Architectural design and optimization of internal structures in 3D printed electrodes for superior supercapacitor performance.

The architecture of electrodes plays a pivotal role in the transfer and transportation of charges during electrochemical reactions. Selecting optimal electrode materials and devising well-conceived electrode structures can substantially enhance the electrochemical performance of devices. This manuscript leverages 3D printing technology to fabricate asymmetric supercapacitor devices featuring regular layered configurations. By investigating the impact of various materials on the internal architecture of printed electrodes, we establish a stratified electrode structure with an orderly arrangement, thereby significantly improving asymmetric charge transfer between electrodes. The application of 3D printing technology to construct electrode structures effectively mitigates the agglomeration of electrode materials. The 3D-printed VCG//MXene devices demonstrate exceptional areal capacitance (205.57 mF cm-2) and energy density (60.03 µWh cm-2), with a power density of 0.174 W cm-2. Consequently, selecting appropriate materials for fabricating printable electrode structures and achieving efficient 3D printing is anticipated to offer novel insights into the construction and enhancement of miniature asymmetric micro-supercapacitor (MSCs) devices.

Size-dependent Copper Nanoparticles Supported on Carbon Nanotubes with Balanced Cu+ and Cu0 Dual Sites for the Selective Hydrogenation of Ethylene Carbonate.

Cyclic carbonate hydrogenation offers an alternative for the efficient indirect CO2 utilization. In this study, a series of carbon nanotubes (CNTs) supported xCu/CNTs catalysts with different Cu loadings were fabricated using a convenient impregnation method, and exhibited excellent catalytic activity for the hydrogenation of ethylene carbonate to methanol and ethylene glycol. The structural and physicochemical properties revealed that acid treatment of CNTs resulted in plentiful oxygen-containing functional groups, providing sufficient anchoring sites for copper species. The calcination process conducted under an inert atmosphere resulted in the formation of ternary CuO, Cu2O, and Cu composites, enhancing the metal-support interaction and facilitating the formation of balanced Cu0 and Cu+ dual sites as well as high active surface area after reduction. Contributed to the synergetic effect of balanced Cu+ and Cu0 species proved by density functional theory calculation and the electron-rich CNTs surface, the 40Cu/CNTs catalyst achieved strengthened catalytic performance with methanol yield of 83%, ethylene glycol yield of 99% at ethylene carbonate conversion of >99%, and 150 h of long-term running stability. Consequently, CNTs supported Cu serve as efficient non-silica based catalyst for ester hydrogenation.

Epidemiological characteristics and prevention of pressure injury in older inpatients of Zhuang and Han ethnicity in Guangxi, China: a cross-sectional study.

BACKGROUND: Pressure injury (PI) is a significant health concern among older inpatients, particularly in regions with diverse ethnic populations. Understanding the epidemiological characteristics and preventive measures is crucial for improving patient outcomes. PURPOSE: To analyze the epidemiological characteristics, prevention status, and influencing factors of pressure injury (PI) in older inpatients of Zhuang and Han nationality in Guangxi, China. METHODS: A total of 2206 inpatients age 60 years or older in 2 class III grade A general hospitals in the Guangxi Zhuang Autonomous Region between April 1, 2021, and May 27, 2021, were included in this cross-sectional study. Epidemiological characteristics-including age, sex, educational background, race, ethnicity, and hospitalization information-were collected using a general information questionnaire designed by the researchers. The PI risk factors were evaluated using the Braden Scale. Prevention status was assessed using the Epidemiology and Prevention Skin Injuries in the Elderly Scale and Skin Injury Survey Scale. RESULTS: Of the total 2206 patients included in the study, 555 (25.16%) were of Zhuang nationality and 1651 (74.84%) were of Han nationality. The overall PI incidence was 2.58%, with PI prevalence of 1.80% and 2.85% in Zhuang and Han patients, respectively. The main influencing factor for PI in Zhuang patients was caregivers (P < .05), whereas in Han patients the main influencing factors were urinary conditions, Alzheimer disease, sedatives, and antihypertensive drugs (P < .05). CONCLUSION: The PI prevalence rates were similar in both ethnic groups. Health care staff in high-risk departments for PI must remain vigilant and take appropriate action.

COVID-19 in the Tibet, China, the roof of the world: a comparative analysis of high-altitude residents and newcomers.

BACKGROUND: After a 920-day hiatus, COVID-19 resurged in the Tibet Autonomous Region of China in August 2022. This study compares the characteristics of COVID-19 between high-altitude residents and newcomers, as well as between newcomers and lowlanders. METHODS: This multi-center cohort study conducted at the Third People's Hospital of Tibet Autonomous Region and Beijing University Shenzhen Hospital, included 520 high-altitude resident patients, 53 high-altitude newcomer patients, and 265 lowlander patients infected with the Omicron variant. Initially, we documented epidemiological, clinical, and treatment data across varying residency at admission. We compared the severity of COVID-19 and various laboratory indicators, including hemoglobin concentration and SpO2%, over a 14-day period from the date of the first positive nucleic acid test, as well as the differences in treatment methods and disease outcomes between highlanders and high-altitude newcomers. We also compared several characteristics of COVID-19 between high-altitude newcomers and lowlanders. Univariate analysis, multivariable logistic regression, and the generalized linear mixed model were utilized for the analysis. RESULTS: No fatalities were observed. The study found no significant differences in COVID-19 severity or in the physiological measures of hemoglobin concentration and SpO2% between high-altitude and lowland residents. Similarly, there were no statistically significant differences in the values or trends of hemoglobin and SpO2% between high-altitude residents and newcomers throughout the 14-day observation period. However, compared to age- and sex-matched lowlander patients (1:5 ratio), high-altitude newcomers exhibited higher heart rates, respiratory rates, and average hemoglobin concentrations, along with lower platelet counts. There were no significant differences in hospital stays between the two groups. CONCLUSIONS: High-altitude residents and newcomer patients exhibit clinical similarities. However, the clinical characteristics of high-altitude newcomers and lowlander patients differ due to the impact of the high-altitude environment. These results highlight potential considerations for public health strategies in high-altitude regions such as Tibet.

Clinical and radiographic evaluation of regenerative endodontic procedures (REPs) with or without concentrated growth factor (CGF) as scaffolds for non-vital immature mandibular premolars.

This study aimed to perform clinical and radiographic investigations of the effect of regenerative endodontic procedures (REPs) with and without concentrated growth factor (CGF). Fifty-six non-vital and immature teeth from 56 patients were randomly categorized into two groups. Following chemical and mechanical preparation, REPs with and without CGF as a scaffold was induced in the blood clot (BLC) group and the CGF group. All patients were clinically and radiographically evaluated at 6-month and 12-month intervals to monitor their progress and treatment outcomes. When considering the total number of patients, the follow-up rate was 96.4% (54 out of 56 patients) over a 12-month period. Favorable clinical and radiographic outcomes were observed in 92.6% of patients (25 out of 27) in both the CGF and BLC groups; there were no significant differences between the two groups in these respects (p > 0.05). Notable differences were, however, observed in radiographic measurements relating to the development of root length and radiographic root area when compared between the CGF and BLC groups at both the 6-month and 12-month follow-up intervals (p < 0.05). REPs have been proven to represent a conservative and effective approach for promoting maturogenesis in non-vital and immature teeth. Furthermore, the incorporation of CGF as scaffolds holds promising potential for enhancing the desired biological outcomes of this regenerative technique. These findings highlight the clinical significance and potential benefits of CGF supplementation in REPs, further supporting its application in the field of endodontics.

Deciphering the cellular landscape and potential targets of nasopharyngeal and oral cancers using single-cell RNA sequencing.

Cellular heterogeneity in nasopharyngeal cancer (NPC) and oral cancer remains unclear. In the current study, using single-cell RNA sequencing techniques, we investigated the cellular landscape in NPC and oral cancers. We identified a diverse range of cell types within the tumor microenvironment (TME) and variations in cell infiltration between NPC and oral cancer. In oral cancer, we observed a predominant infiltration of epithelial cells, fibroblasts, and endothelial cells (ECs), while T cells were the main infiltrating cell population in NPCs. We further classified these infiltrating cells into subclusters. Additionally, we observed complex interactions among cells that led to distinct trajectories. In particular, a unique epithelial subcluster with high expression of major histocompatibility complex class II (MHC-II) molecules was correlated with a favorable outcome and infiltration of CD4+ T cells. In addition, MHC-II+ epithelial cells inhibited mouse tumor growth and promoted T-cell infiltration. Consequently, our findings provide a deep understanding of the TME showing a significant prognostic value and therapeutic potential.

Surgery or radiotherapy improves survival in elderly patients with early non-small cell lung cancer: A population-based analysis.

OBJECTIVE: There is a lack of evidence to support a consensus on whether surgery or radiotherapy is optimal for elderly or very elderly patients with early-stage non-small cell lung cancer (NSCLC). We aimed to assess the impact of surgery or radiotherapy on survival in elderly (≥70 years) and very elderly (≥80 years) patients with early-stage NSCLC. METHODS: Patients aged ≥70 years diagnosed with early-stage NSCLC between January 1, 1975, and December 31, 2018, were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were assessed based on surgery, radiotherapy, and no-treatment groups. RESULTS: Data for 15,224 NSCLC patients aged ≥70 years were collected, which consisted of 6949 (45.6%) patients who underwent surgery alone, 5014 (32.9%) who underwent radiotherapy alone, and 3261 (21.5%) who received no treatment. Surgery significantly improved patient survival compared with no treatment (MST: 74 months vs. 7 months, HR: 0.201, 95% CI: 0.186-0.217, P < 0.001), as did radiotherapy (MST: 28 months vs. 7 months, HR: 0.440; 95% CI: 0.413-0.469, P < 0.001). Surgery also resulted in improved survival compared with radiotherapy (74 months vs. 28 months, HR: 0.455; 95% CI: 0.430-0.482, P < 0.001). A similar conclusion was made from the analysis of CSS. A subgroup analysis further confirmed the survival benefits. CONCLUSIONS: The results of this large-scale retrospective study indicate that both surgery and radiotherapy significantly enhance survival outcomes in patients aged ≥70 or ≥80 years with early-stage NSCLC. The survival benefits of surgery were particularly notable.

Impact of Chemical Corrosion on Mechanical Properties of Boroaluminosilicate Pharmaceutical Glasses.

Boroaluminosilicate (BAS) glasses have excellent chemical durability and mechanical properties and are widely used in the pharmaceutical packaging industry. The corrosion behavior of boroaluminosilicate (BAS) glasses have been investigated for many years; however, the impact of chemical corrosion on mechanical properties of boroaluminosilicate glasses has not been well understood. In this work, the BAS glass samples were corroded in a 20 mM Glycine-NaOH buffer solution (pH = 10) at 80 °C for various durations. Within the corrosion durations, the corrosion of the glass is dominated by congruent dissolution. The results show that the elemental composition and structure of the glass surface are not altered significantly during the congruent dissolution, and the corrosion rate is mainly affected by the Si concentration in the solution. The structural change in the process of micro-crack decay is the main factor affecting the mechanical properties of the glass surface. Corrosion leads to the growth of micro-cracks and tip passivation, which causes the hardness and elastic modulus of the glass to first decrease and then increase. As corrosion proceeds, the microcracks are completely destroyed to form micropores, and the pore size and number increase with the corrosion process, resulting in the decrease in surface mechanical properties again. This work reveals the main influencing factors of congruent dissolution on mechanical properties and provides an important reference for the improvement of pharmaceutical glass strength.

[Knock-down of long noncoding RNA H19 (lncRNA H19) promotes human colorectal cell autophagy and inhibits cell apoptosis induced by lipopolysaccharide].

Objective To investigate the expression levels of lncRNA H19 in ulcerative colitis (UC) patients and its role in UC. Methods Colonic mucosa and serum samples were collected from 25 UC patients and 25 healthy individuals at the General Hospital of Xizang Military Region. The expression levels of lncRNA H19 were detected, and the receiver operating characteristic (ROC) curve analysis was performed using serum samples. An in vitro inflammatory model was established in HT29 colorectal cells under lipopolysaccharide (LPS) stimulation, and the expression levels of lncRNA H19 were observed in HT29 cells through fluorescence quantitative PCR. HT29 cells with downregulated lncRNA H19 was constructed using lentivirus-mediated shRNA. The effect of lncRNA H19 on cell survival was analyzed through MTT assay. Cell apoptosis was detected by flow cytometry, and the protein expression levels of apoptosis and autophagy markers were analyzed through Western blot. After treatment with rapamycin, the survival of HT29 cells was observed by MTT assay. Results lncRNA H19 was highly expressed in the colonic mucosa and serum samples of UC patients with the ROC area being 0.786. Following LPS stimulation, the expression levels of lncRNA H19 was significantly increased in a time-dependent manner. Downregulation of lncRNA H19 can promote cell survival, inhibit cell apoptosis and increase autophagy level in HT29 cells. Treatment with rapamycin significantly increased the cell survival rate. Conclusion Knock-down of lncRNA H19 increases autophagy levels, inhibits LPS-induced apoptosis and promotes the survival of colon cells.

Binary split fluorescent biosensor based on lettuce DNA aptamer for label-free and enzyme-free analysis of hepatitis B viral DNA.

Hepatitis B virus (HBV) acts as a severe public health threat, causing chronic liver diseases. Although the quantified evaluation of HBV infection can be obtained by estimating the capacity of the HBV DNA genome, it still lacks an effective and robust detection method without using enzymes or chemical labeling. Herein, we have designed a binary split fluorescent DNA aptasensor (bsFDA) by rationally splitting the lettuce aptamer into two functional DNA short chains and utilizing the HBV DNA segment complementary sequences (HDs). In this strategy, the bsFDA has been investigated to specifically recognize the HDs, forming a triplex DNA with the lettuce aptamer structure. Meanwhile, the turn-on fluorescence of bsFDA is obtained upon formation of a fluorescent complex between DFHO and the triplex DNA structure, allowing the enzyme-free, label-free, fast-responsive, and reliable fluorescence readout for detecting HDs and the potential HDs mutants. Moreover, bsFDA has been applied for spiked HDs analysis in different real matrixes, including human serum and cell lysate. The satisfactory recovery rates and reproducibility of the bsFDA reveal its potential detection efficacy for HDs analysis in biological samples. Overall, bsFDA holds great potential in developing functionalized aptasensors and realizing viral genome analysis in biological research.

Unlocking the formate utilization of wild-type Yarrowia lipolytica through adaptive laboratory evolution.

Synthetic biology is contributing to the advancement of the global net-negative carbon economy, with emphasis on formate as a member of the one-carbon substrate garnering substantial attention. In this study, we employed base editing tools to facilitate adaptive evolution, achieving a formate tolerance of Yarrowia lipolytica to 1 M within 2 months. This effort resulted in two mutant strains, designated as M25-70 and M25-14, both exhibiting significantly enhanced formate utilization capabilities. Transcriptomic analysis revealed the upregulation of nine endogenous genes encoding formate dehydrogenases when cultivated utilizing formate as the sole carbon source. Furthermore, we uncovered the pivotal role of the glyoxylate and threonine-based serine pathway in enhancing glycine supply to promote formate assimilation. The full potential of Y. lipolytica to tolerate and utilize formate establishing the foundation for pyruvate carboxylase-based carbon sequestration pathways. Importantly, this study highlights the existence of a natural formate metabolic pathway in Y. lipolytica.

OptoLacI: optogenetically engineered lactose operon repressor LacI responsive to light instead of IPTG.

Optogenetics' advancement has made light induction attractive for controlling biological processes due to its advantages of fine-tunability, reversibility, and low toxicity. The lactose operon induction system, commonly used in Escherichia coli, relies on the binding of lactose or isopropyl ß-d-1-thiogalactopyranoside (IPTG) to the lactose repressor protein LacI, playing a pivotal role in controlling the lactose operon. Here, we harnessed the light-responsive light-oxygen-voltage 2 (LOV2) domain from Avena sativa phototropin 1 as a tool for light control and engineered LacI into two light-responsive variants, OptoLacIL and OptoLacID. These variants exhibit direct responsiveness to light and darkness, respectively, eliminating the need for IPTG. Building upon OptoLacI, we constructed two light-controlled E. coli gene expression systems, OptoE.coliLight system and OptoE.coliDark system. These systems enable bifunctional gene expression regulation in E. coli through light manipulation and show superior controllability compared to IPTG-induced systems. We applied the OptoE.coliDark system to protein production and metabolic flux control. Protein production levels are comparable to those induced by IPTG. Notably, the titers of dark-induced production of 1,3-propanediol (1,3-PDO) and ergothioneine exceeded 110% and 60% of those induced by IPTG, respectively. The development of OptoLacI will contribute to the advancement of the field of optogenetic protein engineering, holding substantial potential applications across various fields.

Development and Application of a Selective Analytical Method for Indole Metabolites in Urine: Dietary Exposure Biomarkers for Broccoli Consumption.

The identification of dietary exposure biomarkers is crucial for advancing our understanding of the health benefits of specific foods. Broccoli, a vegetable with well-known anticancer properties, contains active ingredients, such as isothiocyanates with indole side chains. Hence, indole metabolites related to broccoli consumption have the potential to serve as biomarkers of dietary exposure. In this work, we developed a new analytical method for indole metabolites in urine using a poly(deep eutectic solvents)-molecularly imprinted polymer/vinyl-functionalized graphene oxide (PDESs-MIP/VGO) in miniaturized centrifugal pipet-tip solid-phase extraction (CPT-SPE) coupled with liquid chromatography. This method integrates the strengths of PDESs-MIP/VGO, including rich adsorption interactions, high adsorption capacity, and excellent selectivity, with the simplicity and cost-effectiveness of CPT-SPE. The proposed method demonstrated low limits of quantification (1.2-2.5 ng mL-1), high accuracy (91.7-104.8%), and good precision (relative standard deviation ≤4.4%). By applying this method to analyze indole metabolites in urine, our results suggested that indole-3-carbinol and indole-3-acetonitrile have the potential to emerge as reliable dietary exposure biomarkers for broccoli intake. Furthermore, highly selective analytical methods based on molecular imprinting technology are advantageous for precise screening and analysis of dietary exposure biomarkers associated with food consumption.

Quantitative measurement of cell-surface displayed proteins based on split-GFP assembly.

BACKGROUND: Microbial cell surface display technology allows immobilizing proteins on the cell surface by fusing them to anchoring motifs, thereby endowing the cells with diverse functionalities. However, the assessment of successful protein display and the quantification of displayed proteins remain challenging. The green fluorescent protein (GFP) can be split into two non-fluorescent fragments, while they spontaneously assemble and emit fluorescence when brought together through complementation. Based on split-GFP assembly, we aim to: (1) confirm the success display of passenger proteins, (2) quantify the number of passenger proteins displayed on individual cells. RESULTS: In this study, we propose two innovative methods based on split-green fluorescent protein (split-GFP), named GFP1-10/GFP11 and GFP1-9/GFP10-11 assembly, for the purpose of confirming successful display and quantifying the number of proteins displayed on individual cells. We evaluated the display efficiency of SUMO and ubiquitin using different anchor proteins to demonstrate the feasibility of the two split-GFP assembly systems. To measure the display efficiency of functional proteins, laccase expression was measured using the split-GFP assembly system by co-displaying GFP11 or GFP10-11 tags, respectively. CONCLUSIONS: Our study provides two split-GFP based methods that enable qualitative and quantitative analyses of individual cell display efficiency with a simple workflow, thus facilitating further comprehensive investigations into microbial cell surface display technology. Both split-GFP assembly systems offer a one-step procedure with minimal cost, simplifying the fluorescence analysis of surface-displaying cells.

ATP-free in vitro biotransformation of starch-derived maltodextrin into poly-3-hydroxybutyrate via acetyl-CoA.

In vitro biotransformation (ivBT) facilitated by in vitro synthetic enzymatic biosystems (ivSEBs) has emerged as a highly promising biosynthetic platform. Several ivSEBs have been constructed to produce poly-3-hydroxybutyrate (PHB) via acetyl-coenzyme A (acetyl-CoA). However, some systems are hindered by their reliance on costly ATP, limiting their practicality. This study presents the design of an ATP-free ivSEB for one-pot PHB biosynthesis via acetyl-CoA utilizing starch-derived maltodextrin as the sole substrate. Stoichiometric analysis indicates this ivSEB can self-maintain NADP+/NADPH balance and achieve a theoretical molar yield of 133.3%. Leveraging simple one-pot reactions, our ivSEBs achieved a near-theoretical molar yield of 125.5%, the highest PHB titer (208.3 mM, approximately 17.9 g/L) and the fastest PHB production rate (9.4 mM/h, approximately 0.8 g/L/h) among all the reported ivSEBs to date, and demonstrated easy scalability. This study unveils the promising potential of ivBT for the industrial-scale production of PHB and other acetyl-CoA-derived chemicals from starch.

Development and external validation of a multimodal integrated feature neural network (MIFNN) for the diagnosis of malignancy in small pulmonary nodules (≤10 mm).

Objectives. Current lung cancer screening protocols primarily evaluate pulmonary nodules, yet often neglect the malignancy risk associated with small nodules (≤10 mm). This study endeavors to optimize the management of pulmonary nodules in this population by devising and externally validating a Multimodal Integrated Feature Neural Network (MIFNN). We hypothesize that the fusion of deep learning algorithms with morphological nodule features will significantly enhance diagnostic accuracy.Materials and Methods. Data were retrospectively collected from the Lung Nodule Analysis 2016 (LUNA16) dataset and four local centers in Beijing, China. The study includes patients with small pulmonary nodules (≤10 mm). We developed a neural network, termed MIFNN, that synergistically combines computed tomography (CT) images and morphological characteristics of pulmonary nodules. The network is designed to acquire clinically relevant deep learning features, thereby elevating the diagnostic accuracy of existing models. Importantly, the network's simple architecture and use of standard screening variables enable seamless integration into standard lung cancer screening protocols.Results. In summary, the study analyzed a total of 382 small pulmonary nodules (85 malignant) from the LUNA16 dataset and 101 small pulmonary nodules (33 malignant) obtained from four specialized centers in Beijing, China, for model training and external validation. Both internal and external validation metrics indicate that the MIFNN significantly surpasses extant state-of-the-art models, achieving an internal area under the curve (AUC) of 0.890 (95% CI: 0.848-0.932) and an external AUC of 0.843 (95% CI: 0.784-0.891).Conclusion. The MIFNN model significantly enhances the diagnostic accuracy of small pulmonary nodules, outperforming existing benchmarks by Zhanget alwith a 6.34% improvement for nodules less than 10 mm. Leveraging advanced integration techniques for imaging and clinical data, MIFNN increases the efficiency of lung cancer screenings and optimizes nodule management, potentially reducing false positives and unnecessary biopsies.Clinical relevance statement. The MIFNN enhances lung cancer screening efficiency and patient management for small pulmonary nodules, while seamlessly integrating into existing workflows due to its reliance on standard screening variables.

Penetrating the ultra-tough yeast cell wall with finite element analysis model-aided design of microtools.

Microinjecting yeast cells has been challenging for decades with no significant breakthrough due to the ultra-tough cell wall and low stiffness of the traditional injector tip at the micro-scale. Penetrating this protection wall is the key step for artificially bringing foreign substance into the yeast. In this paper, a yeast cell model was built by using finite element analysis (FEA) method to analyze the penetrating process. The key parameters of the yeast cell wall in the model (the Young's modulus, the shear modulus, and the Lame constant) were calibrated according to a general nanoindentation experiment. Then by employing the calibrated model, the injection parameters were optimized to minimize the cell damage (the maximum cell deformation at the critical stress of the cell wall). Key guidelines were suggested for penetrating the cell wall during microinjection.

Green synthesis of superhydrophilic resin/graphene oxide for efficient analysis of multiple pesticide residues in fruits and vegetables.

The escalating use of pesticides on fruits and vegetables has raised concerns about potential health risks. Therefore, we developed a superhydrophilic resin/graphene oxide (SR/GO) with rich adsorption interactions using an eco-friendly synthetic approach. SR/GO demonstrated excellent hydrophilicity, ensuring optimal contact with aqueous sample matrices. The multiple adsorption interactions, including π-π conjugation, hydrogen bonding, and electrostatic adsorption, facilitated multi-pesticide residue co-extraction. The synthesized SR/GO was applied to a miniaturized centrifugation-accelerated pipette-tip extraction method, coupled with high-performance liquid chromatography. The optimized method exhibited low consumption (15.0 mg adsorbent), and high efficiency, with low detection limits (1.4-2.9 ng g-1) and high recoveries (75.3-113.0%). Water-compatible SR/GO, along with a miniaturized extraction process, showcases a potent analytical approach for pesticide residue analysis in fruits and vegetables. The significance of this method lies in its ability to ensure agricultural and food safety by using a low-cost and efficient multi-pesticide residue analytical strategy.

Multibarrier-penetrating drug delivery systems for deep tumor therapy based on synergistic penetration strategy.

Nanotherapies, valued for their high efficacy and low toxicity, frequently serve as antitumor treatments, but do not readily penetrate deep into tumor tissues and cells. Here we developed an improved tumor-penetrating peptide (TPP)-based drug delivery system. Briefly, the established TPP iNGR was modified to generate a linear NGR peptide capable of transporting nanotherapeutic drugs into tumors through a CendR pathway-dependent, neuropilin-1 receptor-mediated process. Although TPPs have been reported to reach intended tumor targets, they often fail to penetrate cell membranes to deliver tumoricidal drugs to intracellular targets. We addressed this issue by harnessing cell penetrating peptide technology to develop a liposome-based multibarrier-penetrating delivery system (mbPDS) with improved synergistic drug penetration into deep tumor tissues and cells. The system incorporated doxorubicin-loaded liposomes coated with nona-arginine (R9) CPP and cyclic iNGR (CRNGRGPDC) molecules, yielding Lip-mbPDS. Lip-mbPDS tumor-targeting, tumor cell/tissue-penetrating and antitumor capabilities were assessed using CD13-positive human fibrosarcoma-derived cell (HT1080)-based in vitro and in vivo tumor models. Lip-mbPDS evaluation included three-dimensional layer-by-layer confocal laser scanning microscopy, cell internalization/toxicity assays, three-dimensional tumor spheroid-based penetration assays and antitumor efficacy assays conducted in an animal model. Lip-mbPDS provided enhanced synergistic drug penetration of multiple biointerfaces for potentially deep tumor therapeutic outcomes.

Systematic Analysis to Identify the MIR99AHG-has-miR-21-5p-EHD1 CeRNA Regulatory Network as Potential Biomarkers in Lung Cancer.

Lung cancer (LC) remains an extremely lethal disease worldwide, and effective prognostic biomarkers are at top priority. With the rapid development of high-throughput sequencing and bioinformatic analysis methods, the quest to characterize cancer transcriptomes continues to move forward. However, the integrated systematic analysis of lncRNA-miRNA-mRNA regulatory network in LC is lacking. In this study, we collected samples of cancer tissues and adjacent normal tissues from patients with lung cancer and conducted transcriptome and small RNA sequencing to identify differentially expressed genes (DEGs), miRNAs (DEMs), and lncRNAs (DELs). The regulatory roles of miRNAs in LC were explained by functional analysis on DEM-targeted genes. The lncRNA-miRNA pairs, miRNA-mRNA pairs, and lncRNA-mRNA pairs were identified and combined to construct the interplay of lncRNA-miRNA-mRNA. We evaluated the prognostic value of selected lncRNA-miRNA-mRNA by Kaplan-Meier analysis. Finally, we analyzed the expression levels of selected DEM, DELs, and DEGs in lung cancer patients and healthy people to verify our findings. A total of 1492 DEGs, 12 DEMs, and 604 DELs were identified in LC patients. Based on the bioinformatic analysis and the regulatory mechanism of ceRNAs, 3 lncRNAs (GATA2-AS1, LINC00632, MIR99AHG), 1 miRNA (hsa-miR-21-5p) and 5 targeted genes (RECK, TIMP3, EHD1, RASGRP1 and ERG) were figured out first. Through further Kaplan-Meier analysis screening the prognostic value, we finally found the hub subnetwork (MIR99AHG-hsa-miR-21-5p-EHD1) by collating lncRNA-miRNA pairs, miRNA-mRNA pairs and lncRNA-mRNA pairs. As the key of ceRNA regulatory network, the expression of miRNA-21-5p in lung cancer patients was significantly higher than that in healthy people (P < 0.01), and its high expression was significantly associated with poor prognosis (P = 0.0025). Our study successfully constructed a MIR99AHG-hsa-miR-21-5p-EHD1 mutually regulatory network, suggesting the potential efficient biomarkers in LC.