Light-driven phase transition of diffractive optical elements based on liquid crystal elastomers.

Diffractive optical element is advantageous for miniaturization, arraying and integration of optical systems. They have been widely used in beam shaping, diffractive imaging, generating beam arrays, spectral optimization and other aspects. Currently, the vast majority of diffractive optics are not tunable. This limits the applicability and functionality of these devices. Here we report a tunable diffractive optical element controlled by light in the visible band. The diffractive optical element consists of a square gold microarray deposited on a deformable substrate. The substrate is made of a liquid crystal elastomer. When pumped by a 532 nm laser, the substrate is deformed to change the crystal lattice. This changes the far-field diffraction pattern of the device. The proposed concept establishes a light-controlled soft platform with great potential for tunable/reconfigurable photonic devices, such as filters, couplers, holograms and structural color displays.

Roles of the cytoskeleton in human diseases.

Recently, researches have revealed the key roles of the cytoskeleton in the occurrence and development of multiple diseases, suggesting that targeting the cytoskeleton is a viable approach for treating numerous refractory diseases. The cytoskeleton is a highly structured and complex network composed of actin filaments, microtubules, and intermediate filaments. In normal cells, these three cytoskeleton components are highly integrated and coordinated. However, the cytoskeleton undergoes drastic remodeling in cytoskeleton-related diseases, causing changes in cell polarity, affecting the cell cycle, leading to senescent diseases, and influencing cell migration to accelerate cancer metastasis. Additionally, mutations or abnormalities in cytoskeletal proteins and their related proteins are closely associated with several congenital diseases. Therefore, this review summarizes the roles of the cytoskeleton in cytoskeleton-related diseases as well as its potential roles in disease treatment to provide insights regarding the physiological functions and pathological roles of the cytoskeleton.

Morphometric analysis program and quantitative positron emission tomography in presurgical localization in MRI-negative epilepsies: a simultaneous PET/MRI study.

PURPOSE: To evaluate morphometric analysis program (MAP) and quantitative positron emission tomography (QPET) in epileptogenic zone (EZ) identification using a simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) system in MRI-negative epilepsies. METHODS: Seventy-one localization-related MRI-negative epilepsies who underwent preoperative simultaneous PET/MRI examination and surgical resection were enrolled retrospectively. MAP was performed on a T1-weighted volumetric sequence, and QPET was analyzed using statistical parametric mapping (SPM) with comparison to age- and gender-matched normal controls. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MAP, QPET, MAP + QPET, and MAP/QPET in EZ localization were assessed. The correlations between surgical outcome and modalities concordant with cortical resection were analyzed. RESULTS: Forty-five (63.4%) patients had Engel I seizure outcomes. The sensitivity, specificity, PPV, and NPV of MAP were 64.4%, 69.2%, 78.3%, and 52.9%, respectively. The sensitivity, specificity, PPV, NPV of QPET were 73.3%, 65.4%, 78.6%, and 58.6%, respectively. MAP + QPET, defined as two tests concordant with cortical resection, had reduced sensitivity (53.3%) but increased specificity (88.5%) relative to individual tests. MAP/QPET, defined as one or both tests concordant with cortical resection, had increased sensitivity (86.7%) but reduced specificity (46.2%) relative to individual tests. The regions determined by MAP, QPET, MAP + QPET, or MAP/QPET concordant with cortical resection were significantly associated with the seizure-free outcome. CONCLUSION: QPET has a superior sensitivity than MAP, while the combined MAP + QPET obtained from a simultaneous PET/MRI scanner may improve the specificity of the diagnostic tests in EZ localization coupled with the preferable surgical outcome in MRI-negative epilepsies.

Combined [18F]FDG-PET with MRI structural patterns in predicting post-surgical seizure outcomes in temporal lobe epilepsy patients.

OBJECTIVES: To integrate the glucose metabolism measured using [18F]FDG PET/CT and anatomical features measured using MRI to forecast the post-surgical seizure outcomes of intractable temporal lobe epilepsy. METHODS: This retrospective study enrolled 63 patients with drug-resistant temporal lobe epilepsy. Z-transform of the patients' PET images based on comparison with a database of healthy controls, cortical thickness, and quantitative anisotropy (QA) of the diffusion spectrum imaging concordant/non-concordant with cortical resection was adopted to quantify their predictive values for the post-surgical seizure outcomes. RESULTS: The PET hypometabolism region was concordant with the surgical field in 47 of the 63 patients. Forty-two patients were seizure-free post-surgery. The sensitivity and specificity of PET in predicting seizure freedom were 89.4% and 68.8%, respectively. Complete resection of foci with overlapped PET, cortical thickness, and QA abnormalities resulted in Engel I in 27 patients, which was a good predictor of seizure freedom with an odds ratio (OR) of 19.57 (95% CI 2.38-161.25, p = 0.006). Hypometabolism involved in multiple lobes (OR = 7.18, 95% CI 1.02-50.75, p = 0.048) and foci of hypometabolism with QA/cortical thickness abnormalities outside surgical field (OR = 14.72, 95% CI 2.13-101.56, p = 0.006) were two major predictors of Engel III/IV outcomes. ORs of QA to predict Engel I and seizure recurrence were 14.64 (95% CI 2.90-73.80, p = 0.001) and 12.01 (95% CI 2.91-49.65, p = 0.001), respectively. CONCLUSION: Combined PET and structural pattern is helpful to predict the post-surgical seizure outcomes and worse outcomes of Engel III/IV. This might decrease unnecessary surgical injuries to patients who are potentially not amenable to surgery. KEY POINTS: • A combined metabolic and structural pattern is helpful to predict the post-surgical seizure outcomes. • Favorable post-surgical seizure outcome was most likely reached in patients whose hypometabolism overlapped with the structural changes. • Hypometabolism in multiple lobes and QA or cortical thickness abnormalities outside the surgical field were predictors of worse seizure outcomes of Engel III/IV.

Curcumin inhibits adverse psychological stress-induced proliferation and invasion of glioma cells via down-regulating the ERK/MAPK pathway.

Curcumin is a natural polyphenol extracted from the rhizome of Curcuma that has an important antitumour effect, but its effect on adverse psychological stress-induced tumour proliferation and invasion has not been reported to date. Here, we found that curcumin not only inhibited the growth of xenografts in chronically stressed nude mice, but also decreased the expression of matrix metalloproteinase (MMP)-2/9 and CD147 in tumour tissues. Exogenous norepinephrine (NE) was used to stimulate glioma cells to simulate the stress environment in vitro, and it was found that curcumin inhibited the NE-induced proliferation and invasion of glioma cells in a dose-dependent manner. Further research found that the effects of NE on glioma cells could lead to the activation of the mitogen-activated protein kinase (MAPK) signalling pathway through ß-adrenergic receptor, while curcumin suppressed the level of extracellular signal-regulated kinase (ERK)1/2 phosphorylation. In addition, blocking ERK1/2 expression with U0126 resulted in the down-regulated expression of CD147, which further led to the decreased expression of MMP-2 and MMP-9. Curcumin could also inhibit the expression of cyclin D1/CDK4/6 and anti-apoptotic protein Bcl-2/Bcl-XL induced by NE, and induced cell cycle changes and increased apoptosis. Therefore, curcumin may be a potential candidate drug for preventing and treating the progression of glioma induced by adverse psychological stress.

Identifying and characterizing projections from the subthalamic nucleus to the cerebellum in humans.

A connection between the subthalamic nucleus (STN) and the cerebellum which has been shown to exist in non-human primates, was recently identified in humans. However, its anatomical features, network properties and function have yet to be elucidated in humans. In the present study, we quantified the STN-cerebellum pathway in humans and explored its function based on structural observations. Anatomical features and asymmetry index (AI) were explored using high definition fiber tractography data of 30 individuals from the Massachusetts General Hospital - Human Connectome Project adult diffusion database. Pearson's correlation analysis was performed to determine the interrelationship between the subdivisions of the STN-cerebellum and the global cortical-STN connections. The pathway was visualized bilaterally in all the subjects. Typically, after setting out from the STN, the STN-cerebellum projections incorporated into the nearby corticopontine tracts, passing through the cerebral peduncle, mediated by the pontine nucleus and then connecting in two opposite directions to join the bilateral middle cerebellar peduncle. On the group averaged level, 78.03% and 62.54% of fibers from the right and left STN respectively, distributed to Crus I in the cerebellum, part of the remaining fibers projected to Crus II, with most of the fibers crossing contralaterally. According to the AI evaluation, 60% of the participants were right STN dominant, 23% were left STN dominant, and 17% were relatively symmetric. Pearson's correlation analysis further indicated that the number of pathways from mesial Brodmann area 8 to the STN (hyperdirect pathway associated with decision making) was positively correlated with the number of fibers from the right STN to Crus I. The insertion and termination, the right-side dominance, and the positive correlation with the hyperdirect pathway all suggest that the STN-cerebellum pathway might be involved in decision-making processes.

Cloud scattering influence on satellite laser altimetry data and its correction.

Satellite laser altimetry can obtain submeter or even centimeter-level surface elevation information over a large range. However, the laser will inevitably be affected by clouds during transmission through the atmosphere, which seriously affects the accuracy of altimetry. In this paper, based on laser altimetry data, cloud optical depth inversion was realized by using the Fernald method. The influence of clouds on the echo waveform data was analyzed with actual data, and a method of cloud scattering error correction was proposed. The existing error correction methods are mostly based on the results of semi-analytical Monte Carlo simulations. In observations, it is difficult to synchronously obtain the parameters required for simulation, which significantly limits the method. Therefore, a method for correcting the cloud scattering error of satellite laser altimetry data based on an exponential model is also proposed. The experimental results show that when the cloud optical depth is 0-2, the root mean square error of the model is 0.05, which can correct the height measurement deviation caused by the cloud to within 5 cm and improve the availability of the laser height measurement data affected by the cloud scattering.

Multifunctional Nanoengineered Hydrogels Consisting of Black Phosphorus Nanosheets Upregulate Bone Formation.

Tissue-engineered hydrogels have received extensive attention as their mechanical properties, chemical compositions, and biological signals can be dynamically modified for mimicking extracellular matrices (ECM). Herein, the synthesis of novel double network (DN) hydrogels with tunable mechanical properties using combinatorial screening methods is reported. Furthermore, nanoengineered (NE) hydrogels are constructed by addition of ultrathin 2D black phosphorus (BP) nanosheets to the DN hydrogels with multiple functions for mimicking the ECM microenvironment to induce tissue regeneration. Notably, it is found that the BP nanosheets exhibit intrinsic properties for induced CaP crystal particle formation and therefore improve the mineralization ability of NE hydrogels. Finally, in vitro and in vivo data demonstrate that the BP nanosheets, mineralized CaP crystal nanoparticles, and excellent mechanical properties provide a favorable ECM microenvironment to mediate greater osteogenic cell differentiation and bone regeneration. Consequently, the combination of bioactive chemical materials and excellent mechanical stimuli of NE hydrogels inspire novel engineering strategies for bone-tissue regeneration.

Automatic labeling of the fanning and curving shape of Meyer's loop for epilepsy surgery: an atlas extracted from high-definition fiber tractography.

BACKGROUND: Visual field defects caused by injury to Meyer's loop (ML) are common in patients undergoing anterior temporal lobectomy during epilepsy surgery. Evaluation of the anatomical shapes of the curving, fanning and sharp angles of ML to guide surgeries is important but still challenging for diffusion tensor imaging. We present an advanced diffusion data-based ML atlas and labeling protocol to reproduce anatomical features in individuals within a short time. METHODS: Thirty Massachusetts General Hospital-Human Connectome Project (MGH-HCP) diffusion datasets (ultra-high magnetic gradient & 512 directions) were warped to standard space. The resulting fibers were projected together to create an atlas. The anatomical features and the tractography correspondence rates were evaluated in 30 MGH-HCP individuals and local diffusion spectrum imaging data (eight healthy subjects and six hippocampal sclerosis patients). RESULTS: In the atlas, features of curves, sharp angles and fanning shapes were adequately reproduced. The distances from the anterior tip of the temporal lobe to the anterior ridge of Meyer's loop were 23.1 mm and 26.41 mm on the left and right sides, respectively. The upper and lower divisions of the ML were revealed to be twisting. Eighty-eight labeled sides were achieved, and the correspondence rates were 87.44% ± 6.92, 80.81 ± 10.62 and 72.83% ± 14.03% for MGH-HCP individuals, DSI-healthy individuals and DSI-patients, respectively. CONCLUSION: Atlas-labeled ML is comparable to high angular resolution tractography in healthy or hippocampal sclerosis patients. Therefore, rapid identification of the ML location with a single modality of T1 is practical. This protocol would facilitate functional studies and visual field protection during neurosurgery.

ZY3-02 Laser Altimeter Footprint Geolocation Prediction.

Successfully launched on 30 May 2016, ZY3-02 is the first Chinese surveying and mapping satellite equipped with a lightweight laser altimeter. Calibration is necessary before the laser altimeter becomes operational. Laser footprint location prediction is the first step in calibration that is based on ground infrared detectors, and it is difficult because the sample frequency of the ZY3-02 laser altimeter is 2 Hz, and the distance between two adjacent laser footprints is about 3.5 km. In this paper, we build an on-orbit rigorous geometric prediction model referenced to the rigorous geometric model of optical remote sensing satellites. The model includes three kinds of data that must be predicted: pointing angle, orbit parameters, and attitude angles. The proposed method is verified by a ZY3-02 laser altimeter on-orbit geometric calibration test. Five laser footprint prediction experiments are conducted based on the model, and the laser footprint prediction accuracy is better than 150 m on the ground. The effectiveness and accuracy of the on-orbit rigorous geometric prediction model are confirmed by the test results. The geolocation is predicted precisely by the proposed method, and this will give a reference to the geolocation prediction of future land laser detectors in other laser altimeter calibration test.

[Low frequency-based non-uniform sampling strategy to improve Chinese recognition in cochlear implant].

To enhance speech recognition, as well as Mandarin tone recognition in noice, we proposed a speech coding strategy called zero-crossing of fine structure in low frequency (LFFS) for cochlear implant based on low frequency non-uniform sampling (LFFS for short). In the range of frequency perceived boundary of human ear, we used zero-crossing time of the fine structure to generate the stimulus pulse sequences based on the frequency selection rule. Acoustic simulation results showed that although on quiet background the performance of LFFS was similar to continuous interleaved sampling (CIS), on the noise background the performance of LFFS in Chinese tones, words and sentences were significantly better than CIS. In addition to this, we also got better Mandarin recognition factors distribution by using the improved index distribution model. LFFS contains more tonal information which was able to effectively improve Mandarin recognition of the cochlear implant.

Injectable Nanocomposite Hydrogels with Strong Antibacterial, Osteoinductive, and ROS-Scavenging Capabilities for Periodontitis Treatment.

Injectable antibacterial and osteoinductive hydrogels have received considerable attention for promoting bone regeneration owing to their versatile functionalities. However, a current hydrogel with antibacterial, osteoinductive, and antioxidant properties by a facile method for periodontitis treatment is still missing. To overcome this issue, we designed an injectable hydrogel system (GPM) composed of gelatin, Ti3C2Tx MXene nanosheets, and poly-l-lysine using a simple enzymatic cross-linking technique. Physicochemical characterization demonstrated that the GPM hydrogel matrix exhibited excellent stability, moderate tissue adhesion ability, and good mechanical behavior. The GPM hydrogels significantly inhibited the growth of Porphyromonas gingivalis, scavenged reactive oxygen species, attenuated inflammatory responses, and enhanced bone tissue regeneration. Intriguingly, the arrangement of the junctional epithelium, alveolar bone volume, and alveolar bone height in the GPM-treated periodontal disease group recovered to that of the healthy group. Therefore, our injectable hydrogel system with versatile functions may serve as an excellent tissue scaffold for the treatment of periodontitis.

Tricarboxylic Acid Cycle Metabolite-Coordinated Biohydrogels Augment Cranial Bone Regeneration Through Neutrophil-Stimulated Mesenchymal Stem Cell Recruitment and Histone Acetylation-Mediated Osteogenesis.

Cranial bone defects remain a major clinical challenge, increasing patients' life burdens. Tricarboxylic acid (TCA) cycle metabolites play crucial roles in facilitating bone tissue regeneration. However, the development of TCA cycle metabolite-modified biomimetic grafts for skull bone regeneration still needs to be improved. The mechanism underlying the release of TCA cycle metabolites from biomaterials in regulating immune responses and mesenchymal stem cell (MSC) fate (migration and differentiation) remains unknown. Herein, this work constructs biomimetic hydrogels composed of gelatin and chitosan networks covalently cross-linked by genipin (CGG hydrogels). A series of TCA cycle metabolite-coordinated CGG hydrogels with strong mechanical and antiswelling performances are subsequently developed. Remarkably, the citrate (Na3Cit, Cit)-coordinated CGG hydrogels (CGG-Cit hydrogels) with the highest mechanical modulus and strength significantly promote skull bone regeneration in rat and murine cranial defects. Mechanistically, using a transgenic mouse model, bulk RNA sequencing, and single-cell RNA sequencing, this work demonstrates that CGG-Cit hydrogels promote Gli1+ MSC migration via neutrophil-secreted oncostatin M. Results also indicate that citrate improves osteogenesis via enhanced histone H3K9 acetylation on osteogenic master genes. Taken together, the immune microenvironment- and MSC fate-regulated CGG-Cit hydrogels represent a highly efficient and facile approach toward skull bone tissue regeneration with great potential for bench-to-bedside translation.

Responsive Liquid Crystal Network Microstructures with Customized Shapes and Predetermined Morphing for Adaptive Soft Micro-Optics.

Stimuli-responsive materials have garnered substantial interest in recent years, particularly liquid crystal networks (LCNs) with sophisticatedly designed structures and morphing capabilities. Extensive efforts have been devoted to LCN structural designs spanning from two-dimensional (2D) to three-dimensional (3D) configurations and their intricate morphing behaviors through designed alignment. However, achieving microscale structures and large-area preparation necessitates the development of novel techniques capable of facilely fabricating LCN microstructures with precise control over both overall shape and alignment, enabling a 3D-to-3D shape change. Herein, a simple and cost-effective in-cell soft lithography (ICSL) technique is proposed to create LCN microstructures with customized shapes and predesigned morphing. The ICSL technique involves two sequential steps: fabricating the desired microstructure as the template by using the photopolymerization-induced phase separation (PIPS) method and reproducing the LCN microstructures through templating. Meanwhile, surface anchoring is employed to design and achieve molecular alignment, accommodating different deformation modes. With the proposed ICSL technique, cylindrical and spherical microlens arrays (CMLAs and SMLAs) have been successfully fabricated with stimulus-driven polarization-dependent focusing effects. This technique offers distinct advantages including high customizability, large-area production, and cost-effectiveness, which pave a new avenue for extensive applications in different fields, exemplified by adaptive soft micro-optics and photonics.

Application of gelatin methacryloyl/minocycline-chitosan-nanoparticles composite hydrogel for the treatment of periodontitis.

OBJECTIVES: This study aimed to investigate the feasibility of gelatin methacryloyl (GelMA) hydrogel loa-ded with minocycline-chitosan-nanoparticles (MCN) for the treatment of periodontitis in vitro and vivo. METHODS: MCN were synthesized by ionic gel method. GelMA/MCN composite hydrogels were prepared by compounding MCN with GelMA hydrogel. The materials were characterized by transmission electron microscope, scanning electron microscopy, and Fourier transform infrared spectroscopy. The degradation behavior and drug release rates of hydrogels were evaluated. The antibacterial activity of GelMA/MCN hydrogel against Porphyromonas gingivalis was detected, and the minimum antibacterial concentration was determined. Biocompatibility and osteogenic experiments were conducted under a simulated periodontitis environment. A rat model of periodontitis was constructed to observe the therapeutic effects of GelMA/MCN hydrogel. RESULTS: MCN was successfully synthesized with a particle size of about 80 nm, while the structures of GelMA/MCN had no significant differences from GelMA. MCN and GelMA/MCN released minocycline slowly and steadily. Bacterial growth was completely inhibited when the MCN concentration was higher than or equal to 0.2 mg·mL-1. GelMA/MCN hydrogels exhibited good biocompatibility at effective antimicrobial concentrations under the simulated periodontitis environment with the enzyme. The in vivo results showed that GelMA/MCN prevented the progression of periodontitis and promoted the repair of bone defects. CONCLUSIONS: GelMA/MCN composite hydrogel can release minocycline slowly and steadily and has good antibacterial activity and biocompatibility to promote the repair of periodontitis bone defects.

Multiscale design of stiffening and ROS scavenging hydrogels for the augmentation of mandibular bone regeneration.

Although biomimetic hydrogels play an essential role in guiding bone remodeling, reconstructing large bone defects is still a significant challenge since bioinspired gels often lack osteoconductive capacity, robust mechanical properties and suitable antioxidant ability for bone regeneration. To address these challenges, we first engineered molecular design of hydrogels (gelatin/polyethylene glycol diacrylate/2-(dimethylamino)ethyl methacrylate, GPEGD), where their mechanical properties were significantly enhanced via introducing trace amounts of additives (0.5 wt%). The novel hybrid hydrogels show high compressive strength (>700 kPa), stiff modulus (>170 kPa) and strong ROS-scavenging ability. Furthermore, to endow the GPEGD hydrogels excellent osteoinductions, novel biocompatible, antioxidant and BMP-2 loaded polydopamine/heparin nanoparticles (BPDAH) were developed for functionalization of the GPEGD gels (BPDAH-GPEGD). In vitro results indicate that the antioxidant BPDAH-GPEGD is able to deplete elevated ROS levels to protect cells viability against ROS damage. More importantly, the BPDAH-GPEGD hydrogels have good biocompatibility and promote the osteo differentiation of preosteoblasts and bone regenerations. At 4 and 8 weeks after implantation of the hydrogels in a mandibular bone defect, Micro-computed tomography and histology results show greater bone volume and enhancements in the quality and rate of bone regeneration in the BPDAH-GPEGD hydrogels. Thus, the multiscale design of stiffening and ROS scavenging hydrogels could serve as a promising material for bone regeneration applications.

Nanosphere Lithography-Enabled Hybrid Ag-Cu Surface-Enhanced Raman Spectroscopy Substrates with Enhanced Absorption of Excitation Light.

We demonstrated a low-cost, highly sensitive hybrid Ag-Cu substrate with enhanced absorption for the excitation laser beam via the nanosphere lithography technique. The hybrid Ag-Cu surface-enhanced Raman spectroscopy (SERS) substrate consists of a Cu nanoarray covered with Ag nanoparticles. The geometry of the deposited Cu nanoarray is precisely determined through a self-assembly nanosphere etching process, resulting in optimized absorption for the excitation laser beam. Further Raman enhancement is achieved by incorporating plasmonic hotspots formed by dense Ag nanoparticles, grown by immersing the prepared Cu nanoarray in a silver nitrate solution. The structural design enables analytical enhancement factor of hybrid Ag-Cu SERS substrates of 1.13 × 105. The Ag-Cu SERS substrates exhibit a highly sensitive and reproducible SERS activity, with a low detection limit of 10-13 M for Rhodamine 6G detection and 10-9 M for 4,4'-Bipyridine. Our strategy could pave an effective and promising approach for SERS-based rapid detection in biosensors, environmental monitoring and food safety.

Divalent Anion-Induced Biohydrogels with High Strength, Anti-swelling, and Bioactive Capability for Enhanced Skull Bone Regeneration.

Increased intracranial pressure after traumatic brain injury (TBI) is an urgent problem in clinical practice. A pliable hydrogel is preferred for cranioplasty applications after TBI since it can protect brain tissue and promote bone healing. Nevertheless, biohydrogels for cranial bone regeneration still face challenges of poor mechanical properties, large swelling ratios, and low osteogenesis activity. Herein, inspired by Hofmeister effects, biopolymer hydrogels composed of protein and polysaccharides were treated with a Hofmeister series including a series of monovalent and divalent anions. Our results reveal that the divalent anion-cross-linked biohydrogels exhibit stronger mechanical properties and lower swelling ratios compared with monovalent-anion treated gels. Intriguingly, the divalent HPO42- anion induced biohybrid hydrogels with excellent mechanical behaviors (3.7 ± 0.58 MPa, 484 ± 76.7 kPa, and 148.3 ± 6.85 kJ/m3), anti-swelling capability (16.7%), and gradual degradation ability, significantly stimulating osteogenic differentiation and in vivo cranial bone regeneration. Overall, this study may provide new insights into the design of biomimetic hydrogels for treating cranial bone defects after TBI.

Toward Earth system modeling with resolved clouds and ocean submesoscales on heterogeneous many-core HPCs.

With the aid of the newly developed 'Sunway' heterogeneous-architecture supercomputer, which has world-leading HPC (high-performance computer) capability, a series of high-resolution coupled Earth system models (SW-HRESMs) with up to 5 km of atmosphere and 3 km of ocean have been developed. These models can meet the needs of multiscale interaction studies with different computational costs. Here we describe the progress of SW-HRESMs development, with an overview of the major advancements made by the international Earth science community in HR-ESMs. We also show the preliminary results of SW-HRESMs with regard to capturing major weather-climate extremes in the atmosphere and ocean, stressing the importance of permitted clouds and ocean submesoscale eddies in modeling tropical cyclones and eddy-mean flow interactions, and paving the way for further model development to resolve finer scales with even higher resolution and more realistic physics. Finally, in addition to increasing model resolution, the development procedure for a non-hydrostatic cloud and ocean submesoscale resolved ESM is discussed, laying out the major scientific directions of such a huge modeling advancement.