeutic strategy for TNBC.

Carbon dots nanozyme for anti-inflammatory therapy via scavenging intracellular reactive oxygen species.

Developing an efficient antioxidant for anti-inflammatory therapy via scavenging reactive oxygen species (ROS) remains a great challenge owing to the insufficient activity and stability of traditional antioxidants. Herein, we explored and simply synthesized a biocompatible carbon dots (CDs) nanozyme with excellent scavenging activity of ROS for anti-inflammatory therapy. As expected, CDs nanozyme effectively eliminate many kinds of free radicals including •OH, O2 •- , and ABTS+•. Benefiting from multienzyme activities against ROS, CDs nanozyme can decrease the levels of pro-inflammatory cytokines, resulting in good anti-inflammatory effect. Taken together, this study not only sheds light on design of bioactive antioxidants but also broadens the biomedical application of CDs in the treatment of inflammation.

The cell cortex-localized protein CHDP-1 is required for dendritic development and transport in C. elegans neurons.

Cortical actin, a thin layer of actin network underneath the plasma membranes, plays critical roles in numerous processes, such as cell morphogenesis and migration. Neurons often grow highly branched dendrite morphologies, which is crucial for neural circuit assembly. It is still poorly understood how cortical actin assembly is controlled in dendrites and whether it is critical for dendrite development, maintenance and function. In the present study, we find that knock-out of C. elegans chdp-1, which encodes a cell cortex-localized protein, causes dendrite formation defects in the larval stages and spontaneous dendrite degeneration in adults. Actin assembly in the dendritic growth cones is significantly reduced in the chdp-1 mutants. PVD neurons sense muscle contraction and act as proprioceptors. Loss of chdp-1 abolishes proprioception, which can be rescued by expressing CHDP-1 in the PVD neurons. In the high-ordered branches, loss of chdp-1 also severely affects the microtubule cytoskeleton assembly, intracellular organelle transport and neuropeptide secretion. Interestingly, knock-out of sax-1, which encodes an evolutionary conserved serine/threonine protein kinase, suppresses the defects mentioned above in chdp-1 mutants. Thus, our findings suggest that CHDP-1 and SAX-1 function in an opposing manner in the multi-dendritic neurons to modulate cortical actin assembly, which is critical for dendrite development, maintenance and function.

pH-Responsive Au@Pd bimetallic core-shell nanorods for enhanced synergistic targeted photothermal-augmented nanocatalytic therapy in the second near-infrared window.

Nanotheranostic agents based on plasmonic nanostructures with their resonance wavelengths located in the second near-infrared window (NIR-II) have gained significant attention in profound tumor photothermal therapy. However, the modulation of localized surface plasmon resonance of gold nanomaterials from the first near-infrared (NIR-I) window to the NIR-II window is still challenging. The structures and compositions of the plasmonic nanomaterials have demonstrated promising characteristics in controlling the optical properties of plasmonic nanostructures. Here, gold nanorod (Au NR) coated with an ultrathin palladium (Pd) shell was developed for tumor-targeted NIR-II photothermal-augmented nanocatalytic therapy through the combination of compositional manipulation and structural evolution strategies. These Au@Pd core-shell hybrid NRs (HNRs) were functionalized with biocompatible chitosan (CS) to acquire lower toxicity and higher stability in physiological systems. Further, Au@Pd-CS HNRs were endowed with an excellent targeting ability by conjugating with folic acid (FA). The as-synthesized Au@Pd-CS-FA HNRs show efficient and complete photothermal ablation of tumor cells upon 1064 nm laser irradiation. The remarkable photothermal conversion efficiency of 69.0% was achieved, which is superior to many reported photothermal agents activated in the NIR-II region. Excitingly, Au@Pd-CS-FA HNRs have peroxidase and catalase activities, simultaneously producing ˙OH for catalytic therapy and O2 for relieving tumor hypoxia and photodynamic therapy. Additionally, in vivo tumor photothermal therapy was carried out, where the biocompatible Au@Pd-CS-FA HNRs penetrate intensely into the tumor cells and consequently show remarkable therapeutic effects. The idea about plasmonic modulation behind the bimetallic core-shell nanostructure in this report can be extended to construct new classes of metal-based nanotheranostic agents with dual-modal combined therapy as an alternative to traditional chemotherapy.

The strategy of precise targeting and in situ oxygenating for enhanced triple-negative breast cancer chemophototherapy.

The absence of effective therapeutic targets and tumor hypoxia are the main causes of failure in the treatment of triple-negative breast cancer (TNBC). Biomimetic nanotechnology and tumor microenvironment (TME) responsiveness bring hope and opportunity to address this problem. Here, we develop a core membrane nanoplatform (HM/D-I-BL) using hollow mesoporous manganese dioxide (HM) coated with a biomimetic cancer cell membrane for enhanced chemotherapy/phototherapy via the strategy of precise drug delivery and hypoxia amelioration. Cancer cell membrane modification endows HM/D-I-BL with excellent homologous targeting and immune escape performance. Cellular uptake and fluorescence imaging studies confirmed that HM/D-I-BL can be accurately delivered to tumor sites. HM/D-I-BL also features efficient in situ O2 generation in tumors upon laser irradiation, and subsequently enhanced chemotherapy/phototherapy, pointing to its usefulness as a TME-responsive nanozyme to alleviate tumor hypoxia in the presence of H2O2. In addition, HM/D-I-BL showed good fluorescence and magnetic resonance imaging performances, which offers a reliable multimodal image-guided combination tumor therapy for precision theranostics in the future. In general, this intelligent biomimetic nanoplatform with its homotypic tumor targeting, in situ alleviation of tumor hypoxia and synergetic chemophototherapy would open up a new dimension for the precision treatment of TNBC.

Fabrication of super-hydrophilic and highly open-porous poly (lactic acid) scaffolds using supercritical carbon dioxide foaming.

Porous poly (lactic acid) (PLA)-based scaffolds have been widely used as a promising product in tissue engineering. However, it is still a challenge to prepare the PLA-based scaffolds with high expansion ratio, good hydrophilicity, and excellent cytocompatibility by a green and cost-effective fabrication approach. Herein, we prepared porous PLA-based scaffolds using carbon dioxide (CO2) as the physical foaming agent. To improve the hydrophilicity and foaming behavior of PLA, poly (ethylene glycol) (PEG) was selected as a good additive to blend with PLA. It revealed that the introduction of PEG could improve the foaming behavior of PLA and promote the formation of opening cells via reducing the matrix strength of PLA. The obtained 3D PLA/PEG scaffolds exhibited high expansion ratio (9.1), high open-cell content (95.2%), and super-hydrophilicity (water contact angle 0°). Additionally, the mouse fibroblast NIH/3T3 cells with live/dead cell fluorescence staining assay was utilized to examine the biocompatibility of PLA/PEG scaffolds. The result demonstrated that the proliferation ratio of NIH/3 T3 cells on the surface of PLA/PEG scaffolds was higher than that of PLA scaffolds, indicating that the highly interconnected cell structure was conducive to cell adhesion and attachment. Consequently, such hydrophilic open-cell structure obtained by adding PEG into PLA possesses great potential for use in tissue engineering.

A tumor microenvironment dual responsive contrast agent for contrary contrast-magnetic resonance imaging and specific chemotherapy of tumors.

Development of magnetic resonance imaging (MRI) contrast agents (CAs) is still one of the research hotspots due to the inherent limitations of T1- or T2-weighted CAs and T1/T2 dual-mode CAs. To dramatically enhance the MRI contrast between tumors and normal tissues, we propose a new concept of contrary contrast-MRI (CC-MRI), whose specific definition is that CC-MRI CAs present a positive or negative signal at normal tissues, but show contrary signals at diseased tissues. To realize CC-MRI of tumors, we designed and developed a tumor microenvironment (TME) dual responsive CA (i.e., SA-FeGdNP-DOX@mPEG), which is almost not responsive under normal physiological conditions, but highly responsive to the acidic and reductive TME. Our SA-FeGdNP-DOX@mPEG shows a negative MRI signal under normal physiological conditions due to the high r2 value (336.9 mM-1 s-1) and high r2/r1 ratio (18.4), but switches to a positive MRI signal in the TME because of the high r1 value (20.32 mM-1 s-1) and low r2/r1 ratio (7.2). Our TME dual responsive SA-FeGdNP-DOX@mPEG significantly enhanced the contrast of MR images between tumors and livers, and the ΔSNR difference reached 501%. In addition, our SA-FeGdNP-DOX2@mPEG2 with tumor targetability and controlled DOX release responding to the TME was also used for tumor-specific chemotherapy with reduced side effects.

Dendritic Polyglycerol-Conjugated Gold Nanostars for Metabolism Inhibition and Targeted Photothermal Therapy in Breast Cancer Stem Cells.

Breast cancer stem cells (CSCs) are believed to be responsible for tumor initiation, invasion, metastasis, and recurrence, which lead to treatment failure. Thus, developing effective CSC-targeted therapeutic strategies is crucial for enhancing therapeutic efficacy. In this work, GNSs-dPG-3BP, TPP, and HA nanocomposite particles are developed by simultaneously conjugating hexokinase 2 (HK2) inhibitor 3-bromopyruvate (3BP), mitochondrial targeting molecule triphenyl phosphonium (TPP), and CSCs targeting agent hyaluronic acid (HA) onto gold nanostars-dendritic polyglycerol (GNSs-dPG) nanoplatforms for efficient eradication of CSCs. The nanocomposite particles possess good biocompatibility and exhibit superior mitochondrial-bound HK2 binding ability via 3BP to inhibit metabolism, and further induce cellular apoptosis by releasing the cytochrome c. Therefore, it enhanced the therapeutic efficacy of CSCs-specific targeted photothermal therapy (PTT), and achieved a synergistic effect for the eradication of breast CSCs. After administration of the synergistic treatment, the self-renewal of breast CSCs and the stemness gene expression are suppressed, CSC-driven mammosphere formation is diminished, the in vivo tumor growth is effectively inhibited, and CSCs are eradicated. Altogether, GNSs-dPG-3BP, TPP, and HA nanocomposite particles have been developed, which will provide a novel strategy for precise and highly efficient targeted eradication of CSCs.

Gd2O3/b-TiO2 composite nanoprobes with ultra-high photoconversion efficiency for MR image-guided NIR-II photothermal therapy.

Photothermal therapy (PTT), as an important noninvasive and effective tumor treatment method, has been extensively developed into a powerful cancer therapeutic technique. Nevertheless, the low photothermal conversion efficiency and the limited tissue penetration of typical photothermal therapeutic agents in the first near-infrared (NIR-I) region (700-950 nm) are still the major barriers for further clinical application. Here, we proposed an organic/inorganic dual-PTT agent of synergistic property driven by polydopamine-modified black-titanium dioxide (b-TiO2@PDA) with excellent photoconversion efficiency in the second NIR (NIR-II) region (1000-1500 nm). More specifically, the b-TiO2 treated with sodium borohydride produced excessive oxygen vacancies resulting in oxygen vacancy band that narrowed the b-TiO2 band gap, and the small band gap led to NIR-II region wavelength (1064 nm) absorbance. Furthermore, the combination of defect energy level trapping carrier recombination heat generation and conjugate heat generation mechanism, significantly improved the photothermal performance of the PTT agent based on b-TiO2. The photothermal properties characterization indicated that the proposed dual-PTT agent possesses excellent photothermal performance and ultra-high photoconversion efficiency of 64.9% under 1064 nm laser irradiation, which can completely kill esophageal squamous cells. Meanwhile, Gd2O3 nanoparticles, an excellent magnetic resonance imaging (MRI) agent, were introduced into the nanosystem with similar dotted core-shell structure to enable the nanosystem achieve real-time MRI-monitored cancer therapeutic performance. We believe that this integrated nanotherapeutic system can not only solve the application of PTT in the NIR-II region, but also provide certain theoretical guidance for the clinical diagnosis and treatment of esophageal cancer.

The Role of Blood Pressure in Carotid Plaque Incidence: Interactions With Body Mass Index, Age, and Sex-Based on a 7-Years Cohort Study.

Background: Although high blood pressure (BP) is a risk factor for carotid plaque, its long-term prognostic value might be underestimated due to its confounding interactions with BMI, age, and gender. Therefore, we conducted a 7-year prospective cohort study to evaluate the prognostic value of BP for the incidence of carotid plaque. Methods: The subjects enrolled in 2011 were free of carotid plaque at baseline and were followed up in 2018. Multivariate Cox proportional-hazards models were used to evaluate the association between BP and carotid plaque incidence. Results: During the follow-up study, the incidence of carotid plaque was 36.5%. The significant positive linear trend showed that subjects with higher BP levels at baseline were more likely to develop carotid plaques at the end. Especially in the female subpopulation, after confounders being adjusted, the carotid plaque was associated with higher BP (adjusted HR 1.52, 95% CI 1.02-2.26), pulse pressure (PP) (adjusted HR 1.15, 95% CI 0.76-1.75), and mean arterial pressure (MAP) (adjusted HR 1.44, 95% CI 1.00-2.08). The adjusted HRs of hypertension, PP, and MAP (HR 27.71, 95% CI 2.27-338.64; HR 14.47, 95% CI 1.53-137.18; HR 9.97, 95% CI 1.29-77.28) were significantly higher after the potential antagonistic interactions between BP categorical indicators and age being adjusted, respectively. Conclusion: High BP indicators might be associated with higher HRs of carotid plaque after adjusting interactions between BP indicators and BMI, age, and gender, which suggests that the incidence of carotid plaque in female adults with high BP indicators might increase significantly with the increase of age.

Retinoic Acid-Loaded Dendritic Polyglycerol-Conjugated Gold Nanostars for Targeted Photothermal Therapy in Breast Cancer Stem Cells.

The existence of cancer stem cells (CSCs) poses a major obstacle for the success of current cancer therapies, especially the fact that non-CSCs can spontaneously turn into CSCs, which lead to the failure of the treatment and tumor relapse. Therefore, it is very important to develop effective strategies for the eradication of the CSCs. In this work, we have developed a CSCs-specific targeted, retinoic acid (RA)-loaded gold nanostars-dendritic polyglycerol (GNSs-dPG) nanoplatform for the efficient eradication of CSCs. The nanocomposites possess good biocompatibility and exhibit effective CSCs-specific multivalent targeted capability due to hyaluronic acid (HA) decorated on the multiple attachment sites of the bioinert dendritic polyglycerol (dPG). With the help of CSCs differentiation induced by RA, the self-renewal of breast CSCs and tumor growth were suppressed by the high therapeutic efficacy of photothermal therapy (PTT) in a synergistic inhibitory manner. Moreover, the stemness gene expression and CSC-driven tumorsphere formation were significantly diminished. In addition, the in vivo tumor growth and CSCs were also effectively eliminated, which indicated superior anticancer activity, effective CSCs suppression, and prevention of relapse. Taken together, we developed a CSCs-specific targeted, RA-loaded GNSs-dPG nanoplatform for the targeted eradication of CSCs and for preventing the relapse.

Sporadic hemangioblastoma of the kidney: a clinicopathologic study of three cases and a literature review.

Much attention has been paid to renal hemangioblastoma, but there are still challenges in its differential diagnosis. Three cases (2 men, 1 woman; age: 40-56 years) presented with renal tumors. The tumors were surrounded by a thick fibrous capsule, well-demarcated from the surrounding renal parenchyma, and composed of sheets or nests of polygonal to short spindle-shaped tumor cells with a rich capillary network. In cases 1 and 3, the large polygonal tumor cells contained abundant pale or eosinophilic cytoplasm, and some possessed intracytoplasmic lipid vacuoles. In case 2, tumor cells were characterized by a uniform size, mild, clear, or lightly stained cytoplasm, and typical "clear cell" appearance. Immunohistochemistry revealed that the polygonal stromal cells were strongly and diffusely positive for α-inhibin, neuron-specific enolase (NSE), S100 protein, and vimentin. Cluster of differentiation (CD)10 and paired box gene (PAX)8 were positive, while epithelial membrane antigen (EMA) and cytokeratin (CK) were focally positive in case 3. CD34 and CD31 outlined the contours and distribution of the vascular networks. Renal hemangioblastoma is rare and prone to misdiagnosis; more attention should be paid to the morphological features and reasonable application of immunohistochemistry in the diagnosis of hemangioblastoma.

A 4D single-cell protein atlas of transcription factors delineates spatiotemporal patterning during embryogenesis.

Complex biological processes such as embryogenesis require precise coordination of cell differentiation programs across both space and time. Using protein-fusion fluorescent reporters and four-dimensional live imaging, we present a protein expression atlas of transcription factors (TFs) mapped onto developmental cell lineages during Caenorhabditis elegans embryogenesis, at single-cell resolution. This atlas reveals a spatiotemporal combinatorial code of TF expression, and a cascade of lineage-specific, tissue-specific and time-specific TFs that specify developmental states. The atlas uncovers regulators of embryogenesis, including an unexpected role of a skin specifier in neurogenesis and the critical function of an uncharacterized TF in convergent muscle differentiation. At the systems level, the atlas provides an opportunity to model cell state-fate relationships, revealing a lineage-dependent state diversity within functionally related cells and a winding trajectory of developmental state progression. Collectively, this single-cell protein atlas represents a valuable resource for elucidating metazoan embryogenesis at the molecular and systems levels.

An intelligent T1-T2 switchable MRI contrast agent for the non-invasive identification of vulnerable atherosclerotic plaques.

Unlike stable atherosclerotic plaques, vulnerable plaques are very likely to cause serious cardio-cerebrovascular diseases. Meanwhile, how to non-invasively identify vulnerable plaques at early stages has been an urgent but challenging problem in clinical practices. Here, we propose a macrophage-targeted and in situ stimuli-triggered T1-T2 switchable magnetic resonance imaging (MRI) nanoprobe for the non-invasive diagnosis of vulnerable plaques. Precisely, single-dispersed iron oxide nanoparticles (IONPs) modified with hyaluronic acid (HA), denoted as IONP-HP, show macrophage targetability and T1 MRI enhancement (r2/r1 = 3.415). Triggered by the low pH environment of macrophage lysosomes, the single-dispersed IONP-HP transforms into a cluster analogue, which exhibits T2 MRI enhancement (r2/r1 = 13.326). Furthermore, an in vivo switch of T1-T2 enhancement modes shows that the vulnerable plaques exhibit strong T1 enhancement after intravenous administration of the nanoprobe, followed by a switch to T2 enhancement after 9 h. In contrast, stable plaques show only slight T1 enhancement but without T2 enhancement. It is therefore imperative that the intelligent and novel nanoplatform proposed in this study achieves a substantial non-invasive diagnosis of vulnerable plaques by means of a facile but effective T1-T2 switchable process, which will significantly contribute to the application of materials science in solving clinical problems.

Single-cell dynamics of chromatin activity during cell lineage differentiation in Caenorhabditis elegans embryos.

Elucidating the chromatin dynamics that orchestrate embryogenesis is a fundamental question in developmental biology. Here, we exploit position effects on expression as an indicator of chromatin activity and infer the chromatin activity landscape in every lineaged cell during Caenorhabditis elegans early embryogenesis. Systems-level analyses reveal that chromatin activity distinguishes cellular states and correlates with fate patterning in the early embryos. As cell lineage unfolds, chromatin activity diversifies in a lineage-dependent manner, with switch-like changes accompanying anterior-posterior fate asymmetry and characteristic landscapes being established in different cell lineages. Upon tissue differentiation, cellular chromatin from distinct lineages converges according to tissue types but retains stable memories of lineage history, contributing to intra-tissue cell heterogeneity. However, the chromatin landscapes of cells organized in a left-right symmetric pattern are predetermined to be analogous in early progenitors so as to pre-set equivalent states. Finally, genome-wide analysis identifies many regions exhibiting concordant chromatin activity changes that mediate the co-regulation of functionally related genes during differentiation. Collectively, our study reveals the developmental and genomic dynamics of chromatin activity at the single-cell level.