Evidence of scaling advantage for the quantum approximate optimization algorithm on a classically intractable problem.

The quantum approximate optimization algorithm (QAOA) is a leading candidate algorithm for solving optimization problems on quantum computers. However, the potential of QAOA to tackle classically intractable problems remains unclear. Here, we perform an extensive numerical investigation of QAOA on the low autocorrelation binary sequences (LABS) problem, which is classically intractable even for moderately sized instances. We perform noiseless simulations with up to 40 qubits and observe that the runtime of QAOA with fixed parameters scales better than branch-and-bound solvers, which are the state-of-the-art exact solvers for LABS. The combination of QAOA with quantum minimum finding gives the best empirical scaling of any algorithm for the LABS problem. We demonstrate experimental progress in executing QAOA for the LABS problem using an algorithm-specific error detection scheme on Quantinuum trapped-ion processors. Our results provide evidence for the utility of QAOA as an algorithmic component that enables quantum speedups.

Agent-based modeling of stress anisotropy driven nematic ordering in growing biofilms.

Living active collectives have evolved with remarkable self-patterning capabilities to adapt to the physical and biological constraints crucial for their growth and survival. However, the intricate process by which complex multicellular patterns emerge from a single founder cell remains elusive. In this study, we utilize an agent-based model, validated through single-cell microscopy imaging, to track the three-dimensional (3D) morphodynamics of cells within growing bacterial biofilms encased by agarose gels. The confined growth conditions give rise to a spatiotemporally heterogeneous stress landscape within the biofilm. In the core of the biofilm, where high hydrostatic and low shear stresses prevail, cell packing appears disordered. In contrast, near the gel-cell interface, a state of high shear stress and low hydrostatic stress emerges, driving nematic ordering, albeit with a time delay inherent to shear stress relaxation. Strikingly, we observe a robust spatiotemporal correlation between stress anisotropy and nematic ordering within these confined biofilms. This correlation suggests a mechanism whereby stress anisotropy plays a pivotal role in governing the spatial organization of cells. The reciprocity between stress anisotropy and cell ordering in confined biofilms opens new avenues for innovative 3D mechanically guided patterning techniques for living active collectives, which hold significant promise for a wide array of environmental and biomedical applications.

Exponentially Enhanced Non-Hermitian Cooling.

Certain non-Hermitian systems exhibit the skin effect, whereby the wave functions become exponentially localized at one edge of the system. Such exponential amplification of wavefunction has received significant attention due to its potential applications in, e.g., classical and quantum sensing. However, the opposite edge of the system, featured by exponentially suppressed wave functions, remains largely unexplored. Leveraging this phenomenon, we introduce a non-Hermitian cooling mechanism, which is fundamentally distinct from traditional refrigeration or laser cooling techniques. Notably, non-Hermiticity will not amplify thermal excitations, but rather redistribute them. Hence, thermal excitations can be cooled down at one edge of the system, and the cooling effect can be exponentially enhanced by the number of auxiliary modes, albeit with a lower bound that depends on the dissipative interaction with the environment. Non-Hermitian cooling does not rely on intricate properties such as exceptional points or nontrivial topology, and it can apply to a wide range of excitations.

Co-exposure to lead and high-fat diet aggravates systemic inflammation in mice by altering gut microbiota and the LPS/TLR4 pathway.

This study reports the toxicity of Pb exposure on systemic inflammation in high-fat-diet (HFD) mice and the potential mechanisms. Results indicated that Pb exacerbated intestinal barrier damage and increased serum levels of lipopolysaccharide (LPS) and diamine oxidase in HFD mice. Elevated LPS activates the colonic and ileal LPS-TLR4 inflammatory signaling pathway and further induces hepatic and adipose inflammatory expression. The 16S rRNA gene sequencing results showed that Pb promoted the abundance of potentially harmful and LPS-producing bacteria such as Coriobacteriaceae_UCG-002, Alloprevotella, and Oscillibacter in the intestines of HFD mice, and their abundance was positively correlated with LPS levels. Additionally, Pb inhibited the abundance of the beneficial bacteria Akkermansia, resulting in lower levels of the metabolite short-chain fatty acids (SCFAs). Meanwhile, Pb inhibited adenosine 5'-monophosphate-activated protein kinase signaling-mediated lipid metabolism pathways, promoting hepatic lipid accumulation. The above results suggest that Pb exacerbates systemic inflammation and lipid disorders in HFD mice by altering the gut microbiota, intestinal barrier, and the mediation of metabolites LPS and SCFAs. Our study provides potential novel mechanisms of human health related to Pb-induced metabolic damage and offers new evidence for a comprehensive assessment of Pb risk.

Structured 3' UTRs destabilize mRNAs in plants.

BACKGROUND: RNA secondary structure (RSS) can influence the regulation of transcription, RNA processing, and protein synthesis, among other processes. 3' untranslated regions (3' UTRs) of mRNA also hold the key for many aspects of gene regulation. However, there are often contradictory results regarding the roles of RSS in 3' UTRs in gene expression in different organisms and/or contexts. RESULTS: Here, we incidentally observe that the primary substrate of miR159a (pri-miR159a), when embedded in a 3' UTR, could promote mRNA accumulation. The enhanced expression is attributed to the earlier polyadenylation of the transcript within the hybrid pri-miR159a-3' UTR and, resultantly, a poorly structured 3' UTR. RNA decay assays indicate that poorly structured 3' UTRs could promote mRNA stability, whereas highly structured 3' UTRs destabilize mRNA in vivo. Genome-wide DMS-MaPseq also reveals the prevailing inverse relationship between 3' UTRs' RSS and transcript accumulation in the transcriptomes of Arabidopsis, rice, and even human. Mechanistically, transcripts with highly structured 3' UTRs are preferentially degraded by 3'-5' exoribonuclease SOV and 5'-3' exoribonuclease XRN4, leading to decreased expression in Arabidopsis. Finally, we engineer different structured 3' UTRs to an endogenous FT gene and alter the FT-regulated flowering time in Arabidopsis. CONCLUSIONS: We conclude that highly structured 3' UTRs typically cause reduced accumulation of the harbored transcripts in Arabidopsis. This pattern extends to rice and even mammals. Furthermore, our study provides a new strategy of engineering the 3' UTRs' RSS to modify plant traits in agricultural production and mRNA stability in biotechnology.

Injectable ultrasound-powered bone-adhesive nanocomposite hydrogel for electrically accelerated irregular bone defect healing.

The treatment of critical-size bone defects with irregular shapes remains a major challenge in the field of orthopedics. Bone implants with adaptability to complex morphological bone defects, bone-adhesive properties, and potent osteogenic capacity are necessary. Here, a shape-adaptive, highly bone-adhesive, and ultrasound-powered injectable nanocomposite hydrogel is developed via dynamic covalent crosslinking of amine-modified piezoelectric nanoparticles and biopolymer hydrogel networks for electrically accelerated bone healing. Depending on the inorganic-organic interaction between the amino-modified piezoelectric nanoparticles and the bio-adhesive hydrogel network, the bone adhesive strength of the prepared hydrogel exhibited an approximately 3-fold increase. In response to ultrasound radiation, the nanocomposite hydrogel could generate a controllable electrical output (-41.16 to 61.82 mV) to enhance the osteogenic effect in vitro and in vivo significantly. Rat critical-size calvarial defect repair validates accelerated bone healing. In addition, bioinformatics analysis reveals that the ultrasound-responsive nanocomposite hydrogel enhanced the osteogenic differentiation of bone mesenchymal stem cells by increasing calcium ion influx and up-regulating the PI3K/AKT and MEK/ERK signaling pathways. Overall, the present work reveals a novel wireless ultrasound-powered bone-adhesive nanocomposite hydrogel that broadens the therapeutic horizons for irregular bone defects.

Characteristics and evaluation of heavy metal pollution in a soil-wheat system of an arid oasis city in northwest China.

In this paper, the Cu and Ni accumulation and contamination levels in agricultural soils and wheat around a smelter in Jinchang City in northwest China were investigated with a combination of field investigations and indoor analytical tests, using a soil-wheat system as the study area. The average Cu and Ni contents in the soil were 119.50 mg kg-1 and 123.40 mg kg-1, respectively, both of which exceeded the local soil background values. The Cu and Ni contents in 46.15% o and 26.92% of sampling sites, respectively, exceeded the screening values for soil contamination risk in agricultural land in China. The average Cu content in different parts of wheat was in the order of roots (24.22 mg kg-1) > leaves (20.11 mg kg-1) > husks (5.51 mg kg-1) > grains (4.05 mg kg-1) > stalks (3.74 mg kg-1). Furthermore, the average Ni content ranked as leaves (24.64 mg kg-1) > roots (21.12 mg kg-1) > husks (6.95 mg kg-1) > stalks (1.75 mg kg-1) > grains (0.38 mg kg-1). The health risk evaluation showed that with average hazard index values of 0.88 for adults and 1.04 for children for Cu and Ni in wheat grain, wheat in this region is unlikely to pose a health risk to adults but may pose a lesser health risk to children. The Ni bio-concentration and translocation factors in the husk and leaves of wheat were greater than those of Cu and smaller than those of Cu in the other parts of wheat. The results of this study provide basic data for the remediation of heavy metal contamination in local agricultural soils.

Piezo-enhanced near infrared photocatalytic nanoheterojunction integrated injectable biopolymer hydrogel for anti-osteosarcoma and osteogenesis combination therapy.

Preventing local tumor recurrence while promoting bone tissue regeneration is an urgent need for osteosarcoma treatment. However, the therapeutic efficacy of traditional photosensitizers is limited, and they lack the ability to regenerate bone. Here, a piezo-photo nanoheterostructure is developed based on ultrasmall bismuth/strontium titanate nanocubes (denoted as Bi/SrTiO3), which achieve piezoelectric field-driven fast charge separation coupling with surface plasmon resonance to efficiently generate reactive oxygen species. These hybrid nanotherapeutics are integrated into injectable biopolymer hydrogels, which exhibit outstanding anticancer effects under the combined irradiation of NIR and ultrasound. In vivo studies using patient-derived xenograft models and tibial osteosarcoma models demonstrate that the hydrogels achieve tumor suppression with efficacy rates of 98.6 % and 67.6 % in the respective models. Furthermore, the hydrogel had good filling and retention capabilities in the bone defect region, which exerted bone repair therapeutic efficacy by polarizing and conveying electrical stimuli to the cells under mild ultrasound radiation. This study provides a comprehensive and clinically feasible strategy for the overall treatment and tissue regeneration of osteosarcoma.

How intrinsically disordered proteins order plant gene silencing.

Intrinsically disordered proteins (IDPs) and proteins with intrinsically disordered regions (IDRs) possess low sequence complexity of amino acids and display non-globular tertiary structures. They can act as scaffolds, form regulatory hubs, or trigger biomolecular condensation to control diverse aspects of biology. Emerging evidence has recently implicated critical roles of IDPs and IDR-contained proteins in nuclear transcription and cytoplasmic post-transcriptional processes, among other molecular functions. We here summarize the concepts and organizing principles of IDPs. We then illustrate recent progress in understanding the roles of key IDPs in machineries that regulate transcriptional and post-transcriptional gene silencing (PTGS) in plants, aiming at highlighting new modes of action of IDPs in controlling biological processes.

Correction of Sunken Upper Eyelid in Asian Blepharoplasty Based on Anatomical and Histological Study of Orbital Fat Fascia Flap.

OBJECTIVES: To explore the clinical application of orbital fat fascia flap in the correction of sunken upper eyelid in Asian blepharoplasty based on anatomical and histological research. METHODS: Observe the histological structure of the orbital fat and its fascia vascularity through cadaver anatomy and histological sections of 10 cadavers. Based on the anatomical and histological characteristics of orbital fat, 36 patients with mild to moderate sunken upper eyelids were corrected by transposition of orbital fat fascia flap with preservation of fascia vascular pedicle. During the operation, the lateral part of the central cellulite of orbital fat was separated longitudinally and transferred to the sunken place to correct the sunken upper eyelid. RESULTS: Anatomy and histology show that the orbital fat was located between the anterior layer of the levator aponeurosis and the posterior layer of the orbital septum and was separated into fat lobules by many fibrous septa. The blood vessels move forward from back to front along the orbital fat interlobular septum, and the blood vessels in the capsule below the orbital fat are abundant. Clinical results showed that the shape of the sunken upper eyelid was significantly improved in 35 cases after correction with this method during the postoperative follow-up from 9 months to 18 months. The mean sunken depth improved from 6.2mm (±1.0 mm) preoperatively to 2.2mm (±0.9 mm) at the last follow-up with a statistical significance. And only 1 case had partial depression in the unilateral eyelid and received autologous granular fat transplantation with satisfactory postoperative results. CONCLUSION: The transposition of orbital fat fascia flap with longitudinal separation and preservation of fascia vascular pedicle can better correct the sunken upper eyelid during blepharoplasty, and the long-term effect is stable, which is worthy of clinical promotion. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Oxidative stress and pro-inflammatory cytokines following perchloroethylene exposure in young female dry-cleaning workers.

BACKGROUND: The involvement of Perchloroethylene (PCE) in the development of autoimmune diseases has been reported. However, few studies investigated immunotoxicity in PCE-exposed workers. OBJECTIVE: To study changes in the oxidative stress and cytokine profile of young female dry-cleaning workers exposed to PCE. METHODS: Thirty-eight exposed workers and 38 unexposed controls were recruited. All the participants were young nonsmoker females. Individual interviews were conducted by a physician. Blood samples were collected and hematological tests were performed by an automated Coulter Counter. Plasma PCE levels were determined using gas chromatography/flame ionization detection. Plasma total antioxidant capacity (TAC), Catalase (CAT), Superoxide dismutase (SOD), and Malondialdehyde (MDA) levels were measured using the colorimetric method. The levels of plasma cytokines interleukin-1ß (IL-1ß), IL-2, IL-4, IL-6, IL-8, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured by commercially kits. RESULTS: The levels of plasma PCE averaged 561±96 ng/ml in the exposed group compared with 1.3±0.5 ng/ml in the controls. The hematological tests failed to find abnormalities in the exposed workers. Exposed workers presented significantly increased plasma levels of MDA, SOD and CAT. There were no significant differences between the two groups for level of plasma TAC. Significantly increased plasma IL-1ß and TNF-α and decreased IL-2 and IL-8 levels were seen in the exposed workers. There were no significant differences between the two groups for IL-4, IL-6, and IFN-γ. CONCLUSION: PCE exposure resulted in changed cytokine profile in dry-cleaning workers, suggesting the potential immunotoxicity of PCE at low exposure levels.

Environmental Cadmium Exposure Exacerbated Bone Loss in NAFLD Mice.

Due to rapid urbanization and industrialization, Cadmium (Cd) contamination is widespread. Meanwhile, the prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing. Cd is linked to bone damage. However, the osteotoxicity of environmental Cd exposure in NAFLD remains unclear. Therefore, this study aimed to investigate the effects and potential mechanisms of Cd on bone metabolism in NAFLD mice. NAFLD mice were treated with 50 mg/L cadmium chloride in drinking water for 12 weeks. Bone microstructures were scanned by Micro-CT. Liver lipid droplets and fibrosis were measured by histopathological staining. Insulin tolerance tests were performed in mice. RT-PCR and Western blot were performed to analyse hepatic inflammation factors. Results show no damage in healthy mice exposed to Cd. However, Cd exacerbated liver fibrosis and significantly reduced cancellous bone mineral density and decreased the number and thickness of trabecular bone in NAFLD mice. Additionally, the morphology of trabecular bone transformed from a plate structure to a rod structure in NAFLD mice after Cd exposure. The underlying mechanism appears to be related to the Cd-induced direct or indirect toxicity. Exacerbated liver fibrosis, increased inflammatory factors (TGF-ß and IL-1ß), and reduced lecithin-cholesterol acyltransferase (LCAT) and insulin-like growth factor-1 (IGF-1) might contribute to bone damages. Collectively, our study illustrates that despite lower dosing Cd exposure did not induce bone damages in healthy mice, Cd caused bone loss in NAFLD mice. Therefore, it is recommended that individuals with metabolic disorders should avoid working in Cd pollution environment and consuming cadmium-contaminated food and water.

H3.1K27me1 loss confers Arabidopsis resistance to Geminivirus by sequestering DNA repair proteins onto host genome.

The H3 methyltransferases ATXR5 and ATXR6 deposit H3.1K27me1 to heterochromatin to prevent genomic instability and transposon re-activation. Here, we report that atxr5 atxr6 mutants display robust resistance to Geminivirus. The viral resistance is correlated with activation of DNA repair pathways, but not with transposon re-activation or heterochromatin amplification. We identify RAD51 and RPA1A as partners of virus-encoded Rep protein. The two DNA repair proteins show increased binding to heterochromatic regions and defense-related genes in atxr5 atxr6 vs wild-type plants. Consequently, the proteins have reduced binding to viral DNA in the mutant, thus hampering viral amplification. Additionally, RAD51 recruitment to the host genome arise via BRCA1, HOP2, and CYCB1;1, and this recruitment is essential for viral resistance in atxr5 atxr6. Thus, Geminiviruses adapt to healthy plants by hijacking DNA repair pathways, whereas the unstable genome, triggered by reduced H3.1K27me1, could retain DNA repairing proteins to suppress viral amplification in atxr5 atxr6.

Physical forces guide curvature sensing and cell migration mode bifurcating.

The ability of cells to sense and adapt to curvy topographical features has been implicated in organ morphogenesis, tissue repair, and tumor metastasis. However, how individual cells or multicellular assemblies sense and differentiate curvatures remains elusive. Here, we reveal a curvature sensing mechanism in which surface tension can selectively activate either actin or integrin flows, leading to bifurcating cell migration modes: focal adhesion formation that enables cell crawling at convex front edges and actin cable assembly that pulls cells forward at concave front edges. The molecular flows and curved front morphogenesis are sustained by coordinated cellular tension generation and transmission. We track the molecular flows and mechanical force transduction pathways by a phase-field model, which predicts that multicellular curvature sensing is more efficient than individual cells, suggesting collective intelligence of cells. The unique ability of cells in curvature sensing and migration mode bifurcating may offer insights into emergent collective patterns and functions of living active systems at different length scales.

Electro-mechanical coupling directs endothelial activities through intracellular calcium ion deployment.

Conversion between mechanical and electrical cues is usually considered unidirectional in cells with cardiomyocytes being an exception. Here, we discover a material-induced external electric field (Eex) triggers an electro-mechanical coupling feedback loop in cells other than cardiomyocytes, human umbilical vein endothelial cells (HUVECs), by opening their mechanosensitive Piezo1 channels. When HUVECs are cultured on patterned piezoelectric materials, the materials generate Eex (confined at the cellular scale) to polarize intracellular calcium ions ([Ca2+]i), forming a built-in electric field (Ein) opposing Eex. Furthermore, the [Ca2+]i polarization stimulates HUVECs to shrink their cytoskeletons, activating Piezo1 channels to induce influx of extracellular Ca2+ that gradually increases Ein to balance Eex. Such an electro-mechanical coupling feedback loop directs pre-angiogenic activities such as alignment, elongation, and migration of HUVECs. Activated calcium dynamics during the coupling further modulate the downstream angiogenesis-inducing eNOS/NO pathway. These findings lay a foundation for developing new ways of electrical stimulation-based disease treatment.

Application of Surgery Combined With Platelet-Rich Plasma in the Correction of Mild to Moderate Blepharoptosis.

OBJECTIVES: To explore the effect of surgery combined with platelet-rich plasma (PRP) in the correction of mild to moderate blepharoptosis. METHODS: A retrospective study was conducted on 36 patients with bilateral mild to moderate blepharoptosis from January 2021 to January 2023, which were corrected by surgery combined with local multi-point injection of PRP. The postoperative effect was observed, and the incidence of postoperative complications and patient satisfaction were calculated. RESULTS: Postoperative follow-up was 3 months to 2 years. Thirty-five cases of blepharoptosis were well corrected; 1 case (2.8%) had insufficient correction and was corrected by reoperation. There were no obvious complications such as incomplete closure, conjunctival prolapse, and exposed keratitis in 36 patients. All patients were satisfied. CONCLUSION: Surgery combined with PRP is effective in the correction of mild to moderate blepharoptosis with few complications and high satisfaction. As far as we know, this is the first time to apply PRP in the correction of blepharoptosis, which may provide a new idea for the clinical treatment of blepharoptosis and is worth popularizing.

Manipulating solid-state spin concentration through charge transport.

Solid-state defects are attractive platforms for quantum sensing and simulation, e.g., in exploring many-body physics and quantum hydrodynamics. However, many interesting properties can be revealed only upon changes in the density of defects, which instead is usually fixed in material systems. Increasing the interaction strength by creating denser defect ensembles also brings more decoherence. Ideally one would like to control the spin concentration at will while keeping fixed decoherence effects. Here, we show that by exploiting charge transport, we can take some steps in this direction, while at the same time characterizing charge transport and its capture by defects. By exploiting the cycling process of ionization and recombination of NV centers in diamond, we pump electrons from the valence band to the conduction band. These charges are then transported to modulate the spin concentration by changing the charge state of material defects. By developing a wide-field imaging setup integrated with a fast single photon detector array, we achieve a direct and efficient characterization of the charge redistribution process by measuring the complete spectrum of the spin bath with micrometer-scale spatial resolution. We demonstrate a two-fold concentration increase of the dominant spin defects while keeping the T2 of the NV center relatively unchanged, which also provides a potential experimental demonstration of the suppression of spin flip-flops via hyperfine interactions. Our work paves the way to studying many-body dynamics with temporally and spatially tunable interaction strengths in hybrid charge-spin systems.

Characterizing Temperature and Strain Variations with Qubit Ensembles for Their Robust Coherence Protection.

Solid-state spin defects, especially nuclear spins with potentially achievable long coherence times, are compelling candidates for quantum memories and sensors. However, their current performances are still limited by dephasing due to variations of their intrinsic quadrupole and hyperfine interactions. We propose an unbalanced echo to overcome this challenge by using a second spin to refocus variations of these interactions while preserving the quantum information stored in the nuclear spin free evolution. The unbalanced echo can be used to probe the temperature and strain distribution in materials. We develop first-principles methods to predict variations of these interactions and reveal their correlation over large temperature and strain ranges. Experiments performed in an ensemble of ∼10^{10} nuclear spins in diamond demonstrate a 20-fold dephasing time increase, limited by other noise sources. We further numerically show that our method can refocus even stronger noise variations than present in our experiments.

Extracellular polymeric substances sustain photoreduction of Cr(VI) by Shewanella oneidensis-CdS biohybrid system.

Photosensitized biohybrid system (PBS) enables bacteria to exploit light energy harvested by semiconductors for rapid pollutants transformation, possessing a promising future for water reclamation. Maintaining a biocompatible environment under photocatalytic conditions is the key to developing PBS-based treatment technologies. Natural microbial cells are surrounded by extracellular polymeric substances (EPS) that either be tightly bound to the cell wall (i.e., tightly bound EPS, tbEPS) or loosely associated with cell surface (i.e., loosely bound EPS, lbEPS), which provide protection from unfavorable environment. We hypothesized that providing EPS fractions can enhance bacterial viability under adverse environment created by photocatalytic reactions. We constructed a model PBS consisting of Shewanella oneidensis and CdS using Cr(VI) as the target pollutant. Results showed complete removal of 25 mg/L Cr(VI) within 90 min without an electron donor, which may mainly rely on the synergistic effect of CdS and bacteria on photoelectron transfer. Long-term cycling experiment of pristine PBS and PBS with extra EPS fractions (including lbEPS and tbEPS) for Cr(VI) treatment showed that PBS with extra lbEPS achieved efficient Cr(VI) removal within five consecutive batch treatment cycles, compared to the three cycles both in pristine PBS and PBS with tbEPS. After addition of lbEPS, the accumulation of reactive oxygen species (ROS) was greatly reduced via the EPS-capping effect and quenching effect, and the toxic metal internalization potential was lowered by complexation with Cd and Cr, resulting in enhanced bacterial viability during photocatalysis. This facile and efficient cytoprotective method helps the rational design of PBS for environmental remediation.

Machine learning traction force maps of cell monolayers.

Cellular force transmission across a hierarchy of molecular switchers is central to mechanobiological responses. However, current cellular force microscopies suffer from low throughput and resolution. Here we introduce and train a generative adversarial network (GAN) to paint out traction force maps of cell monolayers with high fidelity to the experimental traction force microscopy (TFM). The GAN analyzes traction force maps as an image-to-image translation problem, where its generative and discriminative neural networks are simultaneously cross-trained by hybrid experimental and numerical datasets. In addition to capturing the colony-size and substrate-stiffness dependent traction force maps, the trained GAN predicts asymmetric traction force patterns for multicellular monolayers seeding on substrates with stiffness gradient, implicating collective durotaxis. Further, the neural network can extract experimentally inaccessible, the hidden relationship between substrate stiffness and cell contractility, which underlies cellular mechanotransduction. Trained solely on datasets for epithelial cells, the GAN can be extrapolated to other contractile cell types using only a single scaling factor. The digital TFM serves as a high-throughput tool for mapping out cellular forces of cell monolayers and paves the way toward data-driven discoveries in cell mechanobiology.