HMGA1 sensitizes esophageal squamous cell carcinoma to mTOR inhibitors through the ETS1-FKBP12 axis.

Esophageal carcinoma is amongst the prevalent malignancies worldwide, characterized by unclear molecular classifications and varying clinical outcomes. The PI3K/AKT/mTOR signaling, one of the frequently perturbed dysregulated pathways in human malignancies, has instigated the development of various inhibitory agents targeting this pathway, but many ESCC patients exhibit intrinsic or adaptive resistance to these inhibitors. Here, we aim to explore the reasons for the insensitivity of ESCC patients to mTOR inhibitors. We assessed the sensitivity to rapamycin in various ESCC cell lines by determining their respective IC50 values and found that cells with a low level of HMGA1 were more tolerant to rapamycin. Subsequent experiments have supported this finding. Through a transcriptome sequencing, we identified a crucial downstream effector of HMGA1, FKBP12, and found that FKBP12 was necessary for HMGA1-induced cell sensitivity to rapamycin. HMGA1 interacted with ETS1, and facilitated the transcription of FKBP12. Finally, we validated this regulatory axis in in vivo experiments, where HMGA1 deficiency in transplanted tumors rendered them resistance to rapamycin. Therefore, we speculate that mTOR inhibitor therapy for individuals exhibiting a reduced level of HMGA1 or FKBP12 may not work. Conversely, individuals exhibiting an elevated level of HMGA1 or FKBP12 are more suitable candidates for mTOR inhibitor treatment.

Nanogalvanic Cells Release Highly Reactive Electrons in Tumors to Effectively Eliminate Tumors.

External stimuli triggering chemical reactions in cancer cells to generate highly reactive chemical species are very appealing for cancer therapy, in which external irradiation activating sensitizers to transfer energy or electrons to surrounding oxygen or other molecules is critical for generating cytotoxic reactive species. However, poor light penetration into tissue, low activity of sensitizers, and reliance on oxygen supply restrict the generation of cytotoxic chemical species in hypoxic tumors, which lowers the therapeutic efficacy. Here, we present galvanic cell nanomaterials that can directly release highly reactive electrons in tumors without external irradiation or photosensitizers. The released reactive electrons directly react with surrounding biomolecules such as proteins and DNA within tumors to destroy them or react with other surrounding (bio)molecules to yield cytotoxic chemical species to eliminate tumors independent of oxygen. Administering these nanogalvanic cells to mice results in almost complete remission of subcutaneous solid tumors and deep metastatic tumors. The results demonstrate that this strategy can further arouse an immune response even in a hypoxic environment. This method offers a promising approach to effectively eliminate tumors, similar to photodynamic therapy, but does not require oxygen or irradiation to activate photosensitizers. This article is protected by copyright. All rights reserved.

Keap1/Nrf2 signaling pathway participating in the progression of epilepsy via regulation of oxidative stress and ferroptosis in neurons.

OBJECTIVE: This study aims to analyze the relationship between the Kelch-like ECH-associated protein 1 (Keap1)/Nuclear factor-erythroid 2-related factor 2 (Nrf2) and Epilepsy (EP), as well as its mechanism of action. METHODS: Thirty Wistar rats were divided into a control group (without treatment), a model group (EP modeling), and an inhibition group (EP modeling + intervention by Keap1/Nrf2 signaling pathway inhibitor ATRA) and subject to Morris water maze experiment. Then, the expression of Oxidative Stress (OS) markers, ferroptosis-associated proteins and Keap1/Nrf2 pathway in rat hippocampus was measured. In addition, rat hippocampal neuronal cell HT22 was purchased and treated accordingly based on the results of grouping, and cell proliferation and apoptosis in the three groups were determined. RESULTS: Compared with rats in the model group, those in the inhibition group showed shorter escape latency and an increased number of platform crossings (p < 0.05). Significant OS and neuron ferroptosis, increased apoptosis rate, elevated Keap1 expression, and decreased Nrf2 expression were observed in the model group compared to the control group (p < 0.05). The inhibition group exhibited notably improved OS and ferroptosis, as well as enhanced neuronal viability (p < 0.05). CONCLUSION: Inhibition of the Keap1/Nrf2 pathway can reverse the OS and neuron viability in EP rats.

Cross-domain heterogeneous metasurface inverse design based on a transfer learning method.

In this Letter, a transfer learning method is proposed to complete design tasks on heterogeneous metasurface datasets with distinct functionalities. Through fine-tuning the inverse design network and freezing the parameters of hidden layers, we successfully transfer the metasurface inverse design knowledge from the electromagnetic-induced transparency (EIT) domain to the three target domains of EIT (different design), absorption, and phase-controlled metasurface. Remarkably, in comparison to the source domain dataset, a minimum of only 700 target domain samples is required to complete the training process. This work presents a significant solution to lower the data threshold for the inverse design process and provides the possibility of knowledge transfer between different domain metasurface datasets.

Fighting bacteria with bacteria: A biocompatible living hydrogel patch for combating bacterial infections and promoting wound healing.

Bacterial infections are among the most critical global health challenges that seriously threaten the security of human. To address this issue, a biocompatible engineered living hydrogel patch was developed by co-embedding engineered photothermal bacteria (EM), photosensitizer (porphyrin) and reactive oxygen species amplifier (laccase) in a protein hydrogel. Remarkably, the genetice engineered bacteria can express melanin granules in vivo and this allows them to exhibit photothermal response upon being exposed to NIR-II laser (1064 nm) irradiation. Besides, electrostatically adhered tetramethylpyridinium porphyrin (TMPyP) on the bacterial surface and encapsulated laccase (Lac) in protein gel can generate highly toxic singlet oxygen (1O2) and hydroxyl radical (·OH) in the presence of visible light and lignin, respectively. Interestingly, the engineered bacteria hydrogel patch (EMTL@Gel) was successfully applied in synergistic photothermal, photodynamic and chemodynamic therapy, in which it was able to efficiently treat bacterial infection in mouse wounds and enhance wound healing. This work demonstrates the concept of "fighting bacteria with bacteria" combining bacterial engineering and material engineering into an engineered living hydrogel path that can synergistically boost the therapeutic outcome. STATEMENT OF SIGNIFICANCE: Genetically engineered bacteria produce melanin granules in vivo, exhibiting remarkable photothermal properties. These bacteria, along with a photosensitizer (TMPyP) and a reactive oxygen species amplifier (laccase), are incorporated into a biocompatible protein hydrogel patch. Under visible light, the patch generates toxic singlet oxygen (1O2) and hydroxyl radical (·OH), demonstrates outstanding synergistic effects in photothermal, photodynamic, and chemodynamic therapy, effectively treating bacterial infections and promoting wound healing in mice.

Electron Manipulation and Surface Reconstruction of Bimetallic Iron-Nickel Phosphide Nanotubes for Enhanced Alkaline Water Electrolysis.

Developing high-efficiency and stable bifunctional electrocatalysts for water splitting remains a great challenge. Herein, NiMoO4 nanowires as sacrificial templates to synthesize Mo-doped NiFe Prussian blue analogs are employed, which can be easily phosphorized to Mo-doped Fe2xNi2(1-x)P nanotubes (Mo-FeNiP NTs). This synthesis method enables the controlled etching of NiMoO4 nanowires that results in a unique hollow nanotube architecture. As a bifunctional catalyst, the Mo-FeNiP NTs present lower overpotential and Tafel slope of 151.3 (232.6) mV at 100 mA cm-2 and 76.2 (64.7) mV dec-1 for HER (OER), respectively. Additionally, it only requires an ultralow cell voltage of 1.47 V to achieve 10 mA cm-2 for overall water splitting and can steadily operate for 200 h at 100 mA cm-2. First-principles calculations demonstrate that Mo doping can effectively adjust the electron redistribution of the Ni hollow sites to optimize the hydrogen adsorption-free energy for HER. Besides, in situ Raman characterization reveals the dissolving of doped Mo can promote a rapid surface reconstruction on Mo-FeNiP NTs to dynamically stable (Fe)Ni-oxyhydroxide layers, serving as the actual active species for OER. The work proposes a rational approach addressed by electron manipulation and surface reconstruction of bimetallic phosphides to regulate both the HER and OER activity.

Palladium-Catalyzed Three-Component Cascade Carbonylation Reaction to Construct Benzofuran Derivatives.

A novel three-component cyclization carbonylation reaction of iodoarene-tethered propargyl ethers with amine and CO is reported. This palladium-catalyzed cascade reaction undergoes a sequence of oxidative addition, unsaturated bond migration, carbonyl insertion, and nucleophilic attack to deliver the benzofuran skeleton. Both aromatic amines and aliphatic amines could proceed smoothly in this transformation under one atm of CO.

Geographic origin shapes the adaptive divergences of Rotaria rotatoria (Rotifera, Bdelloidea) to thermal stress: Insights from ecology and transcriptomics.

Global warming has raised concerns regarding the potential impact on aquatic biosafety and health. To illuminate the adaptive mechanisms of bdelloid rotifers in response to global warming, the ecological and transcriptomic characteristics of two strains (HX and ZJ) of Rotaria rotatoria were investigated at 25°C and 35°C. Our results showed an obvious genetic divergence between the two geographic populations. Thermal stress significantly reduced the average lifespan of R. rotatoria in both strains, but increased the offspring production in the ZJ strain. Furthermore, the expression levels of genes Hsp70 were significantly upregulated in the HX strain, while GSTo1 and Cu/Zn-SOD were on the contrary. In the ZJ strain, the expression levels of genes Hsp70, CAT2, and GSTo1 were upregulated under thermal stress. Conversely, a significant decrease in the expression level of the Mn-SOD gene was observed in the ZJ strain under thermal stress. Transcriptomic profiling analysis revealed a total of 105 and 5288 differentially expressed genes (DEGs) in the HX and ZJ strains under thermal stress, respectively. The PCA results showed clear differences in gene expression pattern between HX and ZJ strains under thermal stress. Interestingly, compared to the HX strain, numerous downregulated DEGs in the ZJ strain were enriched into pathways related to metabolism under thermal stress, suggesting that rotifers from the ZJ strain prioritize resource allocation to reproduction by suppressing costly metabolic processes. This finding is consistent with the life table results. This study provides new insights into the adaptive evolution of aquatic animals in the context of global climate change.

Biomimetic-Mineralization-Assisted Self-Activation Creates a Delicate Porous Structure in Carbon Material for High-Rate Sodium Storage.

Porous carbons have shown their potential in sodium-ion batteries (SIBs), but the undesirable initial Coulombic efficiency (ICE) and rate capability hinder their practical application. Herein, learning from nature, we report an efficient method for fabricating a carbon framework (CK) with delicate porous structural regulation by biomimetic mineralization-assisted self-activation. The abundant pores and defects of the CK anode can improve the ICE and rate performance of SIBs in ether-based electrolytes, whereas they are confined in carbonate ester-based electrolytes. Notably, ether-based electrolytes enable CK anode to possess excellent ICE (82.9%) and high-rate capability (111.2 mAh g-1 at 50 A g-1). Even after 5500 cycles at a large current density of 10 A g-1, the capacity retention can still be maintained at 73.1%. More importantly, the full cell consisting of the CK anode and Na3V2(PO4)3 cathode delivers a high energy density of 204.4 Wh kg-1, with a power density of 2828.2 W kg-1. Such outstanding performance of the CK anode is attributed to (1) hierarchical pores, oxygen doping, and defects that pave the way for the transportation and storage of Na+, further enhancing ICE; (2) a high-proportion NaF-based solid-electrolyte-interphase (SEI) layer that facilitates Na+ storage kinetics in ether-based electrolytes; and (3) ether-based electrolytes that determine Na+ storage kinetics further to dominate the performance of SIBs. These results provide compelling evidence for the promising potential of our synthetic strategy in the development of carbon-based materials and ether-based electrolytes for electrochemical energy storage.

Construction of cyclobutane-fused tetracyclic skeletons via substrate-dependent EnT-enabled dearomative [2+2] cycloaddition of benzofurans (benzothiophenes)/maleimides.

Herein, a novel and facile organic photosensitizer (thioxanthone)-mediated energy-transfer-enabled (EnT-enabled) dearomative [2+2] cycloaddition of aromatic heterocycles/maleimides for green synthesis of cyclobutane-fused polycyclic skeletons is reported. Mechanistic investigations revealed that different EnT pathways by triplet thioxanthone were initiated when different aromatic heterocycles participated in the reaction, giving the corresponding excited intermediates, which underwent the subsequent intermolecular [2+2] cycloaddition to access the desired highly functionalized cyclobutane-fused polycyclic skeletons.

Exploring the neural correlates of fat taste perception and discrimination: Insights from electroencephalogram analysis.

Understanding neural pathways and cognitive processes involved in the transformation of dietary fats into sensory experiences has profound implications for nutritional well-being. This study presents an efficient approach to comprehending the neural perception of fat taste using electroencephalogram (EEG). Through the examination of neural responses to different types of fatty acids (FAs) in 45 participants, we discerned distinct neural activation patterns associated with saturated versus unsaturated fatty acids. The spectrum analysis of averaged EEG signals revealed notable variations in δ and α-frequency bands across FA types. The topographical distribution and source localization results suggested that the brain encodes fat taste with specific activation timings in primary and secondary gustatory cortices. Saturated FAs elicited higher activation in cortical associated with emotion and reward processing. This electrophysiological evidence enhances our understanding of fundamental mechanisms behind fat perception, which is helpful for guiding strategies to manage hedonic eating and promote balanced fat consumption.

Effect of superheated steam treatment on enzyme inactivation, morphostructural, physicochemical and digestion properties of sand rice (Agriophyllum squarrosum) flour.

The lipase (LA) and peroxidase (POD) activities, as well as morphological structure, physicochemical and digestion properties of sand rice flour (SRF) treated with superheated steam (SS), were investigated. SS treatment at 165 °C completely deactivated LA and resulted in a 98% deactivation of POD activities in SRF. This treatment also intensified gelatinization, induced noticeable color alterations, and decreased pasting viscosities. Furthermore, there was a moderate reduction in crystal structure, lamellar structure, and short-range ordered structure, with a pronounced reduction at temperatures exceeding 170 °C. These alterations significantly impacted SRF digestibility, leading to increased levels of rapidly digestible starch (RDS) and resistant starch (RS), with the highest RS content achieved at 165 °C. The effectiveness of SS treatment depends on temperature, with 165 °C being able to stabilize SRF with moderate changes in color and structure. These findings will provide a scientific foundation for SS applicated in SRF stabilization and modification.

J-Aggregate Promoting NIR-II Emission for Fluorescence/Photoacoustic Imaging-Guided Phototherapy.

J-aggregate is a promising strategy to enhance second near-infrared window (NIR-II) emission, while the controlled synthesis of J-aggregated NIR-II dyes is a huge challenge because of the lack of molecular design principle. Herein, bulk spiro[fluorene-9,9'-xanthene] functionalized benzobisthiadiazole-based NIR-II dyes (named BSFX-BBT and OSFX-BBT) are synthesized with different alkyl chains. The weak repulsion interaction between the donor and acceptor units and the S…N secondary interactions make the dyes to adopt a co-planar molecular conformation and display a peak absorption >880 nm in solution. Importantly, BSFX-BBT can form a desiring J-aggregate in the condensed state, and femtosecond transient absorption spectra reveal that the excited states of J-aggregate are the radiative states, and J-aggregate can facilitate stimulated emission. Consequently, the J-aggregated nanoparticles (NPs) display a peak emission at 1124 nm with a high relative quantum yield of 0.81%. The efficient NIR-II emission, good photothermal effect, and biocompatibility make the J-aggregated NPs demonstrate efficient antitumor efficacy via fluorescence/photoacoustic imaging-guided phototherapy. The paradigm illustrates that tuning the aggregate states of NIR-II dye via spiro-functionalized strategy is an effective approach to enhance photo-theranostic performance.

Factors impacting human exposure to legacy and emerging contaminants in residential dust in Beijing, China: Characteristics of indoor microenvironment.

Exposure to indoor dust is of concern since dust may be contaminated by various toxic chemicals and people spend considerable time indoors. Factors impacting human exposure risks to contaminants in indoor dust may differ from those affecting the loadings of contaminants, but the dominant factors have not yet been well clarified. In this study, the occurrence, human exposure, and related influencing factors of several classes of legacy and emerging contaminants in residential dust across Beijing were investigated, including per- and polyfluoroalkyl substances (PFASs) and three types of flame retardants (FRs), i.e., organophosphate esters (OPEs), polybrominated diphenyl ethers (PBDEs), and novel halogenated FRs (NHFRs). OPEs (median: 3847 ng/g) were the most abundant group, followed by PBDEs (1046 ng/g) and NHFRs (520 ng/g). PFASs (14.3 ng/g) were one to two orders of magnitude lower than FRs. The estimated daily intakes of these contaminants were relatively higher for toddlers than other age groups, with oral ingestion being the main exposure pathway compared with dermal contact. Higher human exposure risks were found in new buildings or newly finished homes due to the elevated intake of emerging contaminants (such as OPEs). Furthermore, higher risks were also found in homes with wooden floors, which were mainly associated with higher levels of PFASs, chloroalkyl and alkyl OPEs, compared with tile floors. Citizens in the urban area also showed higher exposure risks than those in the suburban area. The quantity of household appliances and finishing styles (simple or luxurious) showed an insignificant impact on overall human exposure risks despite their significant effect on the levels of some of the dust contaminants. Results in this study are of importance in understanding human exposure to the co-existence of multiple contaminants in indoor dust.

Establishment of the First National Standard for Neutralizing Antibodies against SARS-CoV-2 XBB Variants.

Neutralizing antibodies (NtAbs) against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are indicators of vaccine efficacy that enable immunity surveillance. However, the rapid mutation of SARS-CoV-2 variants prevents the timely establishment of standards required for effective XBB vaccine evaluation. Therefore, we prepared four candidate standards (No. 11, No. 44, No. 22, and No. 33) using plasma, purified immunoglobulin, and a broad-spectrum neutralizing monoclonal antibody. Collaborative calibration was conducted across nine Chinese laboratories using neutralization methods against 11 strains containing the XBB and BA.2.86 sublineages. This study demonstrated the reduced neutralization potency of the first International Standard antibodies to SARS-CoV-2 variants of concern against XBB variants. No. 44 displayed broad-spectrum neutralizing activity against XBB sublineages, effectively reduced interlaboratory variability for nearly all XBB variants, and effectively minimized the geometric mean titer (GMT) difference between the live and pseudotyped virus. No. 22 showed a broader spectrum and higher neutralizing activity against all strains but failed to reduce interlaboratory variability. Thus, No. 44 was approved as a National Standard for NtAbs against XBB variants, providing a unified NtAb measurement standard for XBB variants for the first time. Moreover, No. 22 was approved as a national reference reagent for NtAbs against SARS-CoV-2, offering a broad-spectrum activity reference for current and potentially emerging variants.

Planar-structured thiadiazoloquinoxaline-based NIR-II dye for tumor phototheranostics.

Second near-infrared (NIR-II) fluorescence imaging shows huge application prospects in clinical disease diagnosis and surgical navigation, while it is still a big challenge to exploit high performance NIR-II dyes with long-wavelength absorption and high fluorescence quantum yield. Herein, based on planar π-conjugated donor-acceptor-donor systems, three NIR-II dyes (TP-DBBT, TP-TQ1, and TP-TQ2) were synthesized with bulk steric hindrance, and the influence of acceptor engineering on absorption/emission wavelengths, fluorescence efficiency and photothermal properties was systematically investigated. Compared with TP-DBBT and TP-TQ2, the TP-TQ1 based on 6,7-diphenyl-[1,2,5]thiadiazoloquinoxaline can well balance absorption/emission wavelengths, NIR-II fluorescence brightness and photothermal effects. And the TP-TQ1 nanoparticles (NPs) possess high absorption ability at a peak absorption of 877 nm, with a high relative quantum yield of 0.69% for large steric hindrance hampering the close π-π stacking interactions. Furthermore, the TP-TQ1 NPs show a desirable photothermal conversion efficiency of 48% and good compatibility. In vivo experiments demonstrate that the TP-TQ1 NPs can serve as a versatile theranostic agent for NIR-II fluorescence/photoacoustic imaging-guided tumor phototherapy. The molecular planarization strategy provides an approach for designing efficient NIR-II fluorophores with extending absorption/emission wavelength, high fluorescence brightness, and outstanding phototheranostic performance.

Nanoplatform-based strategies for enhancing the lethality of current antitumor PDT.

Photodynamic therapy (PDT) exhibits great application prospects in future clinical oncology due to its spatiotemporal controllability and good biosafety. However, the antitumor efficacy of PDT is seriously hindered by many factors, including tumor hypoxia, limited light penetration ability, and strong defense mechanisms of tumors. Considering that it is difficult to completely solve the first two problems, enhancing the lethality of antitumor PDT has become a good idea to extend its clinical application. Herein, we summarize the nanoplatform-involved strategies to effectively amplify the tumoricidal capability of current PDT and then discuss the present bottlenecks and prospects of the nanoplatform-based PDT sensitization strategies in tumor therapy. We hope this review will provide some references for others to design high-performance PDT nanoplatforms for tumor therapy.

Organelle Ca2+/CAM1-SELTP confers somatic cell embryogenic competence acquisition and transformation in plant regeneration.

Somatic cell totipotency in plant regeneration represents the forefront of the compelling scientific puzzles and one of the most challenging problems in biology. How somatic embryogenic competence is achieved in regeneration remains elusive. Here, we discover uncharacterized organelle-based embryogenic differentiation processes of intracellular acquisition and intercellular transformation, and demonstrate the underlying regulatory system of somatic embryogenesis-associated lipid transfer protein (SELTP) and its interactor calmodulin1 (CAM1) in cotton as the pioneer crop for biotechnology application. The synergistic CAM1 and SELTP exhibit consistent dynamical amyloplast-plasmodesmata (PD) localization patterns but show opposite functional effects. CAM1 inhibits the effect of SELTP to regulate embryogenic differentiation for plant regeneration. It is noteworthy that callus grafting assay reflects intercellular trafficking of CAM1 through PD for embryogenic transformation. This work originally provides insight into the mechanisms responsible for embryogenic competence acquisition and transformation mediated by the Ca2+/CAM1-SELTP regulatory pathway, suggesting a principle for plant regeneration and cell/genetic engineering.

Dynamics of Center of Pressure Trajectory in Gait: Unilateral Transfemoral Amputees Versus Non-Disabled Individuals.

The primary goal of rehabilitation for individuals with lower limb amputation, particularly those with unilateral transfemoral amputation (uTFA), is to restore their ability to walk independently. Effective control of the center of pressure (COP) during gait is vital for maintaining balance and stability, yet it poses a significant challenge for individuals with uTFA. This study aims to study the COP during gait in individuals with uTFA and elucidate their unique compensatory strategies. This study involved 12 uTFA participants and age-matched non-disabled controls, with gait and COP trajectory data collected using an instrumented treadmill. Gait and COP parameters between the control limb (CL), prosthetic limb (PL), and intact limb (IL) were compared. Notably, the mediolateral displacement of COP in PL exhibited significant lateral displacement compared to the CL from 30% to 60% of the stance. In 20% to 45% of the stance, the COP forward speed of PL was significantly higher than that of the IL. Furthermore, during the initial 20% of the stance, the vertical ground reaction force of PL was significantly lower than that of IL. Additionally, individuals with uTFA exhibited a distinct gait pattern with altered duration of loading response, single limb support, pre-swing and swing phases, and step time. These findings indicate the adaptability of individuals with uTFA in weight transfer, balance control, and pressure distribution on gait stability. In conclusion, this study provides valuable insights into the unique gait dynamics and balance strategies of uTFA patients, highlighting the importance of optimizing prosthetic design, alignment procedures, and rehabilitation programs to enhance gait patterns and reduce the risk of injuries due to compensatory movements.

Hypoxia-inducible factor 1α inhibits heat stress-induced pig intestinal epithelial cell apoptosis through eif2α/ATF4/CHOP signaling.

Unstoppable global warming and increased frequency of extreme heat leads to human and animals easier to suffer from heat stress (HS), with gastrointestinal abnormalities as one of the initial clinical symptoms. HS induces intestinal mucosal damage owing to intestinal hypoxia and hyperthermia. Hypoxia-inducible factor 1α (HIF-1α) activates numerous genes to mediate cell hypoxic responses; however, its role in HS-treated intestinal mucosa is unknown. This work aimed to explore HIF-1α function and regulatory mechanisms in HS-treated pig intestines. We assigned 10 pigs to control and moderate HS groups. Physical signs, stress, and antioxidant levels were detected, and the intestines were harvested after 72 h of HS treatment to study histological changes and HIF-1α, heat shock protein 90 (HSP90), and prolyl-4-hydroxylase 2 (PHD-2) expression. In addition, porcine intestinal columnar epithelial cells (IPEC-J2) underwent HS treatment (42 °C, 5 % O2) to further explore the functions and regulatory mechanism of HIF-1α. The results of histological examination revealed HS caused intestinal villi damage and increased apoptotic epithelial cell; the expression of HIF-1α and HSP90 increased while PHD-2 showed and opposite trend. Transcriptome sequencing analysis revealed that HS activated HIF-1 signaling. To further explore the role of HIF-1α on HS induced IPEC-J2 apoptosis, the HIF-1α was interfered and overexpression respectively, and the result confirmed that HIF-1α could inhibited cell apoptosis under HS. Furthermore, HS-induced apoptosis depends on eukaryotic initiation factor 2 alpha (eif2α)/activating transcription factor 4 (ATF4)/CCAAT-enhancer-binding protein homologous protein (CHOP) pathway, and HIF-1α can inhibit this pathway to alleviate IPEC-J2 cell apoptosis. In conclusion, this study suggests that HS can promote intestinal epithelial cell apoptosis and cause pig intestinal mucosal barrier damage; the HIF-1α can alleviate cell apoptosis by inhibiting eif2α/ATF4/CHOP signaling. These results indicate that HIF-1α plays a protective role in HS, and offers a potential target for HS prevention and mitigation.