Atramacronoid A induces the PANoptosis-like cell death of human breast cancer cells through the CASP-3/PARP-GSDMD-MLKL pathways.

Breast cancer is the most common malignant tumor and a major cause of mortality among women worldwide. Atramacronoid A (AM-A) is a unique natural sesquiterpene lactone isolated from the rhizome of Atractylodes macrocephala Koidz (known as Baizhu in Chinese). Our study demonstrated that AM-A triggers a specific form of cell death resembling PANoptosis-like cell death. Further analysis indicated that AM-A-induced PANoptosis-like cell death is associated with the CASP-3/PARP-GSDMD-MLKL pathways, which are mediated by mitochondrial dysfunction. These results suggest the potential of AM-A as a lead compound and offer insights for the development of therapeutic agents for breast cancer from natural products.

Synergistic interactions in core microbiome Rhizobiales accelerate 1,4-dioxane biodegradation.

Next-generation sequencing (NGS) has revolutionized taxa identification within contaminant-degrading communities. However, uncovering a core degrading microbiome in diverse polluted environments and understanding its associated microbial interactions remains challenging. In this study, we isolated two distinct microbial consortia, namely MA-S and Cl-G, from separate environmental samples using 1,4-dioxane as a target pollutant. Both consortia exhibited a persistent prevalence of the phylum Proteobacteria, especially within the order Rhizobiales. Extensive analysis confirmed that Rhizobiales as the dominant microbial population (> 90 %) across successive degradation cycles, constituting the core degrading microbiome. Co-occurrence network analysis highlighted synergistic interactions within Rhizobiales, especially within the Shinella and Xanthobacter genera, facilitating efficient 1,4-dioxane degradation. The enrichment of Rhizobiales correlated with an increased abundance of essential genes such as PobA, HpaB, ADH, and ALDH. Shinella yambaruensis emerged as a key degrader in both consortia, identified through whole-genome sequencing and RNA-seq analysis, revealing genes implicated in 1,4-dioxane degradation pathways, such as PobA and HpaB. Direct and indirect co-cultivation experiments confirmed synergistic interaction between Shinella sp. and Xanthobacter sp., enhancing the degradation of 1,4-dioxane within the core microbiome Rhizobiales. Our findings advocate for integrating the core microbiome concept into engineered consortia to optimize 1,4-dioxane bioremediation strategies.

National survey on the current status of airway management in China.

Apparently, understanding airway management status may help to reduce risk and improve clinical practice. Given these facts, our team conducted a second survey on the current status of airway management for mainland China following our 2016 national airway survey. The national survey was conducted from November 7 to November 28, 2022. An electronic survey was sent to the New Youth Anesthesia Forum, where Chinese anesthesiologists completed the questionnaire via WeChat. A total of 3783 respondents completed the survey, with a response rate of 72.14%. So far, in 2022, 34.84% of anesthesiologists canceled or delayed surgery at least once due to difficult airway. For the anticipated difficult airway management, 66.11% of physicians would choose awake intubation under sedation and topical anesthesia, while the percentage seeking help has decreased compared to the 2016 survey. When encountering an emergency, 74.20% of respondents prefer to use the needle cricothyrotomy, albeit less than a quarter have actually performed it. Anesthesiologists with difficult airway training experience reached 72.96%, with a significant difference in participation between participants in Tier 3 hospitals and those in other levels of hospitals (P < 0.001). The videolaryngoscope, laryngeal mask, and flexible intubation scope were equipped at 97.18%, 95.96%, and 62.89%, respectively. Additionally, the percentage of brain damage or death caused by difficult airways was significantly decreased. The study may be the best reference for understanding the current status of airway management in China, revealing the current advancements and deficiencies. The future focus of airway management remains on training and education.

End-expiratory lung volumes as a potential indicator for COVID-19 associated acute respiratory distress syndrome: a retrospective study.

BACKGROUND: End-expiratory lung volume (EELV) has been observed to decrease in acute respiratory distress syndrome (ARDS). Yet, research investigating EELV in patients with COVID-19 associated ARDS (CARDS) remains limited. It is unclear whether EELV could serve as a potential metric for monitoring disease progression and identifying patients with ARDS at increased risk of adverse outcomes. STUDY DESIGN AND METHODS: This retrospective study included mechanically ventilated patients diagnosed with CARDS during the initial phase of epidemic control in Shanghai. EELV was measured using the nitrogen washout-washin technique within 48 h post-intubation, followed by regular assessments every 3-4 days. Chest CT scans, performed within a 24-hour window around each EELV measurement, were analyzed using AI software. Differences in patient demographics, clinical data, respiratory mechanics, EELV, and chest CT findings were assessed using linear mixed models (LMM). RESULTS: Out of the 38 patients enrolled, 26.3% survived until discharge from the ICU. In the survivor group, EELV, EELV/predicted body weight (EELV/PBW) and EELV/predicted functional residual capacity (EELV/preFRC) were significantly higher than those in the non-survivor group (survivor group vs. non-survivor group: EELV: 1455 vs. 1162 ml, P = 0.049; EELV/PBW: 24.1 vs. 18.5 ml/kg, P = 0.011; EELV/preFRC: 0.45 vs. 0.34, P = 0.005). Follow-up assessments showed a sustained elevation of EELV/PBW and EELV/preFRC among the survivors. Additionally, EELV exhibited a positive correlation with total lung volume and residual lung volume, while demonstrating a negative correlation with lesion volume determined through chest CT scans analyzed using AI software. CONCLUSION: EELV is a useful indicator for assessing disease severity and monitoring the prognosis of patients with CARDS.

Genome-wide identification, characterization and expression analysis of the DUF668 gene family in tomato.

The domain of unknown function 668 (DUF668) is a gene family that may play a key role in plant growth and development as well as in responding to adversity coercion stresses. However, the DUF668 gene family has not yet been well identified and characterized in tomato. In this study, a total of nine putative SlDUF668 genes were identified in tomato, distributed on six chromosomes. Phylogenetic analyses revealed that SlDUF668 proteins were classified into two major groups. Members within the same group largely displayed analogous gene structure and conserved motif compositions. Several cis-elements were exhibited in the upstream sequences of the SlDUF668 genes, including elements implicated in plant growth and development processes, abiotic stress and hormone responses. Further, the study assessed the expression patterns of the SlDUF668 gene family in various tomato tissues, five plant hormones treatments, three abiotic stresses using qRT-PCR. The SlDUF668 genes expressed ubiquitously in various tissues, and five genes (SlDUF668-04, SlDUF668-06, SlDUF668-07, SlDUF668-08 and SlDUF668-09) showed tissue specificity. And SlDUF668 genes responded to abiotic stresses such as salt, drought and cold to varying degrees. Overall, our study provided a base for the tomato DUF668 gene family and laid a foundation for further understanding the functional characteristics of DUF668 genes in tomato plants.

The comparison of preoxygenation methods before endotracheal intubation: a network meta-analysis of randomized trials.

Background: Preoxygenation before endotracheal intubation (ETI) maintains asphyxiated oxygenation and reduces the risk of hypoxia-induced adverse events. Previous studies have compared various preoxygenation methods. However, network meta-analyses (NMAs) of the combined comparison of preoxygenation methods is still lacking. Methods: We searched for studies published in PubMed, Embase, Web of Science, Scopus, and the Cochrane Library. Review Manager version 5.3 was used to evaluate the risk of bias. The primary outcome of this meta-analysis was low oxygen saturation (SpO2) during ETI. The secondary outcomes included SpO2 <80%, SpO2 <90%, and apnea time during ETI. NMA was performed using R 4.1.2 software gemtc packages in RStudio. Results: A total of 15 randomized controlled trials were included in this study. Regarding the lowest SpO2, the noninvasive ventilation (NIV) with high-flow nasal cannula (HFNC) group performed better than the other groups. For SpO2 <80%, the NIV group (0.8603467) performed better than the HFNC (0.1373533) and conventional oxygen therapy (COT, 0.0023) groups, according to the surface under the cumulative ranking curve results. For SpO2 <90%, the NIV group (0.60932667) performed better than the HFNC (0.37888667) and COT (0.01178667) groups. With regard to apnea time, the HFNC group was superior to the COT group (mean difference: -50.05; 95% confidence interval: -90.01, -10.09; P = 0.01). Conclusion: Network analysis revealed that NIV for preoxygenation achieved higher SpO2 levels than HFNC and COT and offered a more significant advantage in maintaining patient oxygenation during ETI. Patients experienced a longer apnea time after HFNC preoxygenation. The combination of NIV with HFNC proved to be significantly superior to other methods. Given the scarcity of such studies, further research is needed to evaluate its effectiveness. Systematic review registration: identifier CRD42022346013.

Confinement of ZIF-67-derived N, Co-doped C@Si on a 2D MXene for enhanced lithium storage.

A heterostructure composed of ZIF-67-derived nitrogen and cobalt-doped carbon enfolded silicon (C@Si) nanoparticles anchored on 2D MXene layers was constructed for boosting the performance of lithium-ion batteries (LIBs). The heterostructure anode demonstrated a high initial discharge capacity of 3021 mA h g-1 at 0.2 A g-1, retaining outstanding cycling stability with a reversible capacity of 520 mA h g-1 at 2000 mA g-1, and the coulombic efficiency remained above 97% after 500 cycles. The introduced Ti3C2 nanosheets and the cobalt-doped carbon can not only contribute to the interfacial transfer of Li+ and electrons but also buffer the volume expansion of Si.

Genomic, transcriptomic, and metabolomic analyses provide insights into the evolution and development of a medicinal plant Saposhnikovia divaricata (Apiaceae).

Saposhnikovia divaricata, 2n = 2x = 16, as a perennial species, is widely distributed in China, Mongolia, Russia, etc. It is a traditional Chinese herb used to treat tetanus, rubella pruritus, rheumatic arthralgia, and other diseases. Here, we assembled a 2.07 Gb and N50 scaffold length of 227.67 Mb high-quality chromosome-level genome of S. divaricata based on the PacBio Sequel II sequencing platform. The total number of genes identified was 42 948, and 42 456 of them were functionally annotated. A total of 85.07% of the genome was composed of repeat sequences, comprised mainly of long terminal repeats (LTRs) which represented 73.7% of the genome sequence. The genome size may have been affected by a recent whole-genome duplication event. Transcriptional and metabolic analyses revealed bolting and non-bolting S. divaricata differed in flavonoids, plant hormones, and some pharmacologically active components. The analysis of its genome, transcriptome, and metabolome helped to provide insights into the evolution of bolting and non-bolting phenotypes in wild and cultivated S. divaricata and lays the basis for genetic improvement of the species.

Development and validation of a self-attention network-based algorithm to detect mediastinal lesions on computed tomography images.

Background: Diagnosis of mediastinal lesions on computed tomography (CT) images is challenging for radiologists, as numerous conditions can present as mass-like lesions at this site. This study aimed to develop a self-attention network-based algorithm to detect mediastinal lesions on CT images and to evaluate its efficacy in lesion detection. Methods: In this study, two separate large-scale open datasets [National Institutes of Health (NIH) DeepLesion and Medical Image Computing and Computer Assisted Intervention (MICCAI) 2022 Mediastinal Lesion Analysis (MELA) Challenge] were collected to develop a self-attention network-based algorithm for mediastinal lesion detection. We enrolled 921 abnormal CT images from the NIH DeepLesion dataset into the pretraining stage and 880 abnormal CT images from the MELA Challenge dataset into the model training and validation stages in a ratio of 8:2 at the patient level. The average precision (AP) and confidence score on lesion detection were evaluated in the validation set. Sensitivity to lesion detection was compared between the faster region-based convolutional neural network (R-CNN) model and the proposed model. Results: The proposed model achieved an 89.3% AP score in mediastinal lesion detection and could identify comparably large lesions with a high confidence score >0.8. Moreover, the proposed model achieved a performance boost of almost 2% in the competition performance metric (CPM) compared to the faster R-CNN model. In addition, the proposed model can ensure an outstanding sensitivity with a relatively low false-positive rate by setting appropriate threshold values. Conclusions: The proposed model showed excellent performance in detecting mediastinal lesions on CT. Thus, it can drastically reduce radiologists' workload, improve their performance, and speed up the reporting time in everyday clinical practice.

How to reduce anxiety symptoms through individual sport in youth: A longitudinal study over 8-month observation.

Background: Anxiety symptoms are widely observed among the youth, and engagement in sports has been demonstrated to mitigate these symptoms. Nonetheless, the effectiveness of specific sports and the potential moderating role of psychological factors, such as self-esteem and self-efficacy, on the influence of sports on anxiety, remains to be elucidated. This study was designed to longitudinally assess the impact of sports participation on anxiety symptoms among young individuals. Methods: The study encompassed 163 university students, with a male predominance of 81.6%, and explored the influence of sport-related factors (such as mastery of table tennis skills, level and engagement) and psychological aspects (including self-efficacy, self-esteem and resilience) on anxiety symptoms, employing an 8-month longitudinal approach. Physical activity, sedentary and sleep behaviour, along with age, body mass index (BMI), and sex, were accounted for as confounding variables. Results: The study found that high table tennis performance score was found to buffer the development of anxiety symptoms in students with decreased self-esteem in an exploratory moderation model. Self-esteem and self-efficacy were negatively associated with the development of anxiety symptoms, whereas physical activity factors did not have a direct effect. Conclusion: This study highlights the potential of table tennis as a form of sport to alleviate anxiety symptoms in university students, particularly among those with decreased self-esteem. Future research should address the study's limitations and explore the potential moderating effects of other psychological factors. Overall, these findings suggest a potential new approach to treating anxiety symptoms among university students.

Asymmetric Dearomatization of Indoles through Cobalt-Catalyzed Enantioselective C-H Functionalization Enabled by Photocatalysis.

Photocatalysis holds a pivotal position in modern organic synthesis, capable of inducing novel reactivities under mild and environmentally friendly reaction conditions. However, the merger of photocatalysis and transition-metal-catalyzed asymmetric C-H activation as an efficient and sustainable method for the construction of chiral molecules remains elusive and challenging. Herein, we develop a cobalt-catalyzed enantioselective C-H activation reaction enabled by visible-light photoredox catalysis, providing a synergistic catalytic strategy for the asymmetric dearomatization of indoles with high levels of enantioselectivity (96% to >99% ee). Mechanistic studies indicate that the excited photocatalyst was quenched by divalent cobalt species in the presence of Salox ligand, leading to the formation of catalytically active chiral Co(III) complex. Moreover, stoichiometric reactions of cobaltacycle intermediate with indole suggest that the irradiation of visible light also play a critical role in the dearomatization step.

IRF8 maintains mononuclear phagocyte and neutrophil function in acute kidney injury.

Immune cells are key players in acute tissue injury and inflammation, including acute kidney injury (AKI). Their development, differentiation, activation status, and functions are mediated by a variety of transcription factors, such as interferon regulatory factor 8 (IRF8) and IRF4. We speculated that IRF8 has a pathophysiologic impact on renal immune cells in AKI and found that IRF8 is highly expressed in blood type 1 conventional dendritic cells (cDC1s), monocytes, monocyte-derived dendritic cells (moDCs) and kidney biopsies from patients with AKI. In a mouse model of ischemia‒reperfusion injury (IRI)-induced AKI, Irf8 -/- mice displayed increased tubular cell necrosis and worsened kidney dysfunction associated with the recruitment of a substantial amount of monocytes and neutrophils but defective renal infiltration of cDC1s and moDCs. Mechanistically, global Irf8 deficiency impaired moDC and cDC1 maturation and activation, as well as cDC1 proliferation, antigen uptake, and trafficking to lymphoid organs for T-cell priming in ischemic AKI. Moreover, compared with Irf8 +/+ mice, Irf8 -/- mice exhibited increased neutrophil recruitment and neutrophil extracellular trap (NET) formation following AKI. IRF8 primarily regulates cDC1 and indirectly neutrophil functions, and thereby protects mice from kidney injury and inflammation following IRI. Our results demonstrate that IRF8 plays a predominant immunoregulatory role in cDC1 function and therefore represents a potential therapeutic target in AKI.

Early Diagnosis of Colorectal Cancer Based on Bisulfite-free Site-specific Methylation Identification PCR Strategy: High-Sensitivity, Accuracy, and Primary Medical Accessibility.

Due to its decade-long progression, colorectal cancer (CRC) is most suitable for population screening to achieve a significant reduction in its incidence and mortality. DNA methylation has emerged as a potential marker for the early detection of CRC. However, the current mainstream methylation detection method represented by bisulfite conversion has issues such as tedious operation, DNA damage, and unsatisfactory sensitivity. Herein, a new high-performance CRC screening tool based on the promising specific terminal-mediated polymerase chain reaction (STEM-PCR) strategy is developed. CRC-related methylation-specific candidate CpG sites are first prescreened through The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases using self-developed bioinformatics. Next, 9 homebrew colorectal cancer DNA methylated STEM‒PCR assays (ColoC-mSTEM) with high sensitivity (0.1%) and high specificity are established to identify candidate sites. The clinical diagnostic performance of these selected methylation sites is confirmed and validated by a case-control study. The optimized diagnostic model has an overall sensitivity of 94.8% and a specificity of 95.0% for detecting early-stage CRC. Taken together, ColoC-mSTEM, based on a single methylation-specific site, is a promising diagnostic approach for the early detection of CRC which is perfectly suitable for the screening needs of CRC in primary healthcare institutions.

Correlation study of functional magnetic resonance index and clinicopathological features of rectal cancer.

PURPOSE: To investigate the correlation between DCE-MRI, R2*, IVIM, and clinicopathological features of rectal cancer. METHODS: This was a prospective study, enrolling 42 patients with rectal cancer, 20 of whom underwent rectal mesorectal excision. Dynamic contrast-enhanced magnetic resonance imaging scanning was performed preoperatively in all patients, and additional preoperative scanning of R2* imaging and intravoxel incoherent motion was performed in those who underwent surgery. Artificially delineate the ROI around the tumor. Functional magnetic resonance index parameters Ktrans, Ve, R2*, D, D*, and f were estimated by computer software to analyze postoperative pathological reports of patients undergoing total mesenteric resection. Correlation and significance analyses of imaging metrics and pathologic features were performed by GraphPad Prism 9 to assess statistical significance. RESULTS: DEC-MRI, R2*, and IVIM have certain application values in the distance from the lower margin of the tumor to the anorectal ring, imaging T stage and N stage, tumor markers CEA and CA199, immunohistochemical indexes Ki-76 and P53, lymph node cancer metastasis, and rectal fascia status (P < 0.05). CONCLUSION: DEC-MRI, R2*, and IVIM provide reliable quantitative parameters for preoperative clinicopathological evaluation of patients with rectal cancer.

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.

An "off-on-enhanced on" electrochemiluminescence biosensor based on resonance energy transfer and surface plasmon coupled 3D DNA walker for ultra-sensitive detection of microRNA-21.

In this study, a novel electrochemiluminescence (ECL) biosensor was developed to detect microRNA-21 (miRNA-21) with high sensitivity by leveraging the combined mechanisms of resonance energy transfer (RET) and surface plasmon coupling (SPC). Initially, the glassy carbon electrode (GCE) were coated with Cu-Zn-In-S quantum dots (CZIS QDs), known for their defect-related emission suitable for ECL sensing. Subsequently, a hairpin DNA H3 with gold nanoparticles (Au NPs) attached at the end was modified over the surface of the quantum dots. The Au NPs could effectively quench the ECL signals of CZIS QDs via RET. Further, a significant amount of report DNA was generated through the action of a 3D DNA walker. When the report DNA opened H3-Au NPs, the hairpin structure experienced a conformational change to a linear shape, increasing the gap between the CZIS QDs and the Au NPs. Consequently, the localized surface plasmon resonance ECL (LSPR-ECL) effect replaced ECL resonance energy transfer (ECL-RET). Moreover, the report DNA was released following the addition of H4-Au NPs, resulting in the formation of Au dimers and a surface plasma-coupled ECL (SPC-ECL) effect that enhanced the ECL intensity to 6.97-fold. The integration of new ECL-RET and SPC-ECL biosensor accurately quantified miRNA-21 concentrations from 10-8 M to 10-16 M with a limit of detection (LOD) of 0.08 fM, as well as successfully applied to validate human serum samples.

A Biomimetic Fibrous Composite Scaffold with Nanotopography-Regulated Mineralization for Bone Defect Repair.

The effective regeneration of large bone defects via bone tissue engineering is challenging due to the difficulty in creating an osteogenic microenvironment. Inspired by the fibrillar architecture of the natural extracellular matrix, we developed a nanoscale bioengineering strategy to produce bone fibril-like composite scaffolds with enhanced osteogenic capability. To activate the surface for biofunctionalization, self-adaptive ridge-like nanolamellae were constructed on poly(ε-caprolactone) (PCL) electrospinning scaffolds via surface-directed epitaxial crystallization. This unique nanotopography with a markedly increased specific surface area offered abundant nucleation sites for Ca2+ recruitment, leading to a 5-fold greater deposition weight of hydroxyapatite than that of the pristine PCL scaffold under stimulated physiological conditions. Bone marrow mesenchymal stem cells (BMSCs) cultured on bone fibril-like scaffolds exhibited enhanced adhesion, proliferation, and osteogenic differentiation in vitro. In a rat calvarial defect model, the bone fibril-like scaffold significantly accelerated bone regeneration, as evidenced by micro-CT, histological histological and immunofluorescence staining. This work provides the way for recapitulating the osteogenic microenvironment in tissue-engineered scaffolds for bone repair.

Interactions between plants and bacterial communities for phytoremediation of petroleum-contaminated soil.

Plants can stimulate the microbes to degrade ubiquitous petroleum hydrocarbons (PHCs), which has prompted a novel view on rhizoremediation. In the present study, the degradation rate of PHCs was investigated and 16S rRNA gene analysis was performed to investigate the PHC-degrading bacteria in petroleum-contaminated soil with different plants. Mirabilis jalapa (M. jalapa) has a higher PHC degradation rate than Lolium perenne (L. perenne) under petroleum contamination. The bacterial diversity in rhizospheric soil was decreased but the relative abundance of Actinobacteriota, Proteobacteria, and Candidatus Saccharibacteria were significant increased on 45 days petroleum-contaminated rhizospheric soil. In addition, the relative expression of PHC degradation-related genes, the content of malic acid and citric acid of the root exudates in the two plants was significantly increased in response to petroleum stress. The content of citric acid increased 11.9 times in M. jalapa and 3.4 times in L. perenne, respectively, in response to petroleum stress. These results indicate that M. jalapa changes the hydrocarbon-degrading microbial community to enhance the degradation of PHCs by root exudates and phytostimulation.

Extension and Fusion of Cyclic Polyantimony Units.

The synthesis and characterization of a series of polyantimony anionic clusters are reported. The products [(NbCp)2Sb10]2-, [MSb13]3- (M = Ru/Fe), and [MSb15]3- (M = Ru/Fe) were isolated as either K(18-crown-6) or K([2.2.2]-crypt) salts. The Sb10 ring contained in the [(NbCp)2Sb10]2- cluster can be viewed as an extension of two envelope-like cyclo-Sb5 units and represents by far the largest monocyclic all-antimony species. The clusters [MSb13]3- and [MSb15]3- (M = Ru/Fe) illustrate the variability of crown-like Sb8 ring motifs and reveal the fusion of different antimony fragments featuring unique Sb-Sb chain-like units. The reported synthetic approaches involve the fabrication of a variety of distinctive polyantimony anionic clusters, enhancing our understanding of the coordination chemistry of heavier group 15 elements.

Structuring restricted amorphous molecular chains in the reinforced cellulose film by uniaxial stretching.

The construction of the preferred orientation structure by stretching is an efficient strategy to fabricate high-performance cellulose film and it is still an open issue whether crystalline structure or amorphous molecular chain is the key factor in determining the enhanced mechanical performance. Herein, uniaxial stretching with constant width followed by drying in a stretching state was carried out to cellulose hydrogels with physical and chemical double cross-linking networks, achieving high-performance regenerated cellulose films (RCFs) with an impressive tensile strength of 154.5 MPa and an elastic modulus of 5.4 GPa. The hierarchical structure of RCFs during uniaxial stretching and drying was systematically characterized from micro- to nanoscale, including microscopic morphology, crystalline structure as well as relaxation behavior at a molecular level. The two-dimensional correlation spectra of dynamic mechanical analysis and Havriliak-Negami fitting results verified that the enhanced mechanical properties of RCFs were mainly attributed to the stretch-induced tight packing and restricted relaxation of amorphous molecular chains. The new insight concerning the contribution of molecular chains in the amorphous region to the enhancement of mechanical performance for RCFs is expected to provide valuable guidance for designing and fabricating high-performance eco-friendly cellulose-based films.