Enzyme-responsive liposomes for controlled drug release.

Compared to other nanovectors, liposomes exhibit unique advantages, such as good biosafety and high drug-loading capacity. However, slow drug release from conventional liposomes makes most payloads unavailable, restricting the therapeutic efficacy. Therefore, in the last ∼20 years, enzyme-responsive liposomes have been extensively investigated, which liberate drugs under the stimulation of enzymes overexpressed at disease sites. In this review, we elaborate on the research progress on enzyme-responsive liposomes. The involved enzymes mainly include phospholipases, particularly phospholipase A2, matrix metalloproteinases, cathepsins, and esterases. These enzymes can cleave ester bonds or specific peptide sequences incorporated in the liposomes for controlled drug release by disrupting the primary structure of liposomes, detaching protective polyethylene glycol shells, or activating liposome-associated prodrugs. Despite decades of efforts, there are still a lack marketed products of enzyme-responsive liposomes. Therefore, more efforts should be made to improve the safety and effectiveness of enzyme-responsive liposomes and address the issues associated with production scale-up.

Room­Temperature Antisymmetric Magnetoresistance in van der Waals Ferromagnet Fe3GaTe2 Nanosheets.

Van der Waals (vdW) ferromagnetic materials have emerged as a promising platform for the development of 2D spintronic devices. However, studies to date are restricted to vdW ferromagnetic materials with low Curie temperature (Tc) and small magnetic anisotropy. Here, a chemical vapor transport method is developed to synthesize a high-quality room-temperature ferromagnet, Fe3GaTe2 (c-Fe3GaTe2), which boasts a high Tc = 356 K and large perpendicular magnetic anisotropy. Due to the planar symmetry breaking, an unconventional room-temperature antisymmetric magnetoresistance (MR) is first observed in c-Fe3GaTe2 devices with step features, manifesting as three distinctive states of high, intermediate, and low resistance with the sweeping magnetic field. Moreover, the modulation of the antisymmetric MR is demonstrated by controlling the height of the surface steps. This work provides new routes to achieve magnetic random storage and logic devices by utilizing the room-temperature thickness-controlled antisymmetric MR and further design room-temperature 2D spintronic devices based on the vdW ferromagnet c-Fe3GaTe2.

Image Domain Multi-Material Decomposition Noise Suppression Through Basis Transformation and Selective Filtering.

Spectral CT can provide material characterization ability to offer more precise material information for diagnosis purposes. However, the material decomposition process generally leads to amplification of noise which significantly limits the utility of the material basis images. To mitigate such problem, an image domain noise suppression method was proposed in this work. The method performs basis transformation of the material basis images based on a singular value decomposition. The noise variances of the original spectral CT images were incorporated in the matrix to be decomposed to ensure that the transformed basis images are statistically uncorrelated. Due to the difference in noise amplitudes in the transformed basis images, a selective filtering method was proposed with the low-noise transformed basis image as guidance. The method was evaluated using both numerical simulation and real clinical dual-energy CT data. Results demonstrated that compared with existing methods, the proposed method performs better in preserving the spatial resolution and the soft tissue contrast while suppressing the image noise. The proposed method is also computationally efficient and can realize real-time noise suppression for clinical spectral CT images.

Integrative Analyses of Transcriptomics and Metabolomics in Immune Response of Leguminivora glycinivorella Mats to Beauveria bassiana Infection.

This study utilized Beauveria bassiana to infect Leguminivora glycinivorella, analyzed the effects on the transcriptome and metabolome, and further investigated the antibacterial function of L. glycinivorella. We performed transcriptome and metabolome sequencing on the L. glycinivorella infected with B. bassiana and its control groups, and performed a joint analysis of transcriptome and metabolome results. Upon screening, 4560 differentially expressed genes were obtained in the transcriptome and 71 differentially expressed metabolites were obtained in the metabolome. On this basis, further integration of the use of transcriptomics and metabonomics combined an analysis of common enrichments of pathways of which there were three. They were glutathione S-transferase (GSTs) genes, heat shock protein (HSP) genes, and cytochrome P450 (CYP450) genes. These three pathways regulate the transport proteins, such as ppars, and thus affect the digestion and absorption of sugars and fats, thus regulating the development of pests. The above conclusion indicates that B. bassiana can affect the sugar metabolism, lipid metabolism, and amino acid metabolism pathways of L. glycinivorella, and can consume the necessary energy, protein, and lipids of L. glycinivorella. The research on the immune response mechanism of pests against pathogens can provide an important scientific basis and target for the development of immunosuppressants. This study laid an information foundation for the application of entomogenous fungi to control soybean borer at the molecular level.

Boosting Bifunctional Catalysis by Integrating Active Faceted Intermetallic Nanocrystals and Strained Pt-Ir Functional Shells.

PtIr-based nanostructures are fascinating materials for application in bifunctional oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) catalysis. However, the fabrication of PtIr nanocatalysts with clear geometric features and structural configurations, which are crucial for enhancing the bifunctionality, remains challenging. Herein, PtCo@PtIr nanoparticles are precisely designed and fabricated with a quasi-octahedral PtCo nanocrystal as a highly atomically ordered core and an ultrathin PtIr atomic layer as a compressively strained shell. Owing to their geometric and core-shell features, the PtCo@PtIr nanoparticles deliver approximately six and eight times higher mass and specific activities, respectively, as an ORR catalyst than a commercial Pt/C catalyst. The half-wave potential of PtCo@PtIr exhibits a negligible decrease by 9 mV after 10 000 cycles, indicating extraordinary ORR durability because of the ordered arrangement of Pt and Co atoms. When evaluated using the ORR-OER dual reaction upon the introduction of Ir, PtCo@PtIr exhibits a small ORR-OER overpotential gap of 679 mV, demonstrating its great potential as a bifunctional electrocatalyst for fabricating fuel cells. The findings pave the way for designing precise intermetallic core-shell nanocrystals as highly functional catalysts.

Insights into modifiable risk factors of erectile dysfunction, a wide-angled Mendelian Randomization study.

INTRODUCTION: The causal association between modifiable risk factors and erectile dysfunction (ED) remains unclear, which hinders the early identification and intervention of patients with ED. The present study aimed to clarify the causal association between 42 predominant risk factors and ED. METHODS: Univariate Mendelian Randomization (MR), multivariate MR, and mediation MR analyses were used to investigate the causal association between 42 modifiable risk factors and ED. Combined results were pooled from two independent ED genome-wide association studies to verify the findings. RESULTS: Genetically predicted body mass index (BMI), waist circumference, trunk fat mass, whole body fat mass, poor overall health rating, type 2 diabetes, basal metabolic rate, adiponectin, cigarette consumption, insomnia, snoring, hypertension, stroke, ischemic stroke, coronary heart disease, myocardial infarction, heart failure, and major depressive disorder were found to increase the risk of ED (all P < 0.05). Additionally, genetic liability to higher body fat percentage and alcohol consumption were suggestively associated with an increased risk of ED (P < 0.05 and adjusted P > 0.05). Genetic predisposition to higher sex hormone-binding globulin (SHBG) levels could decrease the risk of ED (P < 0.05). No significant association was detected between lipid levels and ED. Multivariate MR identified type 2 diabetes, basal metabolic rate, cigarette consumption, hypertension, and coronary heart disease as risk factors for ED. The combined results confirmed that waist circumference, whole body fat mass, poor overall health rating, type 2 diabetes, basal metabolic rate, adiponectin, cigarette consumption, snoring, hypertension, ischemic stroke, coronary heart disease, myocardial infarction, heart failure, and major depressive disorder could increase the risk of ED (all P < 0.05), while higher SHBG decreased the risk of ED (P = 0.004). There were suggestive significances of BMI, insomnia, and stroke on ED (P < 0.05 and adjusted P > 0.05). CONCLUSION: This comprehensive MR study supported the causal role of obesity, type 2 diabetes, basal metabolic rate, poor self-health rating, cigarette and alcohol consumption, insomnia and snoring, depression, hypertension, stroke, ischemic stroke, coronary heart disease, myocardial infarction, heart failure, SHBG, and adiponectin in the onset and development of ED.

On-tissue chemical derivatization-enhanced spatially resolved lipidomics reveals abnormal metabolism in type 2 diabetic rat brain.

Neurologic disorders are often accompanied by alterations in lipids and oxylipins in the brain. However, the complexity of the lipidome in the brain and its changes during brain damage caused by diabetes remain poorly understood. Herein, we developed an enhanced spatially resolved lipidomics approach with the assistance of on-tissue chemical derivatization to study lipid metabolism in the rat brain. This method enabled the spatially resolved analysis of 560 lipids and oxylipins in 19 brain microregions in coronal and sagittal sections and remarkably improved the coverage of lipidome detection. We applied this method to lipidomic studies of the diabetic rat brain and found that lipid dysregulation followed a microregion-specific pattern. Carnitines and glycerolipids were mainly elevated in the corpus callosum (midbrain) and pineal gland regions, respectively. In addition, most oxylipins, including fatty aldehydes and oxo fatty acids, were significantly upregulated in nine brain microregions. We produced a spatially resolved analysis of lipids and oxylipins, providing a novel analytical tool for brain metabolism research.

Advances in Metabolic Remodeling and Intervention Strategies in Heart Failure.

The heart is the most energy-demanding organ throughout the whole body. Perturbations or failure in energy metabolism contributes to heart failure (HF), which represents the advanced stage of various heart diseases. The poor prognosis and huge economic burden associated with HF underscore the high unmet need to explore novel therapies targeting metabolic modulators beyond conventional approaches focused on neurohormonal and hemodynamic regulators. Emerging evidence suggests that alterations in metabolic substrate reliance, metabolic pathways, metabolic by-products, and energy production collectively regulate the occurrence and progression of HF. In this review, we provide an overview of cardiac metabolic remodeling, encompassing the utilization of free fatty acids, glucose metabolism, ketone bodies, and branched-chain amino acids both in the physiological condition and heart failure. Most importantly, the latest advances in pharmacological interventions are discussed as a promising therapeutic approach to restore cardiac function, drawing insights from recent basic research, preclinical and clinical studies.

Development of novel peptide-based radiotracers for detecting PD-L1 expression and guiding cancer immunotherapy.

PURPOSE: Due to tumor heterogeneity, immunohistochemistry (IHC) showed poor accuracy in detecting the expression of programmed cell death ligand-1 (PD-L1) in patients. Positron emission tomography (PET) imaging is considered as a non-invasive technique to detect PD-L1 expression at the molecular level visually, real-timely and quantitatively. This study aimed to develop novel peptide-based radiotracers [68Ga]/[18F]AlF-NOTA-IMB for accurately detecting the PD-L1 expression and guiding the cancer immunotherapy. METHODS: NOTA-IMB was prepared by connecting 2,2'-(7-(2-((2,5-dioxopyrrolidin-1-yl)oxy)- 2-oxoethyl)-1,4,7-triazonane-1,4-diyl) diacetic acid (NOTA-NHS) with PD-L1-targeted peptide IMB, and further radiolabeled with 68Ga or 18F-AlF. In vitro binding assay was conducted to confirm the ability of [68Ga]/[18F]AlF-NOTA-IMB to detect the expression of PD-L1. In vivo PET imaging of [68Ga]NOTA-IMB and [18F]AlF-NOTA-IMB in different tumor-bearing mice was performed, and dynamic changes of PD-L1 expression level induced by immunotherapy were monitored. Radioautography, western blotting, immunofluorescence staining and biodistribution analysis were carried out to further evaluate the specificity of radiotracers and efficacy of PD-L1 antibody immunotherapy. RESULTS: [68Ga]NOTA-IMB and [18F]AlF-NOTA-IMB were both successfully prepared with high radiochemical yield (> 95% and > 60%, n = 5) and radiochemical purity (> 95% and > 98%, n = 5). Both tracers showed high affinity to human and murine PD-L1 with the dissociation constant (Kd) of 1.00 ± 0.16/1.09 ± 0.21 nM (A375-hPD-L1, n = 3) and 1.56 ± 0.58/1.21 ± 0.39 nM (MC38, n = 3), respectively. In vitro cell uptake assay revealed that both tracers can specifically bind to PD-L1 positive cancer cells A375-hPD-L1 and MC38 (5.45 ± 0.33/3.65 ± 0.15%AD and 5.87 ± 0.27/2.78 ± 0.08%AD at 120 min, n = 3). In vivo PET imaging and biodistribution analysis showed that the tracer [68Ga]NOTA-IMB and [18F]AlF-NOTA-IMB had high accumulation in A375-hPD-L1 and MC38 tumors, but low uptake in A375 tumor. Treatment of Atezolizumab induced dynamic changes of PD-L1 expression in MC38 tumor-bearing mice, and the tumor uptake of [68Ga]NOTA-IMB decreased from 3.30 ± 0.29%ID/mL to 1.58 ± 0.29%ID/mL (n = 3, P = 0.026) after five treatments. Similarly, the tumor uptake of [18F]AlF-NOTA-IMB decreased from 3.27 ± 0.63%ID/mL to 0.89 ± 0.18%ID/mL (n = 3, P = 0.0004) after five treatments. However, no significant difference was observed in the tumor uptake before and after PBS treatment. Biodistribution, radioautography, western blotting and immunofluorescence staining analysis further demonstrated that the expression level of PD-L1 in tumor-bearing mice treated with Atezolizumab significantly reduced about 3 times and correlated well with the PET imaging results. CONCLUSION: [68Ga]NOTA-IMB and [18F]AlF-NOTA-IMB were successfully prepared for PET imaging the PD-L1 expression noninvasively and quantitatively. Dynamic changes of PD-L1 expression caused by immunotherapy can be sensitively detected by both tracers. Hence, the peptide-based radiotracers [68Ga]NOTA-IMB and [18F]AlF-NOTA-IMB can be applied for accurately detecting the PD-L1 expression in different tumors and monitoring the efficacy of immunotherapy.

Database-Driven Spatially Resolved Lipidomics Highlights Heterogeneous Metabolic Alterations in Type 2 Diabetic Mice.

Spatially resolved lipidomics is pivotal for detecting and interpreting lipidomes within spatial contexts using the mass spectrometry imaging (MSI) technique. However, comprehensive and efficient lipid identification in MSI remains challenging. Herein, we introduce a high-coverage, database-driven approach combined with air-flow-assisted desorption electrospray ionization (AFADESI)-MSI to generate spatial lipid profiles across whole-body mice. Using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), we identified 2868 unique lipids in the serum and various organs of mice. Subsequently, we systematically evaluated the distinct ionization properties of the lipids between LC-MS and MSI and created a detailed MSI database containing 14 123 ions. This method enabled the visualization of aberrant fatty acid and phospholipid metabolism across organs in a diabetic mouse model. As a powerful extension incorporated into the MSIannotator tool, our strategy facilitates the rapid and accurate annotation of lipids, providing new research avenues for probing spatially resolved heterogeneous metabolic changes in response to diseases.

Discovery and construction of surface kagome electronic states induced by p-d electronic hybridization in Co3Sn2S2.

Kagome-lattice materials possess attractive properties for quantum computing applications, but their synthesis remains challenging. Herein, based on the compelling identification of the two cleavable surfaces of Co3Sn2S2, we show surface kagome electronic states (SKESs) on a Sn-terminated triangular Co3Sn2S2 surface. Such SKESs are imprinted by vertical p-d electronic hybridization between the surface Sn (subsurface S) atoms and the buried Co kagome-lattice network in the Co3Sn layer under the surface. Owing to the subsequent lateral hybridization of the Sn and S atoms in a corner-sharing manner, the kagome symmetry and topological electronic properties of the Co3Sn layer is proximate to the Sn surface. The SKESs and both hybridizations were verified via qPlus non-contact atomic force microscopy (nc-AFM) and density functional theory calculations. The construction of SKESs with tunable properties can be achieved by the atomic substitution of surface Sn (subsurface S) with other group III-V elements (Se or Te), which was demonstrated theoretically. This work exhibits the powerful capacity of nc-AFM in characterizing localized topological states and reveals the strategy for synthesis of large-area transition-metal-based kagome-lattice materials using conventional surface deposition techniques.

Automatic Evaluating of Multi-Phase Cranial CTA Collateral Circulation Based on Feature Fusion Attention Network Model.

Stroke is one of the main causes of disability and death, and it can be divided into hemorrhagic stroke and ischemic stroke. Ischemic stroke is more common, and about 8 out of 10 stroke patients suffer from ischemic stroke. In clinical practice, doctors diagnose stroke by using computed tomography angiography (CTA) image to accurately evaluate the collateral circulation in stroke patients. This imaging information is of great significance in assisting doctors to determine the patient's treatment plan and prognosis. Currently, great progress has been made in the field of computer-aided diagnosis technology in medicine by using artificial intelligence. However, in related research based on deep learning algorithms, researchers usually only use single-phase data for training, lacking the temporal dimension information of multi-phase image data. This makes it difficult for the model to learn more comprehensive and effective collateral circulation feature representation, thereby limiting its performance. Therefore, combining data for training is expected to improve the accuracy and reliability of collateral circulation evaluation. In this study, we propose an effective hybrid mechanism to assist the feature encoding network in evaluating the degree of collateral circulation in the brain. By using a hybrid attention mechanism, additional guidance and regularization are provided to enhance the collateral circulation feature representation across multiple stages. Time dimension information is added to the input, and multiple feature-level fusion modules are designed in the multi-branch network. The first fusion module in the single-stage feature extraction network completes the fusion of deep and shallow vessel features in the single-branch network, followed by the multi-stage network feature fusion module, which achieves feature fusion for four stages. Tested on a dataset of multi-phase cranial CTA images, the accuracy rate exceeding 90.43%. The experimental results demonstrate that the addition of these modules can fully explore collateral vessel features, improve feature expression capabilities, and optimize the performance of deep learning network model.

Design, Synthesis, and Biological Evaluation of a Small-Molecule PET Agent for Imaging PD-L1 Expression.

Immunotherapy blocking programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) pathway has achieved great therapeutic effect in the clinic, but the overall response rate is not satisfactory. Early studies showed that response to treatment and overall survival could be positively related to PD-L1 expression in tumors. Therefore, accurate measurement of PD-L1 expression will help to screen cancer patients and improve the overall response rate. A small molecular positron emission tomography (PET) probe [18F]LP-F containing a biphenyl moiety was designed and synthesized for measurement of PD-L1 expression in tumors. The PET probe [18F]LP-F was obtained with a radiochemical yield of 12.72 ± 1.98%, a radiochemical purity of above 98% and molar activity of 18.8 GBq/µmol. [18F]LP-F had good stability in phosphate buffer saline (PBS) and mouse serum. In vitro assay indicated that [18F]LP-F showed moderate affinity to PD-L1. Micro-PET results showed that the tumor accumulation of [18F]LP-F in A375 tumor was inferior to that in A375-hPD-L1 tumor. All the results demonstrated that [18F]LP-F could specifically bind to PD-L1 and had a potential application in non-invasive evaluation of PD-L1 expression in tumors.

Which frequency is better for pediatric shock wave lithotripsy? Low intermediate or high: A systematic review and meta-analysis.

Background: To explore the optimal frequency for pediatric extracorporeal shock wave lithotripsy (ESWL) in the treatment of upper urinary stones. Methods: A systematic literature search was undertaken using PubMed, Embase, Web of Science and Cochrane Central Register of Controlled Trials databases to identify eligible studies published before January 2023. Primary outcomes were perioperative efficacy parameters, including ESWL time, anesthesia time for ESWL sessions, success rates after each session, additional interventions needed, and treatment sessions per patient. Secondary outcomes were postoperative complications and efficiency quotient. Results: Four controlled studies involving 263 pediatric patients were enrolled in our meta-analysis. In the comparison between the low-frequency and intermediate-frequency groups, we observed no significant difference as regards anesthesia time for ESWL session (WMD = -4.98, 95% CI -21.55∼11.58, p = 0.56), success rates after ESWL sessions (first session: OR = 0.02 95%CI -0.12∼0.17, p = 0.74; second session: OR = 1.04 95%CI 0.56∼1.90, p = 0.91; third session: OR = 1.62 95%CI 0.73∼3.60, p = 0.24), treatment sessions needed (WMD = 0.08 95%CI -0.21∼0.36, p = 0.60), additional interventions after ESWL (OR=0.99 95%CI 0.40∼2.47, p = 0.99) and rates of Clavien grade 2 complications (OR = 0.92 95%CI 0.18∼4.69, p = 0.92). However, the intermediate-frequency group may exhibit potential benefits in Clavien grade 1 complications. In the comparison between intermediate-frequency and high-frequency, the eligible studies exhibited higher success rates in the intermediate-frequency group after the first session, the second session and the third session. More sessions may be required in the high-frequency group. With respect to other perioperative, postoperative parameters and major complications, the results were similar. Conclusions: Intermediate-frequency and low-frequency had similar success rates and seemed to be the optimal frequency for pediatric ESWL. Nevertheless, future large-volume, well-designed RCTs are awaited to confirm and update the findings of this analysis. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022333646.

Vitamin D3 improved erectile function recovery by regulating autophagy and apoptosis in a rat model of cavernous nerve injury.

Vitamin D3 is an important element in improving erectile function. However, the mechanisms of vitamin D3 remain unknown. Thus, we explored the effect of vitamin D3 on erectile function recovery after nerve injury in a rat model and investigated its possible molecular mechanisms. Eighteen male Sprague-Dawley rats were used in this study. The rats were randomly divided into three groups: the control, bilateral cavernous nerve crush (BCNC), and BCNC + vitamin D3 groups. BCNC model was established in rats by surgery. The intracavernosal pressure and the ratio of intracavernosal pressure to mean arterial pressure were utilized to evaluate erectile function. Masson trichrome staining, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling and western blot analysis were performed on penile tissues to elucidate the molecular mechanism. The results indicated that vitamin D3 alleviated hypoxia and suppressed the fibrosis signalling pathway by upregulating the expression of eNOS (p = 0.001), nNOS (p = 0.018) and α-SMA (p = 0.025) and downregulating the expression of HIF-1α (p = 0.048) and TGF-ß1 (p = 0.034) in BCNC rats. Vitamin D3 promoted erectile function restoration by enhancing the autophagy process through decreases in the p-mTOR/mTOR ratio (p = 0.02) and p62 (p = 0.001) expression and increases in Beclin1 expression (p = 0.001) and the LC3B/LC3A ratio (p = 0.041). Vitamin D3 application improved erectile function rehabilitation by suppressing the apoptotic process through decreases in the expression of Bax (p = 0.002) and caspase-3 (p = 0.046) and an increase in the expression of Bcl2 (p = 0.004). Therefore, We concluded that vitamin D3 improved the erectile function recovery in BCNC rats by alleviating hypoxia and fibrosis, enhancing autophagy and inhibiting apoptosis in the corpus cavernosum.

Comparison of embryonic development, from HH21 to HH40, between ostrich (Struthio camelus) and chicken (Gallus gallus).

BACKGROUND: The chicken has been a representative model organism to study embryonic development in birds, however important differences exist among this class of species. As a representative of one of oldest existing clades of birds, the African ostrich (Struthio camelus), has the largest body among birds, and has two toes. Our purpose is to establish the corresponding stages in ostrich embryo development that match the well-established HH system of the chicken to facilitate comparative studies between the ostrich and other birds to better understand differences in development. RESULTS: Here we describe in detail the middle period of embryonic development using microscopic images and skeletal staining. We found that clear morphological differentiation between the ostrich and the chicken begins at stage 26. Bird limb cartilage first form in stage 25, while the development of the limb skeletons differs after stage 31. Calcification of limb skeletons in the chicken was completed faster. The first and second toes of the ostrich disappear at stages 36 and 38, respectively. CONCLUSIONS: This study should greatly aid ostrich-related developmental and morphological research and provide a reference for studying the development and evolution of avian limb skeletons, including molecular research. Questions that can now be addressed include studies into the fusion of tarsometatarsal skeleton, ossification, and digit loss.

Antifibrotic Effects of Tetrahedral Framework Nucleic Acids by Inhibiting Macrophage Polarization and Macrophage-Myofibroblast Transition in Bladder Remodeling.

Bladder outlet obstruction (BOO) is a prevalent condition arising from urethral stricture, posterior urethral valves, and benign prostatic hyperplasia. Long-term obstruction can lead to bladder remodeling, which is characterized by inflammatory cell infiltration, detrusor hypertrophy, and fibrosis. Until now, there are no efficacious therapeutic options for BOO-induced remodeling. Tetrahedral framework nucleic acids (tFNAs) are a type of novel 3D DNA nanomaterials that possess excellent antifibrotic effects. Here, to determine the treatment effects of tFNAs on BOO-induced remodeling is aimed. Four single-strand DNAs are self-assembled to form tetrahedral framework DNA nanostructures, and the antifibrotic effects of tFNAs are investigated in an in vivo BOO animal model and an in vitro transforming growth factor beta1 (TGF-ß1)-induced fibrosis model. The results demonstrated that tFNAs could ameliorate BOO-induced bladder fibrosis and dysfunction by inhibiting M2 macrophage polarization and the macrophage-myofibroblast transition (MMT) process. Furthermore, tFNAs regulate M2 polarization and the MMT process by deactivating the signal transducer and activator of transcription (Stat) and TGF-ß1/small mothers against decapentaplegic (Smad) pathways, respectively. This is the first study to reveal that tFNAs might be a promising nanomaterial for the treatment of BOO-induced remodeling.

CHD4 promotes acquired chemoresistance and tumor progression by activating the MEK/ERK axis.

AIMS: Chemoresistance remains a major challenge in gastric cancer (GC). Chromodomain helicase DNA-binding protein 4 (CHD4) mediated chromatin remodeling plays critical roles in various tumor types, but its role in chemoresistance in GC remains uncharacterized. METHODS: CHD4 expression was examined by immunohistochemistry and Western blotting. The role of CHD4 on cell proliferation and chemoresistance of GC was examined in vitro and in vivo. Immunoprecipitation and liquid chromatography-mass spectrometry were used to identify CHD4-binding proteins and a proximity ligation assay was used to explore protein-protein interaction. RESULTS: Chemoresistance is associated with upregulation of CHD4 in the tumor tissues of GC patients. Overexpression of CHD4 increased chemoresistance and cell proliferation. Knockdown of CHD4 induced cell apoptosis and cell cycle arrest. CHD4 mediates the decrease of the intracellular concentration of cisplatin by inducing drug efflux. Additionally, CHD4 promotes the interaction between ERK1/2 and MEK1/2, resulting in continuous activation of MEK/ERK pathway. Knockdown of CHD4 in GC increased sensitivity to chemotherapy and suppressed tumor growth in a mouse xenograft model. CONCLUSIONS: This study identifies CHD4 dominated multi-drug efflux as a promising therapeutic target for overcoming acquired chemoresistance in GC.

Mending a broken heart-targeting cardiomyocyte regeneration: a literature review.

Background and Objectives: Cardiovascular diseases have been the leading cause of death globally for decades. Pharmacological advances targeting the sympathetic nervous system, renin-angiotensin-aldosterone system, and fibrosis slow the progression of diverse cardiovascular diseases. However, ongoing cardiomyocyte loss is inevitable in divergent cardiovascular diseases, eventually leading to heart failure as the end stage. In this review, we focused on the key biomedical findings and underlying principles of cardiomyocyte regeneration. Methods: Literature regarding the key findings in cardiomyocyte regeneration research, including controversies on the origins of newly formed cardiomyocytes, potential barriers and strategies to heart regeneration, and the key animals, models, and methods applied in the study of heart regeneration, were broadly researched using the PubMed and Web of Science databases. Key Content and Findings: In the mammalian heart, cardiomyocytes proliferate during the embryonic and early postnatal stages, while the capability of proliferation disappears in the adult stage. An increasing amount of evidence suggests that cardiomyocytes self-renew at a very limited level and that most newly formed cardiomyocytes originate from pre-existing cardiomyocytes and not cardiac progenitor cells (CPCs). Several potential barriers to heart regeneration have been addressed, including metabolic switch, a large increase in multinucleated and polyploid cardiomyocytes, and alteration in the epigenome and transcriptome. In addition, immune system evolution is also associated with the loss of regenerative capacity. However, the activation of resident cardiomyocytes, somatic cell reprogramming, and direct reprogramming, in addition to the promotion of neovascularization and immune modulation, constitute the new insights into those strategies that can boost cardiac regeneration. Conclusions: Heart regeneration is one of the most popular fields in cardiovascular research and represents a promising avenue of therapeutics for mending a broken heart. Despite the controversies and challenges, a clearer picture of adult mammalian cardiac regeneration is emerging.

Active Asymmetric Electron-Transfer Effect on the Enhanced Piezoelectricity in MoTO (T = S, Se, or Te) Monolayers and Bilayers.

Development of piezoelectric materials is limited partly due to the incompleteness of internal mechanism and the lack of vertical piezoelectricity. Herein, we theoretically identify the stable MoTO (T = S, Se, or Te) monolayers and bilayers. When two elements are given but another element can be changed, the larger the electronegativity difference ratio Rratio is, the stronger the piezoelectricity will be. Vertical piezoelectric coefficient d33 of the MoTeO bilayer reaches 38.907 pm/V, which is 12 times larger than that of the bulk GaN. The "active asymmetric electron-transfer" strategy mainly contributes to the spontaneous remarkable piezoelectricity of MoTO. Importantly, we proposed the new method for calculating the piezoelectric coefficients of two-dimensional (2D) materials, which corresponds to the fact that 2D materials have a certain thickness. This study not only provides novel extraordinary candidates for energy conversion and touch-sensor nanodevices but also promotes a deeper understanding of piezoelectricity of 2D materials.