Microplastic contamination accelerates soil carbon loss through positive priming.

The priming effect, i.e., the changes in soil organic matter (SOM) decomposition following fresh organic carbon (C) inputs is known to influence C storage in terrestrial ecosystems. Microplastics (particle size <5 mm) are ubiquitous in soils due to the increasing use and often inadequate end-of-life management of plastics. Conventional polyethylene and bio-degradable (PHBV) plastics contain large amounts of C within their molecular structure, which can be assimilated by microorganisms. However, the extent and direction of the potential priming effect induced by microplastics is unclear. As such, we added 14C-labeled glucose to investigate how background polyethylene and PHBV microplastics (1 %, w/w) affect SOM decomposition and its potential microbial mechanisms in a short-term. The cumulative CO2 emission in soil contaminated with PHBV was 42-53 % higher than under Polyethylene contaminated soil after 60-day incubation. Addition of glucose increased SOM decomposition and induced a positive priming effect, as a consequence, caused a negative net soil C balance (-59 to -132 µg C g-1 soil) regardless of microplastic types. K-strategists dominated in the PHBV-contaminated soils and induced 72 % higher positive priming effects as compared to Polyethylene-contaminated soils (160 vs. 92 µg C g-1 soil). This was attributed to the enhanced decomposition of recalcitrant SOM to acquire nitrogen. The stronger priming effect associated in PHBVs can be attributed to cooperative decomposition among fungi and bacteria, which metabolize more recalcitrant C in PHBV. Moreover, comparatively higher calorespirometric ratios, lower substrate use efficiency, and larger enzyme activity but shorter turnover time of enzymes indicated that soil contaminated with PHBV release more energy, and have a more efficient microbial catabolism and are more efficient in SOM decomposition and nutrient resource uptake. Overall, microplastics, (especially bio-degradable microplastics) can alter biogeochemical cycles with significant negative consequences for C sequestration via increasing SOM decomposition in agricultural soils and for regional and global C budgets.

Synthesis and Optimization of Small Molecule Inhibitors of Prostate Specific Antigen.

Semen liquefaction is a postejaculation process that transforms semen from a gel-like (coagulated) form to a water-like consistency (liquefied). This process is primarily regulated by serine proteases from the prostate gland, most prominently, prostate-specific antigen (PSA; KLK3). Inhibiting PSA activity has the potential to impede liquefaction of human semen, presenting a promising target for nonhormonal contraception in the female reproductive tract. This study employed triazole B1 as a starting compound. Through systematic design, synthesis, and optimization, we identified compound 20 (CDD-3290) as a 216 nM inhibitor of PSA with better stability in media than triazole B1. Further, we also evaluated the selectivity profile of compound 20 (CDD-3290) by testing against closely related proteases and demonstrated excellent inhibition of PSA versus α-chymotrypsin and elastase and similar potency versus thrombin. Thus, compound 20 is an improved PSA inhibitor that can be tested for efficacy in vitro or in the female reproductive tract.

Non-invasive multimodal CT deep learning biomarker to predict pathological complete response of non-small cell lung cancer following neoadjuvant immunochemotherapy: a multicenter study.

OBJECTIVES: Although neoadjuvant immunochemotherapy has been widely applied in non-small cell lung cancer (NSCLC), predicting treatment response remains a challenge. We used pretreatment multimodal CT to explore deep learning-based immunochemotherapy response image biomarkers. METHODS: This study retrospectively obtained non-contrast enhanced and contrast enhancedbubu CT scans of patients with NSCLC who underwent surgery after receiving neoadjuvant immunochemotherapy at multiple centers between August 2019 and February 2023. Deep learning features were extracted from both non-contrast enhanced and contrast enhanced CT scans to construct the predictive models (LUNAI-uCT model and LUNAI-eCT model), respectively. After the feature fusion of these two types of features, a fused model (LUNAI-fCT model) was constructed. The performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. SHapley Additive exPlanations analysis was used to quantify the impact of CT imaging features on model prediction. To gain insights into how our model makes predictions, we employed Gradient-weighted Class Activation Mapping to generate saliency heatmaps. RESULTS: The training and validation datasets included 113 patients from Center A at the 8:2 ratio, and the test dataset included 112 patients (Center B n=73, Center C n=20, Center D n=19). In the test dataset, the LUNAI-uCT, LUNAI-eCT, and LUNAI-fCT models achieved AUCs of 0.762 (95% CI 0.654 to 0.791), 0.797 (95% CI 0.724 to 0.844), and 0.866 (95% CI 0.821 to 0.883), respectively. CONCLUSIONS: By extracting deep learning features from contrast enhanced and non-contrast enhanced CT, we constructed the LUNAI-fCT model as an imaging biomarker, which can non-invasively predict pathological complete response in neoadjuvant immunochemotherapy for NSCLC.

Multi-ligand strategy for enhanced removal of heavy metal ions by thiol-functionalized defective Zr-MOFs.

Given the significant global concern about heavy metal pollution, the development of effective adsorbents to capture pollutants has become an urgent issue. In this work, thiol-functionalized defective Zr-MSA-DMSA was designed by mixing 2,3-dimercaptosuccinic acid and mercaptosuccinic acid, which was applied for the rapid and efficient removal of M(II) (i.e., Pb(II), Hg(II), Cd(II)) from wastewater. Zr-MSA-DMSA exhibited excellent adsorption performance, and the maximum adsorption capacities for Pb(II), Hg(II), and Cd(II) were 715.2 mg g-1, 862.7 mg g-1, and 450.5 mg g-1. In actual wastewater, Zr-DMSA-MSA exhibited up to 97 % M(II) removal efficiency and excellent anti-interference ability. It also maintained good structural stability after five adsorption/regeneration cycles. Thus, the abundant oxygen vacancies and unsaturated adsorption sites on Zr-MSA-DMSA significantly improved the adsorption performance of M(II). Spectral analysis and DFT calculations confirmed that Zr-MSA-DMSA mainly relied on the coordination of sulfur and oxygen atoms, electrostatic attraction and a large number of defective sites to achieve the adsorption of M(II). Fixed bed experiments showed that Zr-MSA-DMSA exhibited a depletion time of 10500 min and a volume of 7.0 L. In summary, Zr-MSA-DMSA holds significant potential for treating heavy metal wastewater and provides potential applications for defect engineering.

DNA-stable isotope probing and metagenomics reveal Fe(II) oxidation by core microflora in microoxic rhizospheric habitats to mitigate the accumulation of cadmium and phenanthrene in rice.

Rice rhizosphere soil-porewater microdomains exist within an iron (Fe)-rich microoxic habitat during paddy soil flooding. However, the response mechanisms of core microflora in this habitat to Fe(II)-oxidation-mediated cadmium (Cd) and phenanthrene (Phen) remain unclear. Using gel-stabilized gradient systems to replicate the microoxic conditions in the rice rhizosphere porewater, we found that microaerophilic rhizobacteria drove Fe(II) oxidation to yield iron oxides, thereby reducing the Cd and Phen contents in the rhizosphere porewater and rice (Cd and Phen decreased by 15.9%-78.0% and 10.1%-37.4%, respectively). However, co-exposure to Cd and Phen resulted in a greater reduction in the Cd uptake and a greater increase in the Phen uptake in rice as compared to those in the Cd or Phen treatments, possibly attributing to the cation-π interactions between Cd and Phen, as well as competition between the adsorption sites on the roots. The elevation of Cd-tolerant genes and Phen-degradation genes in biogenic cell-mineral aggregates unveiled the survival strategies of rhizobacteria with respect to Cd and Phen in the microoxic habitat. Potential Cd-tolerant rhizobacteria (e.g., Pandoraea and Comamonas) and Phen-degradation rhizobacteria (e.g., Pseudoxanthobacter) were identified through the DNA-SIP and 16S rRNA gene amplicon sequencing. Metagenomic analysis further confirmed that these core microbes harbor Cd-tolerant, Phen-degradation, and Fe(II) oxidation genes, supporting their metabolic potential for Cd and/or Phen in the microoxic habitat of the rice rhizosphere. These findings suggest the potential mechanism and ecological significance of core rhizospheric microbial-driven Fe(II) oxidation in mitigating the bioavailability of Cd and Phen in paddy soil during flooding.

PSVMA+: Exploring Multi-Granularity Semantic-Visual Adaption for Generalized Zero-Shot Learning.

Generalized zero-shot learning (GZSL) endeavors to identify the unseen categories using knowledge from the seen domain, necessitating the intrinsic interactions between the visual features and attribute semantic features. However, GZSL suffers from insufficient visual-semantic correspondences due to the attribute diversity and instance diversity. Attribute diversity refers to varying semantic granularity in attribute descriptions, ranging from low-level (specific, directly observable) to high-level (abstract, highly generic) characteristics. This diversity challenges the collection of adequate visual cues for attributes under a uni-granularity. Additionally, diverse visual instances corresponding to the same sharing attributes introduce semantic ambiguity, leading to vague visual patterns. To tackle these problems, we propose a multi-granularity progressive semantic-visual mutual adaption (PSVMA+) network, where sufficient visual elements across granularity levels can be gathered to remedy the granularity inconsistency. PSVMA+ explores semantic-visual interactions at different granularity levels, enabling awareness of multi-granularity in both visual and semantic elements. At each granularity level, the dual semantic-visual transformer module (DSVTM) recasts the sharing attributes into instance-centric attributes and aggregates the semantic-related visual regions, thereby learning unambiguous visual features to accommodate various instances. Given the diverse contributions of different granularities, PSVMA+ employs selective cross-granularity learning to leverage knowledge from reliable granularities and adaptively fuses multi-granularity features for comprehensive representations. Experimental results demonstrate that PSVMA+ consistently outperforms state-of-the-art methods.

Genetic effect of thyroid function-related diseases on acute respiratory distress syndrome: a Mendelian randomization study.

BACKGROUND: Previous studies have shown an association between acute respiratory distress syndrome (ARDS) and thyroid function. However, their causal relationship remains unspecified. Therefore, this study aims to explore the causal relationship between ARDS and thyroid function-related diseases with Mendelian Randomization (MR) analysis. METHODS: ARDS dataset finn-b-J10_ARDS, finn-b-E4_THYROID dataset of disorders of the thyroid gland (DTG) and finn-b-E4_HYTHYNAS of hypothyroidism were acquired from public database. In univariate MR (UVMR), causal effects between DTG, hypothyroidism and ARDS were investigated using 5 types of algorithms, and reliability was validated by sensitivity analysis. Moreover, multivariate MR (MVMR), enrichment and interaction network analyses of genes corresponding to SNPs of DTG and hypothyroidism were carried out. Significant level was chosen as p<0.05. RESULTS: UVMR identified DTG and hypothyroidism (P < 0.05, OR > 1) as risk factors, and were causally related to ARDS. Reliability of UVMR results was confirmed through sensitivity analysis, and results were stable and reliable. However, DTG and hypothyroidism had no effect on ARDS in MVMR, possibly because these factors had independent effects on ARDS. Ultimately, 96 and 113 genes corresponding to SNPs of DTG and hypothyroidism were found closely related to immune-related pathways. CONCLUSIONS: UVMR and MVMR analysis revealed a causal connection between DTG and hypothyroidism as risk factors with ARDS, providing robust evidence for investigation into relationship of hypothyroidism on ARDS and between DTG and ARDS.

Targeted Muscle Reinnervation in the Upper Arm: A Functional Anatomical Study.

BACKGROUND: The aim of this study was to accurately locate the neural fascicle controlling hand movement in the upper arm, to enhance expression of motor intention after targeted muscle reinnervation. METHODS: The right sides of the median, ulnar and radial nerves were dissected from distal to proximal in 6 fresh cadaver specimens. The sectional location and diameter of the functional fascicle were measured at 10 and 20 cm below the acromion. The diameter of the main muscle branches of muscle reinnervation target muscles was measured. RESULTS: The median nerve branch of finger and wrist flexion was mainly located between the 9 and 12 o'clock positions in the plane 10 and 20 cm below the acromion, where the diameter of the nerve fascicle was 2.07 and 2.04 mm, respectively. The ulnar nerve branch of finger and wrist flexion was mainly located between the 8 and 12 o'clock positions, with a diameter of respectively 1.80 and 1.99 mm. The radial branch of finger and wrist extension was mainly located between the 10 and 2 o'clock positions in the plane 10 cm below the acromion and between 6 and 12 o'clock in the plane 20 cm below the acromion, with a diameter of respectively 2.57 and 3.03 mm. CONCLUSIONS: The nerve fascicles innervating the flexor and extensor fingers were distributed in relatively constant regions of the median, ulnar and radial nerve trunks, and their diameters closely matched the muscle branches of the target muscle.

Deep learning prediction of electrospray ionization tandem mass spectra of chemically derived molecules.

Chemical derivatization is a powerful strategy to enhance sensitivity and selectivity of liquid chromatography-mass spectrometry for non-targeted analysis of chemicals in complex mixtures. However, it remains impossible to obtain large sets of reference spectra for chemically derived molecules (CDMs), representing a major barrier in real-world applications. Herein, we describe a deep learning approach that enables accurate prediction of electrospray ionization tandem mass spectra for CDMs (DeepCDM). DeepCDM is established by transfer learning from a generic spectrum predicting model using a small set of experimentally acquired tandem mass spectra of CDMs, which converts a generic model with low predictability for CDMs into a specialized model with high predictability. We demonstrate DeepCDM by predicting electrospray ionization tandem mass spectra of dansylated molecules. The success in establishing Dns-MS further enables the development of DnsBank, a dansylation-specialized in silico spectral library. DnsBank achieves significant increases of accurate annotation rates of dansylated molecules, facilitating discovery of new hazardous pollutants from an environmental study of leather industrial wastewater. DeepCDM is also highly versatile for other classes of CDMs. Therefore, we envision that DeepCDM will pave a way for high-throughput identification of CDMs in non-targeted analysis to dig unknowns with potential health impacts from emerging anthropogenic chemicals.

Ablation of Mitophagy Receptor FUNDC1 Accentuates Septic Cardiomyopathy through ACSL4-Dependent Regulation of Ferroptosis and Mitochondrial Integrity.

Sepsis evokes compromised myocardial function prompting heart failure albeit target therapy remains dismal. Our study examined the possible role of mitophagy receptor FUNDC1 in septic cardiomyopathy. A sepsis model was established using cecal ligation and puncture (CLP) in FUNDC1 knockout (FUNDC1-/-) and WT mice prior to the evaluation of cardiac morphology, echocardiographic and cardiomyocyte contractile, oxidative stress, apoptosis, necroptosis, and ferroptosis. RNAseq analysis depicted discrepant patterns in mitophagy, oxidative stress and ferroptosis between CLP-challenged and control murine hearts. Septic patients displayed cardiac injury alongside low plasma FUNDC1 and iron levels. CLP evoked interstitial fibrosis, cardiac dysfunction (lowered ejection fraction, fractional shortening, shortening/relengthening velocity, peak shortening and electrically-stimulated intracellular Ca2+ rise, alongside increased LV end systolic diameter and relengthening duration), O2- buildup, apoptosis, necroptosis, and ferroptosis (downregulated GPX4 and SLC7A11), the responses of which were accentuated by FUNDC1 ablation. In particular, levels of lipid peroxidation enzyme acyl-CoA synthetase long-chain family member 4 (ACSL4) were upregulated following CLP procedure, with a more pronounced response in FUNDC1-/- mice. Co-immunoprecipitation and interaction interface revealed an evident interaction between FUNDC1 and ACSL4. In vitro studies revealed that the endotoxin lipopolysaccharide provoked cardiomyocyte contractile and lipid peroxidation anomalies, the responses were reversed by the mitophagy inducer oleanolic acid, inhibition of ACSL4 and ferroptosis. These findings favor a role for FUNDC1-ACSL4-ferroptosis cascade in septic cardiomyopathy.

Long-term exposure to NO2 and PM2.5 and the occurrence of chronic kidney disease among patients with type 2 diabetes in Taiwan.

BACKGROUND: Individuals diagnosed with type 2 diabetes (T2D) frequently exhibit chronic kidney disease (CKD) which may be caused by environmental hazards such as exposure to air pollutants. However, limited research has explored the effects of prolonged exposure to air pollutants on CKD development in this population. This study examines the relationship between long-term exposure to air pollutants and CKD incidence in a longitudinal cohort of individuals with type 2 diabetes in Taiwan METHODS: Between 2003 and 2005, we recruited 1316 T2D patients (693 females [52.66 %]; mean age 56.16 ± 8.97 years). Patients were followed until December 31, 2012, with at least two clinical visits. Baseline demographics, medical history, and biomarker levels were collected. The development of CKD was determined by eGFR level < 60 mL/min/1.73 m2. Monthly averages of nitrogen dioxide (NO2) and fine particulate matter [PM ≤ 2.5 µm in aerodynamic diameter (PM2.5)] were acquired from 72 ambient air monitoring stations. The kriging method was employed to estimate the exposure levels to PM2.5, NO2, temperature, and relative humidity in the participants' residential areas. Cox regression with time-dependent covariates regression was applied to assess the impact of long-term exposure to air pollutants and CKD risk. RESULTS: Of 992 patients with normal renal function at baseline, 411 (41.43 %) experienced CKD occurrence over a median follow-up period of 5.45 years. The incidence of CKD was 93.96 cases per 1000 person-years. In multivariable adjusted models, patients exposed to PM2.5 levels above the third quartile of (>33.44 µg/m3) and NO2 levels above the fourth quartile (>22.55 ppb) were found to have an increased risk of CKD occurrence compared to lower exposure levels. CONCLUSIONS: This longitudinal study highlights the increased risk of CKD in individuals with type 2 diabetes due to prolonged exposure to NO2 and PM2.5, emphasizing the need for tailored air quality management strategies for this high-risk population.

CDK5-cyclin B1 regulates mitotic fidelity.

CDK1 has been known to be the sole cyclin-dependent kinase (CDK) partner of cyclin B1 to drive mitotic progression1. Here we demonstrate that CDK5 is active during mitosis and is necessary for maintaining mitotic fidelity. CDK5 is an atypical CDK owing to its high expression in post-mitotic neurons and activation by non-cyclin proteins p35 and p392. Here, using independent chemical genetic approaches, we specifically abrogated CDK5 activity during mitosis, and observed mitotic defects, nuclear atypia and substantial alterations in the mitotic phosphoproteome. Notably, cyclin B1 is a mitotic co-factor of CDK5. Computational modelling, comparison with experimentally derived structures of CDK-cyclin complexes and validation with mutational analysis indicate that CDK5-cyclin B1 can form a functional complex. Disruption of the CDK5-cyclin B1 complex phenocopies CDK5 abrogation in mitosis. Together, our results demonstrate that cyclin B1 partners with both CDK5 and CDK1, and CDK5-cyclin B1 functions as a canonical CDK-cyclin complex to ensure mitotic fidelity.

Long-term stable electrochemiluminescence of perovskite quantum dots in aqueous media.

We develop a novel electrochemiluminescence (ECL) emitter of aqueous-based perovskite quantum dots, with long-term stable ECL emission in aqueous media. Moreover, an electron transfer annihilation mechanism of ECL generation is proposed, revealed by the experimental results. This study opens a door for exploring efficient perovskite-based ECL emitters.

Appropriate flame-spraying treatment exacerbates thermal oxidative degradation of residual polyethylene films.

In dryland farming, plastic film mulching can significantly increase crop yields, but the resulting residues impair soil health. Heretofore, only few studies had examined how heat treatment facilitates the rapid degradation of polyethylene (PE) residual films. Herein, we characterized the variations in micro-morphology, functional groups, and crystallinity of PE residual films after moderate heat exposure using a self-made flame-spraying equipment. The results revealed that solid residues (SR) obtained from flame-spraying showed a gravimetric weight loss of 9.39 %-15.35 % compared with untreated PE residual films (UPF). Scanning electron microscope equipped with energy dispersive X-ray spectroscopy revealed considerable pits, cracks, and visible roughness in appearance and an increase in the oxygen-to-carbon (O/C) atomic ratio. Fourier-transform infrared spectroscopy identified characteristic oxygen-containing functional groups and double bonds. X-ray diffraction showed that flame-spraying treatments did not alter the crystal form of polymer, but increased the crystallinity. Higher flame-spraying temperatures resulted in larger oxygen-containing bond indices and lower crystallinity, suggesting a more severe decomposition of PE residual film. The possible volatile gaseous products at different reaction temperatures were predicted using thermogravimetric analysis coupled with Fourier transform infrared spectroscopy (TG-FTIR). Degradation of the PE residual film started at 220 °C, and concentrated release of major products such as long-chain aliphatic hydrocarbons, ketones, and CO2, occurred in the temperature range of 340 °C-440 °C. These results highlighted the effectiveness of the moderate flame-spraying method in accelerating rapid decomposition of residual films, and a flame-spraying temperature range of 220 °C-340 °C should be recommended to avoid potential environmental risks induced by the release of large quantities of degradation products. This study will contribute to enhance our understanding of the thermal oxidative degradation behavior of PE waste and provide a scientific basis for the rapid and clean establishment of PE residual films mitigation in agricultural fields.

Acid-Stable Cu Cluster Precatalysts Enable High Energy and Carbon Efficiency in CO2 Electroreduction.

The electrochemical reduction of CO2 in acidic media offers the advantage of high carbon utilization, but achieving high selectivity to C2+ products at a low overpotential remains a challenge. We identified the chemical instability of oxide-derived Cu catalysts as a reason that advances in neutral/alkaline electrolysis do not translate to acidic conditions. In acid, Cu ions leach from Cu oxides, leading to the deactivation of the C2+-active sites of Cu nanoparticles. This prompted us to design acid-stable Cu cluster precatalysts that are reduced in situ to active Cu nanoparticles in strong acid. Operando Raman and X-ray spectroscopy indicated that the bonding between the Cu cluster precatalyst ligand and in situ formed Cu nanoparticles preserves a high density of undercoordinated Cu sites, resulting in a C2H4 Faradaic efficiency of 62% at a low overpotential. The result is a 1.4-fold increase in energy efficiency compared with previous acidic CO2-to-C2+ electrocatalytic systems.

Emulsifying properties of cellulose nanocrystals with different structures and morphologies from various solanaceous vegetable residues.

The stems of solanaceous vegetables with attractive source of cellulose, have caused severe environmental problems as agricultural residues. For the reutilization of the residues, this study isolated cellulose nanocrystals (CNs) from the stems of tomato, eggplant, and pepper to explore their applications in Pickering emulsions. Detailed analyses of the crystalline structure and morphology revealed differences in their emulsifying properties. Tomato stem CNs had higher crystallinity of 82.1 % and a short, straight rod-like shape with a low aspect ratio of 8.0, while eggplant and pepper CNs were long, curved whisker-like fibers with lower crystallinities of 75.3 % and 75.4 %, respectively. Tomato stem CNs exhibited the best emulsifying properties, attributed to their relatively higher crystallinity and larger crystal brick size enhancing amphiphilicity, along with their lower aspect ratio improving interface coverage, which resulted in stable emulsions across different temperatures, pH levels, and ionic strengths. This study enhances our understanding of how the structure and morphology of CNs influence their emulsifying properties, thereby contributing to the promotion of agricultural waste reutilization.

Molecular basis of pigment structural diversity in echinoderms.

The varied pigments found in animals play both ecological and physiological roles. Virtually all echinoderms contain putative pigment biosynthetic enzymes, the polyketide synthases (PKSs). Among these, crinoids have complex pigments found both today and in ancient fossils. Here, we characterize a key pigment biosynthetic enzyme, CrPKS from the crinoid Anneissia japonica. We show that CrPKS produces 14-carbon aromatic pigment precursors. Despite making a compound previously found in fungi, the crinoid enzyme operates by different biochemical principles, helping to explain the diverse animal PKSs found throughout the metazoan (animal) kingdom. Unlike SpPks1 from sea urchins that had strict starter unit selectivity, CrPKS also incorporated starter units butyryl- or ethylmalonyl-CoA to synthesize a crinoid pigment precursor with a saturated side chain. By performing biochemical experiments, we show how changes in the echinoderm pigment biosynthetic enzymes unveil the vast variety of colors found in animals today.

SPRY4 regulates ERK1/2 phosphorylation to affect oxidative stress and steroidogenesis in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of childbearing age. The role of Sprouty RTK Signaling Antagonist 4 (SPRY4) in ovarian function in PCOS was investigated herein focusing on its regulation of ERK1/2 phosphorylation. PCOS models were established in mice using dehydroepiandrosterone (DHEA). The expression levels of SPRY4 in ovarian tissues were analyzed through RT-qPCR and immunohistochemistry. SPRY4 knockdown was achieved via lentivirus, and its effects on endocrine function, ovarian morphology, oxidative stress, and ERK1/2 phosphorylation were evaluated. Afterwards, granulosa cells were isolated and treated with DHEA and ERK2 agonist tert-Butylhydroquinone. The impacts of ERK2 activation on the regulation of SPRY4 knockdown were assessed using ELISA, fluorescent probes, western blotting, and biochemical assays. SPRY4 knockdown normalized the estrous cycle, reduced serum levels of testosterone, anti-Müllerian hormone, and luteinizing hormone/follicle-stimulating hormone ratio, and improved ovarian morphology. Additionally, SPRY4 knockdown alleviated oxidative stress by decreasing reactive oxygen species and malondialdehyde levels while increasing superoxide dismutase activity. It also restored steroidogenic enzyme expression, which were disrupted by DHEA induction. In vitro, SPRY4 knockdown enhanced granulosa cell viability and reduced ERK1/2 phosphorylation, with tert-Butylhydroquinone reversing these effects and restoring oxidative stress and steroidogenesis disruptions. Together, SPRY4 modulates ERK1/2 phosphorylation to influence oxidative stress and steroidogenesis in PCOS. Targeting SPRY4 may provide novel therapeutic avenues for improving ovarian function and managing PCOS.