Efficacy and safety of Trastuzumab Emtansine in treating human epidermal growth factor receptor 2-positive metastatic breast cancer in Chinese population: a real-world multicenter study.

Background: Trastuzumab emtansine (T-DM1) has been approved worldwide for treating metastatic breast cancer (mBC) in patients who have received first-line therapy, shown disease progression, and are human epidermal growth factor receptor 2 (HER2)-positive. T-DM1 received approval in China to treat early-stage breast cancer (BC) in 2020 and for mBC in 2021. In March 2023, T-DM1 was included in medical insurance coverage, significantly expanding the eligible population. Materials and methods: This post-marketing observational study aimed to assess the safety and effectiveness of T-DM1 in real-world clinical practice in China. This study enrolled 31 individuals with HER2-positive early-stage BC and 70 individuals with HER2-positive advanced BC from 8 study centers in Shandong Province, China. The T-DM1 dosage was 3.6 mg/kg injected intravenously every 3 weeks until the disease advanced or the drug toxicity became uncontrollable, whichever occurred earlier. Additionally, efficacy and safety information on T-DM1 were collected. Results: During the 7-month follow-up period, no recurrence or metastases were observed in patients who had early-stage BC. The disease control rate was 31.43% (22/70) in patients with advanced BC. The most common adverse effect of T-DM1 was thrombocytopenia, with an incidence of 69.31% (70/101), and the probability of Grade ≥ 3 thrombocytopenia was 11.88% (12/101). Conclusion: This real-world study demonstrated that T-DM1 had good efficacy and was well tolerated by both HER2-positive early-stage BC and mBC patients.

Hierarchical Structure with Microcrater Covered with Nanograss Enhancing Condensation and Its Antifrosting/Anti-Icing Performance Inspired by Euphorbia helioscopia L.

Over an extended period of evolution and natural selection, a multitude of species developed a diverse array of biological interface features with specific functions. These biological structures provide a rich source of inspiration for the design of bionic structures on superhydrophobic surfaces. Understanding the functional mechanism of plant leaves is of paramount importance for the advancement of new engineering materials and the further promotion of engineering applications of bionic research. The hierarchical structure of microcrater-covered nanograss (MCNG) on the surface of E. helioscopia L. leaf provided the inspiration for the bionic MCNG surface, which was successfully prepared on a copper substrate by hybrid laser micromachining technology and chemical etching. The combined action of texture structure and surface chemistry resulted in a contact angle of 169° ± 1° for MCNG surface droplets and a rolling angle of less than 1°. Notably, the condensation-induced adhesion force does not augment with the increase of the temperature difference, which facilitated the shedding of hot droplets from the surface. The microscope observation revealed a high density of condensed droplets on the MCNG surface and the tangible jumping behavior of the droplets. The fabricated MCNG also demonstrated excellent antifrost/anti-icing abilities in low-temperature and high-humidity environments. Finally, the study confirmed the exceptional mechanical durability and reusability of the MCNG surface through various tests, including scratch damage, sandpaper wear, water flow impact and flushing, and condensation-drying cycle tests. The nanograss can be effectively protected within the microcrater structure. This research presents a promising approach for preventing and/or removing unwanted droplets in numerous engineering applications.

Superhydrophobic Surfaces with Excellent Ice Prevention and Drag Reduction Properties Inspired by Iridaceae Leaf.

The anti-icing and drag-reduction properties of diverse microstructured surfaces have undergone extensive study over the past decade. Nonetheless, tough environments enforce stringent demands on the composite characteristics of superhydrophobic surfaces (SHS). In this study, fresh composite structures were fabricated on a metal substrate by nanosecond laser machining technology, drawing inspiration from the hardy plant Iridaceae. The prepared sample surface mainly consists of a periodic microrhombus array and irregular nanosheets. To comprehensively investigate the effect of its special structure on surface properties, three surfaces with different sizes of rhombic structures were used for comparative analysis, and the results show that the SH-S2 sample is optimal. This can significantly delay the freezing time by an impressive 1404 s at -10 °C while revealing the sample surface anti-icing strategy. In addition, the rheological experiments determined over 300 µm of slip length for the SH-S2 sample, and the drag reduction rate of the surface reaches nearly 40%, which is well aligned with the results of the delayed icing experiments. Finally, the mechanical durability of the SH-S2 surface was investigated through scratch damage, sandpaper abrasion, reparability trials, and icing and melting cycle tests. This research presents a new approach and methodology for the application of SHS on polar ship surfaces.

Conserved immuno-collagenic subtypes predict response to immune checkpoint blockade.

BACKGROUND: Immune checkpoint blockade (ICB) has revolutionized the treatment of various cancer types. Despite significant preclinical advancements in understanding mechanisms, identifying the molecular basis and predictive biomarkers for clinical ICB responses remains challenging. Recent evidence, both preclinical and clinical, underscores the pivotal role of the extracellular matrix (ECM) in modulating immune cell infiltration and behaviors. This study aimed to create an innovative classifier that leverages ECM characteristics to enhance the effectiveness of ICB therapy. METHODS: We analyzed transcriptomic collagen activity and immune signatures in 649 patients with cancer undergoing ICB therapy. This analysis led to the identification of three distinct immuno-collagenic subtypes predictive of ICB responses. We validated these subtypes using the transcriptome data from 9,363 cancer patients from The Cancer Genome Atlas (TCGA) dataset and 1,084 in-house samples. Additionally, novel therapeutic targets were identified based on these established immuno-collagenic subtypes. RESULTS: Our categorization divided tumors into three subtypes: "soft & hot" (low collagen activity and high immune infiltration), "armored & cold" (high collagen activity and low immune infiltration), and "quiescent" (low collagen activity and immune infiltration). Notably, "soft & hot" tumors exhibited the most robust response to ICB therapy across various cancer types. Mechanistically, inhibiting collagen augmented the response to ICB in preclinical models. Furthermore, these subtypes demonstrated associations with immune activity and prognostic predictive potential across multiple cancer types. Additionally, an unbiased approach identified B7 homolog 3 (B7-H3), an available drug target, as strongly expressed in "armored & cold" tumors, relating with poor prognosis. CONCLUSION: This study introduces histopathology-based universal immuno-collagenic subtypes capable of predicting ICB responses across diverse cancer types. These findings offer insights that could contribute to tailoring personalized immunotherapeutic strategies for patients with cancer.

Quantitative systems pharmacology modeling of HER2-positive metastatic breast cancer for translational efficacy evaluation and combination assessment across therapeutic modalities.

HER2-positive (HER2+) metastatic breast cancer (mBC) is highly aggressive and a major threat to human health. Despite the significant improvement in patients' prognosis given the drug development efforts during the past several decades, many clinical questions still remain to be addressed such as efficacy when combining different therapeutic modalities, best treatment sequences, interindividual variability as well as resistance and potential coping strategies. To better answer these questions, we developed a mechanistic quantitative systems pharmacology model of the pathophysiology of HER2+ mBC that was extensively calibrated and validated against multiscale data to quantitatively predict and characterize the signal transduction and preclinical tumor growth kinetics under different therapeutic interventions. Focusing on the second-line treatment for HER2+ mBC, e.g., antibody-drug conjugates (ADC), small molecule inhibitors/TKI and chemotherapy, the model accurately predicted the efficacy of various drug combinations and dosing regimens at the in vitro and in vivo levels. Sensitivity analyses and subsequent heterogeneous phenotype simulations revealed important insights into the design of new drug combinations to effectively overcome various resistance scenarios in HER2+ mBC treatments. In addition, the model predicted a better efficacy of the new TKI plus ADC combination which can potentially reduce drug dosage and toxicity, while it also shed light on the optimal treatment ordering of ADC versus TKI plus capecitabine regimens, and these findings were validated by new in vivo experiments. Our model is the first that mechanistically integrates multiple key drug modalities in HER2+ mBC research and it can serve as a high-throughput computational platform to guide future model-informed drug development and clinical translation.

Phyllostachys Viridis-Leaf-like MLMN Surfaces Constructed by Nanosecond Laser Hybridization for Superhydrophobic Antifogging and Anti-Icing.

In nature, many species commonly evolve specific functional surfaces to withstand harsh external environments. In particular, structured wettability of surfaces has attracted tremendous interest due to its great potential in antifogging and anti-icing properties. Phyllostachys Viridis is a resistant low-temperature (-18 °C) plant with superhydrophobicity and ice resistivity behaviors. In this work, with inspiration from the representative cold-tolerant plants leaves, a unique multilevel micronano (MLMN) surface was fabricated on copper substrate by ultrafast laser process, which exhibited superior superhydrophobic characteristics with the water contact angle > 165° and rolling angle< 2°. In the dynamic wettability experiment, the rebound efficiency of the droplet on the MLMN surface reached 20.6%, and the contact time was only 10.6 ms. In the condensation experiment, the nucleation, growth, merging, and bouncing of fog drops on the surface was distinctly observed, indicating that rational texture structures can improve the antifogging performance of the surface. In the anti-icing experiment, the freezing time was delayed to 921 s at -10 °C, and the freezing time of salt water reached a staggering 1214 s. Moreover, the mechanical durability of MLMN surfaces was confirmed by scratch damage, sandpaper abrasion, and icing and melting cycle tests, and their repairability was evaluated for product applications in practice. Finally, the underlying antifogging/anti-icing strategy of the MLMN surface was also revealed. We anticipate that the investigations offer a promising way to handily design and fabricate multiscale hierarchical structures with reliable antifogging and anti-icing performance, especially in saltwater-related applications.

Towards high-performance nonlinear optical materials through embedding a D-A system into ß-ketoenamine-linked COFs.

Two covalent organic framework (COF) films supported by a glass substrate were obtained by solvothermal reaction of an electron donor with electron acceptor 1,3,5-triformylbenzene (TF) or 2,4,6-triformylphloroglucinol (TFP), respectively. The TFP-BD film exhibits a nonlinear absorption coefficient of -3.01 × 105 cm GW-1. The TFP-BD film can aggregate electrons around the connected monomer through the D-A effect due to its highly polar and electronegative carbonyl oxygen atoms, thereby modulating the electronic structure of the COFs. This work provides a novel approach for the structural modulation of optical materials with strong nonlinearity.

Recent advances in prevailing antifogging surfaces: structures, materials, durability, and beyond.

In past decades, antifogging surfaces have drawn more and more attention owing to their promising and wide applications such as in aerospace, traffic transportation, optical devices, the food industry, and medical and other fields. Therefore, the potential hazards caused by fogging need to be solved urgently. At present, the up-and-coming antifogging surfaces have been developing swiftly, and can effectively achieve antifogging effects primarily by preventing fog formation and rapid defogging. This review analyzes and summarizes current progress in antifogging surfaces. Firstly, some bionic and typical antifogging structures are described in detail. Then, the antifogging materials explored thus far, mainly focusing on substrates and coatings, are extensively introduced. After that, the solutions for improving the durability of antifogging surfaces are explicitly classified in four aspects. Finally, the remaining big challenges and future development trends of the ascendant antifogging surfaces are also presented.

Life events and parent style for mental health in children: a cross-sectional study.

BACKGROUND: Life events and parenting styles might play an important role in children's mental health. AIMS: This study aims to explore how life events and parenting styles influence children's mental health based on a Chinese sample. METHODS: A total of 3535 participants had at least one mental disorder (positive group), while a total of 3561 participants had no mental disorders (negative group). The Child Behavior Checklist (CBCL), Adolescent Self-Rating Life Events Check List (ASLEC) and Egna Minnen Beträffande Uppfostran (EMBU) were used for screening these two groups. RESULTS: CBCL total scores differed significantly by sex in the Positive group according to the Mann-Whitney tests (Z = -5.40, p < 0.001). Multiple regression analyses showed that the dimensions of punishment (p = 0.014) and other (p = 0.048) in the ASLEC scale can significantly predict CBCL total scores in the Positive group. Sex, age and overprotection from the father were risk factors (p < 0.001) according to binary logistic regression. CONCLUSIONS: Life events and parenting styles may have impacts on mental health. Fathers play a very important role in children's growth. Punitive education and fathers' overprotection might be risk factors for children's mental health. IMPACT: It is a large sample (3535) study of Chinese children and adolescents It provides evidence that life events and parenting styles have impacts on mental health and that fathers play a very important role in children's growth. It is conducive to the development of interventions for the mental health of children and adolescents.

Protocol of a randomized controlled trial to investigate the efficacy and neural correlates of mindfulness-based habit reversal training in children with Tourette syndrome.

Background: Tourette syndrome (TS) is a developmental neuropsychiatric disorder. Behavior therapy, especially habit reversal training (HRT), has gradually become regarded as one of the core therapies for TS. Mindfulness approaches can improve psychological adjustment and reduce stress and anxiety, suggesting potential benefits when incorporated into behavior therapy. To improve the efficacy of HRT, we combined it with mindfulness, an approach named mindfulness-based habitual reversal training (MHRT). The aim of this protocol is to investigate the efficacy and neural mechanisms of MHRT for TS. Methods/design: We will perform a randomized control trial (RCT) to evaluate the efficacy and neural mechanisms of MHRT. The sample will include 160 participants (including 120 patients with TS and 40 healthy controls). The patient sample will be randomly divided into three groups exposed to three different types of training: MHRT, HRT, and psychoeducation and supportive therapy (PST). Participants will be assessed and undergo resting-state fMRI scans at baseline and at the end of the 12-week training. The Yale Global Tic Severity Scale (YGTSS) and Premonitory Urge for Tic Scale (PUTS) will be used to assess the severity of tic symptoms and premonitory urges. The primary outcomes are change scores on the YGTSS and other assessments from baseline and the end of the training. The secondary outcomes are the neural correlates of these trainings among these groups based on graph theory, which is used to characterize brain functional connectivity networks. The default mode network (DMN) and the salience network (SN) will be assessed (which have been associated with mindfulness as well as the generation of tic symptoms) by network parameters, including clustering coefficients and shortest path lengths. Changes in these network parameters will be regarded as the neural correlates of the behavioral training. Discussion: MHRT was newly developed for the treatment of TS. MHRT may lead to greater reductions in tic severity than traditional HRT. Changes in the network parameters of the DMN and SN may show associations with the efficacy of MHRT. Clinical trial registration: http://www.chictr.org.cn, ChiCTR2100053077, China.

Ultrafast Self-Healing Superhydrophobic Surface for Underwater Drag Reduction.

The self-healing superhydrophobic surfaces have attracted great interest owing to restoring superhydrophobicity without preparation crafts. However, the self-healing superhydrophobic surface still faces the dilemma of long repairing time. Especially in aqueous environments, superhydrophobic surfaces are highly susceptible to contamination and damage. In the current study, a superhydrophobic surface with ultrafast repairability was developed, which apply for drag reduction in aqueous medium. The prepared superhydrophobic surface can recover superhydrophobicity in only 30 s after severe physical and chemical damage. In addition, this research pioneered the combination of superhydrophobicity and porous structures for underwater drag reduction. The study of drag reduction confirms that the superhydrophobic surface can reduce the frictional drag by about 43% in the water. However, the drag reduction rate of the superhydrophobic surface with the porous structure can be improved to 76% due to increased stability of the air layer. More importantly, the porous structure with the average pore size of 50 µm has the most excellent stability through further experiments on the underwater air layer. This is attributed to the proper size of the pore to effectively balance the capillary force and resist wetting in the marginal region. This study will bring inspiration for the large-scale application of superhydrophobic surfaces and long-term drag reduction.

Gray Matter Alterations in Pediatric Schizophrenia and Obsessive-Compulsive Disorder: A Systematic Review and Meta-Analysis of Voxel-Based Morphometry Studies.

Objective: The aim of this study is comparing gray matter alterations in SCZ pediatric patients with those suffering from obsessive-compulsive disorder (OCD) based on a systematic review and an activation likelihood estimation (ALE) meta-analysis. Methods: A systematic literature search was performed in PubMed, Elsevier, and China National Knowledge Infrastructure (CNKI). A systematic review and an ALE meta-analysis were performed to quantitatively examine brain gray matter alterations. Results: Children and adolescents with schizophrenia had decreased gray matter volume (GMV) mainly in the prefrontal cortex (PFC), temporal cortex (such as the middle temporal gyrus and transverse temporal gyrus), and insula, while children and adolescents with OCD mainly had increased GMV in the PFC and the striatum (including the lentiform nucleus and caudate nucleus), and decreased GMV in the parietal cortex. Conclusions: Our results suggest that gray matter abnormalities in the PFC may indicate homogeneity between the two diseases. In children and adolescents, structural alterations in schizophrenia mainly involve the fronto-temporal and cortico-insula circuits, whereas those in OCD mainly involve the prefrontal-parietal and the prefrontal-striatal circuits.

The Behavioral and Emotional Profile of Pediatric Tourette Syndrome Based on CBCL in a Chinese Sample.

Background: Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder that has a unique status of a quintessentially neuropsychiatric condition at the interface of neurology (movement disorder) and psychiatry (behavioral/emotional condition). However, the behavioral and emotional profile has seemed to be neglected in the literature thus far. This study aimed to investigate the behavioral and emotional profile of TS. Methods: A total of 124 patients aged 6-16 years with TS were included in this study, including age- and sex-matched health control, attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), and major depressive disorder (MDD) groups. The Child Behavior Checklist (CBCL) was used to screen the behavioral and emotional profile of the TS and other compared groups. The Yale Global Tic Severity Scale (YGTSS) was used to assess TS tic severity. Analysis of variance (ANOVA) was used to investigate the difference between the TS and other compared groups. Results: The results showed that the eight factors of the CBCL had no association with motor tics, vocal tics, or tic severity (p > 0.05). However, positive correlations were identified between functional impairments (subscales of YGTSS) and thought problems (TP) and rule-breaking behavior (RBB). Based on the eight-factor profile of the CBCL, TS showed a similar profile to MDD but different from ADHD and OCD, which showed similar profiles. Conclusions: Based on the assessment of the CBCL of TS, it was found that "pure" TS might show fewer behavioral and emotional problems than OCD, ADHD, and MDD. Similar behavioral and emotional profiles were identified between TS and MDD, but not OCD and ADHD. More attention needs to be paid to the thought problems and rule break problems in the CBCL in the screening stage, which might have a potential influence on the functional impairments of TS.

Comparison of diagnostic validity of two autism rating scales for suspected autism in a large Chinese sample.

BACKGROUND: Autism is the most common clinical developmental disorder in children. The childhood autism rating scale (CARS) and autistic autism behavior checklist (ABC) are the most commonly used assessment scales for diagnosing autism. However, the diagnostic validations and the corresponding cutoffs for CARS and ABC in individuals with suspected autism spectrum disorder (ASD) remain unclear. Furthermore, for suspected ASD in China, it remains unclear whether CARS is a better diagnostic tool than ABC. Also unclear is whether the current cutoff points for ABC and CARS are suitable for the accurate diagnosis of ASD. AIM: To investigate the diagnostic validity of CARS and ABC based on a large Chinese sample. METHODS: A total of 591 outpatient children from the ASD Unit at Beijing Children's Hospital between June and November 2019 were identified. First, the Clancy autism behavior scale (CABS) was used to screen out suspected autism from these children. Then, each suspected ASD was evaluated by CARS and ABC. Receiver operating characteristic (ROC) curve analysis was used to compare diagnostic validations. We also calculated the area under the curve (AUC) for both CARS and ABC. RESULTS: We found that the Cronbach alpha coefficients of CARS and ABC were 0.772 and 0.426, respectively. Therefore, the reliability of the CARS was higher than that of the ABC. In addition, we found that the correlation between CARS and CABS was 0.732. Next, we performed ROC curve analysis for CARS and ABC, which yielded AUC values of 0.846 and 0.768, respectively. The cutoff value, which is associated with the maximum Youden index, is usually applied as a decision threshold. We found that the cutoff values of CARS and ABC were 34 and 67, respectively. CONCLUSION: This result indicated that CARS is superior to ABC in the Chinese population with suspected ASD.

Differential sleep/wake response and sex differences following acute suvorexant, MK-1064 and zolpidem administration in the rTg4510 mouse model of tauopathy.

BACKGROUND AND PURPOSE: Transgenic mouse models of tauopathy display prominent sleep/wake disturbances which manifest primarily as a hyperarousal phenotype during the active phase, suggesting that tau pathology contributes to sleep/wake changes. However, no study has yet investigated the effect of sleep-promoting compounds in these models. Such information has implications for the use of hypnotics as potential therapeutic tools in tauopathy-related disorders. EXPERIMENTAL APPROACH: This study examined polysomnographic recordings in 6-6.5-month-old male and female rTg4510 mice following acute administration of suvorexant (50 mg·kg-1 ), MK-1064 (30 mg·kg-1 ) or zolpidem (10 mg·kg-1 ), administered at the commencement of the active phase. KEY RESULTS: Suvorexant, a dual OX receptor antagonist, promoted REM sleep in rTg4510 mice, without affecting wake or NREM sleep. MK-1064, a selective OX2 receptor antagonist, reduced wake and increased NREM and total sleep time. MK-1064 normalised the hyperarousal phenotype of male rTg4510 mice, whereas female rTg4510 mice exhibited a more transient response. Zolpidem, a GABAA receptor positive allosteric modulator, decreased wake and increased NREM sleep in both male and female rTg4510 mice. Of the three compounds, the OX2 receptor antagonist MK-1064 promoted and normalised physiologically normal sleep, especially in male rTg4510 mice. CONCLUSIONS AND IMPLICATIONS: Our findings indicate that hyperphosphorylated tau accumulation and associated hyperarousal does not significantly alter the responses of tauopathy mouse models to hypnotics. However, the sex differences observed in the sleep/wake response of rTg4510 mice to MK-1064, but not suvorexant or zolpidem, raise questions about therapeutic implications for the use of OX2 receptor antagonists in human neurodegenerative disorders.

VAV2 is required for DNA repair and implicated in cancer radiotherapy resistance.

Radiotherapy remains the mainstay for treatment of various types of human cancer; however, the clinical efficacy is often limited by radioresistance, in which the underlying mechanism is largely unknown. Here, using esophageal squamous cell carcinoma (ESCC) as a model, we demonstrate that guanine nucleotide exchange factor 2 (VAV2), which is overexpressed in most human cancers, plays an important role in primary and secondary radioresistance. We have discovered for the first time that VAV2 is required for the Ku70/Ku80 complex formation and participates in non-homologous end joining repair of DNA damages caused by ionizing radiation. We show that VAV2 overexpression substantially upregulates signal transducer and activator of transcription 1 (STAT1) and the STAT1 inhibitor Fludarabine can significantly promote the sensitivity of radioresistant patient-derived ESCC xenografts in vivo in mice to radiotherapy. These results shed new light on the mechanism of cancer radioresistance, which may be important for improving clinical radiotherapy.

Metabolic remodeling by TIGAR overexpression is a therapeutic target in esophageal squamous-cell carcinoma.

Rationale: Whole-genome sequencing has identified many amplified genes in esophageal squamous-cell carcinoma (ESCC). This study investigated the role and clinical relevance of these genes in ESCC. Methods: We collected ESCC and non-tumor esophageal tissues from 225 individuals who underwent surgery. Clinical data were collected and survival time was measured from the date of diagnosis to the date of last follow-up or death. Patient survival was compared with immunohistochemical staining score using Kaplan-Meier methods and hazard ratios were calculated by Cox models. Cells with gene overexpression and knockout were analyzed in proliferation, migration and invasion assays. Cells were also analyzed for levels of intracellular lactate, NADPH, ATP and mRNA and protein expression patterns. Protein levels in cell line and tissue samples were measured by immunoblotting or immunohistochemistry. ESCC cell were grown as xenograft tumors in nude mice. Primary ESCC in genetically engineered mice and patient-derived xenograft mouse models were established for test of therapeutic effects. Results: We show that TP53-induced glycolysis and apoptosis regulator (TIGAR) is a major player in ESCC progression and chemoresistance. TIGAR reprograms glucose metabolism from glycolysis to the glutamine pathway through AMP-activated kinase, and its overexpression is correlated with poor disease outcomes. Tigar knockout mice have reduced ESCC tumor burden and growth rates. Treatment of TIGAR-overexpressing ESCC cell xenografts and patient-derived tumor xenografts in mice with combination of glutaminase inhibitor and chemotherapeutic agents achieves significant more efficacy than chemotherapy alone. Conclusion: These findings shed light on an important role of TIGAR in ESCC and might provide evidence for targeted treatment of TIGAR-overexpressing ESCC.

Silencing FUNDC1 alleviates chronic obstructive pulmonary disease by inhibiting mitochondrial autophagy and bronchial epithelium cell apoptosis under hypoxic environment.

Chronic obstructive pulmonary disease (COPD) is a major global epidemic with increasing incidence worldwide. The pathogenesis of COPD is involved with mitochondrial autophagy. Recently, it has been reported that FUN14 domain containing 1 (FUNDC1) is a mediator of mitochondrial autophagy. Therefore, we hypothesized that FUNDC1 was involved in cigarette smoke (CS)-induced COPD progression by regulating mitochondrial autophagy. In vitro cigarette smoke extract (CSE)-treated human bronchial epithelial cell (hBEC) Beas-2B cell line and in vivo CS-induced COPD mouse models were developed, in which FUNDC1 expression was measured. Next, whether FUNDC1 interacted with dynamin-related protein 1 (DRP1) in COPD was investigated. The functional mechanism of FUNDC1 in COPD was evaluated through gain- or loss-of-function studies. Then, pulmonary function, mitochondrial transmembrane potential (MTP) and mucociliary clearance (MCC) were examined. Levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and expression of autophagy-specific markers (light chain 3 [LC3] II, LC3 I, and Tom20) were measured. Finally, apoptosis and mitochondrial autophagy were assessed. FUNDC1 was highly expressed in CSE-treated hBECs and COPD mice. Meanwhile, FUNDC1 was proved to interact with DRP1 in CSE-treated cells. Moreover, in CSE-treated hBECs, silencing FUNDC1 was observed to reduce levels of IL-6 and TNF-α, and MTP but increase MCC, and inhibit CSE-induced mitochondrial autophagy and Beas-2B cell apoptosis, which was consistent with the trend in COPD mouse models. In addition, pulmonary function of COPD mouse models was increased in response to FUNDC1 silencing. Finally, silencing of DRP1 also inhibited mitochondrial autophagy and Beas-2B cell apoptosis. Collectively, FUNDC1 silencing could suppress the progression of COPD by inhibiting mitochondrial autophagy and hBEC apoptosis through interaction with DRP1, highlighting a potential therapeutic target for COPD treatment.