Vacuum bell therapy for pectus excavatum: a retrospective study.

BACKGROUND: Pectus excavatum, the most common chest wall deformity, is frequently treated with Nuss procedure. Here we will describe non-invasive procedure and analyze the variables associated vacuum bell therapy for patients with pectus excavatum. METHODS: Retrospective case-control study in a single center between July 2018 and February 2022, including patients with pectus excavatum treated with vacuum bell. Follow-up was continued to September 2022. The Haller index and Correction index was calculated before and after treatment to analysis the effectiveness of vacuum bell therapy. RESULTS: There were 98 patients enrolled in the treatment group, with 72 available for analysis, and the follow-up period ranged from 1.1 to 4.4 years (mean 3.3 years). When analyzing with the Haller Index, 18 patients (25.0%) showed excellent correction, 13 patients (18.1%) achieved good correction, and 4 patients (5.6%) had fair correction. The remaining patients had a poor outcome. Characteristics predicting a non-poor prognosis included initial age ≤ 11 years (OR = 3.94, p = 0.013) and patients with use over 24 consecutive months (OR = 3.95, p = 0.013). A total of 9 patients (12.5%) achieved a CI reduction below 10. Patients who started vacuum bell therapy at age > 11 had significantly less change compared to those who started at age ≤ 11 (P < 0.05). Complications included chest pain (5.6%), swollen skin (6.9%), chest tightness (1.4%) and erythema (15.3%). CONCLUSIONS: A certain percentage of patients with pectus excavatum can achieve excellent correction when treated with pectus excavatum therapy. Variables predicting better outcome including initial age ≤ 11 years both in HI and CI and vacuum bell use over 24 consecutive months in HI. In summary, pectus excavatum is an emerging non-invasive therapy for pectus excavatum and will be widely performed in a certain group of patients.

Splicing inhibition mediated by reduced splicing factors and helicases is associated with the cellular response of lung cancer cells to cisplatin.

Lung cancer's mortality is predominantly linked to post-chemotherapy recurrence, driven by the reactivation of dormant cancer cells. Despite the critical role of these reactivated cells in cancer recurrence and metastasis, the molecular mechanisms governing their therapeutic selection remain poorly understood. In this study, we conducted an integrative analysis by combining PacBio single molecule real-time (SMRT) sequencing with short reads Illumina RNA-seq. Our study revealed that cisplatin-induced dormant and reactivated cancer cells exhibited a noteworthy reduction in gene transcripts and alternative splicing events. Particularly, the differential alternative splicing events were found to be overlapping with the differentially expression genes and enriched in genes related to cell cycle and cell division. Utilizing ENCORI database and correlation analysis, we identified key splicing factors, including SRSF7, SRSF3, PRPF8, and HNRNPC, as well as RNA helicase such as EIF4A3, DDX39A, DDX11, and BRIP1, which were associated with the observed reduction in alternative splicing and subsequent decrease in gene expression. Our study demonstrated that lung cancer cells reduce gene transcripts through diminished alternative splicing events mediated by specific splicing factors and RNA helicase in response to the chemotherapeutic stress. These findings provide insights into the molecular mechanisms underlying the therapeutic selection and reactivation of dormant cancer cells. This discovery opens a potential avenue for the development of therapeutic strategies aimed at preventing cancer recurrence following chemotherapy.

EphB1 promotes the differentiation and maturation of dendritic cells in non-small cell lung cancer.

EphB1 is implicated in numerous physiological and pathological processes, including nervous system diseases, cardiovascular diseases and cancers. It binds to membrane-bound ligands and drives bidirectional signaling. EphB1, along with its ligand ehrinB, plays a pivotal role in activating immune cells. However, despite its presence in dendritic cells (DCs), EphB1's involvement in the differentiation and maturation of DCs in cancers remains inadequately understood. In this study, we found compromised differentiation and maturation of DCs in EphB1-/- mice bearing lung adenocarcinoma syngeneic tumors. Our in vitro assays revealed that EphB1 phosphorylation induced DC differentiation and maturation. Cox-2, a key enzyme involved in the production of proinflammatory molecules, is implicated in DC differentiation induced by phosphorylated EphB1. Additionally, the study has identified lead compounds that specifically target EphB1 phosphorylation sites. Collectively, this research on EphB1 phosphorylation has provided valuable insights into the regulation of immune cell functionality and holds the potential for the development of innovative therapeutic strategies for a range of diseases.

Water-responsive supercontractile polymer films for bioelectronic interfaces.

Connecting different electronic devices is usually straightforward because they have paired, standardized interfaces, in which the shapes and sizes match each other perfectly. Tissue-electronics interfaces, however, cannot be standardized, because tissues are soft1-3 and have arbitrary shapes and sizes4-6. Shape-adaptive wrapping and covering around irregularly sized and shaped objects have been achieved using heat-shrink films because they can contract largely and rapidly when heated7. However, these materials are unsuitable for biological applications because they are usually much harder than tissues and contract at temperatures higher than 90 °C (refs. 8,9). Therefore, it is challenging to prepare stimuli-responsive films with large and rapid contractions for which the stimuli and mechanical properties are compatible with vulnerable tissues and electronic integration processes. Here, inspired by spider silk10-12, we designed water-responsive supercontractile polymer films composed of poly(ethylene oxide) and poly(ethylene glycol)-α-cyclodextrin inclusion complex, which are initially dry, flexible and stable under ambient conditions, contract by more than 50% of their original length within seconds (about 30% per second) after wetting and become soft (about 100 kPa) and stretchable (around 600%) hydrogel thin films thereafter. This supercontraction is attributed to the aligned microporous hierarchical structures of the films, which also facilitate electronic integration. We used this film to fabricate shape-adaptive electrode arrays that simplify the implantation procedure through supercontraction and conformally wrap around nerves, muscles and hearts of different sizes when wetted for in vivo nerve stimulation and electrophysiological signal recording. This study demonstrates that this water-responsive material can play an important part in shaping the next-generation tissue-electronics interfaces as well as broadening the biomedical application of shape-adaptive materials.

Exploration of lung mycobiome in the patients with non-small-cell lung cancer.

As the Human Microbiome Project (HMP) progresses, the relationship between microbes and human health has been receiving increasing attention. A growing number of reports support the correlation between cancer and microbes. However, most studies have focused on bacteria, rather than fungal communities. In this study, we studied the alteration in lung mycobiome in patients with non-small-cell lung cancer (NSCLC) using metagenomic sequencing and qPCR. The higher fungal diversity and more complex network were observed in the patients with NSCLC. In addition, Alternaria arborescens was found as the most relevant fungus to NSCLC, and the enrichment of it in cancerous tissue was also detected. This study proposes that the changes in fungal communities may be closely related to lung cancer, and provides insights into further exploration the relationship between lung cancer and fungi.

Shape morphing of plastic films.

Three-dimensional (3D) architectures have qualitatively expanded the functions of materials and flexible electronics. However, current fabrication techniques for devices constrain their substrates to 2D geometries and current post-shape transformation strategies are limited to heterogenous or responsive materials and are not amenable to free-standing inert plastic films such as polyethylene terephthalate (PET) and polyimide (PI), which are vital substrates for flexible electronics. Here, we realize the shape morphing of homogeneous plastic films for various free-standing 3D frameworks from their 2D precursors by introducing a general strategy based on programming the plastic strain in films under peeling. By modulating the peeling parameters, previously inaccessible free-standing 3D geometries ranging from millimeter to micrometer were predicted theoretically and obtained experimentally. This strategy is applicable to most materials capable of plastic deformation, including polymers, metals, and composite materials, and can even enable 4D transformation with responsive plastic films. Enhanced performance of 3D circuits and piezoelectric systems demonstrates the enormous potential of peeling-induced shape morphing for 3D devices.

Cell-cell contact-driven EphB1 cis- and trans- signalings regulate cancer stem cells enrichment after chemotherapy.

Reactivation of chemotherapy-induced dormant cancer cells is the main cause of relapse and metastasis. The molecular mechanisms underlying remain to be elucidated. In this study, we introduced a cellular model that mimics the process of cisplatin responsiveness in NSCLC patients. We found that during the process of dormancy and reactivation induced by cisplatin, NSCLC cells underwent sequential EMT-MET with enrichment of cancer stem cells. The ATAC-seq combined with motif analysis revealed that OCT4-SOX2-TCF-NANOG motifs were associated with the enrichment of cancer stem cells induced by chemotherapy. Gene expression profiling suggested a dynamic regulatory mechanism during the process of enrichment of cancer stem cells, where Nanog showed upregulation in the dormant state and SOX2 showed upregulation in the reactivated state. Further, we showed that EphB1 and p-EphB1 showed dynamic expression in the process of cancer cell dormancy and reactivation, where the expression profiles of EphB1 and p-EphB1 showed negatively correlated. In the dormant EMT cells which showed disrupted cell-cell contacts, ligand-independent EphB1 promoted entry of lung cancer cells into dormancy through activating p-p38 and downregulating E-cadherin. On the contrary, in the state of MET, in which cell-cell adhesion was recovered, interactions of EphB1 and ligand EphrinB2 in trans promoted the stemness of cancer cells through upregulating Nanog and Sox2. In conclusion, lung cancer stem cells were enriched during the process of cellular response to chemotherapy. EphB1 cis- and trans- signalings function in the dormant and reactivated state of lung cancer cells respectively. It may provide a therapeutic strategy that target the evolution process of cancer cells induced by chemotherapy.

Wet-Adhesive On-Skin Sensors Based on Metal-Organic Frameworks for Wireless Monitoring of Metabolites in Sweat.

Metal-organic frameworks (MOFs) with well-defined porous structures and tailored functionalities have been widely used in chemical sensing. However, the integration of MOFs with flexible electronic devices for wearable sensing is challenging because of their low electrical conductivity and fragile mechanical properties. Herein, a wearable sweat sensor for metabolite detection is presented by integrating an electrically conductive Ni-MOF with a flexible nanocellulose substrate. The MOF-based layered film sensor with inherent conductivity, highly porous structure, and active catalytic properties enables the selective and accurate detection of vitamin C and uric acid. More importantly, the lightweight sensor can conformably self-adhere to sweaty skin and exhibits high water-vapor permeability. Furthermore, a wireless epidermal nutrition tracking system for the in situ monitoring of the dynamics of sweat vitamin C is demonstrated, the results of which are comparable to those tested by high-performance liquid chromatography. This study opens a new avenue for integrating MOFs as the active layer in wearable electronic devices and holds promise for the future development of high-performance electronics with enhanced sensing, energy production, and catalytic capabilities through the implementation of multifunctional MOFs.

Chromatin accessibility regulates chemotherapy-induced dormancy and reactivation.

Cisplatin-based chemotherapy remains the standard care for non-small cell lung cancer (NSCLC) patients. Relapse after chemotherapy-induced dormancy affects the overall survival of patients. The evolution of cancer cells under chemotherapy stress is regulated by transcription factors (TFs) with binding sites initially buried deep within inaccessible chromatin. The transcription machinery and dynamic epigenetic alterations during the process of dormancy-reactivation of lung cancer cells after chemotherapy need to be investigated. Here, we investigated the chromatin accessibility of lung cancer cells after cisplatin treatment, using an assay for transposase-accessible chromatin sequencing (ATAC-seq). We observed that global chromatin accessibility was extensively improved. Transcriptional Regulatory Relationships Unraveled by Sentence-based Text mining (TRRUST) v.2 was used to elucidate TF-target interaction during the process of dormancy and reactivation. Enhancer regions and motifs specific to key TFs including JUN, MYC, SMAD3, E2F1, SP1, CTCF, SMAD4, STAT3, NFKB1, and KLF4 were enriched in differential loci ATAC-seq peaks of dormant and reactivated cancer cells induced by chemotherapy. The findings suggest that these key TFs regulated gene expressions during the process of dormancy and reactivation of cancer cells through altering promoter accessibility of target genes. Our study helps advance understanding of how cancer cells adapt to the stress induced by chemotherapy through TF binding motif accessibility.

Proteomic profiling of extracellular vesicles and particles reveals the cellular response to cisplatin in NSCLC.

BACKGROUND: Cisplatin-based chemotherapy is a therapeutic strategy against non-small cell lung cancer (NSCLC). However, cancers relapse after chemotherapy due to a dormant state of residual cancer cells. Extracellular vesicles and particles (EVPs) are active carriers of proteins and nucleic acid. Here, we aimed to study the molecular alterations and proteomic characteristics of EPV in dormant and reactivated cancer cells induced by cisplatin. METHODS: We used a short-term single dose of cisplatin to induce the dormant and reactivated cell status. We examined the gene expressional profiling and proteomic profiling of EVPs from dormant and reactivated cancer cells by RNA-sequencing and LC-MS/MS. RESULTS: We found substantial changes in gene expression and protein level in EVP. The genes with higher expression in dormant cancer cells were lipid transporter- and lipid metabolic-related genes. A total of 111 EVP proteins were upregulated in dormant cancer cells compared to those in control cells. Fifty differential expressed proteins (DEPs) were identified in EVPs from reactivated cancer cells compared to those in dormant cancer cells. Among the DEPs, we found that apolipoproteins such as APOA1 and APOE were significantly increased in dormant cancer cell-derived EVPs. Integration of EVP proteomes with transcriptional profiles of cancer cells revealed that the proteomic profiling of EVP derived from cancer cells can reflect the cellular status of cancer cells, which showed an activated lipid metabolism in dormant state. CONCLUSION: Lipoproteins enriched in EVPs reflect the activated lipid metabolism in dormant cancer cells and may provide potential biomarkers or therapeutic targets for cisplatin-based therapy.

Solution-based fabrication of a highly catalytically active 3D network constructed from 1D metal-organic framework-coated polymeric worm-like micelles.

A 3D network constructed from metal-organic framework composite nanowires with a uniform width and a loose (swollen) structure has been prepared. It contained micro-, meso- and macro-pores, which make the 3D network ideal for use as a catalyst, as evidenced by its high catalytic activity in the Knoevenagel reaction.