Effect of nutrition-based prehabilitation on the postoperative outcomes of patients with esophagogastric cancer undergoing surgery: A systematic review and meta-analysis.

BACKGROUND: Meta-analyses have primarily focused on the effects of exercise-based prehabilitation on postoperative outcomes and ignored the role of nutritional intervention. In this study, we filled this gap by investigating the effect of nutrition-based prehabilitation on the postoperative outcomes of patients who underwent esophagectomy and gastrectomy. METHODS: Five electronic databases, namely, PubMed, the Web of Science, Embase, Cochrane Library, and CINAHL, were searched. Adults diagnosed with esophagogastric cancer who were scheduled to undergo surgery and had undergone uni- or multimodal prehabilitation, with at least a week of mandatory nutritional intervention, were included. Forest plots were used to extract and visualize the data from the included studies. The occurrence of any postoperative complication was considered the primary endpoint. RESULTS: Eight studies met the eligibility criteria, with five randomized controlled trials (RCTs) and three cohort studies. In total, 661 patients were included. Any prehabilitation, that is, unimodal (only nutrition) and multimodal prehabilitation, collectively decreased the risk of any postoperative complication by 23% (95% confidence interval [CI] = 0.66-0.90). A similar effect was exclusively observed for multimodal prehabilitation (risk ratio [RR] = 0.78, 95% CI = 0.66-0.93); however, it was not significant for unimodal prehabilitation. Any prehabilitation significantly decreased the length of hospital stay (LOS) (weighted mean difference = -0.77, 95% CI = -1.46 to -0.09). CONCLUSIONS: Nutrition-based prehabilitation, particularly multimodal prehabilitation, confers protective effects against postoperative complications after esophagectomy and gastrectomy. Our findings suggest that prehabilitation slightly decreases LOS; however, the finding is not clinically significant. Therefore, additional rigorous RCTs are warranted for further substantiation.

Predictive Roles of Basal Metabolic Rate and Muscle Mass in Lung Function among Patients with Obese Asthma: A Prospective Cohort Study.

BACKGROUND: The metabolic-status-related mechanisms underlying the deterioration of the lung function in obese asthma have not been completely elucidated. OBJECTIVE: This study aimed to investigate the basal metabolic rate (BMR) in patients with obese asthma, its association with the lung function, and its mediating role in the impact of obesity on the lung function. METHODS: A 12-month prospective cohort study (n = 598) was conducted in a real-world setting, comparing clinical, body composition, BMR, and lung function data between patients with obese (n = 282) and non-obese (n = 316) asthma. Path model mediation analyses for the BMR and skeletal muscle mass (SMM) were conducted. We also explored the effects of the BMR on the long-term lung function in patients with asthma. RESULTS: Patients with obese asthma exhibited greater airway obstruction, with lower FEV1 (1.99 vs. 2.29 L), FVC (3.02 vs. 3.33 L), and FEV1/FVC (65.5 vs. 68.2%) values compared to patients with non-obese asthma. The patients with obese asthma also had higher BMRs (1284.27 vs. 1210.08 kcal/d) and SMM (23.53 vs. 22.10 kg). Both the BMR and SMM mediated the relationship between obesity and the lung function spirometers (FEV1, %FEV1, FVC, %FVC, and FEV1/FVC). A higher BMR or SMM was associated with better long-term lung function. CONCLUSIONS: Our study highlights the significance of the BMR and SMM in mediating the relationship between obesity and spirometry in patients with asthma, and in determining the long-term lung function. Interventions for obese asthma should focus not only on reducing adiposity but also on maintaining a high BMR.

Chemically Programmed Hydrogels for Spatiotemporal Modulation of the Cardiac Pathological Microenvironment.

After myocardial infarction (MI), sustained ischemic events induce pathological microenvironments characterized by ischemia-hypoxia, oxidative stress, inflammatory responses, matrix remodeling, and fibrous scarring. Conventional clinical therapies lack spatially targeted and temporally responsive modulation of the infarct microenvironment, leading to limited myocardial repair. Engineered hydrogels have a chemically programmed toolbox for minimally invasive localization of the pathological microenvironment and personalized responsive modulation over different pathological periods. Chemically programmed strategies for crosslinking interactions, interfacial binding, and topological microstructures in hydrogels enable minimally invasive implantation and in situ integration tailored to the myocardium. This enhances substance exchange and signal interactions within the infarcted microenvironment. Programmed responsive polymer networks, intelligent micro/nanoplatforms, and biological therapeutic cues contribute to the formation of microenvironment-modulated hydrogels with precise targeting, spatiotemporal control, and on-demand feedback. Therefore, this review summarizes the features of the MI microenvironment and chemically programmed schemes for hydrogels to conform, integrate, and modulate the cardiac pathological microenvironment. Chemically programmed strategies for oxygen-generating, antioxidant, anti-inflammatory, provascular, and electrointegrated hydrogels to stimulate iterative and translational cardiac tissue engineering are discussed.

Structure-activity relationships of the intramolecular disulphide bonds in LEAP2, an antimicrobial peptide from Acrossocheilus fasciatus.

BACKGROUND: The liver-expressed antimicrobial peptide 2 (LEAP2) plays a pivotal role in the host's immune response against pathogenic microorganisms. Numerous such antimicrobial peptides have recently been shown to mitigate infection risk in fish, and studying those harboured by the economically important fish Acrossocheilus fasciatus is imperative for enhancing its immune responses against pathogenic microorganisms. In this study, we cloned and sequenced LEAP2 cDNA from A. fasciatus to examine its expression in immune tissues and investigate the structure-activity relationships of its intramolecular disulphide bonds. RESULTS: The predicted amino acid sequence of A. fasciatus LEAP2 was found to include a signal peptide, pro-domain, and mature peptide. Sequence analysis indicated that A. fasciatus LEAP2 is a member of the fish LEAP2A cluster and is closely related to Cyprinus carpio LEAP2A. A. fasciatus LEAP2 transcripts were expressed in various tissues, with the head kidney exhibiting the highest mRNA levels. Upon exposure to Aeromonas hydrophila infection, LEAP2 expression was significantly upregulated in the liver, head kidney, and spleen. A mature peptide of A. fasciatus LEAP2, consisting of two disulphide bonds (Af-LEAP2-cys), and a linear form of the LEAP2 mature peptide (Af-LEAP2) were chemically synthesised. The circular dichroism spectroscopy result shows differences between the secondary structures of Af-LEAP2 and Af-LEAP2-cys, with a lower proportion of alpha helix and a higher proportion of random coil in Af-LEAP2. Af-LEAP2 exhibited potent antimicrobial activity against most tested bacteria, including Acinetobacter guillouiae, Pseudomonas aeruginosa, Staphylococcus saprophyticus, and Staphylococcus warneri. In contrast, Af-LEAP2-cys demonstrated weak or no antibacterial activity against the tested bacteria. Af-LEAP2 had a disruptive effect on bacterial cell membrane integrity, whereas Af-LEAP2-cys did not exhibit this effect. Additionally, neither Af-LEAP2 nor Af-LEAP2-cys displayed any observable ability to hydrolyse the genomic DNA of P. aeruginosa. CONCLUSIONS: Our study provides clear evidence that linear LEAP2 exhibits better antibacterial activity than oxidised LEAP2, thereby confirming, for the first time, this phenomenon in fish.

Neurotoxicity of manganese via ferroptosis induced by redox imbalance and iron overload.

Manganese (Mn) is an essential trace element for maintaining bodily functions. Excessive exposure to Mn can pose serious health risks to humans and animals, particularly to the nervous system. While Mn has been implicated as a neurotoxin, the exact mechanism of its toxicity remains unclear. Ferroptosis is a form of programmed cell death that results from iron-dependent lipid peroxidation. It plays a role in various physiological and pathological cellular processes and may be closely related to Mn-induced neurotoxicity. However, the mechanism of ferroptosis in Mn-induced neurotoxicity has not been thoroughly investigated. Therefore, this study aims to investigate the role and mechanism of ferroptosis in Mn-induced neurotoxicity. Using bioinformatics, we identified significant changes in genes associated with ferroptosis in Mn-exposed animal and cellular models. We then evaluated the role of ferroptosis in Mn-induced neurotoxicity at both the animal and cellular levels. Our findings suggest that Mn exposure causes weight loss and nervous system damage in mice. In vitro and in vivo experiments have shown that exposure to Mn increases malondialdehyde, reactive oxygen species, and ferrous iron, while decreasing glutathione and adenosine triphosphate. These findings suggest that Mn exposure leads to a significant increase in lipid peroxidation and disrupts iron metabolism, resulting in oxidative stress injury and ferroptosis. Furthermore, we assessed the expression levels of proteins and mRNAs related to ferroptosis, confirming its significant involvement in Mn-induced neurotoxicity.

PSAEEGNet: pyramid squeeze attention mechanism-based CNN for single-trial EEG classification in RSVP task.

Introduction: Accurate classification of single-trial electroencephalogram (EEG) is crucial for EEG-based target image recognition in rapid serial visual presentation (RSVP) tasks. P300 is an important component of a single-trial EEG for RSVP tasks. However, single-trial EEG are usually characterized by low signal-to-noise ratio and limited sample sizes. Methods: Given these challenges, it is necessary to optimize existing convolutional neural networks (CNNs) to improve the performance of P300 classification. The proposed CNN model called PSAEEGNet, integrates standard convolutional layers, pyramid squeeze attention (PSA) modules, and deep convolutional layers. This approach arises the extraction of temporal and spatial features of the P300 to a finer granularity level. Results: Compared with several existing single-trial EEG classification methods for RSVP tasks, the proposed model shows significantly improved performance. The mean true positive rate for PSAEEGNet is 0.7949, and the mean area under the receiver operating characteristic curve (AUC) is 0.9341 (p < 0.05). Discussion: These results suggest that the proposed model effectively extracts features from both temporal and spatial dimensions of P300, leading to a more accurate classification of single-trial EEG during RSVP tasks. Therefore, this model has the potential to significantly enhance the performance of target recognition systems based on EEG, contributing to the advancement and practical implementation of target recognition in this field.

DNMT1-mediated epigenetic suppression of FBXO32 expression promoting cyclin dependent kinase 9 (CDK9) survival and esophageal cancer cell growth.

Esophageal cancer (EC) is a common and serious form of cancer, and while DNA methyltransferase-1 (DNMT1) promotes DNA methylation and carcinogenesis, the role of F-box protein 32 (FBXO32) in EC and its regulation by DNMT1-mediated methylation is still unclear. FBXO32 expression was examined in EC cells with high DNMT1 expression using GSE163735 dataset. RT-qPCR assessed FBXO32 expression in normal and EC cells, and impact of higher FBXO32 expression on cell proliferation, migration, and invasion was evaluated, along with EMT-related proteins. The xenograft model established by injecting EC cells transfected with FBXO32 was used to evaluate tumor growth, apoptosis, and tumor cells proliferation and metastasis. Chromatin immunoprecipitation (ChIP) assay was employed to study the interaction between DNMT1 and FBXO32. HitPredict, co-immunoprecipitation (Co-IP), and Glutathione-S-transferase (GST) pulldown assay analyzed the interaction between FBXO32 and cyclin dependent kinase 9 (CDK9). Finally, the ubiquitination assay identified CDK9 ubiquitination, and its half-life was measured using cycloheximide and confirmed through western blotting. DNMT1 negatively correlated with FBXO32 expression in esophageal cells. High FBXO32 expression was associated with better overall survival in patients. Knockdown of DNMT1 in EC cells increased FBXO32 expression and suppressed malignant phenotypes. FBXO32 repressed EC tumor growth and metastasis in mice. Enrichment of DNMT1 in FBXO32 promoter region led to increased DNA methylation and reduced transcription. Mechanistically, FBXO32 degraded CDK9 through promoting its ubiquitination.

Multiband task related components enhance rapid cognition decoding for both small and similar objects.

The cortically-coupled target recognition system based on rapid serial visual presentation (RSVP) has a wide range of applications in brain computer interface (BCI) fields such as medical and military. However, in the complex natural environment backgrounds, the identification of event-related potentials (ERP) of both small and similar objects that are quickly presented is a research challenge. Therefore, we designed corresponding experimental paradigms and proposed a multi-band task related components matching (MTRCM) method to improve the rapid cognitive decoding of both small and similar objects. We compared the areas under the receiver operating characteristic curve (AUC) between MTRCM and other 9 methods under different numbers of training sample using RSVP-ERP data from 50 subjects. The results showed that MTRCM maintained an overall superiority and achieved the highest average AUC (0.6562 ± 0.0091). We also optimized the frequency band and the time parameters of the method. The verification on public data sets further showed the necessity of designing MTRCM method. The MTRCM method provides a new approach for neural decoding of both small and similar RSVP objects, which is conducive to promote the further development of RSVP-BCI.

Deubiquitinase Mysm1 regulates neural stem cell proliferation and differentiation by controlling Id4 expression.

Neural stem cells (NSCs) are critical for brain development and maintenance of neurogenesis. However, the molecular mechanisms that regulate NSC proliferation and differentiation remain unclear. Mysm1 is a deubiquitinase and is essential for the self-renewal and differentiation of several stem cells. It is unknown whether Mysm1 plays an important role in NSCs. Here, we found that Mysm1 was expressed in NSCs and its expression was increased with age in mice. Mice with Mysm1 knockdown by crossing Mysm1 floxed mice with Nestin-Cre mice exhibited abnormal brain development with microcephaly. Mysm1 deletion promoted NSC proliferation and apoptosis, resulting in depletion of the stem cell pool. In addition, Mysm1-deficient NSCs skewed toward neurogenesis instead of astrogliogenesis. Mechanistic investigations with RNA sequencing and genome-wide CUT&Tag analysis revealed that Mysm1 epigenetically regulated Id4 transcription by regulating histone modification at the promoter region. After rescuing the expression of Id4, the hyperproliferation and imbalance differentiation of Mysm1-deficient NSCs was reversed. Additionally, knockdown Mysm1 in aged mice could promote NSC proliferation. Collectively, the present study identified a new factor Mysm1 which is essential for NSC homeostasis and Mysm1-Id4 axis may be an ideal target for proper NSC proliferation and differentiation.

Ferroptosis at the crossroads of manganese-induced neurotoxicity: A retrospective study.

Manganese is an essential trace element, but overexposure can cause neurotoxicity and subsequent neurodegenerative diseases. Ferroptosis is a form of cell death characterized by lipid peroxidation and iron overload inside cells, which is closely related to manganese neurotoxicity. Manganese can induce ferroptosis through multiple pathways: causing oxidative stress and increased cellular reactive oxygen species (ROS), resulting in lipid peroxidation; depleting glutathione (GSH) and weakening the antioxidant capacity of cells; disrupting iron metabolism and increasing iron-dependent lipid peroxidation; damaging mitochondrial function and disrupting the electron transport chain, leading to increased ROS production. Oxidative stress, iron metabolism disorders, lipid peroxidation, GSH depletion, and mitochondrial dysfunction, typical features of ferroptosis, have been observed in animal and cell models after manganese exposure. In summary, manganese can participate in the pathogenesis of neurodegenerative diseases by inducing events related to ferroptosis. This provides new insights into studying the mechanism of manganese neurotoxicity and developing therapeutic drugs.

EEG-Based Target Detection Using an RSVP Paradigm under Five Levels of Weak Hidden Conditions.

Although target detection based on electroencephalogram (EEG) signals has been extensively investigated recently, EEG-based target detection under weak hidden conditions remains a problem. In this paper, we proposed a rapid serial visual presentation (RSVP) paradigm for target detection corresponding to five levels of weak hidden conditions quantitively based on the RGB color space. Eighteen subjects participated in the experiment, and the neural signatures, including P300 amplitude and latency, were investigated. Detection performance was evaluated under five levels of weak hidden conditions using the linear discrimination analysis and support vector machine classifiers on different channel sets. The experimental results showed that, compared with the benchmark condition, (1) the P300 amplitude significantly decreased (8.92 ± 1.24 µV versus 7.84 ± 1.40 µV, p = 0.021) and latency was significantly prolonged (582.39 ± 25.02 ms versus 643.83 ± 26.16 ms, p = 0.028) only under the weakest hidden condition, and (2) the detection accuracy decreased by less than 2% (75.04 ± 3.24% versus 73.35 ± 3.15%, p = 0.029) with a more than 90% reduction in channel number (62 channels versus 6 channels), determined using the proposed channel selection method under the weakest hidden condition. Our study can provide new insights into target detection under weak hidden conditions based on EEG signals with a rapid serial visual presentation paradigm. In addition, it may expand the application of brain-computer interfaces in EEG-based target detection areas.

On-demand electrically controlled melatonin release from PEDOT/SNP composite improves quality of chronic neural recording.

Long-time and high-quality signal acquisition performance from implantable electrodes is the key to establish stable and efficient brain-computer interface (BCI) connections. The chronic performance of implantable electrodes is hindered by the inflammatory response of brain tissue. In order to solve the material limitation of biological interface electrodes, we designed sulfonated silica nanoparticles (SNPs) as the dopant of Poly (3,4-ethylenedioxythiophene) (PEDOT) to modify the implantable electrodes. In this work, melatonin (MT) loaded SNPs were incorporated in PEDOT via electrochemical deposition on nickel-chromium (Ni-Cr) alloy electrode and carbon nanotube (CNT) fiber electrodes, without affecting the acute neural signal recording capacity. After coating with PEDOT/SNP-MT, the charge storage capacity of both electrodes was significantly increased, and the electrochemical impedance at 1 kHz of the Ni-Cr alloy electrodes was significantly reduced, while that of the CNT electrodes was significantly increased. In addition, this study inspected the effect of electrically triggered MT release every other day on the quality and longevity of neural recording from implanted neural electrodes in rat hippocampus for 1 month. Both MT modified Ni-Cr alloy electrodes and CNT electrodes showed significantly higher spike amplitude after 26-day recording. Significantly, the histological studies showed that the number of astrocytes around the implanted Ni-Cr alloy electrodes was significantly reduced after MT release. These results demonstrate the potent outcome of PEDOT/SNP-MT treatment in improving the chronic neural recording quality possibly through its anti-inflammatory property.

Ultrasound-Sensitive Intelligent Nanosystems: A Promising Strategy for the Treatment of Neurological Diseases.

Neurological diseases are a major global health challenge, affecting hundreds of millions of people worldwide. Ultrasound therapy plays an irreplaceable role in the treatment of neurological diseases due to its noninvasive, highly focused, and strong tissue penetration capabilities. However, the complexity of brain and nervous system and the safety risks associated with prolonged exposure to ultrasound therapy severely limit the applicability of ultrasound therapy. Ultrasound-sensitive intelligent nanosystems (USINs) are a novel therapeutic strategy for neurological diseases that bring greater spatiotemporal controllability and improve safety to overcome these challenges. This review provides a detailed overview of therapeutic strategies and clinical advances of ultrasound in neurological diseases, focusing on the potential of USINs-based ultrasound in the treatment of neurological diseases. Based on the physical and chemical effects induced by ultrasound, rational design of USINs is a prerequisite for improving the efficacy of ultrasound therapy. Recent developments of ultrasound-sensitive nanocarriers and nanoagents are systemically reviewed. Finally, the challenges and developing prospects of USINs are discussed in depth, with a view to providing useful insights and guidance for efficient ultrasound treatment of neurological diseases.

A Novel Asynchronous Brain Signals-Based Driver-Vehicle Interface for Brain-Controlled Vehicles.

Directly applying brain signals to operate a mobile manned platform, such as a vehicle, may help people with neuromuscular disorders regain their driving ability. In this paper, we developed a novel electroencephalogram (EEG) signal-based driver-vehicle interface (DVI) for the continuous and asynchronous control of brain-controlled vehicles. The proposed DVI consists of the user interface, the command decoding algorithm, and the control model. The user interface is designed to present the control commands and induce the corresponding brain patterns. The command decoding algorithm is developed to decode the control command. The control model is built to convert the decoded commands to control signals. Offline experimental results show that the developed DVI can generate a motion control command with an accuracy of 83.59% and a detection time of about 2 s, while it has a recognition accuracy of 90.06% in idle states. A real-time brain-controlled simulated vehicle based on the DVI was developed and tested on a U-turn road. Experimental results show the feasibility of the DVI for continuously and asynchronously controlling a vehicle. This work not only advances the research on brain-controlled vehicles but also provides valuable insights into driver-vehicle interfaces, multimodal interaction, and intelligent vehicles.

PtNPs/PEDOT:PSS-Modified Microelectrode Arrays for Detection of the Discharge of Head Direction Cells in the Retrosplenial Cortex of Rats under Dissociation between Visual and Vestibular Inputs.

The electrophysiological activities of head direction (HD) cells under visual and vestibular input dissociation are important to understanding the formation of the sense of direction in animals. In this paper, we fabricated a PtNPs/PEDOT:PSS-modified MEA to detect changes in the discharge of HD cells under dissociated sensory conditions. The electrode shape was customized for the retrosplenial cortex (RSC) and was conducive to the sequential detection of neurons at different depths in vivo when combined with a microdriver. The recording sites of the electrode were modified with PtNPs/PEDOT:PSS to form a three-dimensional convex structure, leading to closer contact with neurons and improving the detection performance and signal-to-noise ratio of the MEA. We designed a rotating cylindrical arena to separate the visual and vestibular information of the rats and detected the changes in the directional tuning of the HD cells in the RSC. The results showed that after visual and vestibular sensory dissociation, HD cells used visual information to establish newly discharged directions which differed from the original direction. However, with the longer time required to process inconsistent sensory information, the function of the HD system gradually degraded. After recovery, the HD cells reverted to their newly established direction rather than the original direction. The research based on our MEAs revealed how HD cells process dissociated sensory information and contributes to the study of the spatial cognitive navigation mechanism.

Orthotopic Transplantation of Functional Bioengineered Livers in Rats.

Functional bioengineered livers (FBLs) are promising alternatives to orthotopic liver transplantation. However, orthotopic transplantation of FBLs has not yet been reported. This study aimed to perform the orthotopic transplantation of FBLs in rats subjected to complete hepatectomy. FBLs were developed using rat whole decellularized liver scaffolds (DLSs) with human umbilical vein endothelial cells implanted via the portal vein, and human bone marrow mesenchymal stem cells (hBMSCs) and mouse hepatocyte cell line implanted via the bile duct. FBLs were evaluated in terms of endothelial barrier function, biosynthesis, and metabolism and orthotopically transplanted into rats to determine the survival benefit. The FBLs with well-organized vascular structures exhibited endothelial barrier function, with reduced blood cell leakage. The implanted hBMSCs and hepatocyte cell line were well aligned in the parenchyma of the FBLs. The high levels of urea, albumin, and glycogen in the FBLs indicated biosynthesis and metabolism. Orthotopic transplantation of FBLs achieved a survival time of 81.38 ± 4.263 min in rats (n = 8) subjected to complete hepatectomy, whereas control animals (n = 4) died within 30 min (p < 0.001). After transplantation, CD90-positive hBMSCs and the albumin-positive hepatocyte cell line were scattered throughout the parenchyma, and blood cells were limited within the vascular lumen of the FBLs. In contrast, the parenchyma and vessels were filled with blood cells in the control grafts. Thus, orthotopic transplantation of whole DLS-based FBLs can effectively prolong the survival of rats subjected to complete hepatectomy. In summary, this work was the first to perform the orthotopic transplantation of FBLs, with limited survival benefits, which still has important value for the advancement of bioengineered livers.

A Matrix-Metalloproteinase-Responsive Hydrogel System for Modulating the Immune Microenvironment in Myocardial Infarction.

Injectable hydrogels carrying therapeutic factors to modulate the infarct immune microenvironment show great potential in the treatment of myocardial infarction (MI). However, conventional injectable hydrogels release therapeutic factors in an uncontrolled manner, which leads to poor treatment efficacy and acute side effects on normal tissues. In this work, a matrix metalloproteinase (MMP)2/9-responsive hydrogel system (MPGC4) is developed, considering the characteristics of the post-MI microenvironment. MPGC4 consists of tetra-poly(ethylene glycol) (PEG) hydrogels and a composite gene nanocarrier (CTL4) that is composed of carbon dots (CDots) coupled with interleukin-4 plasmid DNA via electrostatic interactions. MPGC4 can be automatically triggered to release CTL4 on demand after MI to regulate the infarct immune microenvironment. In addition, due to the photoluminescence properties of CDots, a large amount of viscoelastic MPGC4 is found to be retained in situ after injection into the infarct region without leakage. The in vitro results demonstrate that CTL4 promotes proinflammatory M1 macrophage polarization to the anti-inflammatory M2 subtype and contributes to cardiomyocyte survival through macrophage transition. In a rat model of MI, MPGC4 clears MMPs and precisely targets CTL4 to the infarcted region. In particular, MPGC4 improves cardiac function by modulating macrophage transition to reduce early inflammatory responses and proangiogenic activity.

Injectable Hydrogels Encapsulating Dual-Functional Au@Pt Core-Shell Nanoparticles Regulate Infarcted Microenvironments and Enhance the Therapeutic Efficacy of Stem Cells through Antioxidant and Electrical Integration.

Injectable functional biomaterials have made significant progress in cardiac regenerative. In addition, how to adjust the abominable infarction microenvironment and introduce therapeutic stem cells to improve the healing effect has become a hotspot. Herein, injectable stem cell vector is prepared by combining natural alginate hydrogel and Au@Pt nanoparticles (Au@Pt/Alg hydrogel) to encapsulate brown adipose stem cells (BASCs). Au@Pt nanoparticles with both antioxidative and conductive properties could effectively eliminate reactive oxygen species, enhance the frequency of action potential release of cardiomyocytes, and further reduce the inflammatory factors of macrophage in vitro. The Au@Pt/Alg hydrogel enhances the antioxidant, differentiation, and paracrine capability of BASCs. The effect of BASCs loaded Au@Pt/Alg hydrogel is evaluated in a rat myocardial infarction (MI) model. The antioxidant, anti-inflammatory, and heart electrical integration are showed in the MI model. More interestingly, Au@Pt/Alg hydrogel can effectively maintain the paracrine efficiency and pro-angiogenesis effects of BASCs in the infarcted area. This study led us to recognize the great value of Au@Pt/Alg hydrogels for their ability to actively regulate the microenvironment and carry stem cells for MI treatment.

The Role of the LINC01234/miR-433-3p/GRB2 ceRNA Network in NSCLC Cell Malignant Proliferation.

BACKGROUND: Non-small cell lung cancer (NSCLC) is associated with high morbidity and mortality. Dysregulation of lncRNAs leads to NSCLC progression. OBJECTIVE: This study aims to explore the regulatory mechanism of lncRNA LINC01234 in NSCLC. MATERIALS AND METHODS: LINC01234 expression in NSCLC cells was determined. Cell proliferation was detected using CCK-8, colony formation, and EDU assays after transfection of siRNA LINC01234 into H1299 cells and transfection of pcDNA3.1-LINC01234 into H1975 cells. Subcellular localization of LINC01234 was predicted and the binding relations between LINC01234 and miR-433-3p as well as miR-433-3p and GRB2 were verified. The expression levels of miR-433-3p and GRB2 in NSCLC cells were determined. Joint experiments of miR-433-3p inhibitor + si- LINC01234-1 or oe-GRB2 + si-LINC01234-1 were conducted to verify the role of miR-433-3p and GRB2 in NSCLC cell malignant proliferation. RESULTS: LINC01234 was abundantly expressed in NSCLC cells. LINC01234 silencing reduced NSCLC cell proliferation while LINC01234 overexpression enhanced cell proliferation. LINC01234 competitively bound to miR-433-3p and miR-433-3p directly targeted GRB2. miR- 433-3p knockdown or GRB2 overexpression counteracted the repressive effect of LINC01234 silencing on NSCLC cell malignant proliferation. CONCLUSION: LINC01234 competitively bound to miR-433-3p and promoted GRB2 transcription to augment NSCLC cell malignant proliferation.