In silico discovery of potential PPI inhibitors for anti-lung cancer activity by targeting the CCND1-CDK4 complex via the P21 inhibition mechanism.

Non-Small Cell Lung Cancer (NSCLC) is a prevalent and deadly form of lung cancer worldwide with a low 5-year survival rate. Current treatments have limitations, particularly for advanced-stage patients. P21, a protein that inhibits the CCND1-CDK4 complex, plays a crucial role in cell proliferation. Computer-Aided Drug Design (CADD) based on pharmacophores can screen and design PPI inhibitors targeting the CCND1-CDK4 complex. By analyzing known inhibitors, key pharmacophores are identified, and computational methods are used to screen potential PPI inhibitors. Molecular docking, pharmacophore matching, and structure-activity relationship studies optimize the inhibitors. This approach accelerates the discovery of CCND1-CDK4 PPI inhibitors for NSCLC treatment. Molecular dynamics simulations of CCND1-CDK4-P21 and CCND1-CDK4 complexes showed stable behavior, comprehensive sampling, and P21's impact on complex stability and hydrogen bond formation. A pharmacophore model facilitated virtual screening, identifying compounds with favorable binding affinities. Further simulations confirmed the stability and interactions of selected compounds, including 513457. This study demonstrates the potential of CADD in optimizing PPI inhibitors targeting the CCND1-CDK4 complex for NSCLC treatment. Extended simulations and experimental validations are necessary to assess their efficacy and safety.

Role of long non-coding RNA in chemoradiotherapy resistance of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant tumor originating from the nasopharyngeal epithelial cells. Common treatment methods for NPC include radiotherapy, chemotherapy, and surgical intervention. Despite these approaches, the prognosis for NPC remains poor due to treatment resistance and recurrence. Hence, there is a crucial need for more comprehensive research into the mechanisms underlying treatment resistance in NPC. Long non coding RNAs (LncRNAs) are elongated RNA molecules that do not encode proteins. They paly significant roles in various biological processes within tumors, such as chemotherapy resistance, radiation resistance, and tumor recurrence. Recent studies have increasingly unveiled the mechanisms through which LncRNAs contribute to treatment resistance in NPC. Consequently, LncRNAs hold promise as potential biomarkers and therapeutic targets for diagnosing NPC. This review provides an overview of the role of LncRNAs in NPC treatment resistance and explores their potential as therapeutic targets for managing NPC.

Tailored Succinic Acid-Derived Molecular Structures toward 25.41%-Efficiency and Stable Perovskite Solar Cells.

Minimizing interfacial charged traps in perovskite films is crucial for reducing the non-radiative recombination and improving device performance. In this study, succinic acid (SA) derivatives varying active sites and spatial configurations are designed to modulate defects and crystallization in perovskite film. The SA derivative with two symmetric Br atoms, dibromosuccinic acid (DBSA), exhibits the optimal spatial arrangement for defect passivation. Experimental and theoretical results indicate that the carboxyl group and atomic Br in DBSA synergistically interact with the under-coordinated Pb2+ . Moreover, the strong electronegativity of Br efficiently stabilizes the formamidinium cation via electrostatic interaction. Consequently, film quality is significantly improved and non-radiative recombination is markedly depressed, resulting in a photoluminesence lifetime of exceeding 4 µs of and a carrier diffusion length of 3 µm. An exceptional efficiency of 25.41% (certified at 25.00%) along with a high fill factor of 84.39% and excellent long-term operational stability have been achieved finally.

The lipid metabolism remodeling: A hurdle in breast cancer therapy.

Lipids, as one of the three primary energy sources, provide energy for all cellular life activities. Lipids are also known to be involved in the formation of cell membranes and play an important role as signaling molecules in the intracellular and microenvironment. Tumor cells actively or passively remodel lipid metabolism, using the function of lipids in various important cellular life activities to evade therapeutic attack. Breast cancer has become the leading cause of cancer-related deaths in women, which is partly due to therapeutic resistance. It is necessary to fully elucidate the formation and mechanisms of chemoresistance to improve breast cancer patient survival rates. Altered lipid metabolism has been observed in breast cancer with therapeutic resistance, indicating that targeting lipid reprogramming is a promising anticancer strategy.

Transcription Factor MITF Inhibits the Transcription of CPT1B to Regulate Fatty Acid ß-Oxidation and Thus Affects Stemness in Lung Adenocarcinoma Cells.

INTRODUCTION: Cancer stem cells (CSCs) play critical roles in lung adenocarcinoma (LUAD) progression, and fatty acid oxidation is key for CSC growth and survival. Therefore, investigating the molecular mechanisms regulating fatty acid ß-oxidation in LUAD is important for its treatment. METHODS: Bioinformatics analysis assessed CPT1B and MITF expression and their correlation in LUAD tissues, as well as the pathways enriched by CPT1B. qRT-PCR assessed expression of CPT1B and MITF, while CCK-8 and sphere-forming assays were used to measure cell viability and stemness, respectively. Dual staining detected lipid accumulation, while kits were used to measure fatty acid ß-oxidation and glycerol content. qRT-PCR was used to assay expression of lipid oxidation genes. Western blot was used to examine expression of stem cell-related markers. Dual-luciferase assay and ChIP assay were used to verify the binding relationship between MITF and CPT1B. RESULTS: CPT1B was found to be highly expressed in LUAD and enriched in linoleic acid metabolism pathway and α-linolenic acid metabolism pathway. Functional experiments showed that CPT1B could promote stemness in LUAD cells by regulating fatty acid ß-oxidation. Additionally, CPT1B was found to be regulated by the upstream transcription factor MITF, which was lowly expressed in LUAD and could downregulate CPT1B expression. Rescue experiments revealed that CPT1B/MITF axis could affect stemness in LUAD cells by regulating fatty acid ß-oxidation. CONCLUSION: Transcription factor MITF inhibited transcription of CPT1B to regulate fatty acid ß-oxidation, thereby suppressing stemness in LUAD cells. MITF and CPT1B may become new targets for LUAD.

Numerical simulation on seismic pounding damage in a simply-supported steel bridge.

Steel bridges are generally considered to perform well during seismic activity. Nevertheless, they still suffered much unexpected seismic damage in the Kumamoto earthquake, especially seismic pounding damage. Previous studies on bridge pounding damage have generally focused on reinforced concrete bridges. However, steel bridges' dynamic characteristics are more complex, the stiffness of each component varies significantly, and relevant research remains limited. Therefore, the numerical simulation method is adopted in this paper to study the pounding damage of simple-supported steel bridges under seismic events in detail. The multiscale, fine three-dimensional finite element model was built using the general finite element calculation platform Abaqus, and dynamic implicit analysis was performed. Numerical results show that large and near-fault seismic activity results in obvious pounding damage to steel beams. Specifically, longitudinal pounding causes damage to the steel beam's ends; however, the damage is typically localized and mild. Lateral pounding further causes direct damage to the steel beams, resulting in extensive and serious damage. Horizontal pounding which combines longitudinal and lateral causes rotation of the bridge deck and aggravates the lateral damage to steel beams. In addition, a pounding identification method based only on displacement data is proposed, and a feasible preventive measure for lateral pounding damage is suggested.

ER stress aggravates diaphragm weakness through activating PERK/JNK signaling in obesity hypoventilation syndrome.

OBJECTIVE: Obesity hypoventilation syndrome is associated with diaphragmatic dysfunction. This study aimed to explore the role of endoplasmic reticulum (ER) stress in mediating obesity-induced diaphragmatic dysfunction. METHODS: A pulmonary function test and ultrasound were applied to evaluate diaphragmatic function and magnetic resonance imaging was applied to measure diaphragmatic lipid deposition in human patients. For the mechanistic study, obese mice were introduced to a high-fat diet for 24 weeks, followed by diaphragmatic ultrasound measurement, transcriptomic sequencing, and respective biochemical analysis. Automatic force mapping was applied to measure the mechanical properties of C2C12 myotubes. RESULTS: People with obesity showed significant diaphragm weakness and lipid accumulation, which was further confirmed in obese mice. Consistently, diaphragms from obese mice showed altered gene expression profile in lipid metabolism and activation of ER stress response, indicated by elevated protein kinase R-like ER kinase (PERK) and c-Jun NH2 -terminal kinase (JNK) activation. In C2C12 myotubes, inhibition of PERK or JNK signaling abrogated lipotoxicity-induced intracellular lipid deposition and insulin resistance. Inhibition of JNK signaling reversed lipotoxicity-induced impairment of elasticity in C2C12 myotubes. CONCLUSIONS: These data suggest that ectopic lipid deposition impairs the diaphragmatic function of people with obesity. Activation of PERK/JNK signaling is involved in the pathogenesis of lipotoxicity-induced diaphragm weakness in obesity hypoventilation syndrome.

Regulating the Anion Redox and Suppressing the Structural Distortion of Cation-Disordered Rock-Salt Cathode Materials to Improve Cycling Durability through Chlorine Substitution.

Owing to the capacity boost from anion redox activities, cation-disordered rock-salt oxides are considered as potential candidates for the next-generation of high energy density Li-ion cathode materials. Unfortunately, the anion redox process that affords ultra-high specific capacity often triggers irreversible O2 release, which brings about structural degradation and rapid capacity decay. In this study, we present a partial chlorine (Cl) substitution strategy to synthesize a new cation-disordered rock-salt compound of Li1.225Ti0.45Mn0.325O1.9Cl0.1 and investigate the impact of Cl substitution on the oxygen redox process and the structural stability of cation-disordered rock-salt cathodes. We find that partial replacement of O2- by Cl- expands the cell volume and promotes anion redox reaction reversibility, thus increasing the Li+ ion diffusion rate and suppressing irreversible lattice oxygen loss. As a result, the Li1.225Ti0.45Mn0.325O1.9Cl0.1 cathode exhibits significantly improved cycling durability at high current densities, compared with the pristine Li1.225Ti0.45Mn0.325O2 cathode. This work demonstrates the promising feasibility of the Cl substitution process for advanced cation-disordered rock-salt cathode materials.

The role of LINC01419 in regulating the cell stemness in lung adenocarcinoma through recruiting EZH2 and regulating FBP1 expression.

BACKGROUND: Recent years have witnessed a growing academic interest in the effects of lncRNAs on tumors. LINC01419 is found to facilitate proliferation and metastasis of lung adenocarcinoma (LUAD) cells, but there is a great deal of uncertainty about how LINC01419 works on LUAD cell stemness. For this reason, the focus of this research is centered on the regulatory impact of LINC01419 on LUAD cell stemness. METHODS: For the detection of the expression level of LINC01419 in LUAD, qRT-PCR was performed. And how oe-LINC01419 and sh-LINC01419 affected LUAD cell proliferation as well as stem cell sphere-formation were examined by CCK-8 and cell sphere-forming assays. In addition, whether LINC01419 could recruit EZH2 and regulate FBP1 expression were determined by bioinformatics analysis, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP). Western blot was utilized to detect the protein expression levels of FBP1, CD44, CD133, and ALDH-1 as well. RESULTS: On the basis of the findings from those assays, an up-regulation of LINC01419 level was demonstrated in LUAD cell lines, and a remarkable upregulation of it in CD44 + LUAD cells. In LUAD cells, proliferation and stem cell sphere-formation that were attenuated by LINC01419 knockdown were discovered to be facilitated by LINC01419 overexpression. And a binding relationship between LINC01419 and EZH2 was determined by RIP assay. Besides, EZH2 was capable of binding to FBP1 promoter region, as found by ChIP-PCR assay. Finally, it was demonstrated by in vitro experiments that LINC01419 could inhibit FBP1 expression by recruiting EZH2, resulting in promotion of LUAD cell proliferation and stemness. SIGNIFICANCE: To summarize, our findings demonstrate a cancer-promoting role of LINC01419 in LUAD. LINC01419, by recruiting EZH2 and regulating FBP1 expression, contributes to LUAD cell stemness. According to these findings, the potential of LINC01419 to be the target for LUAD treatment is hence determined, which also adds more possibility to the enrichment of therapeutic strategies for lung cancer stem cells.

Structural Stabilization of Cation-Disordered Rock-Salt Cathode Materials: Coupling between a High-Ratio Inactive Ti4+ Cation and a Mn2+/Mn4+ Two-Electron Redox Pair.

Cation-disordered rock-salt cathode materials are featured by their extraordinarily high specific capacities in lithium-ion batteries primarily contributed by anion redox reactions. Unfortunately, anion redox reactions can trigger oxygen release in this class of materials, leading to fast capacity fading and major safety concern. Despite the capability of absorbing structural distortions, high-ratio d0 transition-metal cations are considered to be unfavorable in design of a new cation-disordered rock-salt structure because of their electrochemically inactive nature. Herein, we report a new cation-disordered rock-salt compound of Li1.2Ti0.6Mn0.2O2 with the stoichiometry of Ti4+ as high as 0.6. The capacity reducing effect by the low-ratio active transition-metal center can be balanced by using a Mn2+/Mn4+ two-electron redox couple. The strengthened networks of strong Ti-O bonds greatly retard the oxygen release and improve the structural stability of cation-disordered rock-salt cathode materials. As expected, Li1.2Ti0.6Mn0.2O2 delivers significantly improved electrochemical performances and thermal stability compared to the low-ratio Ti4+ counterpart of Li1.2Ti0.4Mn0.4O2. Theoretical simulations further reveal that the improved electrochemical performances of Li1.2Ti0.6Mn0.2O2 are attributed to its lower Li+ diffusion energy barrier and enhanced unhybridized O 2p states compared to Li1.2Ti0.4Mn0.4O2. This concept might be helpful for the improvement of structural stability and electrochemical performances of other cation-disordered rock-salt metal oxide cathode materials.

Preparation of single-crystal ternary cathode materials via recycling spent cathodes for high performance lithium-ion batteries.

With the rapid consumption of lithium-ion batteries (LIBs), the recycling of spent LIBs is becoming imperative. However, the development of effective and environmentally friendly methods towards the recycling of spent LIBs, especially waste electrode materials, still remains a great challenge. Herein, on the basis of a Li-based molten salt, we have developed a facile and effective strategy to recycle spent polycrystalline ternary cathode materials into single-crystal cathodes. The regenerated plate-like single-crystal LiNi0.6Co0.2Mn0.2O2 material with exposed {010} planes achieves an excellent rate performance and outstanding cycling stability. In particular, a high capacity of 155.1 mA h g-1 and a superior capacity retention of 94.3% can be achieved by the recycled cathode material even after 240 cycles at 1 C. Meanwhile the single-crystal structure can be well reserved without any cracks or pulverization being observed. Moreover, this recycling method can be expanded to recycle other waste Ni-Co-Mn ternary cathode materials (NCM) or their mixtures for producing high-performance single-crystal cathode materials, demonstrating its versatility and flexibility in practical applications. Therefore, the strategy of converting spent NCM cathodes into single-crystal ones with satisfactory electrochemical performance may open up a cost-effective pathway for resolving the issues caused by the large amounts of spent LIBs, thus facilitating the sustainable development of LIBs.

ADAMTS9-AS2 regulates PPP1R12B by adsorbing miR-196b-5p and affects cell cycle-related signaling pathways inhibiting the malignant process of esophageal cancer.

This study explored the mechanism that ADAMTS9-AS2/miR-196b-5p/PPP1R12B/cell cycle pathway axis in inhibiting the malignant progression of esophageal cancer (EC), providing a new idea for targeted molecular therapy of EC. The expression data of EC tissue were acquired from TCGA database. The target lncRNA, downstream miRNA and its target gene were determined by bioinformatics analysis. ADAMTS9-AS2, miR-196b-5p and PPP1R12B levels in EC tissue and cells were assayed through qRT-PCR. Western blot was applied to assess protein level of PPP1R12B in cells and tissues, as well as protein expression of CDK1, cyclin A2, cyclin B1 and Plk1 in EC cells. Cell proliferation was assayed via CCK-8 assay. Cell cycle distribution was analyzed by flow cytometry. Cell migratory and invasive abilities were measured through scratch healing and transwell assays. Pearson correlation analysis was utilized to analyze relationship among ADAMTS9-AS2, miR-196b-5p and PPP1R12B. RIP was introduced to assess binding among the three. Dual-luciferase assay was utilized to verify targeted binding sites. The tumor formation in nude mice assay was utilized to detect tumorigenesis of EC cells in vivo. ADAMTS9-AS2 was significantly lowly expressed while miR-196b-5p was increased in EC tissue and cells. ADAMTS9-AS2 bound to miR-196b-5p and constrained its expression. Overexpressed ADAMTS9-AS2 inhibited EC cell malignant progression via downregulating miR-196b-5p, while overexpressed miR-196b-5p reversed this inhibitory effect. ADAMTS9-AS2 modulated PPP1R12B level by competitively inhibiting miR-196b-5p. PPP1R12B played a modulatory role in EC by inhibiting cell cycle pathway. Overexpressed ADAMTS9-AS2 regulated the tumor-forming ability of EC cells in vivo through miR-196b-5p/PPP1R12B/cell cycle signaling pathway axis. ADAMTS9-AS2 downregulated PPP1R12B by adsorbing miR-196b-5p, so as to regulate the cell cycle signaling pathway to inhibit EC malignant progression.

Construction of a hetero-epitaxial nanostructure at the interface of Li-rich cathode materials to boost their rate capability and cycling performances.

Lithium-rich cathode materials are considered to be promising candidate cathode materials for next-generation Li-ion batteries owing to their high specific capacities and low cost. Nevertheless, they still suffer from undesirable capacity loss and voltage decay during cycling. In this work, we propose a facile strategy to coat lithiated transition metal phosphates on the surface of Li-rich cathode materials. Strikingly, the coated material shows a hetero-epitaxial nanostructure at the interface between the coating layer and the cathode material. Such a coating layer with a unique interfacial structure could effectively boost the Li+ solid-state diffusion kinetics, protect the cathode material from the corrosion of the electrolyte, and suppress the oxygen loss during the charge-discharge processes. Moreover, the lithiated phosphate coating layer can inhibit the formation of residual Li compounds upon long-term storage under an ambient atmosphere. Based on the above favorable properties, the lithiated phosphate coated Li-rich cathode material shows a high rate capability with a discharge capacity of 156 mA h g-1 obtained at 5 C and decent cyclic stability with a capacity retention of 93.4% achieved at 0.5 C after 140 cycles. This study investigates the interfacial engineering of Li-rich cathode materials via the construction of a Li+-conductive lithiated phosphate coating layer with a hetero-epitaxial interfacial nanostructure, which may offer an effective way to further improve the electrochemical performances of Li-rich cathode materials.

Andrographolide inhibits non-small cell lung cancer cell proliferation through the activation of the mitochondrial apoptosis pathway and by reprogramming host glucose metabolism.

BACKGROUND: The main aim of this research was to explore the role and mechanism of Andrographolide (Andro) in controlling non-small cell lung cancer (NSCLC) cell proliferation. METHODS: Human NSCLC H1975 cells were treated with Andro (0-20 µM) for 4-72 h. B-cell leukemia/lymphoma 2 (Bcl-2)-antagonist/killer (Bak)-small interfering RNA (siRNA) (Bak-siRNA) and fructose-1,6-bisphosphatase (FBP1)-siRNA were transfected into H1975 cells to inhibit the endogenic Bak and FBP1 expression, respectively, and their expressions were detected by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting (WB). Cellular proliferation ability was determined through various assessments, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, and cell counting kit-8 (CCK-8) assays. Cell apoptosis ability was measured using flow cytometry. Pro-apoptotic-related proteins (cleaved caspase 9, cleaved caspase 8, and cleaved caspase 3) and mitochondrial apoptosis pathway proteins [Bcl2-associated X (Bax), Bak, Bcl-2, and cytochrome C (cyto C)] were assessed by WB. Aerobic glycolysis-associated genes [pyruvate kinase M2 (PKM2), lactate dehydrogenase A (LDHA), and glucose transporter 1 (GLUT1)] and gluconeogenesis genes [phosphoenolpyruvate carboxykinase 1 (PEPCK1), fructose-1,6-bisphosphatase 1 (FBP1), and phosphofructokinase (PFK)] were measured by qRT-PCR. The mitochondrial membrane depolarization sensor, 5, 50, 6, 60-tetrachloro-1, 10, 3, 30 tetraethyl benzimidazolo carbocyanine iodide (JC-1) assay was used for the measurement of mitochondrial membrane potential (ΔΨm). Additionally, glycolytic metabolism, lactate production, and adenosine triphosphate (ATP) synthesis were also analyzed. RESULTS: Andro inhibited human NSCLC cellular proliferation and induced apoptosis in a dose-time or dose-dependent manner via activation of the mitochondrial apoptosis pathway. Andro inhibited glycolysis, promoted the gluconeogenesis pathway, and increased the levels of cleaved caspase 9, cleaved caspase 8, cleaved caspase 3, Bax, Bak, PEPCK1, FBP1, and PFK, and decreased the levels of Bcl-2, PKM2, LDHA, and GLUT1. Moreover, it also decreased the ΔΨm and facilitated the release of cyto C from mitochondria into the cytoplasm. Furthermore, Andro enhanced the mitochondrial translocation of Bak, glucose uptake, lactate release, and intracellular ATP synthesis. Suppression of endogenic Bak and FBP1 expression significantly reduced the effects of Andro in H1975 cells. CONCLUSIONS: Andro represses NSCLC cell proliferation through the activation of the mitochondrial apoptosis pathway and by reprogramming glucose metabolism.

Clinical Significance and Potential Regulatory Mechanisms of Serum Response Factor in 1118 Cases of Thyroid Cancer Based on Gene Chip and RNA-Sequencing Data.

BACKGROUND Thyroid cancer (TC) is one of the most prevalent endocrine malignancies and there may be many unclarified molecular events and gene types involved in TC. The objective of this study was to assess the clinical implications and potential mechanisms of serum response factor (SRF) in TC. MATERIAL AND METHODS RNA-sequencing and gene chip data with TC expression were collected from The Cancer Genome Atlas/Genotype-Tissue Expression, Gene Expression Omnibus, ArrayExpress, Sequence Read Archive, and Oncomine. SRF expression of all TC and adjacent non-cancerous tissue were calculated using the t test, STATA, and Meta-DiSc. The related pathways of the potential SRF target genes and target miRNAs were explored. Dual-luciferase reporter assay was performed to validate the association between SRF and its putative miRNA. RESULTS One RNA-sequencing and 15 gene chips were collected, and the pooled standardized mean difference of SRF was -1.00. Furthermore, the area under the curve of sROC of SRF in TC was 0.8251, indicating a dramatic decreased expression of SRF in TC tissues based on 1118 cases. The intersection of differentially expressed genes in TC, SRF co-expressed genes, and SRF potential target genes achieved from Cistrome Cancer led to 169 overlapped genes. miR-330-5p was predicted to target SRF, which was further confirmed by dual-luciferase reporter assay. CONCLUSIONS The reduction of SRF appears to play a crucial role in the origin of TC. These properties are accomplished by the target genes of SRF, as a transcription factor, or by the axes with the associated miRNAs.

Defect mitigation using d-penicillamine for efficient methylammonium-free perovskite solar cells with high operational stability.

Trap-dominated non-radiative charge recombination is one of the key factors that limit the performance of perovskite solar cells (PSCs), which was widely studied in methylammonium (MA) containing PSCs. However, there is a need to elucidate the defect chemistry of thermally stable, MA-free, cesium/formamidinium (Cs/FA)-based perovskites. Herein, we show that d-penicillamine (PA), an edible antidote for treating heavy metal ions, not only effectively passivates the iodine vacancies (Pb2+ defects) through coordination with the -SH and -COOH groups in PA, but also finely tunes the crystallinity of Cs/FA-based perovskite film. Benefiting from these merits, a reduction of non-radiative recombination and an increase in photoluminescence lifetime have been achieved. As a result, the champion MA-free device exhibits an impressive power conversion efficiency (PCE) of 22.4%, an open-circuit voltage of 1.163 V, a notable fill factor of 82%, and excellent long-term operational stability. Moreover, the defect passivation strategy can be further extended to a mini module (substrate: 4 × 4 cm2, active area: 7.2 cm2) as well as a wide-bandgap (∼1.73 eV) Cs/FA perovskite system by delivering PCEs of 16.3% and 20.2%, respectively, demonstrating its universality in defect passivation for efficient PSCs.

Local application of MDL28170-loaded PCL film improves functional recovery by preserving survival of motor neurons after traumatic spinal cord injury.

Neuronal death and organization degeneration can happen inordinately after spinal cord injury (SCI), which lead to nerve dysfunction. We aimed to determine whether local application of a cell permeable calpain I inhibitor (MDL28170) can promote SCI recovery by increasing neuronal cell viability. MDL28170-loaded polycaprolactone (PCL) film was fabricated. Scanning electron microscopy showed the surface of PCL film was smooth with holes (diameter at µM level). The PCL film was non-toxic, biological compatibility, and had good neuron adhension and slow release characteristic. MDL28170 increased VSC4.1 motor neurons' viability under tunicamycin (an endoplasmic reticulum stress) induced injury. In a traumatic SCI rat model, MDL28170-loaded PCL film reduced the area of lesion cavity, and promoted recovery of locomotor behavior. Moreover, the expression of GAP-43 was upregulated after MDL28170-loaded PCL film treatment. Thus, our findings demonstrated that localized delivery of MDL28170 could promote SCI recovery by inhibiting endoplasmic reticulum stress, preserving survival of the motor neurons, which may point out a promising therapeutic target for treating SCI patient.