Computational Exploration of 1,2-Carboamine Carbonylation Catalyzed by Nickel.

Nickel-catalyzed carbonylation of alkenes is a stereoselective and regioselective method for the synthesis of amide compounds. Theoretical predictions with density functional theory calculations revealed the mechanism and origin of stereoselectivity and regioselectivity for the nickel-catalyzed carbonylation of norbornene. The carbonylation reaction proceeds through oxidative addition, migration insertion of alkenes, and subsequent reduction elimination to afford cis-carbonylation product. The C-N bond activation of amides is unfavorable because the oxidative addition ability of the C-C bond is stronger than that of the C-N bond. The determining step of stereoselectivity is the migratory insertion of the strained olefin. The structural analysis shows that steroselectivity is controlled by the steric hindrance of methyl groups to olefins and substituents to IMes in ligands.

Mechanism and Origins of Regio- and Stereoselective Alkylboration of Endocyclic Olefins Enabled by Nickel Catalysis.

The Ni-catalyzed alkylboration of endocyclic olefins is a stereo- and regioselective approach for the synthesis of boron-containing compounds. We report a detailed density functional theory (DFT) study to elucidate the mechanism and origins of the stereo-, chemo-, and regioselectivity of alkylboration of endocyclic olefins enabled by nickel catalysis. The alkylboration proceeds via the migratory insertion of alkenes, ß-H elimination of the Ni(II) complex, subsequent migratory insertion leading to a new Ni(II) complex, combined with an alkyl radical, and reductive eliminations. The electronic effects of the endocyclic olefins synergistically control the regioselectivity toward the C1- and C2-position boration. In C1-position boration, a more electron-deficient carbon atom tends to combine with an electron-rich -Bpin group and leads to C1-position boration products. The stereoselectivity is influenced by the solvent effect, and the interaction between the substrate and Ni-catalyzed groups, the low-polarity solvent 1,4-dioxane, and a favorable steric hindrance effect result in the cis-alkylboration product. Chemoselectivity toward 1,3-alkylboration results from the steric hindrance effects of the -Bpin group.

Cyclometalated Half-Sandwich Ruthenium Complexes: Preparation, Structure, and Catalytic Synthesis of Phenolic Esters from Aryl Halides without Using External CO under Air.

A series of cyclometalated C,N-chelate half-sandwich ruthenium complexes based on N-heterocyclic ligands were prepared through a simple route with good yields. These air- and moisture-stable cyclometalated ruthenium complexes showed excellent catalytic efficiency in phenoxy carbonylation of aryl halides with phenyl formate derivatives as a CO source and phenol as a coupling partner under air. Ester products were obtained with high yields at room temperature and without the need for an inert atmosphere. The excellent catalytic activity, broad substrate range, and mild reaction conditions made this catalytic system potential for industrial production. In addition, DFT study has been carried out to elaborate the possible mechanism of this Ru-catalyzed reaction.

Optogenetic therapy restores retinal activity in primate for at least a year following photoreceptor ablation.

All retina-based vision restoration approaches rely on the assumption that photoreceptor loss does not preclude reactivation of the remaining retinal architecture. Whether extended periods of vision loss limit the efficacy of restorative therapies at the retinal level is unknown. We examined long-term changes in optogenetic responsivity of foveal retinal ganglion cells (RGCs) in non-human primates following localized photoreceptor ablation by high-intensity laser exposure. By performing fluorescence adaptive optics scanning light ophthalmoscopy (AOSLO) of RGCs expressing both the calcium indicator GCaMP6s and the optogenetic actuator ChrimsonR, it was possible to track optogenetic-mediated calcium responses in deafferented RGCs over time. Fluorescence fundus photography revealed a 40% reduction in ChrimsonR fluorescence from RGCs lacking photoreceptor input over the 3 weeks following photoreceptor ablation. Despite this, in vivo imaging revealed good cellular preservation of RGCs 3 months after the loss of photoreceptor input, and histology confirmed good structural preservation at 2 years. Optogenetic responses of RGCs in primate persisted for at least 1 year after the loss of photoreceptor input, with a sensitivity index similar to optogenetic responses recorded in intact retina. These results are promising for all potential therapeutic approaches to vision restoration that rely on preservation and reactivation of RGCs.

Dynamic 3D phase-shifting profilometry based on a corner optical flow algorithm.

Real-time 3D reconstruction has been applied in many fields, calling for many ongoing efforts to improve the speed and accuracy of the used algorithms. Phase shifting profilometry based on the Lucas-Kanade optical flow method is a fast and highly precise method to construct and display the three-dimensional shape of objects. However, in this method, a dense optical flow calculation is required for the modulation image corresponding to the acquired deformed fringe pattern, which consumes a lot of time and affects the real-time performance of 3D reconstruction and display. Therefore, this paper proposes a dynamic 3D phase shifting profilometry based on a corner optical flow algorithm to mitigate this issue. Therein, the Harris corner algorithm is utilized to locate the feature points of the measured object, so that the optical flow needs to calculate for only the feature points which, greatly reduces the amount of calculation time. Both our experiments and simulations show that our method improves the efficiency of pixel matching by four times and 3D reconstruction by two times.

G protein subunit gamma 5 promotes the proliferation, metastasis and glycolysis of breast cancer cells through the Wnt/ß-catenin pathway.

GNG5 is suggested to exert a critical effect on tumor development in human beings; however, its function and related mechanism within breast cancer (BC) are still unclear. In this regard, the present work focused on identifying and evaluating GNG5's function and revealing its possible molecular mechanism. Subcutaneous tumorigenesis model of nude mice and in-vitro cell model was established. The relationship between GNG5 expression and BC was studied through knockdown and overexpression experiments. The proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of liver cancer cell lines overexpressing or silencing GNG5 were detected. Furthermore, the pathway mechanism of GNG5 was evaluated at the molecular level and was performed to further verify the possible targets and mechanisms of action. In comparison with that in normal tissue, GNG5 level within BC tissue was higher. In addition, GNG5 overexpression stimulated BC cell proliferation, invasion, migration and EMT. BC cells with reduced GNG5 expression exhibited significant decreases in glucose uptake, lactate levels, and ATP concentrations. In addition, GNG5 knockdown inhibited Wnt/ß-catenin signaling. This study indicates that GNG5 may generate a vital function in BC. The results of the current work demonstrated GNG5's effect on BC pathological process, also providing a reference for developing new targeted therapies for BC.

Protective effect of methionine on the intestinal oxidative stress and microbiota change induced by nickel.

Nickel is a common heavy metal pollutant in industrial areas and can cause oxidative damage to human and animal organs. As an essential amino acid with antioxidant function, methionine (Met) may protect the body from the oxidative stress induce by nickel, however, there is not enough research to study in this aspect. The study aims at investigating the effect of Met on the nickel-induced intestinal oxidative stress and further detected the gut microbiota changes. Mice were gavaged with quantitative NiCl2 (1.6 mg/ml, 0.25 ml) and fed with different doses of methionine in each group. The contents of intestinal oxidation product and antioxidant enzymes were determined by different biochemical quantitative methods, and the data showed that NiCl2 increased the content of intestinal oxidation product (MDA), and the antioxidant enzymes (GSH-Px, GR, SOD and CAT) were decreased. But this situation was alleviated in the group fed with additional methionine solution (0.5 mg/ml). In addition, we detected changes in the gut microbiota using high-throughput sequencing, the results showed that the structure of intestinal flora was disturbed by NiCl2, but methionine restored the germs with antioxidant capacity. Based on the results, we speculate that methionine can alleviate the impact of NiCl2 on the intestinal by enhancing the activity of antioxidant enzymes and the number of gut bacteria with anti-oxidation, suggesting that methionine as a nutritional additive may have the potential to treat nickel poisoning.

The Effect of Posture on Maximum Grip Strength Measurements.

INTRODUCTION/BACKGROUND: The purpose of this study was to compare the grip strength values obtained under 4 postures, and to identify the position providing the maximum grip strength value. We also explored the effects of different body positions on grip strength measurements and the significance of the selection of measurement position for guiding the screening and diagnosis of sarcopenia. METHODOLOGY: A total of 764 people (409 males and 355 females) participated in this study. Grip strength was measured in 4 positions: (1) standing with the elbow fully extended; (2) standing with arms raised; (3) sitting with the elbow flexed 90°; and (4) sitting with the elbow extended. Multiple linear regression model was used to compare the grip strength measurements obtained from these 4 positions by each hand when considering the influence of age, gender, body mass index, and other factors. RESULTS: Both male and female grip strength values in the standing position with the elbow fully extended were significantly greater than those in other positions. In addition, the grip strength measured by standing posture was generally greater than measured by sitting posture. In contrast, grip strength values in the 2 sitting positions did not differ significantly. The grip strength of men was generally greater than that of women. CONCLUSIONS: The findings reveal that grip strength measured while standing with the elbow fully extended is greater than that measured while sitting, which is the posture currently recommended in clinical practice. Clinicians and researchers should choose the appropriate and optimal postures to measure grip strength.

miR-326 reverses chemoresistance in human lung adenocarcinoma cells by targeting specificity protein 1.

Cisplatin resistance is a major obstacle in the treatment of lung adenocarcinoma (LAD), and its mechanism has not been fully elucidated. Here, we report that miR-326 is downregulated in cisplatin-resistant A549/CDDP cells compared with parental A549 cells. Overexpression of miR-326 reversed cisplatin chemoresistance of LAD cells in vitro and in vivo. Moreover, we identified the specificity protein 1 (SP1) gene as a novel direct target of miR-326. Knockdown of SP1 revealed similar effects as that of ectopic miR-326 expression. Decreased miR-326 expression was also detected in tumor tissues sampled from LAD patients treated with cisplatin-based chemotherapy and was proved to be correlated with high expression of SP1 and decreased sensitivity to cisplatin. Furthermore, we show that the long noncoding RNA HOTAIR repression reverses chemoresistance of LAD cells partially through modulation of miR-326/SP1 pathway. In summary, we unveil a branch of the HOTAIR/miR-326/SP1 pathway that regulates chemoresistance of LAD cells.

Mechanism of Ligand-Controlled Regioselectivity-Switchable Copper-Catalyzed Alkylboration of Alkenes.

Cu-catalyzed alkylboration of alkenes with bis(pinacolato)diboron ((Bpin)2 ) and alkyl halides provides a ligand-controlled regioselectivity-switchable method for the construction of complex boron-containing compounds. Here, we employed DFT methods to elucidate the mechanistic details of this reaction and the origin of the different regioselectivity induced by Xantphos and Cy-Xantphos. The calculation results reveal that the catalytic cycle mainly proceeds through the migratory insertion of alkenes on Cu-Bpin complex, the oxidative addition of alkyl halides, and the reductive elimination of a C-C bond. Meanwhile, the rate- determining step is the oxidative addition of alkyl halides and the regioselectivity-determining step is the migratory insertion of alkenes. The bulky cyclohexyl group of Cy-Xantphos facilitates the approach of the substituents of alkenes to Bpin in the migratory insertion step and thus leads to the Markovnikov products. The less bulky phenyl group on Xantphos prefers keeping the substituents of alkenes away from the Bpin moiety in the migratory insertion step and thus results in anti-Markovnikov products.

Ligand-Controlled Regiodivergent Copper-Catalyzed Alkylboration of Alkenes.

A novel copper-catalyzed regiodivergent alkylboration of alkenes with bis(pinacolato)diboron and alkyl halides has been developed. The regioselectivity of the alkylboration was controlled by subtle differences in the ligand structure. The reaction thus enables the practical, regiodivergent synthesis of two different alkyl boronic esters with complex structures from a single alkene.

A novel PANoptosis-related long non-coding RNA index to predict prognosis, immune microenvironment and personalised treatment in hepatocellular carcinoma.

BACKGROUND: PANoptosis is involved in the interaction of apoptosis, necroptosis and pyroptosis, playing a role in programmed cell death. Moreover, long non-coding RNAs (lncRNAs) regulate the PCD. This work aims to explore the role of PANoptosis-associated lncRNAs in hepatocellular carcinoma (HCC). METHODS: Co-expression analysis identified PANoptosis-associated lncRNAs in HCC. Cox and Least Absolute Shrinkage and Selection Operator (LASSO) algorithms were utilised to filter lncRNAs and establish a PANoptosis-related lncRNA index (PANRI). Additionally, Cox, Kaplan-Meier and receiver operating characteristic (ROC) curves were utilised to systematically evaluate the PANRI. Furthermore, Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE), single sample gene set enrichment analysis (ssGSEA) and immune checkpoints were performed to analyse the potential of the PANRI in differentiating different tumour immune microenvironment (TIME) populations. The consensus clustering algorithm was used to distinguish individuals with HCC having different TIME subtypes. Finally, HCC cell lines HepG2 were utilised for further validation in in vitro experiments. RESULTS: The PANRI differentiates patients according to risk. Notably, ESTIMATE and ssGSEA algorithms revealed a high immune infiltration status in high-risk patients. Additionally, consensus clustering divided the patients into three clusters to identify different subtypes of TIME. Moreover, in vitro results showed that siRNA-mediated silencing of AL049840.4 inhibited the viability and migration of HepG2 cells and promoted apoptosis. CONCLUSIONS: This is the first PANoptosis-related, lncRNA-based risk index in HCC to assess patient prognosis, TIME and response to immunotherapy. This study offers novel perspectives on the role of PANoptosis-associated lncRNAs in HCC.

Enhanced enantioselective separation of racemic menthol via reverse-phase high-performance liquid chromatography: Method development and computational insights for pre-screening.

A robust and efficient enantioselective separation of racemic menthol was achieved on a standard C18 column with reverse-phase high-performance liquid chromatography (RP-HPLC) and UV detector. (R)-α-hydroxy-4-methylbenzeneacetic acid was utilized as the pre-column derivatization reagent. The impact of mobile phase composition on diastereomer selectivity was thoroughly investigated, resulting in a high resolution of 2.11 under optimized conditions. The method was rigorously validated for linearity, precision, accuracy, limit of detection (LOD) and limit of quantification (LOQ). Notably, a separation pre-screening mechanism (SPM) and a prediction model was developed based on density functional theory (DFT) studies. This model elucidated the relationship between molecular polarity differences (△MPI) and chromatographic behavior, facilitating the interpretation and prediction of racemic menthol resolution with various chiral derivatization reagents. The present work not only presents an efficient and economical approach for menthol enantiomeric separation, but also offers valuable insights for the innovative design and advancement of chromatographic methodologies for a wide array of chiral enantiomers.

Foveal RGCs develop altered calcium dynamics weeks after photoreceptor ablation.

Objective or purpose: Physiological changes in retinal ganglion cells (RGCs) have been reported in rodent models of photoreceptor (PR) loss but this has not been investigated in primates. By expressing both a calcium indicator (GCaMP6s) and an optogenetic actuator (ChrimsonR) in foveal RGCs of the macaque, we reactivated RGCs in vivo and assessed their response in the weeks and years following PR loss. Design: We used an in vivo calcium imaging approach to record optogenetically evoked activity in deafferented RGCs in primate fovea. Cellular scale recordings were made longitudinally over a 10 week period following photoreceptor ablation and compared to responses from RGCs that had lost photoreceptor input more than two years prior. Participants: Three eyes received photoreceptor ablation, OD of a male Macaca mulatta (M1), OS of a female Macaca fascicularis (M2) and OD of a male Macaca fascicularis (M3). Two animals were used for in vivo recording, one for histological assessment. Methods: Cones were ablated with an ultrafast laser delivered through an adaptive optics scanning light ophthalmoscope (AOSLO). A 0.5 s pulse of 25Hz 660nm light optogenetically stimulated RGCs, and the resulting GCaMP fluorescence signal was recorded using AOSLO. Measurements were repeated over 10 weeks immediately after PR ablation, at 2.3 years and in control RGCs. Main Outcome measures: The calcium rise time, decay constant and sensitivity index of optogenetic mediated RGC were derived from GCaMP fluorescence recordings from 221 RGCs (Animal M1) and 218 RGCs (Animal M2) in vivo. Results: Following photoreceptor ablation, the mean decay constant of the calcium response in RGCs decreased 1.5 fold (1.6±0.5 s to 0.6±0.3 s SD) over the 10 week observation period in subject 1 and 2.1 fold (2.5±0.5 s to 1.2±0.2 s SD) within 8 weeks in subject 2. Calcium rise time and sensitivity index were stable. Optogenetic reactivation remained possible 2.3 years after PR ablation. Conclusions: Altered calcium dynamics developed in primate foveal RGCs in the weeks after photoreceptor ablation. The mean decay constant of optogenetic mediated calcium responses decreased 1.5 - 2-fold. This is the first report of this phenomenon in primate retina and further work is required to understand the role these changes play in cell survival and activity.

The biological function of demethylase ALKBH1 and its role in human diseases.

AlkB homolog 1 (ALKBH1) is a member of the AlkB family of dioxygenases that are dependent on Fe(II) and α-ketoglutarate. Mounting evidence demonstrates that ALKBH1 exhibits enzymatic activity against various substrates, including N6-methyladenosine (m6A), N1-methyladenosine (m1A), N3-methylcytidine (m3C), 5-methylcytosine (m5C), N6-methyladenine (N6-mA, 6mA), and H2A, indicating its dual roles in different biological processes and involvement in human diseases. Up to the present, there is ongoing debate regarding ALKBH1's enzymatic activity. In this review, we present a comprehensive summary of recent research on ALKBH1, including its substrate diversity and pathological roles in a wide range of human disorders, the underlying mechanisms of its functions, and its dysregulation. We also explored the potential of ALKBH1 as a prognostic target.

Dual beam optical coherence tomography angiography for decoupling axial velocity gradient.

Axial velocity gradient (AVG) in the optical coherence tomography angiography (OCTA) signal affects measurement accuracy when the flow is not perpendicular to the scanning beam. We developed a dual beam OCTA method to decouple the contribution of AVG from the decorrelation signal. Decoupling is first verified by phantom experiments which reduces measurement uncertainty from 1.5 to 0.7% (standard deviation). We also tested the method in human skin in vivo and the results indicate that the contribution of AVG to decorrelation signal is reduced.

Foveal Retinal Ganglion Cells Develop Altered Calcium Dynamics Weeks After Photoreceptor Ablation.

Purpose: Physiological changes in retinal ganglion cells (RGCs) have been reported in rodent models of photoreceptor (PR) loss, but this has not been investigated in primates. By expressing both a calcium indicator (GCaMP6s) and an optogenetic actuator (ChrimsonR) in foveal RGCs of the macaque, we reactivated RGCs in vivo and assessed their response in the weeks and years after PR loss. Design: We used an in vivo calcium imaging approach to record optogenetically evoked activity in deafferented RGCs in primate fovea. Cellular scale recordings were made longitudinally over a 10-week period after PR ablation and compared with responses from RGCs that had lost PR input >2 years prior. Participants: Three eyes received PR ablation, the right eye of a male Macaca mulatta (M1), the left eye of a female Macaca fascicularis (M2), and the right eye of a male Macaca fascicularis (M3). Two animals were used for in vivo recording, 1 for histological assessment. Methods: Cones were ablated with an ultrafast laser delivered through an adaptive optics scanning light ophthalmoscope (AOSLO). A 0.5 second pulse of 25 Hz 660 nm light optogenetically stimulated RGCs, and the resulting GCaMP fluorescence signal was recorded using an AOSLO. Measurements were repeated over 10 weeks immediately after PR ablation, at 2.3 years and in control RGCs. Main Outcome Measures: The calcium rise time, decay constant, and sensitivity index of optogenetic-mediated RGC were derived from GCaMP fluorescence recordings from 221 RGCs (animal M1) and 218 RGCs (animal M2) in vivo. Results: After PR ablation, the mean decay constant of the calcium response in RGCs decreased 1.5-fold (standard deviation 1.6 ± 0.5 seconds to 0.6 ± 0.3 seconds) over the 10-week observation period in subject 1 and 2.1-fold (standard deviation 2.5 ± 0.5 seconds to 1.2 ± 0.2 seconds) within 8 weeks in subject 2. Calcium rise time and sensitivity index were stable. Optogenetic reactivation remained possible 2.3 years after PR ablation. Conclusions: Altered calcium dynamics developed in primate foveal RGCs in the weeks after PR ablation. The mean decay constant of optogenetic-mediated calcium responses decreased 1.5- to twofold. This is the first report of this phenomenon in primate retina and further work is required to understand the role these changes play in cell survival and activity. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Coaxial Bright and Dark Field Optical Coherence Tomography.

To improve the signal collection efficiency of Optical Coherence Tomography (OCT) for biomedical applications. A novel coaxial optical design was implemented, utilizing a wavefront-division beam splitter in the sample arm with a 45-degree rod mirror. This design allowed for the simultaneous collection of bright and dark field signals. The bright field signal was detected within its circular aperture in a manner similar to standard OCT, while the dark field signal passed through an annular-shaped aperture and was collected by the same spectrometer via a fiber array. This new configuration improved the signal collection efficiency by ∼3 dB for typical biological tissues. Dark-field OCT images were found to provide higher resolution, contrast and distinct information compared to standard bright-field OCT. By compounding bright and dark field images, speckle noise was suppressed by ∼ √2 . These advantages were validated using Teflon phantoms, chicken breast ex vivo, and human skin in vivo. This new OCT configuration significantly enhances signal collection efficiency and image quality, offering great potential for improving OCT technology with better depth, contrast, resolution, speckles, and signal-to-noise ratio. We believe that the bright and dark field signals will enable more comprehensive tissue characterization with the angled scattered light. This advancement will greatly promote the OCT technology in various clinical and biomedical research applications.

A novel sphingolipid metabolism-related long noncoding RNA signature predicts the prognosis, immune landscape and therapeutic response in pancreatic adenocarcinoma.

Sphingolipid metabolism affects prognosis and resistance to immunotherapy in patients with cancer and is an emerging target in cancer therapy with promising diagnostic and prognostic value. Long noncoding ribonucleic acids (lncRNAs) broadly regulate tumour-associated metabolic reprogramming. However, the potential of sphingolipid metabolism-related lncRNAs in pancreatic adenocarcinoma (PAAD) is poorly understood. In this study, coexpression algorithms were employed to identify sphingolipid metabolism-related lncRNAs. The least absolute shrinkage and selection operator (LASSO) algorithm was used to develop a sphingolipid metabolism-related lncRNA signature (SMLs). The prognostic predictive stability of the SMLs was validated using Kaplan-Meier. Univariate and multivariate Cox, receiver operating characteristic (ROC) and clinical stratification analyses were used to comprehensively assess the SMLs. Gene set variation analysis (GSVE), gene ontology (GO) and tumor mutation burden (TMB) analysis explored the potential mechanisms. Additionally, single sample gene set enrichment analysis (ssGSEA), ESTIMATE, immune checkpoints and drug sensitivity analysis were used to investigate the potential predictive function of the SMLs. Finally, an SMLs-based consensus clustering algorithm was utilized to differentiate patients and determine the suitable population for immunotherapy. The results showed that the SMLs consists of seven sphingolipid metabolism-related lncRNAs, which can well determine the clinical outcome of individuals with PAAD, with high stability and general applicability. In addition, the SMLs-based consensus clustering algorithm divided the TCGA-PAAD cohort into two clusters, with Cluster 1 showing better survival than Cluster 2. Additionally, Cluster 1 had a higher level of immune cell infiltration than Cluster 2, which combined with the higher levels of immune checkpoints in Cluster 1 suggests that Cluster 1 is more consistent with an immune 'hot tumor' profile and may respond better to immune checkpoint inhibitors (ICIs). This study offers new insights regarding the potential role of sphingolipid metabolism-related lncRNAs as biomarkers in PAAD. The constructed SMLs and the SMLs-based clustering are valuable tools for predicting clinical outcomes in PAAD and provide a basis for clinical selection of individualized treatments.

Hormetic responses to cadmium exposure in wheat seedlings: insights into morphological, physiological, and biochemical adaptations.

Cadmium is commonly recognized as toxic to plant growth, low-level Cd has promoting effects on growth performance, which is so-called hormesis. Although Cd toxicity in wheat has been widely investigated, knowledge of growth response to a broad range of Cd concentrations, especially extremely low concentrations, is still unknown. In this study, the morphological, physiological, and biochemical performance of wheat seedlings to a wide range of Cd concentrations (0-100 µΜ) were explored. Low Cd treatment (0.1-0.5 µM) improved wheat biomass and root development by enhancing the photosynthetic system and antioxidant system ability. Photosynthetic rate (Pn) was improved by 5.72% under lower Cd treatment (1 µΜ), but inhibited by 6.05-49.85% from 5 to 100 µΜ. Excessive Cd accumulation induced oxidative injury manifesting higher MDA content, resulting in lower photosynthetic efficiency, stunted growth, and reduction of biomass. Further, the contents of ascorbate, glutathione, non-protein thiols, and phytochelatins were improved under 5-100 µΜ Cd treatment. The ascorbate peroxidase activity in the leaf showed a hormetic dose-response characteristic. Correlation analysis and partial least squares (PLS) results indicated that antioxidant enzymes and metabolites were closely correlated with Cd tolerance and accumulation. The results of the element network, correlation analysis, and PLS showed a crucial role for exogenous Cd levels in K, Fe, Cu, and Mn uptake and accumulation. These results provided a deeper understanding of the hormetic effect of Cd in wheat, which would be beneficial for improving the quality of hazard and risk assessments.