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Abstract The spatiotemporal distribution of intangible cultural heritage in Fujian Province, China, and the factors that influence it were explored using multiple spatial scales. The samples include five batches of Chinese national-level and six batches of Chinese provincial-level intangible cultural heritage items, totaling 554. The samples involve city-scale, county-scale, and traditional dwellings, and the analysis uses various methods, such as gravity migration theory and the GeoDetector model. The results show that, in terms of historical timescales, the moving trajectory of the center of gravity of the intangible cultural heritage distribution in Fujian Province involves reciprocation from north to south, and the center moves south in time from the pre-Qin period to the modern period. Spatially, intangible cultural heritage in Fujian Province forms an overall aggregate pattern, among which traditional skills fall into an aggregate pattern; five categories, including traditional drama, fall into an aggregate-random pattern; and four categories, including traditional medicine, fall into a random pattern. The traditional art category and other intensive distribution areas are located in coastal areas, and the traditional dance category is scattered in northwestern Fujian Province. Experiments on the factors influencing intangible cultural heritage distribution were conducted at the city and county levels. At the city level, human geography factors, such as the resident population, urbanization rate, and gross domestic product, have a greater influence on distribution. At the county level, the influence of physical geographical factors clearly increases. The dominant factors for coastal cities are the normalized difference vegetation index (NDVI), average precipitation, and coastline, and that for inland cities is elevation. From the perspective of categories, the dominant factors of traditional music and Quyi are human geography factors, and those of other types of intangible cultural heritage are the synergistic effects of physical geography and human geography. The conclusions of this study are helpful for systematically protecting and developing the intangible cultural heritage industry and improving research theories and methodological systems of the spatiotemporal distribution and mechanism influencing intangible cultural heritage.

G protein-coupled receptors (GPCRs) play a pivotal role in fundamental biological processes and disease development. GPCR isoforms, derived from alternative splicing, can exhibit distinct signaling patterns. Some highly-truncated isoforms can impact functional performance of full-length receptors, suggesting their intriguing regulatory roles. However, how these truncated isoforms interact with full-length counterparts remains largely unexplored. Here, we computationally investigated the interaction patterns of three human GPCRs from three different classes, ADORA1 (Class A), mGlu2 (Class C) and SMO (Class F) with their respective truncated isoforms because their homodimer structures have been experimentally determined, and they have truncated isoforms deposited and identified at protein level in Uniprot database. Combining the neural network-based AlphaFold2 and two physics-based protein-protein docking tools, we generated multiple complex structures and assessed the binding affinity in the context of atomistic molecular dynamics simulations. Our computational results suggested all the four studied truncated isoforms showed potent binding to their counterparts and overlapping interfaces with homodimers, indicating their strong potential to block homodimerization of their counterparts. Our study offers insights into functional significance of GPCR truncated isoforms and supports the ubiquity of their regulatory roles.

Abstract Membrane proteins are critical to biological processes and central to life sciences and modern medicine. However, membrane proteins are notoriously challenging to study, mainly owing to difficulties dictated by their highly hydrophobic nature. Previously, we reported QTY code, which is a simple method for designing water-soluble membrane proteins. Here, we apply QTY code to a transmembrane receptor, histidine kinase CpxA, to render it completely water-soluble. The designed CpxAQTY exhibits expected biophysical properties and highly preserved native molecular function, including the activities of (i) autokinase, (ii) phosphotransferase, (iii) phosphatase, and (iv) signaling receptor, involving a water-solubilized transmembrane domain. We probe the principles underlying the balance of structural stability and activity in the water-solubilized transmembrane domain. Computational approaches suggest that an extensive and dynamic hydrogen-bond network introduced by QTY code and its flexibility may play an important role. Our successful functional preservation further substantiates the robustness and comprehensiveness of QTY code.

ABSTRACT: Leg disorders have become increasingly common in broilers, leading to lower meat quality and major economic losses. This study evaluated the effects of dietary supplementation with Clostridium butyricum (C. butyricum) and 25-hydroxyvitamin D3 (25-OH-D3) on bone development by comparing growth performance, tibial parameters, Ca and P contents of tibial ash, bone development-related indicators’ level, and cecal short-chain fatty acids in Cobb broilers. All birds were divided into four treatment groups, which birds fed either a basal diet (Con), basal diet + 75 mg chlortetracycline/kg (Anti), basal diet + C. butyricum at 109 CFU/kg (Cb), basal diet + C. butyricum at 109 CFU/kg and 25-OH-D3 at 25 μg/kg (CbD), or basal diet + 25-OH-D3 at 25 μg/kg (CD). Our results suggest that the dietary supplementation in Cb, CbD, and CD significantly increased the body weight (BW) and average daily gain (ADG), and reduced the feed-to-weight ratio (F/G) at different stages of growth (P < 0.05). Dietary supplementation in Cb, CbD, and CD prolonged (P < 0.05) the behavioral responses latency-to-lie (LTL) time, reduced (P < 0.05) the levels of osteocalcin (BGP) and peptide tyrosine (PYY), and increased (P < 0.05) serotonin (5-HT) and dopamine (DA). Treatment with Cb increased (P < 0.05) the levels of acetic acid, isobutyric acid, butyric acid, and isovaleric acid compared with those in Con group. The cecal metagenome showed that Alistipes spp. were significantly more abundant in Cb, CbD, and CD groups (P < 0.05). A total of 12 metabolic pathways were significantly affected by supplementation, including the signaling pathways of glucagon, insulin, and PI3K-AKT; primary and secondary bile acid biosynthesis; and P-type Ca 2+ transporters (P < 0.05). Hence, the CbD supplementation modulates bone metabolism by regulating the mediators of gut–brain axis, which may inform strategies to prevent leg diseases and improve meat quality in broilers.

Objective To explore the related factors of weekly blood pressure variability (BPV) on maintenance peritoneal dialysis (MPD).Methods A total of 142 patients on MPD for at least 3 months were recruited. Blood pressure was assessed weekly by variation coefficient (CV) of systolic blood pressure in morning. The relevant clinical data was collected. The association of BPV and predictors were estimated by a mixed-effect linear model. Results Longer dialysis vintage was associated with elevated weekly BPV (P0.05). Conclusions Weekly BPV may be affected by dialysis vintage, hemoglobin concentration, daily fluid removal and dosing of calcium antagonists.

Abstract In recent years, as a promising way to realize digital transformation, digital twin shop-floor (DTS) plays an important role in smart manufacturing. The core feature of DTS is the synchronization. How to implement and maintain the synchronization is critical for DTS. However, there is still a lack of a common definition for synchronization in DTS. Besides, a systematic synchronization mechanism for DTS is strongly needed. This paper first summarizes the definition and requirements of synchronization in DTS, to clarify the understanding of synchronization in DTS. Then, a 5M synchronization mechanism for DTS is proposed, where 5M refers to multi-system data, multi-fidelity model, multi-resource state, multi-level state, and multi-stage operation. As a bottom-up synchronization mechanism, 5M synchronization mechanism for DTS has the potential to support DTS to achieve and maintain physical-virtual state synchronization, and to realize operation synchronization of DTS. The implementation methods of 5M synchronization mechanism for DTS are also introduced. Finally, the proposed synchronization mechanism is validated in a digital twin satellite assembly shop-floor, which proves the effectiveness and feasibility of the mechanism.

The fungus Rhizopus arrhizus (=R. oryzae) is commonly saprotrophic, exhibiting a nature of decomposing organic matter. Additionally, it serves as a crucial starter in food fermentation and can act as a pathogen causing mucormycosis in humans and animals. In this study, two distinct endofungal bacteria (EFBs), associated with individual strains of R. arrhizus, were identified using live/dead staining, fluorescence in situ hybridization, transmission electron microscopy, and 16S rDNA sequencing. The roles of these bacteria were elucidated through antibiotic treatment, pure cultivation, and comparative genomics. The bacterial endosymbionts, Pandoraea sputorum EFB03792 and Mycetohabitans endofungorum EFB03829, were purified from the host fungal strains R. arrhizus XY03792 and XY03829, respectively. Notably, this study marks the first report of Pandoraea as an EFB genus. Compared to its free-living counterparts, P. sputorum EFB03792 exhibited 28 specific virulence factor-related genes, six specific CE10 family genes, and 74 genes associated with type III secretion system (T3SS), emphasizing its pivotal role in invasion and colonization. Furthermore, this study introduces R. arrhizus as a new host for EFB M. endofungorum, with EFB contributing to host sporulation. Despite a visibly reduced genome, M. endofungorum EFB03829 displayed a substantial number of virulence factor-related genes, CE10 family genes, T3SS genes, mobile elements, and significant gene rearrangement. While EFBs have been previously identified in R. arrhizus, their toxin-producing potential in food fermentation has not been explored until this study. The discovery of these two new EFBs highlights their potential for toxin production within R. arrhizus, laying the groundwork for identifying suitable R. arrhizus strains for fermentation processes.

ABSTRACT Robust chassis are critical to facilitate advances in synthetic biology. This study describes a comprehensive characterization of a new yeast isolate Saccharomyces cerevisiae XP that grows faster than commonly used research and industrial S. cerevisiae strains. The genomic, transcriptomic, and metabolomic analyses suggest that the fast growth rate is, in part, due to the efficient electron transport chain and key growth factor synthesis. A toolbox for genetic manipulation of the yeast was developed; we used it to construct l-lactic acid producers for high lactate production. The development of genetically malleable yeast strains that grow faster than currently used strains may significantly enhance the uses of S. cerevisiae in biotechnology.IMPORTANCEYeast is known as an outstanding starting strain for constructing microbial cell factories. However, its growth rate restricts its application. A yeast strain XP, which grows fast in high concentrations of sugar and acidic environments, is revealed to demonstrate the potential in industrial applications. A toolbox was also built for its genetic manipulation including gene insertion, deletion, and ploidy transformation. The knowledge of its metabolism, which could guide the designing of genetic experiments, was generated with multi-omics analyses. This novel strain along with its toolbox was then tested by constructing an l-lactic acid efficient producer, which is conducive to the development of degradable plastics. This study highlights the remarkable competence of nonconventional yeast for applications in biotechnology.

Objective: To investigate the short-term efficacy and safety of different chemotherapy regimens combined with thalidomide, in the treatment of low-income patients with newly diagnosed HIV-associated diffuse large B-cell lymphoma. Methods: A retrospective analysis was performed on 42 patients with HIV-DLBCL who were admitted to the Infectious Diseases Department of Yunnan Provincial Infectious Diseases Hospital from January 2018 to December 2020. 14 cases (including 1 case in stage II and 13 cases in stage III/IV) were treated with R-CHOP, 24 cases (including 1 case in stage II and 23 cases in stage III/IV) were treated with R-DAEPOCH, and 4 cases (including 1 case in stage II and 3 cases in stage III/IV) were treated with EPOCH. All patients were treated with thalidomide. The ART regimen was adjusted. At least 1 and up to 6 intrathecal injections were given during chemotherapy, and cotrimoxazole was taken orally to prevent infection. The clinical efficacy was evaluated after 4 cycles of chemotherapy, and adverse events were evaluated at each cycle of chemotherapy. Results: All patients received 1–8 cycles of chemotherapy. CR (64.2 %) was achieved in 9 patients in R-CHOP group, and 5 patients died. In the R-DAEPOCH group, 17 patients achieved CR (70.8 %) and 7 died. In the EPOCH group, 2 patients reached CR (50 %) and 2 died. The main adverse reactions were grade II and above myelosuppression. Conclusion: Combined treatment with thalidomide can improve the prognosis of low-income patients with newly diagnosed HIV-DLBCL.

Human ATP-binding cassette (ABC) transporters are one of the largest families of membrane proteins and perform diverse functions. Many of them are associated with multidrug resistance that often results in cancer treatment with poor outcomes. Here, we present the structural bioinformatics study of six human ABC membrane transporters with experimentally determined cryo-electron microscopy (CryoEM) structures including ABCB7, ABCC8, ABCD1, ABCD4, ABCG1, ABCG5, and their AlphaFold2-predicted water-soluble QTY variants. In the native structures, there are hydrophobic amino acids such as leucine (L), isoleucine (I), valine (V), and phenylalanine (F) in the transmembrane alpha helices. These hydrophobic amino acids are systematically replaced by hydrophilic amino acids glutamine (Q), threonine (T), and tyrosine (Y). Therefore, these QTY variants become water soluble. We also present the superposed structures of native ABC transporters and their water-soluble QTY variants. The superposed structures show remarkable similarity with root mean square deviations between 1.064 and 3.413 Å despite significant (41.90–54.33%) changes to the protein sequence of the transmembrane domains. We also show the differences in hydrophobicity patches between the native ABC transporters and their QTY variants. We explain the rationale behind why the QTY membrane protein variants become water soluble. Our structural bioinformatics studies provide insight into the differences between the hydrophobic helices and hydrophilic helices and will likely further stimulate designs of water-soluble multispan transmembrane proteins and other aggregated proteins. The water-soluble ABC transporters may be useful as soluble antigens to generate therapeutic monoclonal antibodies for combating multidrug resistance in clinics.

Abstract Membrane proteins are critical mediators for tumor progression and present enormous therapeutic potentials. Although gene profiling can identify their cancer-specific signatures, systematic correlations between protein functions and tumor-related mechanisms are still unclear. We present here the CrMP-Sol database ( https://bio-gateway.aigene.org.cn/g/CrMP ), which aims to breach the gap between the two. Machine learning was used to extract key functional descriptions for protein visualization in the 3D-space, where spatial distributions provide function-based predictive connections between proteins and cancer types. CrMP-Sol also presents QTY-enabled water-soluble designs to facilitate native membrane protein studies despite natural hydrophobicity. Five examples with varying transmembrane helices in different categories were used to demonstrate the feasibility. Native and redesigned proteins exhibited highly similar characteristics, predicted structures and binding pockets, and slightly different docking poses against known ligands, although task-specific designs are still required for proteins more susceptible to internal hydrogen bond formations. The database can accelerate therapeutic developments and biotechnological applications of cancer-related membrane proteins.

Members of the Vibrionaceae family are predominantly fast-growing and halophilic microorganisms that have captured the attention of researchers owing to their potential applications in rapid biotechnology. Among them, Vibrio alginolyticus FA2 is a particularly noteworthy halophilic bacterium that exhibits superior growth capability. It has the potential to serve as a biotechnological platform for sustainable and eco-friendly open fermentation with seawater. To evaluate this hypothesis, we integrated the N-acetylglucosamine (GlcNAc) pathway into V. alginolyticus FA2. Seven nag genes were knocked out to obstruct the utilization of GlcNAc, and then 16 exogenous gna1s co-expressing with EcglmS were introduced to strengthen the flux of GlcNAc pathway, respectively. To further enhance GlcNAc production, we fine-tuned promoter strength of the two genes and inactivated two genes alsS and alsD to prevent the production of acetoin. Furthermore, unsterile open fermentation was carried out using simulated seawater and a chemically defined medium, resulting in the production of 9.2 g/L GlcNAc in 14 h. This is the first report for de-novo synthesizing GlcNAc with a Vibrio strain, facilitated by an unsterile open fermentation process employing seawater as a substitute for fresh water. This development establishes a basis for production of diverse valuable chemicals using Vibrio strains and provides insights into biomanufacture.

Abstract Underwater adhesive proteins secreted by organisms greatly inspires the development of underwater glue. However, except for specific proteins such as mussel adhesive protein, barnacle cement proteins, curli protein and their related recombinant proteins, it is believed that abundant common proteins cannot be converted into underwater glue. Here, we demonstrate that unfolded common proteins exhibit high affinity to surfaces and strong internal cohesion via amyloid-like aggregation in water. Using bovine serum albumin (BSA) as a model protein, we obtain a stable unfolded protein by cleaving the disulfide bonds and maintaining the unfolded state by means of stabilizing agents such as trifluoroethanol (TFE) and urea. The diffusion of stabilizing agents into water exposes the hydrophobic residues of an unfolded protein and initiates aggregation of the unfolded protein into a solid block. A robust and stable underwater glue can thus be prepared from tens of common proteins. This strategy deciphers a general code in common proteins to construct robust underwater glue from abundant biomass.

Due to the intricate complexity of the original microbiota, residual heat-resistant enzymes, and chemical components, identifying the essential factors that affect dairy quality using traditional methods is challenging. In this study, raw milk, pasteurized milk, and ultra-heat-treated (UHT) milk samples were collectively analyzed using metagenomic next-generation sequencing (mNGS), high-throughput liquid chromatography-mass spectrometry (LC-MS), and gas chromatography–mass spectrometry (GC-MS). The results revealed that raw milk and its corresponding heated dairy products exhibited different trends in terms of microbiota shifts and metabolite changes during storage. Via the analysis of differences in microbiota and correlation analysis of the microorganisms present in differential metabolites in refrigerated pasteurized milk, the top three differential microorganisms with increased abundance, Microbacterium (p < 0.01), unclassified Actinomycetia class (p < 0.05), and Micrococcus (p < 0.01), were detected; these were highly correlated with certain metabolites in pasteurized milk (r > 0.8). This indicated that these genera were the main proliferating microorganisms and were the primary genera involved in the metabolism of pasteurized milk during refrigeration-based storage. Microorganisms with decreased abundance were classified into two categories based on correlation analysis with certain metabolites. It was speculated that the heat-resistant enzyme system of a group of microorganisms with high correlation (r > 0.8), such as Pseudomonas and Acinetobacter, was the main factor causing milk spoilage and that the group with lower correlation (r < 0.3) had a lower impact on the storage process of pasteurized dairy products. By comparing the metabolic pathway results based on metagenomic and metabolite annotation, it was proposed that protein degradation may be associated with microbial growth, whereas lipid degradation may be linked to raw milk’s initial heat-resistant enzymes. By leveraging the synergy of metagenomics and metabolomics, the interacting factors determining the quality evolution of dairy products were systematically investigated, providing a novel perspective for controlling dairy processing and storage effectively.

The WRKY gene family is crucial for regulating plant growth and development. However, the WRKY gene is rarely studied in naked kernel formation in hull-less Cucurbita pepo L. (HLCP), a natural mutant that lacks the seed coat. In this research, 76 WRKY genes were identified through bioinformatics-based methods in C. pepo, and their phylogenetics, conserved motifs, synteny, collinearity, and temporal expression during seed coat development were analyzed. The results showed that 76 CpWRKYs were identified and categorized into three main groups (I−III), with Group II further divided into five subgroups (IIa−IIe). Moreover, 31 segmental duplication events were identified in 49 CpWRKY genes. A synteny analysis revealed that C. pepo shared more collinear regions with cucumber than with melon. Furthermore, quantitative RT-PCR (qRT-PCR) results indicated the differential expression of CpWRKYs across different varieties, with notable variations in seed coat development between HLCP and CP being attributed to differences in CpWRKY5 expression. To investigate this further, CpWRKY5-overexpression tobacco plants were generated, resulting in increased lignin content and an upregulation of related genes, as confirmed by qRT-PCR. This study offers valuable insights for future functional investigations of CpWRKY genes and presents novel information for understanding the regulation mechanism of lignin synthesis.

Abstract Background Dietary bamboo leaf flavonoids (BLFs) are rarely used in poultry production, and it is unknown whether they influence meat texture profile, perceived color, or microstructure. Results A total of 720 one-day-old Arbor Acres broilers were supplemented with a basal diet with 20 mg bacitracin/kg, 50 mg BLFs/kg, or 250 mg BLFs/kg or without additions. Data showed that the dietary BLFs significantly (P

Since land resources are essential to human survival, the over-exploitation and unreasonable utilization of land threatens the sustainability of human society. This paper uses the well-developed Yangtze River Delta (YRD) region as a case study, and adopts an improved Mixed-cell Cellular Automata Model (MCCA) to simulate the potential utilization of land resources in 2025 and 2035. Then, the paper attempts to construct a comprehensive assessment system that integrates multiple indicators, and evaluates regional risk changes at a micro patch-cell level and a macro city. The results suggest that (1) The utilization of land resources varies greatly in the YRD region from 2020 to 2035. While Shanghai will continue to make use of available built up land resources, the majority of land resources in Jiangsu Province will shift away from being agricultural in nature. Since forests make up a majority of the land resources in Zhejiang Province, and forests and agricultural land make up a majority of land resources in Anhui Province, the change in land utilization in these two provinces will be more gradual. (2) Changes in land utilization are also likely to cause ecological risks. The risk level in Shanghai is the highest, it is relatively high in Zhejiang but is likely to decrease, relatively low in Jiangsu but likely to increase, and Anhui has the lowest risk level. (3) The K-means clustering method obtained three ecological risk zones of the YRD, and the overall risk level is the highest in the central-eastern zoning ③, followed by the southern zoning ②, and the lowest in the northern zoning ①. Furthermore, the agglomeration pattern of the three zones transforms from L-L to H-H. (4) This paper puts forward corresponding suggestions and countermeasures for four aspects, including the strengthening of agricultural land protection, the regulation of built-up land use expansion, the coordination of an all-rounded approach of urban development, and the fostering of regional sustainable development, in hopes of optimizing land usage and alleviating ecological risk levels. Scientific estimations of potential ecological risks are critical to avoiding future ecological crises thus contributing to more sustainability.

Composite materials are widely used in many fields due to their excellent properties. Quality defects in composite materials can lead to lower quality components, creating potential risk of accidents. Experimental and simulation methods are commonly used to predict the quality of composite materials. However, it is difficult to predict the quality of composite materials accurately due to the uncertain curing environment and incomplete feature space. To address this problem, a digital twin (DT) visual model of a composite material is first constructed. Then, a static autoclave DT virtual model is coupled with a variable composite material DT virtual model to construct a model of the curing process. Features are added to the proposed model by generating simulated data to enhance the quality prediction. An extreme learning machine (ELM) for quality prediction is trained with the generated data. Finally, the effectiveness of the proposed method is verified through result analysis.

With rapid development of Artificial Intelligence (AI), researchers have found many bioinspired AI applications, such as bioinspired images and speech processing, which can increase accuracy [...]

Herein, the use of biomolecules is reviewed as raw materials for creating functional responsive materials with a variety of tunable properties, including physicochemical and mechanical properties. Through self‐assembly/coassembly, self‐powered smart devices can be designed, which aim to create efficient and stable transformation systems within existing energy relations. These systems can respond to various chemical or physical stimuli, triggering reassembly and completing potential energy conversion through conformational changes at the molecular and mesoscopic scales. This energy conversion provides the necessary energy for macroscopic feedback behavior. Herein, bionic devices are presented that can perform energy conversion completely and autonomously and discuss the mechanism of energy conversion between different chemical potentials, kinetic, or thermal energies.

BackgroundReports on Lenvatinib-based therapies show promising treatment outcomes for patients with unresectable hepatocellular carcinoma (uHCC). However, the effect and safety of Lenvatinib-based therapies still need to be further studies.MethodsThis was a retrospective, single-center study on the safety and treatment efficacy of Lenvatinib-based combination therapies for uHCC Patients. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were progressive disease (PD), stable disease (SD), partial response (PR), and complete response (CR).ResultsOf 91 patients, there were 16 females and 75 males with uHCC who received systemic therapies based on Lenvatinib in our center. Forty-six patients (50.5%) received Lenvatinib combined with PD-1 antibody treatment. All these patients also received local therapy with the exception of 2 patients. The remaining 36 patinets received Lenvatinib combined with transcatheter arterial chemoembolization (TACE), 1 patient treated Lenvatinib combined with radiotherapy, 8 patients received Lenvatinib alone. At a median treatment time of 8 months, the objective response rate (ORR) of the entire cohort was 58.2% (53 patients), including 7 patients with CR and 46 patients with PR. 21 patients (23.1%) had SD. The disease control rate (DCR) of all patients was 81.3% (74 patients). However, 17 patients (18.7%) developed PD. The 1- and 2-year cumulative OS rates for the entire cohort were 66.8% and 39.3%, while the corresponding PFS rates were 38.0% and 17.1%, respectively. Univariate and multivariate Cox regression analysis revealed multiple tumor sites to be an independent OS risk factor for uHCC patients (HR=2.204, 95% CI=1.104-4.399, P=0.025). The most frequently reported adverse events in all patients were AST elevation (51.6%), followed by hypertension (33.0%), ALT elevation (26.4%), and decreased appetite (25.3%). After a combination treatment of Lenvatinib-based therapies, 15 patients met the criteria for salvage liver resection and underwent down-staging hepatectomy with a curative intent. The combination of PD-1 treatment was not very effective in improving the prognosis of uHCC patients treated with Lenvatinib combined with TACE.ConclusionOur study demonstrated that a proportive of patients benefited from Lenvatinib-based combination therapies with manageable safety profiles, allowing these patients to undergo downstaging surgery with curative intent.

Summary: Synthetic biology, relying on Design-Build-Test-Learn (DBTL) cycle, aims to solve medicine, manufacturing, and agriculture problems. However, the DBTL cycle’s Learn (L) step lacks predictive power for the behavior of biological systems, resulting from the incompatibility between sparse testing data and chaotic metabolic networks. Herein, we develop a method, “RespectM,” based on mass spectrometry imaging, which is able to detect metabolites at a rate of 500 cells per hour with high efficiency. In this study, 4,321 single cell level metabolomics data were acquired, representing metabolic heterogeneity. An optimizable deep neural network was applied to learn from metabolic heterogeneity and a “heterogeneity-powered learning (HPL)” based model was trained as well. By testing the HPL based model, we suggest minimal operations to achieve high triglyceride production for engineering. The HPL strategy could revolutionize rational design and reshape the DBTL cycle.