Insufficient FUNDC1-dependent mitophagy due to early environmental cadmium exposure triggers mitochondrial redox imbalance to aggravate diet-induced lipotoxicity.

Cadmium (Cd) is a toxic contaminant widely spread in natural and industrial environments. Adolescent exposure to Cd increases risk for obesity-related morbidity in young adults including type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD). Despite this recognition, the direct impact of adolescent Cd exposure on the progression of MASLD later in life, and the mechanisms underlying these effects, remain unclear. Here, adolescent rats received control diet or diets containing 2 mg Cd2+/kg feed for 4 weeks, and then HFD containing 15% lard or control diet in young adult rats was selected for 6 weeks to clarify this issue. Data firstly showed that HFD-fed rats in young adulthood due to adolescent Cd exposure exhibited more severe MASLD, evidenced by increased liver damage, disordered serum and hepatic lipid levels, and activated NLRP3 inflammasome. Hepatic transcriptome analysis revealed the potential effects of mitochondrial dysfunction in aggravated MASLD due to Cd exposure. Verification data further confirmed that mitochondrial structure and function were targeted and disrupted during this process, shown by broken mitochondrial ridges, decreased mitochondrial membrane potential, imbalanced mitochondrial dynamic, insufficient ATP concentration, and enhanced mitochondrial ROS generation. However, mitophagy is inactively involved in clearance of damaged mitochondria induced by early Cd in HFD condition due to inhibited mitophagy receptor FUNDC1. In contrast, FUNDC1-dependent mitophagy activation prevents lipotoxicity aggravated by early Cd via suppressing mitochondrial ROS generation. Collectively, our data show that insufficient FUNDC1-dependent mitophagy can drive the transition from HFD-induced MASLD to MASH, and accordingly, these findings will provide a better understanding of potential mechanism of diet-induced metabolic diseases in the context of early environmental Cd exposure.

Highly Curative Treatment of High-Risk Acute Promyelocytic Leukemia: Induction and Consolidation with ATRA+ATO+anthracyclines and Maintenance with ATRA+RIF.

Background: The aim of the study was to evaluate the efficacy and safety of induction and consolidation with all-trans retinoic acid (ATRA) +arsenic trioxide (ATO) +anthracyclines and maintenance with ATRA +Realgar-Indigo naturalis formula (RIF) for high-risk APL. Methods: Twenty-one patients with high-risk APL treated with ATRA+ATO+ anthracyclines for induction and consolidation and ATRA+RIF for maintenance from 2012 to 2021 were analyzed. Endpoints include morphological complete remission (CR) and complete molecular remission (CMR), early death (ED) and relapse, survival and adverse events (AEs). Results: After induction treatment, all 21 patients (100%) achieved morphological CR and 14 people (66.7%) achieved CMR. Five of the 21 patients did not undergo immunological minimal residual disease (MRD) examination after induction; however, 14 of the remaining 16 patients were MRD negative (87.5%). The median time to achieve CR and CMR was 26 days (range: 16-44) and 40 days (range: 22-75), respectively. The cumulative probability of achieving CR and CMR in 45 days was 100% and 76.2% (95% CI: 56.9-91.3%), respectively. All patients achieved CMR and MRD negativity after the three courses of consolidation treatment. The median follow-up was 66 months (25-142), with no central nervous system relapse and bone marrow morphological or molecular relapse until now, and all patients survived with 100% overall survival and 100% event-free survival. Grade 4 adverse events (AEs) were observed in 3 patients (14.3%) during the induction period including arrhythmia (n = 1), pulmonary infection (n = 1) and respiratory failure (n = 1); and the most frequent grade 3 AEs were pulmonary infection, accounting for 62.0% and 28.6%, respectively, during induction and consolidation treatment, followed by neutropenia, accounting for 42.9% and 38.1%, respectively. Conclusion: For newly diagnosed high-risk APL patients, induction and consolidation with ATRA+ATO+anthracyclines and maintenance with ATRA+RIF is a highly curative treatment approach.

Artificial intelligence-based predictive model for guidance on treatment strategy selection in oral and maxillofacial surgery.

Application of deep learning (DL) and machine learning (ML) is rapidly increasing in the medical field. DL is gaining significance for medical image analysis, particularly, in oral and maxillofacial surgeries. Owing to the ability to accurately identify and categorize both diseased and normal soft- and hard-tissue structures, DL has high application potential in the diagnosis and treatment of tumors and in orthognathic surgeries. Moreover, DL and ML can be used to develop prediction models that can aid surgeons to assess prognosis by analyzing the patient's medical history, imaging data, and surgical records, develop more effective treatment strategies, select appropriate surgical modalities, and evaluate the risk of postoperative complications. Such prediction models can play a crucial role in the selection of treatment strategies for oral and maxillofacial surgeries. Their practical application can improve the utilization of medical staff, increase the treatment accuracy and efficiency, reduce surgical risks, and provide an enhanced treatment experience to patients. However, DL and ML face limitations, such as data drift, unstable model results, and vulnerable social trust. With the advancement of social concepts and technologies, the use of these models in oral and maxillofacial surgery is anticipated to become more comprehensive and extensive.

Clinical efficacy and immune response of neoadjuvant camrelizumab plus chemotherapy in resectable locally advanced oesophageal squamous cell carcinoma: a phase 2 trial.

BACKGROUND: Neoadjuvant immunotherapy is under intensive investigation for esophageal squamous cell carcinoma (ESCC). This study assesses the efficacy and immune response of neoadjuvant immunochemotherapy (nICT) in ESCC. METHODS: In this phase II trial (ChiCTR2100045722), locally advanced ESCC patients receiving nICT were enrolled. The primary endpoint was the pathological complete response (pCR) rate. Multiplexed immunofluorescence, RNA-seq and TCR-seq were conducted to explore the immune response underlying nICT. RESULTS: Totally 42 patients were enrolled, achieving a 27.0% pCR rate. The 1-year, 2-year DFS and OS rates were 89.2%, 64.4% and 97.3%, 89.2%, respectively. RNA-seq analysis highlighted T-cell activation as the most significantly enriched pathway. The tumour immune microenvironment (TIME) was characterised by high CD4, CD8, Foxp3, and PD-L1 levels, associating with better pathological regression (TRS0/1). TIME was categorised into immune-infiltrating, immune-tolerant, and immune-desert types. Notably, the immune-infiltrating type and tertiary lymphoid structures correlated with improved outcomes. In the context of nICT, TIM-3 negatively influenced treatment efficacy, while elevated TIGIT/PD-1 expression post-nICT correlated positively with CD8+ T cell levels. TCR-seq identified three TCR rearrangements, underscoring the specificity of T-cell responses. CONCLUSIONS: Neoadjuvant camrelizumab plus chemotherapy is effective for locally advanced, resectable ESCC, eliciting profound immune response that closely associated with clinical outcomes.

Operation strategy and capacity configuration of digital renewable energy power station with energy storage.

As the utilization of renewable energy sources continues to expand, energy storage systems assume a crucial role in enabling the effective integration and utilization of renewable energy. This underscores their fundamental significance in mitigating the inherent intermittency and variability associated with renewable energy sources. This study focuses on the involvement of photovoltaic (PV) plants in medium and long-term transactions. It also explores the participation of battery energy storage system (BESS) in electricity trading and frequency regulation ancillary services. The objective is to establish a strategic research model for maximizing the benefits of PV plant and the BESS in the energy arbitrage and frequency regulation markets. Sensitivity analysis was conducted to assess the impact of variations in both the rated power and maximum continuous energy storage duration of the BESS. Base on the NSGA-II algorithm and TOPSIS algorithm, an optimization model for energy storage capacity configuration is developed. The optimal capacity configuration and maximum continuous energy storage duration are determined through computational analysis, yielding values of 30.8 MW and 4.521 h, respectively. At this configuration, the daily average revenue is 2.362 × 105 yuan, the initial investment cost is 1.45 × 109 yuan, and the payback period is 4.562 years.

Molecular mechanisms underlying natural deficient and ultraviolet-induced accumulation of anthocyanin in the peel of 'Jinxiu' peach.

Peach varieties that differ in red coloration due to varied anthocyanin accumulation result from transcriptional regulation by PpMYB10s, a group of specific R2R3 MYBs. Here we investigated the mechanisms driving a lack of anthocyanin in yellow-skinned 'Jinxiu' peach peel, as well as accumulation induced by UV irradiance. It was found that PpMYB10.1, PpMYB10.2 and PpMYB10.3 were positive regulators of anthocyanin accumulation, but the stimulation by PpMYB10.2 was weak. Low expression of PpMYB10.1 causes natural anthocyanin deficiency in 'Jinxiu' peel. However, the promoter sequences of PpMYB10.1 were identical in 'Jinxiu' and a naturally red-coloured peach 'Hujingmilu'. Therefore, potential negative regulator(s) upstream of PpMYB10.1 were explored. A novel R2R3-MYB repressor termed PpMYB80 was identified through comparative transcriptomic analysis and then functionally confirmed via transiently overexpressing and silencing in peach fruit, as well as transformation in tobacco. PpMYB80 directly binds to the promoter of PpMYB10.1 and inhibits its expression, but does not affect PpMYB10.3. In UV-exposed 'Jinxiu' fruit, expression of PpMYB10.3 was upregulated, while PpMYB10.1 remained low and PpMYB80 enhanced, which results in accumulation of anthocyanin in peel. This study revealed a transcriptional cascade involving PpMYB activators and repressors in regulating basal and UV-induced anthocyanin accumulation in peach peel.

FCSSL: fusion enhanced contrastive self-supervised learning method for parallel MRI reconstruction.

The implementation of deep learning in Magnetic Resonance Imaging (MRI) has significantly advanced the reduction of data acquisition times. However, these techniques face substantial limitations in scenarios where acquiring fully sampled datasets is unfeasible or costly. To tackle this problem, we propose a Fusion enhanced Contrastive Self-Supervised Learning (FCSSL) method for parallel MRI reconstruction, eliminating the need for fully sampled k-space training dataset and coil sensitivity maps. First, we introduce a strategy based on two pairs of re-undersampling masks within a contrastive learning framework, aimed at enhancing the representational capacity to achieve higher quality reconstruction. Subsequently, a novel adaptive fusion network, trained in a self-supervised learning manner, is designed to integrate the reconstruction results of the framework. Experimental results on knee datasets under different sampling masks demonstrate that the proposed FCSSL achieves superior reconstruction performance compared to other self-supervised learning methods. Moreover, the performance of FCSSL approaches that of the supervised methods, especially under the 2DRU and RADU masks. The proposed FCSSL, trained under the 3× 1DRU and 2DRU masks, can effectively generalize to unseen 1D and 2D undersampling masks, respectively. For target domain data that exhibit significant differences from source domain data, the proposed model, fine-tuned with just a few dozen instances of undersampled data in the target domain, achieves reconstruction performance comparable to that achieved by the model trained with the entire set of undersampled data. The novel FCSSL model offers a viable solution for reconstructing high-quality MR images without needing fully sampled datasets, thereby overcoming a major hurdle in scenarios where acquiring fully sampled MR data is difficult.

MicroRNA-505-3p mediates cell motility of epithelial ovarian cancer via suppressing PEAK1 expression.

MicroRNAs (miRNAs) are a class of small RNA genes with important roles in cancer biology regulation. There are considerable studies regarding the roles of microRNA-505-3p (miR-505-3p) in cancer development and progression, but the function of miR-505-3p in epithelial ovarian cancer (EOC) has not been fully clarified. Comparative analysis of miRNA expression data set was used to select differentially expressed miRNAs. Quantitative real-time polymerase chain reaction was applied to detect expression levels of RNAs, while western blot and immunofluorescence staining were performed to detect expression levels of proteins of interest. The motility of EOC cells was assessed by wound healing and transwell assays. The binding and regulating relationship between miRNA and its direct target gene was investigated by dual-luciferase assay. Our results show that miR-505-3p was upregulated in recurrent EOC, which significantly inhibits EOC cell motility via modulating cell epithelial-mesenchymal transition. Furthermore, our results indicated that PEAK1 expression was inhibited by direct binding of miR-505-3p into its 3'-URT in EOC cells. Importantly, knockdown of PEAK1 attenuated the effect of mi-505-3p inhibitor on EOC cell migration and invasion. In conclusion, our findings indicate that miRNA-505-3p inhibits EOC cell motility by targeting PEAK1.

Association between Pre-operative Body Mass Index and Surgical Infection in Perihilar Cholangiocarcinoma Patients Treated with Curative Resection: A Multi-center Study.

Background: The objective of this study was to investigate the association between pre-operative body mass index (BMI) and surgical infection in perihilar cholangiocarcinoma (pCCA) patients treated with curative resection. Methods: Consecutive pCCA patients were enrolled from four tertiary hospitals between 2008 and 2022. According to pre-operative BMI, the patients were divided into three groups: low BMI (≤18.4 kg/m2), normal BMI (18.5-24.9 kg/m2), and high BMI (≥25.0 kg/m2). The incidence of surgical infection among the three groups was compared. Multivariable logistic regression models were used to determine the independent risk factors associated with surgical infection. Results: A total of 371 patients were enrolled, including 283 patients (76.3%) in the normal BMI group, 30 patients (8.1%) in the low BMI group, and 58 patients (15.6%) in the high BMI group. The incidence of surgical infection was significantly higher in the patients in the low BMI and high BMI groups than in the normal BMI group. The multivariable logistic regression model showed that low BMI and high BMI were independently associated with the occurrence of surgical infection. Conclusions: The pCCA patients with a normal BMI treated with curative resection could have a lower risk of surgical infection than pCCA patients with an abnormal BMI.

Depletion of NUAK2 blocks the stemness and angiogenesis and facilitates senescence of lung adenocarcinoma cells via enhancing ferroptosis.

BACKGROUND: NUAK family kinase 2 (NUAK2) has been identified as an important mediator for tumor progression in multiple malignancies. Nevertheless, its role in lung adenocarcinoma (LUAD) remains unclear. METHODS: Bioinformatic analysis was performed to assess the expression and prognosis of NUAK2 in patients with LUAD. The NUAK2 expression was measured in multiple LUAD cell lines, and the loss-of-function experiment was conducted. Cell proliferation ability was assessed using CCK-8 and colony formation assays. Spheroid formation, alkaline phosphatase (AP) staining, tube formation and SA-ß-gal staining assays were performed to examine stemness, angiogenesis and senescence. Lipid peroxidase was assessed by TBARS production and lipid ROS. Western blot was used to detect critical proteins. In addition, A549 cells were treated with ferroptosis inhibitor ferrostatin-1 (Fer-1) for a rescue assay. Finally, A549 cells were subcutaneously injected into the right flank of mice to establish LUAD-bearing mouse model, and the tumor weight and size were detected. RESULTS: NUAK2 was upregulated in patients with LUAD and LUAD cell lines. NUAK2 depletion inhibited cell viability, colonies, tumor spheres and decreased Oct4 and Nanog expression, confirming NUAK2 depletion inhibited proliferation and stemness of A549 cells. Meanwhile, NUAK2 depletion blocked angiogenesis via reducing formed tubes and VEGFR1/2 expression, and promoted senescence of A549 cells by elevating SA-ß-gal-positive cells and p16, p21 and p53 expression. Moreover, NUAK2 depletion elevated lipid ROS, TBARS production and Fe2+ level, demonstrating that NUAK2 depletion could trigger ferroptosis in A549 cells. Furthermore, the rescue experiments revealed that the impacts of NUAK2 depletion on malignant behaviors in A549 cells were partly weakened by additional Fer-1 treatment. Finally, in vivo experiments demonstrated that NUAK2 knockdown greatly inhibited tumor growth in LUAD-bearing mice. CONCLUSION: In summary, NUAK2 depletion impeded oncogenic phenotypes of A549 cells partly via triggering ferroptosis, suggesting NUAK2 as a novel target for treating LUAD.

SWI/SNF Complex Connects Signaling and Epigenetic State in Cells of Nervous System.

SWI/SNF protein complexes are evolutionarily conserved epigenetic regulators described in all eukaryotes. In metameric animals, the complexes are involved in all processes occurring in the nervous system, from neurogenesis to higher brain functions. On the one hand, the range of roles is wide because the SWI/SNF complexes act universally by mobilizing the nucleosomes in a chromatin template at multiple loci throughout the genome. On the other hand, the complexes mediate the action of multiple signaling pathways that control most aspects of neural tissue development and function. The issues are discussed to provide insight into the molecular basis of the multifaceted role of SWI/SNFs in cell cycle regulation, DNA repair, activation of immediate-early genes, neurogenesis, and brain and connectome formation. An overview is additionally provided for the molecular basis of nervous system pathologies associated with the SWI/SNF complexes and their contribution to neuroinflammation and neurodegeneration. Finally, we discuss the idea that SWI/SNFs act as an integration platform to connect multiple signaling and genetic programs.

Gp93 inhibits unfolded protein response-mediated c-Jun N-terminal kinase activation and cell invasion.

In eukaryotes, Hsp90B1 serves as a vital chaperonin, facilitating the accurate folding of proteins. Interestingly, Hsp90B1 exhibits contrasting roles in the development of various types of cancers, although the underlying reasons for this duality remain enigmatic. Through the utilization of the Drosophila model, this study unveils the functional significance of Gp93, the Drosophila ortholog of Hsp90B1, which hitherto had limited reported developmental functions. Employing the Drosophila cell invasion model, we elucidated the pivotal role of Gp93 in regulating cell invasion and modulating c-Jun N-terminal kinase (JNK) activation. Furthermore, our investigation highlights the involvement of the unfolded protein response-associated IRE1/XBP1 pathway in governing Gp93 depletion-induced, JNK-dependent cell invasion. Collectively, these findings not only uncover a novel molecular function of Gp93 in Drosophila, but also underscore a significant consideration pertaining to the testing of Hsp90B1 inhibitors in cancer therapy.

Tip60-FOXO regulates JNK signaling mediated apoptosis in Drosophila.

The JNK signaling pathway plays crucial roles in various physiological processes, including cell proliferation, differentiation, migration, apoptosis, and stress response. Dysregulation of this pathway is closely linked to the onset and progression of numerous major diseases, such as developmental defects and tumors. Identifying and characterizing novel components of the JNK signaling pathway to enhance and refine its network hold significant scientific and clinical importance for the prevention and treatment of associated cancers. This study utilized the model organism Drosophila and employed multidisciplinary approaches encompassing genetics, developmental biology, biochemistry, and molecular biology to investigate the interplay between Tip60 and the JNK signaling pathway, and elucidated its regulatory mechanisms. Our findings suggest that loss of Tip60 acetyltransferase activity results in JNK signaling pathway activation and subsequent induction of JNK-dependent apoptosis. Genetic epistasis analysis reveals that Tip60 acts downstream of JNK, paralleling with the transcription factor FOXO. The biochemical results confirm that Tip60 can bind to FOXO and acetylate it. Introduction of human Tip60 into Drosophila effectively mitigates apoptosis induced by JNK signaling activation, underscoring conserved regulatory role of Tip60 in the JNK signaling pathway from Drosophila to humans. This study further enhances our understanding of the regulatory network of the JNK signaling pathway. By revealing the role and mechanism of Tip60 in JNK-dependent apoptosis, it unveils new insights and potential therapeutic avenues for preventing and treating associated cancers.

Integration of single-cell and bulk RNA sequencing data reveals that CYTOR is a potential prognostic and immunotherapeutic response marker for skin cutaneous melanoma.

Skin cutaneous melanoma (SKCM) is a highly malignant tumor that is prone to immune escape and distant metastasis. Immunotherapy is considered to be the best treatment for patients with SKCM. However, not all patients benefit from it. We observed a significant differential expression of the lncRNA CYTOR in patients with SKCM based on single-cell and bulk RNA sequencing data mining results. The results showed that compared to normal tissue lncRNA CYTOR expression was significantly upregulated in SKCM tissue. Subsequently, we validated this finding in clinical samples, and we also found that the expression of lncRNA CYTOR in SKCM was higher as it progressed. lncRNA CYTOR was differentially expressed in patients who responded to immunotherapy, suggesting that it may serve as a biomarker to predict the efficacy of SKCM immunotherapy. In-depth analysis revealed that lncRNA CYTOR expression was strongly correlated with immune cell infiltration, immune response, and immune checkpoint expression. Meanwhile, our experiments revealed that CYTOR affects SKCM cell invasion and clone formation and is associated with the activation of the EMT pathway. In summary, our findings illustrate, for the first time, the value of CYTOR as a potential prognostic and immunotherapeutic response marker in SKCM.

Arsenic Trioxide Suppresses Angiogenesis in Non-small Cell Lung Cancer via the Nrf2-IL-33 Signaling Pathway.

BACKGROUND: Non-Small Cell Lung Cancer (NSCLC) ranks as a leading cause of cancer-related mortality, necessitating the urgent search for cost-effective and efficient anti-NSCLC drugs. Our preliminary research has demonstrated that arsenic trioxide (ATO) significantly inhibits NSCLC angiogenesis, exerting anti-tumor effects. In conjunction with existing literature reports, the Nrf2-IL-33 pathway is emerging as a novel mechanism in NSCLC angiogenesis. OBJECTIVE: This study aimed to elucidate whether ATO can inhibit NSCLC angiogenesis through the Nrf2-IL-33 pathway. METHODS: Immunohistochemistry was employed to assess the expression of Nrf2, IL-33, and CD31 in tumor tissues from patients with NSCLC. DETA-NONOate was used as a nitric oxide (NO) donor to mimic high levels of NO in the tumor microenvironment. Western blot, quantitative real-time PCR, and enzyme-linked immunosorbent assay were utilized to evaluate the expression of Nrf2 and IL-33 in the NCI-H1299 cell line. Subcutaneous xenograft models were established in nude mice by implanting NCI-H1299 cells to assess the anti-tumor efficacy of ATO. RESULTS: High expression levels of Nrf2 and IL-33 were observed in tumor samples from patients with NSCLC, and Nrf2 expression positively correlated with microvascular density in NSCLC. In vitro, NO (released from 1mM DETA-NONOate) promoted activation of the Nrf2-IL-33 signaling pathway in NCI-H1299 cells, which was reversed by ATO. Additionally, both Nrf2 deficiency and ATO treatment significantly attenuated NOinduced IL-33 expression. In vivo, both ATO and the Nrf2 inhibitor ML385 demonstrated significant inhibitory effects on angiogenesis tumor growth. CONCLUSION: Nrf2-IL-33 signaling is usually activated in NSCLC and positively correlates with tumor angiogenesis. ATO effectively disrupts the activation of the Nrf2-IL-33 pathway in NSCLC and thus inhibits angiogenesis, suggesting its potential as an anti-angiogenic agent for use in the treatment of NSCLC.

An Imidazo[1, 2-a]Pyridine Based Fluorescent Probe for the Continuous "on-off-on" Detection of Fe3+ and F.

An "on-off-on" fluorescent probe LK was synthesized from 2-benzoylpyridine and o-vanillin, which could sequentially detect Fe3+ and F- in DMSO/H2O solutions (v/v = 1/1, HEPES buffer, 1.0 mM, pH 7.0) with large Stokes shift (178 nm). LK exhibited not only high selectivity and sensitivity towards Fe3+ and F-, but also strong anti-interference ability to other ions. LK was coordinated with Fe3+ at a ratio of 2:1, with a binding constant (Ka) of 1.3 × 104 M- 1. The detection limits for Fe3+ and F- were 6.9 × 10- 8 M and 3.0 × 10- 7 M, respectively. Due to its excellent sensing performance, LK was successfully applied in actual water samples and test papers for the detection of Fe3+ and F-.

Extracorporeal closed-loop respiratory regulation for patients with respiratory difficulty using a soft bionic robot.

OBJECTIVE: Respiratory regulation is critical for patients with respiratory dysfunction. Clinically used ventilators can lead to long-term dependence and injury. Extracorporeal assistance approaches such as iron-lung devices provide a noninvasive alternative, however, artificial actuator counterparts have not achieved marvelous biomimetic ventilation as human respiratory muscles. Here, we propose a bionic soft exoskeleton robot that can achieve extracorporeal closed-loop respiratory regulation by emulating natural human breath. METHODS: For inspiration, a soft vacuum chamber is actuated to produce negative thoracic pressure and thus expand lung volume by pulling the rib cage up and outward through use of external negative pressure. For expiration, a soft origami array under positive pressure pushes the abdominal muscles inward and the diaphragm upward. To achieve in vitro measurement of respiratory profile, we describe a wireless respiratory monitoring device to measure respiratory profiles with high accuracy, validated by quantitative comparisons with spirometer as gold-standard reference. By constructing a human-robot coupled respiratory mechanical model, a model-based proportional controller is designed for continuous tracking of the target respiratory profile. RESULTS: In experiments with ten healthy participants and ten patients with respiratory difficulty, the robot can adjust its assistive forces in real time and drive human-robot coupling respiratory system to track the target profile. CONCLUSION: The biomimetic robot can achieve extracorporeal closed-loop respiratory regulation for a diverse population. SIGNIFICANCE: The soft robot has important potential to assist respiration for people with respiratory difficulty, whether in a hospital or a home setting.

Selective degradation of PL2L60 by metabolic stresses­induced autophagy suppresses multi­cancer growth.

It has been reported that PL2L60 proteins, a product of PIWIL2 gene which might be activated by an intragenic promoter, could mediate a common pathway specifically for tumorigenesis. In the present study, it was further identified by using western blot assay that the PL2L60 proteins could be degraded in cancer cells through a mechanism of selective autophagy in response to oxidative stress. The PL2L60 was downregulated in various types of cancer cells under the hypoxic condition independently of HIF­1α, resulting in apoptosis of cancer cells. Inhibition of autophagy by small interfering RNA targeting of either Beclin­1 (BECN1) or Atg5 resulted in restoration of PL2L60 expression in hypoxic cancer cell. The hypoxic degradation of PL2L60 was also blocked by the attenuation of the autophagosome membrane protein Atg8/microtubule­associated protein 1 light chain 3 (LC3) or autophagy cargo protein p62 expression. Surprisingly, Immunofluorescence analysis demonstrated that LC3 could be directly bound to PL2L60 and was required for the transport of PL2L60 from the nucleus to the cytoplasm for lysosomal flux under basal or activated autophagy in cancer cells. Moreover, flow cytometric analysis displayed that knocking down of PL2L60 mRNA but not PIWIL2 mRNA effectively inhibited cancer cell proliferation and promoted apoptosis of cancer cells. The similar results were obtained from in vivo tumorigenic experiment, in which PL2L60 downregulation in necroptosis areas was confirmed by immunohistochemistry. These results suggested that various cancer could be suppressed by promoting autophagy. The present study revealed a key role of autophagic degradation of PL2L60 in hypoxia­induced cancer cell death, which could be used as a novel therapeutic target of cancer.