TabHLH27 orchestrates root growth and drought tolerance to enhance water use efficiency in wheat.

Cultivating high-yield wheat under limited water resources is crucial for sustainable agriculture in semiarid regions. Amid water scarcity, plants activate drought response signaling, yet the delicate balance between drought tolerance and development remains unclear. Through genome-wide association studies and transcriptome profiling, we identified a wheat atypical basic helix-loop-helix (bHLH) transcription factor (TF), TabHLH27-A1, as a promising quantitative trait locus candidate for both relative root dry weight and spikelet number per spike in wheat. TabHLH27-A1/B1/D1 knock-out reduced wheat drought tolerance, yield, and water use efficiency (WUE). TabHLH27-A1 exhibited rapid induction with polyethylene glycol (PEG) treatment, gradually declining over days. It activated stress response genes such as TaCBL8-B1 and TaCPI2-A1 while inhibiting root growth genes like TaSH15-B1 and TaWRKY70-B1 under short-term PEG stimulus. The distinct transcriptional regulation of TabHLH27-A1 involved diverse interacting factors such as TaABI3-D1 and TabZIP62-D1. Natural variations of TabHLH27-A1 influence its transcriptional responses to drought stress, with TabHLH27-A1Hap-II associated with stronger drought tolerance, larger root system, more spikelets, and higher WUE in wheat. Significantly, the excellent TabHLH27-A1Hap-II was selected during the breeding process in China, and introgression of TabHLH27-A1Hap-II allele improved drought tolerance and grain yield, especially under water-limited conditions. Our study highlights TabHLH27-A1's role in balancing root growth and drought tolerance, providing a genetic manipulation locus for enhancing WUE in wheat.

Ultrasound modification on milk fat globule membrane and soy lecithin to improve the physicochemical properties, microstructure and stability of mimicking human milk fat emulsions.

Starting from the consideration of the structure of human milk fat globule (MFG), this study aimed to investigate the effects of ultrasonic treatment on milk fat globule membrane (MFGM) and soy lecithin (SL) complexes and their role in mimicking human MFG emulsions. Ultrasonic power significantly affected the structure of the MFGM-SL complex, further promoting the unfolding of the molecular structure of the protein, and then increased solubility and surface hydrophobicity. Furthermore, the microstructure of mimicking MFG emulsions without sonication was unevenly distributed, and the average droplet diameter was large. After ultrasonic treatment, the droplets of the emulsion were more uniformly dispersed, the particle size was smaller, and the emulsification properties and stability were improved to varying degrees. Especially when the ultrasonic power was 300 W, the mimicking MFG emulsion had the highest encapsulation rate and emulsion activity index and emulsion stability index were increased by 60.88 % and 117.74 %, respectively. From the microstructure, it was observed that the spherical droplets of the mimicking MFG emulsion after appropriate ultrasonic treatment remain well separated without obvious flocculation. This study can provide a reference for the screening of milk fat globules mimicking membrane materials and the further utilization and development of ultrasound in infant formula.

One-step biofabrication of liquid core-GelMa shell microbeads for in situ hollow cell ball self-assembly.

There are many instances of hollow-structure morphogenesis in the development of tissues. Thus, the fabrication of hollow structures in a simple, high-throughput and homogeneous manner with proper natural biomaterial combination is valuable for developmental studies and tissue engineering, while it is a significant challenge in biofabrication field. We present a novel method for the fabrication of a hollow cell module using a coaxial co-flow capillary microfluidic device. Sacrificial gelatin laden with cells in the inner layer and GelMa in the outer layer are used via a coaxial co-flow capillary microfluidic device to produce homogenous micro-beads. The overall and core sizes of core-shell microbeads were well controlled. When using human vein vascular endothelial cells to demonstrate how cells line the inner surface of core-shell beads, as the core liquifies, a hollow cell ball with asymmetric features is fabricated. After release from the GelMa shell, individual cell balls are obtained and deformed cell balls can self-recover. This platform paves way for complex hollow tissue modeling in vitro, and further modulation of matrix stiffness, curvature and biochemical composition to mimic in vivo microenvironments.

Research advances on production and application of algal biochar in environmental remediation.

Algae, comprising microalgae and macroalgae, have emerged as a promising feedstock for the production of functional biochar. Recently, the application of algal biochar in environmental remediation gains increasing attention. This review summarizes research advancements in the synthesis and application of algal biochar, a versatile and sustainable material for environmental remediation ranging from wastewater treatment to soil improvement. Algal biochar can be prepared by pyrolysis, microwave-assisted pyrolysis, and hydrothermal carbonization. Physical and chemical modifications have proven to be effective for improving biochar properties. Algal biochar is promising for removing diverse pollutants including heavy metals, organic pollutants, and microplastics. The role in soil improvement signifies a sustainable approach to enhancing soil structure, nutrient retention, and microbial activity. Research gaps are identified based on current understanding, necessitating further exploration into variations in biochar characteristics, the performance improvement, large-scale applications, and the long-term evaluation for environmental application. This review provides a better understanding of algal biochar as a sustainable and effective tool in environmental remediation.

Effects of different chemical modifications on physicochemical and antioxidation properties of Lycium barbarum seed dreg polysaccharides.

Recent studies have witnessed that chemical modification can improve the physicochemical and functional properties of plants' polysaccharides. Herein, we modified the natural Lycium barbarum seed dreg polysaccharides (LBSDPs) by sulfation (S-LBSDPs), phosphorylation (P-LBSDPs), and carboxymethylation (C-LBSDPs), and evaluated the chemical composition and antioxidant activity of their derivatives. Natural polysaccharides and their derivatives exhibited typical polysaccharide absorption peaks and characteristic group absorption peaks in FT-IR spectra along with maximum UV absorption. After modification, the total sugar and protein contents of the derivatives were decreased, whereas the uronic acid content was increased. Among the three derivatives, sulfated polysaccharides displayed excellent thermal stability. S-LBSDP and P-LBSDP showed the highest ABTS radical scavenging and reducing power while S-LBSDPs and C-LBSDPs showed better DPPH radical scavenging effect, and P-LBSDPs showed considerable Fe2+ chelating ability. Our data indicate that chemical modifications can impart a positive effect on the antioxidant potential of plant-derived polysaccharides.

Mesenchymal stem/stromal cells from human pluripotent stem cell-derived brain organoid enhance the ex vivo expansion and maintenance of hematopoietic stem/progenitor cells.

BACKGROUND: Mesenchymal stem/stromal cells (MSCs) are of great therapeutic value due to their role in maintaining the function of hematopoietic stem/progenitor cells (HSPCs). MSCs derived from human pluripotent stem cells represent an ideal alternative because of their unlimited supply. However, the role of MSCs with neural crest origin derived from HPSCs on the maintenance of HSPCs has not been reported. METHODS: Flow cytometric analysis, RNA sequencing and differentiation ability were applied to detect the characteristics of stromal cells from 3D human brain organoids. Human umbilical cord blood CD34+ (UCB-CD34+) cells were cultured in different coculture conditions composed of stromal cells and umbilical cord MSCs (UC-MSCs) with or without a cytokine cocktail. The hematopoietic stroma capacity of stromal cells was tested in vitro with the LTC-IC assay and in vivo by cotransplantation of cord blood nucleated cells and stroma cells into immunodeficient mice. RNA and proteomic sequencing were used to detect the role of MSCs on HSPCs. RESULTS: The stromal cells, derived from both H1-hESCs and human induced pluripotent stem cells forebrain organoids, were capable of differentiating into the classical mesenchymal-derived cells (osteoblasts, chondrocytes, and adipocytes). These cells expressed MSC markers, thus named pluripotent stem cell-derived MSCs (pMSCs). The pMSCs showed neural crest origin with CD271 expression in the early stage. When human UCB-CD34+ HSPCs were cocultured on UC-MSCs or pMSCs, the latter resulted in robust expansion of UCB-CD34+ HSPCs in long-term culture and efficient maintenance of their transplantability. Comparison by RNA sequencing indicated that coculture of human UCB-CD34+ HSPCs with pMSCs provided an improved microenvironment for HSC maintenance. The pMSCs highly expressed the Wnt signaling inhibitors SFRP1 and SFRP2, indicating that they may help to modulate the cell cycle to promote the maintenance of UCB-CD34+ HSPCs by antagonizing Wnt activation. CONCLUSIONS: A novel method for harvesting MSCs with neural crest origin from 3D human brain organoids under serum-free culture conditions was reported. We demonstrate that the pMSCs support human UCB-HSPC expansion in vitro in a long-term culture and the maintenance of their transplantable ability. RNA and proteomic sequencing indicated that pMSCs provided an improved microenvironment for HSC maintenance via mechanisms involving cell-cell contact and secreted factors and suppression of Wnt signaling. This represents a novel method for large-scale production of MSCs of neural crest origin and provides a potential approach for development of human hematopoietic stromal cell therapy for treatment of dyshematopoiesis.

Ultrasound-induced structural changes of different milk fat globule membrane protein-phospholipids complexes and their effects on physicochemical and functional properties of emulsions.

Ultrasonic technology is a non-isothermal processing technology that can be used to modify the physicochemical properties of food ingredients. This study investigated the effects of ultrasonic time (5 min, 10 min, 15 min) and power (150 W,300 W,500 W) on the structural properties of three types of phospholipids composed of different fatty acids (milk fat globule membrane phospholipid (MPL), egg yolk lecithin (EYL), soybean lecithin (SL)) and milk fat globule membrane protein (MFGMP). We found that the ultrasound treatment changed the conformation of the protein, and the emulsions prepared by the pretreatment showed better emulsification and stability, the lipid droplets were also more evenly distributed. Meanwhile, the flocculation phenomenon of the lipid droplets was significantly improved compared with the non-ultrasonic emulsions. Compared with the three complexes, it was found that ultrasound had the most significant effect on the properties of MPL-MFGMP, and its emulsion state was the most stable. When the ultrasonic condition was 300 W, the particle size of the emulsion decreased significantly (from 441.50 ±â€¯4.79 nm to 321.77 ±â€¯9.91 nm) at 15 min, and the physical stability constants KE decreased from 14.49 ±â€¯0.702 % to 9.4 ±â€¯0.261 %. It can be seen that proper ultrasonic pretreatment can effectively improve the stability of the system. At the same time, the emulsification performance of the emulsion had also been significantly improved. While the accumulation phenomenon occurred when the ultrasonic power was 150 W and 500 W. These results showed that ultrasonic pretreatment had great potential to improve the properties of emulsions, and this study would provide a theoretical basis for the application of emulsifier in the emulsions.

Discovery of a dual-acting inhibitor of interleukin-1ß and STATs for the treatment of inflammatory bowel disease.

Currently, a significant proportion of inflammatory bowel disease (IBD) patients fail to respond to conventional drug therapy such as immunosuppressants and biologic agents. Interference with the JAK/STAT pathway and blocking of IL-1 signaling are two promising therapeutic strategies for these unresponsive IBD patients. This work describes the discovery of an inhibitor 10v that not only blocks NLRP3 and AIM-2 inflammasome-mediated IL-1ß signaling, but also reduces the expression of STAT1 and STAT5 in the JAK/STAT pathway. Importantly, 10v exhibits a significant anti-IL-1ß effect and decreases the levels of STAT1 and STAT5 in a mouse model of colitis. As a result, a novel small molecule is identified with a dual inhibitory capacity towards both inflammasomes/IL-1ß and STAT pathways, which supports further exploration of the therapeutic potential for IBD patients that do not respond to current drug therapy.

N/S Co-Doped Graphene Aerogels as Superior Anode Materials for High-Rate Lithium-Ion Batteries.

The nitrogen and sulfur co-doped graphene aerogel (SNGA) was synthesized by a one-pot hydrothermal route using graphene oxide as the starting material and thiourea as the S and N source. The obtained SNGA with a three-dimensionally hierarchical structure, providing more available pathways for the transport of lithium ions. The existing form of S and N was regulated by changing the calcination temperature and thiourea doping amount. The results revealed that high temperature could decompose -SOX- functional groups and promote the transformation of C-S-C to C-S, ensuring the cyclic stability of electrode materials, and increasing the thiourea dosage amount introduced more pyridine nitrogen, improving the multiplicative performance of electrode materials. Benefiting from the synergistic effect of sulfur and nitrogen atoms, the prepared SNGA showed superior rate capability (107.8 mAh g-1 at 5 A g-1), twice more than that of GA (52.8 mAh g-1), and excellent stability (232.1 mAh g-1 at 1 A g-1 after 300 cycles), 1.85 times more than that of GA (125.6 mAh g-1). The present study provides a detailed report on thiourea as a dopant to provide a sufficient basis for SNGA and a theoretical guide for further modifying.

Engineering High-Spin State Cobalt Cations in Sulfide Spinel for Enhancing Water Oxidation.

The spin states of active sites have a significant impact on the adsorption/desorption ability of the reaction intermediates during the oxygen evolution reaction (OER). Sulfide spinel is not generally considered a highly efficient OER catalyst owing to the low spin state of Co3+ and the lack of unpaired electrons available for adsorption of reaction intermediates. Herein, it is proposed a novel Nd-evoked valence electronic adjustment strategy to engineer the spin state of Co ions. The unique f-p-d orbital electronic coupling effect stimulates the rearrangement of Co d orbital electrons and increases the eg electron filling to achieve high-spin state Co ions, which promotes charge transport by propagating a spin channel and generates a high number of active sites for intermediate adsorption. The optimized CuCo1.75 Nd0.25 S4 catalyst exhibits outstanding electrocatalytic properties with a low overpotential of 320 mV at 500 mA cm-2 and a 48 h stability at 300 mA cm-2 . In situ synchrotron radiation infrared spectra confirm the quick accumulation of key *OOH and *O intermediates. This work deepens the comprehensive understanding of the relationship between OER activity and spin configurations of Co ions and offers a new design strategy for spinel compound catalysts.

Novel trends and challenges in fat modification of next-generation infant formula: Considering the structure of milk fat globules to improve lipid digestion and metabolism of infants.

Differences in the composition and structure of lipid droplets in infant formula (IF) and human milk (HM) can affect the fat digestion of infants, leading to high risk of metabolic diseases during later stages of growth. Recently, interest in simulating HM fat (HMF) has gradually increased due to its beneficial functions for infants. Much research focuses on the simulation of fatty acids and triacylglycerols. Enzymatic combined with new technologies such as carbodiimide coupling immobilization enzymes, solvent-free synthesis, and microbial fermentation can improve the yield of simulated HMF. Furthermore, fat modification in next-generation IF requires attention to the impact on the structure and function of milk fat globules (MFG). This review also summarizes the latest reports on MFG structure simulation, mainly related to the addition method and sequence of membrane components, and other milk processing steps. Although some of the simulated HMF technologies and products have been applied to currently commercially available IF, the cost is still high. Furthermore, understanding the fat decomposition of simulated HMF during digestion and assessing its nutritional effects on infants later in life is also a huge challenge. New process development and more clinical studies are needed to construct and evaluate simulated HMF in the future.

Preparation and Characterization of Eugenol Incorporated Pullulan-Gelatin Based Edible Film of Pickering Emulsion and Its Application in Chilled Beef Preservation.

The purpose of this study was to develop a composite film composed of eugenol Pickering emulsion and pullulan-gelatin, and to evaluate its preservation effect on chilled beef. The prepared composite film was comprehensively evaluated in terms of the stability of emulsion, the physical properties of the film, and an analysis of freshness preservation for chilled beef. The emulsion size (296.0 ± 10.2 nm), polydispersity index (0.457 ± 0.039), and potential (20.1 ± 0.9 mV) proved the success of emulsion. At the same time, the films displayed good mechanical and barrier properties. The index of beef preservation also indicated that eugenol was a better active ingredient than clove essence oil, which led to the rise of potential of hydrogen, chroma and water content, and effectively inhibited microbial propagation, protein degradation and lipid oxidation. These results suggest that the prepared composites can be used as promising materials for chilled beef preservation.

Robustness of Trion State in Gated Monolayer MoSe2 under Pressure.

Quasiparticles consisting of correlated electron(s) and hole(s), such as excitons and trions, play important roles in the optical phenomena of van der Waals semiconductors and serve as unique platforms for studies of many-body physics. Herein, we report a gate-tunable exciton-to-trion transition in pressurized monolayer MoSe2, in which the electronic band structures are modulated continuously within a diamond anvil cell. The emission energies of both the exciton and trion undergo large blueshifts over 90 meV with increasing pressure. Surprisingly, the trion binding energy remains constant at 30 meV, regardless of the applied pressure. Combining ab initio density functional theory calculations and quantum Monte Carlo simulations, we find that the remarkable robustness of the trion binding energy originates from the spatially diffused nature of the trion wave function and the weak correlation between its constituent electron-hole pairs. Our findings shed light on the optical properties of correlated excitonic quasiparticles in low-dimensional materials.

Engineering Unsymmetrically Coordinated Fe Sites via Heteroatom Pairs Synergetic Contribution for Efficient Oxygen Reduction.

Single-atom Fe catalysts are considered as the promising catalysts for oxygen reduction reaction (ORR). However, the high electronegativity of the symmetrical coordination N atoms around Fe site generally results in too strong adsorption of *OOH intermediates on the active site, severely limiting the catalytic performance. Herein, a "heteroatom pair synergetic modulation" strategy is proposed to tailor the coordination environment and spin state of Fe sites, enabling breaking the shackles of unsuitable adsorption of intermediate products on the active centers toward a more efficient ORR pathway. The unsymmetrically Co and B heteroatomic coordinated Fe single sites supported on an N-doped carbon (Fe─B─Co/NC) catalyst perform excellent ORR activity with high half-wave potential (E1/2 ) of 0.891 V and a large kinetic current density (Jk ) of 60.6 mA cm-2 , which is several times better than those of commercial Pt/C catalysts. By virtue of in situ electrochemical impedance and synchrotron infrared spectroscopy, it is observed that the optimized Fe sites can effectively accelerate the evolution of O2 into the *O intermediate, overcoming the sluggish O─O bond cleavage of the *OOH intermediate, which is responsible for fast four-electron reaction kinetics.

Platelet-Rich Plasma for Androgenetic Alopecia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Platelet-rich plasma (PRP) contains a variety of growth factors and has been widely used in maxillofacial surgery, orthopedics, plastic surgery, ophthalmology, and other fields. In recent years, with the increasing morbidity of androgenetic alopecia (AGA), the use of PRP has also increased. The objective of this article was to evaluate the efficacy and safety of PRP for AGA. We searched PubMed, Embase, Web of Science, and Cochrane Library, covering the databases from their earliest records until March 2022. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to explore the effects of PRP for hair density, hair count, and hair diameter in AGA. Nine trials involving 238 patients were included. The meta-analysis showed that PRP for AGA increased hair density at 3 and 6 months with statistically significant differences compared with the placebo (P < .05). PRP also increased hair count and hair diameter compared with the baseline, but there was no significant difference compared with the placebo (P > .05). Two of the 7 studies reported adverse reactions. No serious adverse reactions were found. In conclusion, PRP is an effective and safe treatment for increasing the hair density in AGA. Trial registration: The systematic review was registered with PROSPERO (CRD42022362432).

A controllable gelatin-based microcarriers fabrication system for the whole procedures of MSCs amplification and tissue engineering.

Biopolymer microbeads present substantial benefits for cell expansion, tissue engineering, and drug release applications. However, a fabrication system capable of producing homogeneous microspheres with high precision and controllability for cell proliferation, passaging, harvesting and downstream application is limited. Therefore, we developed a co-flow microfluidics-based system for the generation of uniform and size-controllable gelatin-based microcarriers (GMs) for mesenchymal stromal cells (MSCs) expansion and tissue engineering. Our evaluation of GMs revealed superior homogeneity and efficiency of cellular attachment, expansion and harvest, and MSCs expanded on GMs exhibited high viability while retaining differentiation multipotency. Optimization of passaging and harvesting protocols was achieved through the addition of blank GMs and treatment with collagenase, respectively. Furthermore, we demonstrated that MSC-loaded GMs were printable and could serve as building blocks for tissue regeneration scaffolds. These results suggested that our platform held promise for the fabrication of uniform GMs with downstream application of MSC culture, expansion and tissue engineering.

Straw-derived biochar for the removal of antibiotics from water: Adsorption and degradation mechanisms, recent advancements and challenges.

Antibiotics, a kind of containments with the properties of widely distributed and difficult to degrade, has aroused extensive attention in the world. As a prevalent agricultural waste, straws can be utilized to prepare biochar (straw-derived biochar, SBC) to remove antibiotics from aquatic environment. To date, although a number of review papers have summarized and discussed research on biochar application in wastewater treatment and soil remediation, there are few reviews on SBC for antibiotic removal. Due to the limitations of poor adsorption and degradation performance of the pristine SBC, it is necessary to modify SBC to improve its applications for antibiotics removal. The maximum antibiotic removal capacity of modified SBC could reach 1346.55 mg/g. Moreover, the adsorption mechanisms between modified SBC and antibiotics mainly involve π-π interactions, electrostatic interactions, hydrophobic interactions, and charge dipole interactions. In addition, the modified SBC could completely degrade antibiotics within 6 min by activating oxidants, such as PS, PDS, H2O2, and O3. The mechanisms of antibiotic degradation by SBC activated oxidants mainly include free radicals (including SO4•-, •OH, and O2•-) and non-free radical pathway (such as, 1O2, electrons transfer, and surface-confined reaction). Although SBC and modified SBC have demonstrated excellent performance in removing antibiotics, they still face some challenges in practical applications, such as poor stability, high cost, and difficulties in recycling. Therefore, the further research directions and trends for the development of SBC and biochar-based materials should be taken into consideration.

Biochar/layered double hydroxides composites as catalysts for treatment of organic wastewater by advanced oxidation processes: A review.

Heterogeneous advanced oxidation process has been widely studied as an effective method for removing organic pollutants in wastewater, but the development of efficient catalysts is still challenging. This review summaries the present status of researches on biochar/layered double hydroxides composites (BLDHCs) as catalysts for treatment of organic wastewater. The synthesis methods of layered double hydroxides, the characterizations of BLDHCs, the impacts of process factors influencing catalytic performance, and research advances in various advanced oxidation processes are discussed in this work. The integration of layered double hydroxides and biochar provides synthetic effects for improving pollutant removal. The enhanced pollutant degradation in heterogeneous Fenton, sulfate radical-based, sono-assisted, and photo-assisted processes using BLDHCs have been verified. Pollutant degradation in heterogeneous advanced oxidation processes using BLDHCs is influenced by process factors such as catalyst dosage, oxidant addition, solution pH, reaction time, temperature, and co-existing substances. BLDHCs are promising catalysts due to the unique features including easy preparation, distinct structure, adjustable metal ions, and high stability. Currently, catalytic degradation of organic pollutants using BLDHCs is still in its infancy. More researches should be conducted on the controllable synthesis of BLDHCs, the in-depth understanding of catalytic mechanism, the improvement of catalytic performance, and large-scale application of treating real wastewater.

Harnessing the power of natural minerals: A comprehensive review of their application as heterogeneous catalysts in advanced oxidation processes for organic pollutant degradation.

The release of untreated wastewater into water bodies has become a significant environmental concern, resulting in the accumulation of refractory organic pollutants that pose risks to human health and ecosystems. Wastewater treatment methods, including biological, physical, and chemical techniques, have limitations in achieving complete removal of the refractory pollutants. Chemical methods, particularly advanced oxidation processes (AOPs), have gained special attention for their strong oxidation capacity and minimal secondary pollution. Among the various catalysts used in AOPs, natural minerals offer distinct advantages, such as low cost, abundant resources, and environmental friendliness. Currently, the utilization of natural minerals as catalysts in AOPs lacks thorough investigation and review. This work addresses the need for a comprehensive review of natural minerals as catalysts in AOPs. The structural characteristics and catalytic performance of different natural minerals are discussed, emphasizing their specific roles in AOPs. Furthermore, the review analyzes the influence of process factors, including catalyst dosage, oxidant addition, pH value, and temperature, on the catalytic performance of natural minerals. Strategies for enhancing the catalytic efficiency of AOPs mediated by natural minerals are explored, mainly including physical fields, reductant addition, and cocatalyst utilization. The review also examines the practical application prospects and main challenges associated with the use of natural minerals as heterogeneous catalysts in AOPs. This work contributes to the development of sustainable and efficient approaches for organic pollutant degradation in wastewater.

The Peptide Fractions of Cheddar Cheese Made with Lactobacillus helveticus 1.0612 Play Protective Effects in H2O2-Induced Oxidative-Damaged Caco-2 Cells Models.

In this study, water-soluble peptide (WSP) fractions of cheddar cheese made with Lactobacillus helveticus 1.0612 were purified into WSP-Ⅰ (<3 kDa), WSP-Ⅱ (3-10 kDa), and WSP-Ⅲ (>10 kDa). The protective effects of WSP, WSP-Ⅰ, WSP-Ⅱ, and WSP-Ⅲ fractions against oxidative stress in Caco-2 cells were assayed, and the cytoprotective mechanism of WSP-Ⅰ on cells oxidative damage was elucidated via metabolomics. The results showed that all four peptide fractions were able to attenuate the decrease in cell viability caused by oxidative stress and also could reduce the production of reactive oxygen species and malondialdehyde caused by oxidative stress, and increased cellular catalase and superoxide dismutase activities, thereby enhancing cellular antioxidant capacity. The WSP-Ⅰ fraction with the highest protective effect was used for metabolomics analysis, and 15 significantly different metabolites were screened. Functional pathway analysis revealed that the protective effect of the WSP-I fraction was related with nine metabolic pathways and weakened the metabolic disorders caused by H2O2 via regulating energy metabolism and amino acid metabolism. All in all, peptide fractions of cheddar cheese showed a cytoprotective effect through improved cellular metabolism.