Farmland's silent threat: Comprehensive multimedia assessment of micropollutants through non-targeted screening and targeted analysis in agricultural systems.

Intricate agricultural ecosystems markedly influence the dynamics of organic micropollutants, posing substantial threats to aquatic organisms and human health. This study examined the occurrence and distribution of organic micropollutants across soils, ditch sediment, and water within highly intensified farming setups. Using a non-targeted screening method, we identified 405 micropollutants across 10 sampling sites, which mainly included pesticides, pharmaceuticals, industrial chemicals, and personal care products. This inventory comprised emerging contaminants, banned pesticides, and controlled pharmaceuticals that had eluded detection via conventional monitoring. Targeted analysis showed concentrations of 3.99-1021 ng/g in soils, 4.67-2488 ng/g in sediment, and 12.5-9373 ng/L in water, respectively, for Σ40pesticides, Σ8pharmaceuticals, and Σ3industrial chemicals, indicating notable spatial variability. Soil organic carbon content and wastewater discharge were likely responsible for their spatial distribution. Principal component analysis and correlation analysis revealed a potential transfer of micropollutants across the three media. Particularly, a heightened correlation was decerned between soil and sediment micropollutant levels, highlighting the role of sorption processes. Risk quotients surpassed the threshold of 1 for 13-23 micropollutants across the three media, indicating high environmental risks. This study highlights the importance of employing non-targeted and targeted screening in assessing and managing environmental risks associated with micropollutants.

Roles of m6A modification in regulating PPER pathway in cadmium-induced pancreatic ß cell death.

Cadmium can lead to the death of pancreatic ß cells, thus affecting the synthesis and secretion of insulin. However, the specific mechanisms underlying the cadmium-induced pancreatic ß cell death have not been fully understood. In this study, roles of m6A modification in regulating protein processing in endoplasmic reticulum (PPER) pathway in cadmium-induced pancreatic ß cell death were explored. Our results demonstrated that cell viability and RNA m6A modification level were decreased, while apoptosis rates increased after CdSO4 treatment in pancreatic ß cells (NIT-1). In addition, expressions of Bcl-2, Xbp1, Col3a1, Bax, Chop, Dnajb1, and Hsp90aa1 were all significantly changed in CdSO4 treatment cells. The m6A agonist entacapone (Ent) can prominently reverse the cytotoxicity effects of CdSO4 and alleviate the changes of protein expression induced by CdSO4 treatment. By contrast, m6A inhibitor 3-Deazaadenosine (DAA) can synergistically enhance the cytotoxicity of CdSO4 and aggravate the disorder of protein levels caused by CdSO4 treatment. Interestingly, the results of the immunoprecipitation experiment indicate that Ythdc2, one of m6A binding proteins, may regulate the PPER pathway molecules in an m6A-dependent manner. In summary, our findings provide new directions for the prevention and treatment of the impairment of pancreatic ß cell function induced by cadmium.

A hydrogen generator composed of poly (lactic-co-glycolic acid) nanofibre membrane loaded iron nanoparticles for infectious diabetic wound repair.

Diabetic wound, which is chronic skin disease, poses a significant challenge in clinical practice because of persistent inflammation and impaired angiogenesis. Recently, hydrogen has emerged as a novel therapeutic agent due to its superior antioxidant and anti-inflammatory properties. In this study, we engineered a poly (lactic-co-glycolic acid) (PLGA) electrospun nanofibre membrane loaded with citric acid (CA) and iron (Fe) nanoparticles, referred to as Fe@PLGA + CA. Our in vitro assays demonstrated that the Fe@PLGA + CA membrane continuously generated and released hydrogen molecules via a chemical reaction between Fe and CA in an acidic microenvironment created by CA. We also discovered that hydrogen can ameliorate fibroblast migration disorders by reducing the levels of matrix metalloproteinase 9 (MMP9). Furthermore, we confirmed that hydrogen can scavenge or biochemically neutralise accumulated reactive oxygen species (ROS), inhibit pro-inflammatory responses, and induce anti-inflammatory reactions. This, in turn, promotes vessel formation, wound-healing and accelerates skin regeneration. These findings open new possibilities for using elemental iron in skin dressings and bring us one step closer to implementing hydrogen-releasing biomedical materials in clinical practice.

Pressure-induced hydrogen bonding modulating Fermi resonance between fundamental modes in xylitol molecule.

Xylitol, as a typical polyol, has a broad range of application prospects. However, the molecular states of xylitol under different environments are rarely reported until now. In this work, the state changes of xylitol molecules under high pressure were analyzed by Raman spectra. A Fermi resonance phenomenon in the fundamental mode of xylitol at 2945 (±0.06) cm-1 and 2955 (±0.41) cm-1 was observed at 0.99 GPa. The Fermi doublets possess the same symmetry and close energy levels, which had not been changed by pressures. However, the high pressure shortened the atomic distances and applied the extra disturbance, providing the necessary conditions for energy transfer. Besides, the Fermi doublets decoupling happened at 4 GPa due to the breaking of hydrogen bonding. This work provides an important reference for studying molecular states and weak interactions of polyols under high pressures.

Inoculum source determines the stress resistance of electroactive functional taxa in biofilms: A metagenomic perspective.

The inoculum has a crucial impact on bioreactor initialization and performance. However, there is currently a lack of guidance on selecting appropriate inocula for applications in environmental biotechnology. In this study, we applied microbial electrolysis cells (MECs) as models to investigate the differences in the functional potential of electroactive microorganisms (EAMs) within anodic biofilms developed from four different inocula (natural or artificial), using shotgun metagenomic techniques. We specifically focused on extracellular electron transfer (EET) function and stress resistance, which affect the performance and stability of MECs. Community profiling revealed that the family Geobacteraceae was the key EAM taxon in all biofilms, with Geobacter as the dominant genus. The c-type cytochrome gene imcH showed universal importance for Geobacteraceae EET and was utilized as a marker gene to evaluate the EET potential of EAMs. Additionally, stress response functional genes were used to assess the stress resistance potential of Geobacter species. Comparative analysis of imcH gene abundance revealed that EAMs with comparable overall EET potential could be enriched from artificial and natural inocula (P > 0.05). However, quantification of stress response gene copy numbers in the genomes demonstrated that EAMs originating from natural inocula possessed superior stress resistance potential (196 vs. 163). Overall, this study provides novel perspectives on the inoculum effect in bioreactors and offers theoretical guidance for selecting inoculum in environmental engineering applications.

The alpha2-adrenergic receptor agonist clonidine protects against cerebral ischemia/reperfusion induced neuronal apoptosis in rats.

Apoptosis is the crucial pathological mechanism following cerebral ischemic injury. Our previous studies demonstrated that clonidine, one agonist of alpha2-adrenergic receptor (α2-AR), could attenuate cerebral ischemic injury in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). However, it's unclear whether clonidine exerts neuroprotective effects by regulating neuronal apoptosis. In this study, we elucidated whether clonidine can exert anti-apoptotic effects in cerebral ischemic injury, and further explored the possible mechanisms. Neurological deficit score was measured to evaluate the neurological function. TTC staining was used for the measurement of brain infarct size. Hematoxylin-Eosin (HE) staining was applied to examine the cell morphology. TUNEL and DAPI fluorescent staining methods were used to analyze the cell apoptosis in brain tissue. Fluorescence quantitative real-time PCR was performed to assess the gene expression of Caspase-3 and P53. Western blotting assay was applied to detect the protein expression of Caspase-3 and P53. The results showed that clonidine improved neurological function, reduced brain infarct size, alleviated neuronal damage, and reduced the ratio of cell apoptosis in the brain with MCAO/R injury. moreover, clonidine down-regulated the gene and protein expression of Caspase-3 and P53 which were over-expressed after MCAO/R injury. Whereas, yohimbine (one selective α2-AR antagonist) mitigated the anti-apoptosis effects of clonidine, accompanied by reversed gene and protein expression changes. The results indicated that clonidine attenuated cerebral MCAO/R injury via suppressing neuronal apoptosis, which may be mediated, at least in part, by activating α2-AR.

Identification and expression of the Di19 gene family in response to abiotic stress in common bean (Phaseolus vulgaris L.).

Drought-induced 19 (Di19) protein plays critical biological functions in response to adversity as well as in plant growth and development. Exploring the role and mechanism of Di19 in abiotic stress responses is of great significance for improving plant tolerance. In this study, six Di19 genes were identified in the common bean (Phaseolus vulgaris L.), which were mainly derived from segmental duplications. These genes share conserved exon/intron structures and were classified into three subfamilies based on their phylogenetic relationships. The composition and arrangement of conserved motifs were consistent with their phylogenetic relationships. Many hormone- and stress-responsive elements were distributed in the promoters region of PvDi19 genes. Variations in histidine residues in the Cys2/His2 (C2H2) zinc-finger domains resulted in an atypical tertiary structure of PvDi19-5. Gene expression analysis showed rapid induction of PvDi19-1 in roots by 10% PEG treatment, and PvDi19-2 in leaves by 20% PEG treatment, respectively. Most PvDi19s exhibited insensitivity to saline-alkali stress, except for PvDi19-6, which was notably induced during later stages of treatment. The most common bean Di19 genes were inhibited or not regulated by cadmium stress, but the expression of PvDi19-6 in roots was significantly upregulated when subjected to lower concentrations of cadmium (5 mmol). Moreover, Di19s exhibited greater sensitivity to severe cold stress (6°C). These findings enhance our understanding of the role of PvDi19s in common bean abiotic stress responses and provide a basis for future genetic enhancements in common bean stress tolerance.

Comprehensive pan-cancer investigation of carnosine dipeptidase 1 and its prospective prognostic significance in hepatocellular carcinoma.

Carnosine dipeptidase 1 (CNDP1), an enzyme integral to the hydrolysis of dipeptides containing histidine, plays an indispensable role in myriad physiological processes, including hydrolysis of proteins, maturation of specific biochemical functionalities within proteins, tissue regeneration, and regulation of cell cycle. However, the implications of CNDP1 in oncogenesis and its prognostic value are not yet fully elucidated. Initially, we procured the GSE40367 dataset from the Gene Expression Omnibus and established a protein-protein interaction network. Thereafter, we conducted functional and pathway enrichment analyses utilizing GO, KEGG, and GSEA. Moreover, we undertook an association analysis concerning the expression of CNDP1 with immune infiltration, along with survival analysis across various cancers and specifically in hepatocellular carcinoma (HCC). Our study uncovered a total of 2,248 differentially expressed genes, with a down-regulation of CNDP1 in HCC and other cancers. Our explorations into the relationship between CNDP1 and immune infiltration disclosed a negative correlation between CNDP1 expression and the presence of immune cells in HCC. Survival analyses revealed that diminished expression of CNDP1 correlates with an adverse prognosis in HCC and several other types of cancer. These observations intimate that CNDP1 holds promise as a novel prognostic biomarker for both pan-cancer and HCC.

Predictive efficacy of combined tumor markers and gastrin for recurrence after endoscopic submucosal dissection in early gastric cancer patients.

OBJECTIVE: This study aims to evaluate the predictive value of tumor markers combined with gastrin for tumor recurrence after endoscopic submucosal dissection (ESD) in patients with early gastric cancer. METHODS: The clinicopathological data of 169 patients with early gastric cancer treated with ESD between March 2019 and January 2021 were retrospectively analyzed. The patients were divided into a relapse group (n=45) and a non-recurrence group (n=124). Clinical data such as carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), alpha-fetoprotein (AFP), gastrin 17, pepsinogen I and pepsinogen II, as well as tumor size and degree of infiltration were examined to construct a recurrence prediction model using lasso regression. RESULTS: The comprehensive model showed superior predictive power (AUC=0.958, C-index=0.966) over biomarker-only models (AUC=0.925), indicating a significant improvement in the prediction of recurrence risk. Decision curve analysis confirmed the clinical utility of the model with a maximum net benefit of 73.37%. Key indicators such as CEA, CA19-9, AFP, gastrin 17 and pepsinogens I and II were statistically significant in predicting recurrence with P values < 0.01. CONCLUSION: The comprehensive model combining tumor markers with clinical data provides a more accurate and clinically valuable tool for predicting recurrence in early gastric cancer patients after ESD. This approach facilitates personalized risk assessment and may significantly improve prognostic management, emphasizing the importance of a multifaceted strategy in the management of early gastric cancer.

Enhancing dark fermentative hydrogen production from wheat straw through synergistic effects of active electric fields and enzymatic hydrolysis pretreatment.

Hydrogen, a clean and sustainable energy source, faces challenges from energy-intensive pre-processing technologies. This study explores the synergistic enhancement of active electric fields on enzymolysis of wheat straw and hydrogen production through dark fermentation. The active electric field enzymolysis system improved the adsorption capacity of wheat straw to cellulase, increasing cellulase activity by 18.0 %, causing a 39.1 % increase in reducing sugar content. In the active fermentation system, Clostridium_sensu_stricto_1 activity was enhanced in the first stage, increasing hydrogenase activity by 23.0 %, prolonging the first hydrogen production peak. Elevated reducing sugars were observed in the second stage, with Prevotella_9 and Bacteroides becoming the dominant hydrogen-producing bacteria in the third stage, leading to a second hydrogen production peak. Overall, cumulative hydrogen production was enhanced by 50.9 % compared to the control. The synergistic pretreatment with an active electric field and cellulase provides a novel approach for efficiently utilizing wheat straw.

Molecular ferroelectric with low-magnetic-field magnetoelectricity at room temperature.

Magnetoelectric materials, which encompass coupled magnetic and electric polarizabilities within a single phase, hold great promises for magnetic controlled electronic components or electric-field controlled spintronics. However, the realization of ideal magnetoelectric materials remains tough due to the inborn competion between ferroelectricity and magnetism in both levels of symmetry and electronic structure. Herein, we introduce a methodology for constructing single phase paramagnetic ferroelectric molecule [TMCM][FeCl4], which shows low-magnetic-field magnetoelectricity at room temperature. By applying a low magnetic field (≤1 kOe), the halogen Cl‧‧‧Cl distance and the volume of [FeCl4]- anions could be manipulated. This structural change causes a characteristic magnetostriction hysteresis, resulting in a substantial deformation of ~10-4 along the a-axis under an in-plane magnetic field of 2 kOe. The magnetostrictive effect is further qualitatively simulated by density functional theory calculations. Furthermore, this mechanical deformation significantly dampens the ferroelectric polarization by directly influencing the overall dipole configuration. As a result, it induces a remarkable α31 component (~89 mV Oe-1 cm-1) of the magnetoelectric tensor. And the magnetoelectric coupling, characterized by the change of polarization, reaches ~12% under 40 kOe magnetic field. Our results exemplify a design methodology that enables the creation of room-temperature magnetoelectrics by leveraging the potent effects of magnetostriction.

QM-DLA: an efficient qubit mapping method based on dynamic look-ahead strategy.

Quantum computing has already demonstrated great computational potential across multiple domains and has received more and more attention. However, due to the connectivity limitations of Noisy Intermediate-Scale Quantum (NISQ) devices, most of the quantum algorithms cannot be directly executed without the help of inserting SWAP gates. Nevertheless, more SWAP gates lead to a longer execution time and, inevitably, lower fidelity of the algorithm. To this end, this paper proposes an optimized qubit mapping algorithm based on a dynamic look-ahead strategy to minimize the number of SWAP gates inserted. Firstly, a heuristic algorithm is proposed based on maximizing physical qubit connectivity to generate the optimal initial qubit mapping, which reduces the need for logical qubit shifts during subsequent SWAP gate insertion. Secondly, in the form of directed acyclic graphs, we identify quantum gates that violate the constraints of physical coupling and insert SWAP gates to remap qubits, thereby overcoming the limitations of qubit interactions. Finally, the optimal SWAP gate insertion strategy is built by comparing the cost of different SWAP gate insertion strategies through a multi-window look-ahead strategy to reduce the number of SWAP gates inserted. The experimental results show that the strategy in this paper decreases the number of SWAP gate insertions and significantly reduces the depth of quantum circuits when performing qubit mapping compared with state-of-the-art methods.

Biosynthesis of GMGT lipids by a radical SAM enzyme associated with anaerobic archaea and oxygen-deficient environments.

Archaea possess characteristic membrane-spanning lipids that are thought to contribute to the adaptation to extreme environments. However, the biosynthesis of these lipids is poorly understood. Here, we identify a radical S-adenosyl-L-methionine (SAM) enzyme that synthesizes glycerol monoalkyl glycerol tetraethers (GMGTs). The enzyme, which we name GMGT synthase (Gms), catalyzes the formation of a C(sp3)-C(sp3) linkage between the two isoprenoid chains of glycerol dialkyl glycerol tetraethers (GDGTs). This conclusion is supported by heterologous expression of gene gms from a GMGT-producing species in a methanogen, as well as demonstration of in vitro activity using purified Gms enzyme. Additionally, we show that genes encoding putative Gms homologs are present in obligate anaerobic archaea and in metagenomes obtained from oxygen-deficient environments, and appear to be absent in metagenomes from oxic settings.

Mitochondrial Uncoupling Protein-2 Ameliorates Ischemic Stroke by Inhibiting Ferroptosis-Induced Brain Injury and Neuroinflammation.

Ischemic stroke is a devastating disease in which mitochondrial damage or dysfunction substantially contributes to brain injury. Mitochondrial uncoupling protein-2 (UCP2) is a member of the UCP family, which regulates production of mitochondrial superoxide anion. UCP2 is reported to be neuroprotective for ischemic stroke-induced brain injury. However, the molecular mechanisms of UCP2 in ischemic stroke remain incompletely understood. In this study, we investigated whether and how UCP2 modulates neuroinflammation and regulates neuronal ferroptosis following ischemic stroke in vitro and in vivo. Wild-type (WT) and UCP2 knockout (Ucp2-/-) mice were subjected to middle cerebral artery occlusion (MCAO). BV2 cells (mouse microglial cell line) and HT-22 cells (mouse hippocampal neuronal cell line) were transfected with small interfering (si)-RNA or overexpression plasmids to knockdown or overexpress UCP2 levels. Cells were then exposed to oxygen-glucose deprivation and reoxygenation (OGD/RX) to simulate hypoxic injury in vitro. We found that UCP2 expression was markedly reduced in a time-dependent manner in both in vitro and in vivo ischemic stroke models. In addition, UCP2 was mainly expressed in neurons. UCP2 deficiency significantly enlarged infarct volumes, aggravated neurological deficit scores, and exacerbated cerebral edema in mice after MCAO. In vitro knockdown of Ucp2 and in vivo genetic depletion of Ucp2 (Ucp2-/- mice) increased neuronal ferroptosis-related indicators, including Fe2+, malondialdehyde, glutathione, and lipid peroxidation. Overexpression of UCP2 in neuronal cells resulted in reduced ferroptosis. Moreover, knockdown of UCP2 exacerbated neuroinflammation in BV2 microglia and mouse ischemic stroke models, suggesting that endogenous UCP2 inhibits neuroinflammation following ischemic stroke. Upregulation of UCP2 expression in microglia appeared to decrease the release of pro-inflammatory factors and increase the levels of anti-inflammatory factors. Further investigation showed that UCP2 deletion inhibited expression of AMPKα/NRF1 pathway-related proteins, including p-AMPKα, t-AMPKα, NRF1, and TFAM. Thus, UCP2 protects the brain from ischemia-induced ferroptosis by activating AMPKα/NRF1 signaling. Activation of UCP2 represents an attractive strategy for the prevention and treatment of ischemic stroke.

Identification of LRRC46 as a novel candidate gene for high myopia.

High myopia (HM) is the primary cause of blindness, with the microstructural organization and composition of collagenous fibers in the cornea and sclera playing a crucial role in the biomechanical behavior of these tissues. In a previously reported myopic linkage region, MYP5 (17q21-22), a potential candidate gene, LRRC46 (c.C235T, p.Q79X), was identified in a large Han Chinese pedigree. LRRC46 is expressed in various eye tissues in humans and mice, including the retina, cornea, and sclera. In subsequent cell experiments, the mutation (c.C235T) decreased the expression of LRRC46 protein in human corneal epithelial cells (HCE-T). Further investigation revealed that Lrrc46-/- mice (KO) exhibited a classical myopia phenotype. The thickness of the cornea and sclera in KO mice became thinner and more pronounced with age, the activity of limbal stem cells decreased, and microstructural changes were observed in the fibroblasts of the sclera and cornea. We performed RNA-seq on scleral and corneal tissues of KO and normal control wild-type (WT) mice, which indicated a significant downregulation of the collagen synthesis-related pathway (extracellular matrix, ECM) in KO mice. Subsequent in vitro studies further indicated that LRRC46, a member of the important LRR protein family, primarily affected the formation of collagens. This study suggested that LRRC46 is a novel candidate gene for HM, influencing collagen protein VIII (Col8a1) formation in the eye and gradually altering the biomechanical structure of the cornea and sclera, thereby promoting the occurrence and development of HM.

Multifunctional N, Fe-doped carbon dots with peroxidase-like activity for the determination of H2O2 and ascorbic acid and cell protection against oxidation.

Multifunctional N, Fe-doped carbon dots (N, Fe-CDs) were synthesized by the one-step hydrothermal method using ferric ammonium citrate and dicyandiamide as raw materials. The N, Fe-CDs exhibited peroxidase-like (POD) activity by catalyzing the oxidization of 3,3',5,5'-tetramethylbenzidine (TMB) to the green oxidation state ox-TMB in the presence of hydrogen peroxide (H2O2). Subsequently, based on the POD activity of N, Fe-CDs, an efficient and sensitive colorimetric method for the detection of H2O2 and ascorbic acid (AA) was established with a limit of detection of 0.40 µM and 2.05 µM. The proposed detection method has been successfully applied to detect AA in fruit juice, vitamin C tablets, and human serum samples and has exhibited excellent application prospects in biotechnology and food fields. Furthermore, N, Fe-CDs also showed a protective effect on the cell damage caused by H2O2 and could be used as an antioxidant agent.

Mn-based Prussian blue analogues: Multifunctional nanozymes for hydrogen peroxide detection and photothermal therapy of tumors.

Nanozymes have the advantages of simple synthesis, high stability, low cost and easy recycling, and can be applied in many fields including molecular detection, disease diagnosis and cancer therapy. However, most of the current nanozymes suffer from the defects of low catalytic activity and single function, which limits their sensing sensitivity and multifunctional applications. The development of highly active and multifunctional nanozymes is an important way to realize multidisciplinary applications. In this work, Mn-based Prussian blue analogues (Mn-PBA) and their derived double-shelled nanoboxes (DSNBs) are synthesized by co-precipitation method. The nanobox structure of DSNBs formed by etching Mn-PBA with tannic acid endows Mn-PBA DSNBs with better peroxidase-like activity than Mn-PBA. A colorimetric method for the rapid and sensitive determination of H2O2 is developed using Mn-PBA DSNBs-1.5 as a sensor with a detection limit as low as 0.62 µM. Moreover, Mn-PBA DSNBs-2 has excellent photothermal conversion ability, which can be applied to the photothermal therapy of tumors to inhibit the proliferation of tumor cells without damaging other tissues and organs. This study provides a new idea for the rational design of nanozymes and the expansion of their multi-functional applications in various fields.

Tumor-resident microbiota contributes to colorectal cancer liver metastasis by lactylation and immune modulation.

The role of tumor-resident microbiota in modulating tumor immunity remains unclear. Here, we discovered an abundance of intra-tumoral bacteria, such us E.coli, residing and resulting in Colorectal cancer liver metastasis (CRLM). E.coli enhanced lactate production, which mediated M2 macrophage polarization by suppressing nuclear factor-κB -gene binding (NF-κB) signaling through retinoic acid-inducible gene 1 (RIG-I) lactylation. Lactylation of RIG-I suppressed recruitment of NF-κB to the Nlrp3 promoter in macrophages, thereby reducing its transcription. This loss of Nlrp3 affected the immunosuppressive activities of regulatory T cells (Tregs) and the antitumor activities of and CD8+ T cells. Small-molecule compound screening identified a RIG-I lactylation inhibitor that suppressed M2 polarization and sensitized CRLM to 5-fluorouracil (5-FU). Our findings suggest that tumor-resident microbiota may be a potential target for preventing and treating CRLM.

Bioinspired Nanolayered Structure Tuned by Extensional Stress: A Scalable Way to High-Performance Biodegradable Polyesters.

The nacre-inspired multi-nanolayer structure offers a unique combination of advanced mechanical properties, such as strength and crack tolerance, making them highly versatile for various applications. Nevertheless, a significant challenge lies in the current fabrication methods, which is difficult to create a scalable manufacturing process with precise control of hierarchical structure. In this work, a novel strategy is presented to regulate nacre-like multi-nanolayer films with the balance mechanical properties of stiffness and toughness. By utilizing a co-continuous phase structure and an extensional stress field, the hierarchical nanolayers is successfully constructed with tunable sizes using a scalable processing technique. This strategic modification allows the robust phase to function as nacre-like platelets, while the soft phase acts as a ductile connection layer, resulting in exceptional comprehensive properties. The nanolayer-structured films demonstrate excellent isotropic properties, including a tensile strength of 113.5 MPa in the machine direction and 106.3 MPa in a transverse direction. More interestingly, these films unprecedentedly exhibit a remarkable puncture resistance at the same time, up to 324.8 N mm-1, surpassing the performance of other biodegradable films. The scalable fabrication strategy holds significant promise in designing advanced bioinspired materials for diverse applications.