TCR-induced sumoylation of the kinase PKC-θ controls T cell synapse organization and T cell activation.

Sumoylation regulates many cellular processes, but its role in signaling via the T cell antigen receptor (TCR) remains unknown. We found that the kinase PKC-θ was sumoylated upon costimulation with antigen or via the TCR plus the coreceptor CD28, with Lys325 and Lys506 being the main sumoylation sites. We identified the SUMO E3 ligase PIASxß as a ligase for PKC-θ. Analysis of primary mouse and human T cells revealed that sumoylation of PKC-θ was essential for T cell activation. Desumoylation did not affect the catalytic activity of PKC-θ but inhibited the association of CD28 with PKC-θ and filamin A and impaired the assembly of a mature immunological synapse and central co-accumulation of PKC-θ and CD28. Our findings demonstrate that sumoylation controls TCR-proximal signaling and that sumoylation of PKC-θ is essential for the formation of a mature immunological synapse and T cell activation.

ß-Hydroxybutyrate Prevents Vascular Senescence through hnRNP A1-Mediated Upregulation of Oct4.

ß-hydroxybutyrate (ß-HB) elevation during fasting or caloric restriction is believed to induce anti-aging effects and alleviate aging-related neurodegeneration. However, whether ß-HB alters the senescence pathway in vascular cells remains unknown. Here we report that ß-HB promotes vascular cell quiescence, which significantly inhibits both stress-induced premature senescence and replicative senescence through p53-independent mechanisms. Further, we identify heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) as a direct binding target of ß-HB. ß-HB binding to hnRNP A1 markedly enhances hnRNP A1 binding with Octamer-binding transcriptional factor (Oct) 4 mRNA, which stabilizes Oct4 mRNA and Oct4 expression. Oct4 increases Lamin B1, a key factor against DNA damage-induced senescence. Finally, fasting and intraperitoneal injection of ß-HB upregulate Oct4 and Lamin B1 in both vascular smooth muscle and endothelial cells in mice in vivo. We conclude that ß-HB exerts anti-aging effects in vascular cells by upregulating an hnRNP A1-induced Oct4-mediated Lamin B1 pathway.

Modulating the d-Band Center of RuO2 via Ni Incorporation for Efficient and Durable Li-O2 batteries.

Rechargeable Li-O2 batteries (LOBs) are considered as one of the most promising candidates for new-generation energy storage devices. One of major impediments is the poor cycle stability derived from the sluggish reaction kinetics of unreliable cathode catalysts, hindering the commercial application of LOBs. Therefore, the rational design of efficient and durable catalysts is critical for LOBs. Optimizing surface electron structure via the negative shift of the d-band center offers a reasonable descriptor for enhancing the electrocatalytic activity. In this study, the construction of Ni-incorporating RuO2 porous nanospheres is proposed as the cathode catalyst to demonstrate the hypothesis. Density functional theory calculations reveal that the introduction of Ni atoms can effectively modulate the surface electron structure of RuO2 and the adsorption capacities of oxygen-containing intermediates, accelerating charge transfer between them and optimizing the growth pathway of discharge products. Resultantly, the LOBs exhibit a large discharge specific capacity of 19658 mA h g-1 at 200 mA g-1 and extraordinary cycle life of 791 cycles. This study confers the concept of d-band center modulation for efficient and durable cathode catalysts of LOBs.

Platelet Membrane-Coated Curcumin-PLGA Nanoparticles Promote Astrocyte-Neuron Transdifferentiation for Intracerebral Hemorrhage Treatment.

Intracerebral hemorrhage (ICH) is a hemorrhagic disease with high mortality and disability rates. Curcumin is a promising drug for ICH treatment due to its multiple biological activities, but its application is limited by its poor watersolubility and instability. Herein, platelet membrane-coated curcumin polylactic-co-glycolic acid (PLGA) nanoparticles (PCNPs) are prepared to achieve significantly improved solubility, stability, and sustained release of curcumin. Fourier transform infrared spectra and X-ray diffraction assays indicate good encapsulation of curcumin within nanoparticles. Moreover, it is revealed for the first time that curcumin-loaded nanoparticles can not only suppress hemin-induced astrocyte proliferation but also induce astrocytes into neuron-like cells in vitro. PCNPs are used to treat rat ICH by tail vein injection, using in situ administration as control. The results show that PCNPs are more effective than curcumin-PLGA nanoparticles in concentrating on hemorrhagic lesions, inhibiting inflammation, suppressing astrogliosis, promoting neurogenesis, and improving motor functions. The treatment efficacy of intravenously administered PCNPs is comparable to that of in situ administration, indicating a good targeting effect of PCNPs on the hemorrhage site. This study provides a potent treatment for hemorrhagic injuries and a promising solution for efficient delivery of water-insoluble drugs using composite materials of macromolecules and cell membranes.

A Deep Learning Model for Accurate Diagnosis of Infection Using Antibody Repertoires.

The adaptive immune receptor repertoire consists of the entire set of an individual's BCRs and TCRs and is believed to contain a record of prior immune responses and the potential for future immunity. Analyses of TCR repertoires via deep learning (DL) methods have successfully diagnosed cancers and infectious diseases, including coronavirus disease 2019. However, few studies have used DL to analyze BCR repertoires. In this study, we collected IgG H chain Ab repertoires from 276 healthy control subjects and 326 patients with various infections. We then extracted a comprehensive feature set consisting of 10 subsets of repertoire-level features and 160 sequence-level features and tested whether these features can distinguish between infected individuals and healthy control subjects. Finally, we developed an ensemble DL model, namely, DL method for infection diagnosis (https://github.com/chenyuan0510/DeepID), and used this model to differentiate between the infected and healthy individuals. Four subsets of repertoire-level features and four sequence-level features were selected because of their excellent predictive performance. The DL method for infection diagnosis outperformed traditional machine learning methods in distinguishing between healthy and infected samples (area under the curve = 0.9883) and achieved a multiclassification accuracy of 0.9104. We also observed differences between the healthy and infected groups in V genes usage, clonal expansion, the complexity of reads within clone, the physical properties in the α region, and the local flexibility of the CDR3 amino acid sequence. Our results suggest that the Ab repertoire is a promising biomarker for the diagnosis of various infections.

Acovenosigenin A ß-glucoside mediates JAK2-STAT3 signaling pathway by targeting GP130 in A549 and H460 cells based on integrative analysis of transcriptome and proteome and biological verification.

Acovenosigenin A ß-glucoside (AAG) is a cardiac glycoside derived from Streptocaulon juventas (Lour.) Merr, which exhibited the potential in treating lung cancer in our previous research. However, the action mechanism remains unclear. In this research, JAK2-STAT3 signaling pathway was predicted to be the critical regulation pathway based on the integrative analysis of transcriptome and proteome. Western blotting and qPCR assays were performed to identify that AAG can regulate JAK2-STAT3 signaling pathway and its downstream genes, such as c-Myc, Survivin, Cyclin B1, CDK1, Bcl-2. And this action of AAG depended on the suppression of STAT3 phosphorylation and its nuclear translocation through the experiments of Immunofluorescence, transient transfection and cryptotanshinone treatment. Additionally, AAG was discovered to mediate the JAK2-STAT3 pathway in IL-6-driven A549 and H460 cells, which in turn inhibited cell proliferation, promoted mitochondria-related apoptosis, and arrested the cell cycle progression. By molecular docking analysis, CETSA and SIP experiments, the protein of GP130 was identified as the specific target of AAG in A549 and H460 cells. Further studies suggested that AAG inhibited JAK2-STAT3 pathway and its downstream genes by targeting GP130 in nude mice xenograft model in vivo. This research presented that AAG exhibits the promising potential in the treatment of NSCLC.

Phenolic acids from Prunella vulgaris alleviate cardiac remodeling following myocardial infarction partially by suppressing NLRP3 activation.

Acute myocardial infarction (MI) is one of the leading causes of mortality around the world. Prunella vulgaris (Xia-Ku-Cao in Chinese) is used in traditional Chinese medicine practice for the treatment of cardiovascular diseases. However, its active ingredients and mechanisms of action on cardiac remodeling following MI remain unknown. In this study, we investigated the cardioprotective effect of P. vulgaris on MI rat models. MI rats were treated with aqueous extract of P. vulgaris or phenolic acids from P. vulgaris, including caffeic acid, ursolic acid or rosmarinic acid, 1 day after surgery and continued for the following 28 days. Then the cardioprotective effect, such as cardiac function, inflammatory status, and fibrosis areas were evaluated. RNA-sequencing (RNA-seq) analysis, real-time polymerase chain reaction (PCR), western blotting, and ELISA were used to explore the underlying mechanism. In addition, ultra-high performance liquid chromatography/mass spectrometer analysis was used to identify the chemicals from P. vulgaris. THP-1NLRP3-GFP cells were used to confirm the inhibitory effect of P. vulgaris and phenolic acids on the expression and activity of NLRP3. We found that P. vulgaris significantly improved cardiac function and reduced infarct size. Meanwhile, P. vulgaris protected cardiomyocyte against apoptosis, evidenced by increasing the expression of anti-apoptosis protein Bcl-2 in the heart and decreasing lactate dehydrogenase (LDH) levels in serum. Results from RNA-seq revealed that the therapeutic effect of P. vulgaris might relate to NLRP3-mediated inflammatory response. Results from real-time PCR and western blotting confirmed that P. vulgaris suppressed NLRP3 expression in MI heart. We also found that P. vulgaris suppressed NLRP3 expression and the secretion of HMGB1, IL-1ß, and IL-18 in THP-1NLRP3-GFP cells. Further studies indicated that the active components of P. vulgaris were three phenolic acids, those were caffeic acid, ursolic acid, and rosmarinic acid. These phenolic acids inhibited LPS-induced NLRP3 expression and activity in THP-1 cells, and improved cardiac function, suppressed inflammatory aggregation and fibrosis in MI rat models. In conclusion, our study demonstrated that P. vulgaris and phenolic acids from P. vulgaris, including caffeic acid, ursolic acid, and rosmarinic acid, could improve cardiac function and protect cardiomyocytes from ischemia injury during MI. The mechanism was partially related to inhibiting NLRP3 activation.

Preparation, characterisation, and pharmacodynamic study of myricetin pH-sensitive liposomes.

AIMS: Myricetin (MYR) was incorporated into pH-sensitive liposomes in order to improve its bioavailability and anti-hyperuricemic activity. METHODS: The MYR pH-sensitive liposomes (MYR liposomes) were prepared using thin film dispersion method, and assessed by particle size (PS), polydispersed index (PDI), zeta potential (ZP), encapsulation efficiency, drug loading, and in vitro release rate. Pharmacokinetics and anti-hyperuricemic activities were also evaluated. RESULTS: The PS, PDI, ZP, encapsulation efficiency, and drug loading of MYR liposomes were 184.34 ± 1.05 nm, 0.215 ± 0.005, -38.46 ± 0.30 mV, 83.42 ± 1.07%w/w, and 6.20 ± 0.31%w/w, respectively. The release rate of MYR liposomes was higher than free MYR, wherein the cumulative value responded to pH. Besides, the Cmax of MYR liposomes was 4.92 ± 0.20 µg/mL. The level of uric acid in the M-L-H group (200 mg/kg) was reduced by 54.74%w/v in comparison with the model group. CONCLUSION: MYR liposomes exhibited pH sensitivity and could potentially enhance the oral bioavailability and anti-hyperuricemic efficacy of MYR.

Isolation, Purification of Phenolic Glycoside 1 from Moringa oleifera Seeds and Formulation of Its Liposome Delivery System.

In this study, N, N '-bis {4- [(α-L- rhamnosyloxy) benzyl]} thiourea (PG-1), a phenolic glycoside compound was purified from Moringa seed. The PG-1 has attracted extensive attention due to its anti-cancer, antioxidant, anti-inflammatory and hypoglycemic properties. However, some of its physicochemical properties such as oral bioavailability has not been studied. Herein, a highly purified PG-1 was extracted and incorporated in multiple layered liposomes (PG-1-L) to avoid its burst release and enhance oral bioavailability. After appropriate characterization, it was discovered that the obtained PG-1-L was stable, homogeneous and well dispersed with the average particle size being 89.26 ± 0.23 nm. Importantly, the in vitro release and in vivo oral bioavailability of PG-1-L were significantly improved compared with PG-1. In addition, MTT results showed that compared with the free PG-1, PG-1-L displayed obvious inhibitory effect on the HepG2 cells, while the inhibitory effect on healthy non-malignant 3T6 and LO-2 cells was not significant, indicating that PG-1-L had high safety. In conclusion, PG-1-L can be used as a promising delivery system and an ideal novel approach to improve the oral bioavailability and anticancer activity of PG-1.

Fabrication and Separation of EGaIn Microparticles from Human Blood Based on Dielectrophoresis Force and a W-Type Electrode.

Harmful particles such as heavy metal particles in the human body can cause many problems such as kidney stones, gallstones, and cerebrovascular diseases. Therefore, it is critical to separate them from the blood and perform a systematic analysis as early as possible. Here, we apply eutectic gallium indium (EGaIn) microparticles as a model to study the separation of particles from blood, thanks to their properties of low toxicity, excellent degradability, and negligible vapor pressure. In particular, the dielectrophoresis (DEP) separation method is employed to separate EGaIn of different sizes and characteristics in blood. First, the screen-printing method is used to create EGaIn microparticles with diameters of 15, 23, 18, and 11 µm. According to the lifetime test, these microparticles can last more than 1 month, as evidenced by their surface oxidation characteristics. Moreover, a DEP platform with W-type electrodes is developed to sort EGaIn particles from whole human blood. The results show that a sorting efficiency of 95% can be attained, which is similar to the separation efficiency of 98% achieved by finite element analysis (FEA) using COMSOL software based on the orthogonal array experiment method. The proposed study successfully validates the use of the DEP method to separate particles from human blood, providing insights into heavy metal particle separating, drug screening, and cell sorting and potentially broadening the applications in environmental analysis, food engineering, and bioengineering.

Deep learning-based identification of spine growth potential on EOS radiographs.

OBJECTIVES: To develop an automatic computer-based method that can help clinicians in assessing spine growth potential based on EOS radiographs. METHODS: We developed a deep learning-based (DL) algorithm that can mimic the human judgment process to automatically determine spine growth potential and the Risser sign based on full-length spine EOS radiographs. A total of 3383 EOS cases were collected and used for the training and test of the algorithm. Subsequently, the completed DL algorithm underwent clinical validation on an additional 440 cases and was compared to the evaluations of four clinicians. RESULTS: Regarding the Risser sign, the weighted kappa value of our DL algorithm was 0.933, while that of the four clinicians ranged from 0.909 to 0.930. In the assessment of spine growth potential, the kappa value of our DL algorithm was 0.944, while the kappa values of the four clinicians were 0.916, 0.934, 0.911, and 0.920, respectively. Furthermore, our DL algorithm obtained a slightly higher accuracy (0.973) and Youden index (0.952) compared to the best values achieved by the four clinicians. In addition, the speed of our DL algorithm was 15.2 ± 0.3 s/40 cases, much faster than the inference speeds of the clinicians, ranging from 177.2 ± 28.0 s/40 cases to 241.2 ± 64.1 s/40 cases. CONCLUSIONS: Our algorithm demonstrated comparable or even better performance compared to clinicians in assessing spine growth potential. This stable, efficient, and convenient algorithm seems to be a promising approach to assist doctors in clinical practice and deserves further study. CLINICAL RELEVANCE STATEMENT: This method has the ability to quickly ascertain the spine growth potential based on EOS radiographs, and it holds promise to provide assistance to busy doctors in certain clinical scenarios. KEY POINTS: • In the clinic, there is no available computer-based method that can automatically assess spine growth potential. • We developed a deep learning-based method that could automatically ascertain spine growth potential. • Compared with the results of the clinicians, our algorithm got comparable results.

Effect of boundary angle on aero-optical imaging deviation of the blunt-headed side-window vehicle.

This paper defines the intersection angle between the tangent plane at the boundary of aero-optical flow field and the body axis as the boundary angle and focuses on the influence of the boundary angle on the imaging deviation. This paper shows that the boundary angle of the aero-optical flow field is different at different flight conditions, which means the location of the zero value of imaging deviation is different.  With the increase of the line of sight angle, the imaging deviation decreases first and then increases in the opposite direction.  After the change of flight conditions, the boundary angle decreases with the increase of the compression of the flow field.  The imaging deviation increases if the incident light is on the right side of the normal and decreases in the opposite direction.

Influence of the deviated center of rotation on the range of motion after cervical disc arthroplasty -an in vivo study with a minimum of 10-year follow-up.

BACKGROUND: Short-term researches have studied the change of the center of rotation (COR) after the Bryan Cervical disc arthroplasty (CDA). But there is a lack of long-term studies focusing on the location of COR and its influence after surgery. METHODS: Clinical and radiographic materials of patients who received CDA were retrospectively reviewed. Written informed consents were obtained. Clinical outcome was accessed by Japanese Orthopaedic Association (JOA), Neck Disability Index (NDI), and Odom's scale. Radiographic evaluation underwent before surgery, at early (3 months) follow-up and final (minimal 10 years) follow-up. The ROM of the global cervical spine and index level, the functional spine unit (FSU) angle and C2-C7 angle were measured. COR was identified and its coordinates were calculated. The absolute change of COR-x and COR-y were compared in subgroup analysis. RESULTS: Sixty patients were included, with an average age of 55.9 ± 8.1 years old. The mean duration of follow up was 135.1 ± 16.1 (120-155) months. JOA, NDI and Odom's scale showed significant improvements at 10 years after surgery. The COR of index level was located in the posterior superior half of the caudal vertebral body. Following the implant of Bryan Disc, the COR shifted forward and downward. During the 10-year follow-up, the location of COR remained stable. ROM at the index level decreased from 10.6 ± 4.0° preoperatively to 9.3 ± 4.0° at the early follow-up (p = 0.03). The ROM at the index level remained unchanged from early follow-up to the final follow-up (9.3 ± 4.0° vs 9.5 ± 5.2°, p = 0.80). In subgroup analysis, larger changes of both COR-x and COR-y were related with decreased ROM. CONCLUSIONS: Our study illustrated that Bryan CDA could achieved favorable clinical and radiographic outcome over a minimal 10-year follow-up. The reduction of the flexion-extension ROM may be correlated with a more deviated postoperative COR. More attention should be paid to preoperative design and intraoperative technique to obtain a more native COR.

A Mathematical Prediction Model for Postoperative Infection Based on Logistic Multiple Regression Analysis in the Assessment of Surgical Outcome and Prediction of Infection in Elderly Spinal Fractures.

Objective: Investigating postoperative infection risk factors in elderly spinal fracture patients is crucial for optimizing surgical outcomes, improving patient safety, and guiding clinical decision-making in the management of these complex cases. To investigate the risk factors for postoperative infection in elderly patients with spinal fractures, with the goal of giving clinical care guidelines. Methods: From January 2019 to January 2022, 120 elderly patients admitted to our hospital for elective spinal fracture surgery were featured as the study subjects, and the patients were divided into infected and non-infected categories according to whether they had postoperative infection or not. A mathematical prediction model was built after using logistic multiple regression to investigate the parameters influencing postoperative infection of a spinal fracture. Results: There were 20 patients in the infected category and 100 patients in the non-infected category. Univariate analysis showed that the proportion of patients in the infected category with male, age ≥65 years, multiple fractures, use of hormones or combined diabetes was notably higher than that in the non-infected category (P < .05). Male gender, age ≥65 years, multiple fractures, and certain medical conditions are independent risk factors for postoperative infection. Conclusions: Logistic regression analysis revealed that male, age ≥65 years, multiple fractures, use of hormones, or combined diabetes was an independent risk factor for postoperative infection in elderly patients with spinal fracture. Our study provides valuable insights that can guide clinical care and decision-making for elderly patients with spinal fractures. By applying these findings in practice, clinicians can refine their treatment strategies, improve patient outcomes, and enhance the overall quality of care provided to this vulnerable population.

Degradation Profiling of Nardosinone at High Temperature and in Simulated Gastric and Intestinal Fluids.

Nardosinone, a predominant bioactive product from Nardostachys jatamansi DC, is well-known for its promising therapeutic applications, such as being used as a drug on anti-inflammatory, antidepressant, cardioprotective, anti-neuroinflammatory, anti-arrhythmic, anti-periodontitis, etc. However, its stability under varying environmental conditions and its degradation products remain unclear. In this study, four main degradation products, including two previously undescribed compounds [2-deoxokanshone M (64.23%) and 2-deoxokanshone L (1.10%)] and two known compounds [desoxo-narchinol A (2.17%) and isonardosinone (3.44%)], were firstly afforded from the refluxed products of nardosinone in boiling water; their structures were identified using an analysis of the extensive NMR and X-ray diffraction data and the simulation and comparison of electronic circular dichroism spectra. Compared with nardosinone, 2-deoxokanshone M exhibited potent vasodilatory activity without any of the significant anti-neuroinflammatory activity that nardosinone contains. Secondly, UPLC-PDA and UHPLC-DAD/Q-TOF MS analyses on the degradation patterns of nardosinone revealed that nardosinone degraded more easily under high temperatures and in simulated gastric fluid compared with the simulated intestinal fluid. A plausible degradation pathway of nardosinone was finally proposed using nardosinonediol as the initial intermediate and involved multiple chemical reactions, including peroxy ring-opening, keto-enol tautomerization, oxidation, isopropyl cleavage, and pinacol rearrangement. Our findings may supply certain guidance and scientific evidence for the quality control and reasonable application of nardosinone-related products.

Photothermal Therapy Mediated Hybrid Membrane Derived Nano-formulation for Enhanced Cancer Therapy.

Emodin is applied as an antitumor drug in many tumor therapies. However, its pharmacology performances are limited due to its low solubility. Herein, we fused erythrocyte and macrophage to form a hybrid membrane (EMHM) and encapsulated emodin to form hybrid membrane-coated nanoparticles. We employed glycyrrhizin to increase the solubility of emodin first and prepared the hybrid membrane nanoparticle-coated emodin and glycyrrhizin (EG@EMHM NPs) which exhibited an average particle size of 170 ± 20 nm and encapsulation efficiency of 98.13 ± 0.67%. The half-inhibitory concentrations (IC50) of EG@EMHM NPs were 1.166 µg/mL, which is half of the free emodin. Based on the photosensitivity of emodin, the reactive oxygen species (ROS) results disclosed that ROS levels of the photodynamic therapy (PDT) section were higher than the normal section (P < 0.05). Compared to the normal section, PDT-mediated EG@EMHM NPs could induce an early stage of apoptosis of B16. The western blot and flow cytometry results verified that PDT-mediated EG@EMHM NPs can significantly improve the solubility of emodin and perform a remarkably antitumor effect on melanoma via BAX and BCL-2 pathway. The application of the combined chemical and PDT therapy could provide an improving target therapy for cutaneous melanoma and also may offer an idea for other insoluble components sources of traditional Chinese medicine. Schematic of EG@EMHM NPs formulation.

Microfluidic Generation of Near-Infrared Photothermal Vitexin/ICG Liposome with Amplified Photodynamic Therapy.

Glioma, in which a malignant tumor cell occurs in neural mesenchymal cells, has a rapid progression and poor prognosis, which is still far from desirable in clinical treatments. We developed a lab-on-a-chip (LOC) device for the rapid and efficient preparation of vitexin/indocyanine green (ICG) liposomes. Vitexin could be released from liposome to kill cancer cell, which can potentially improve the glioma therapeutic effect and reduce the treatment time through synergistic photodynamic/photothermal therapies (PDT/PTT). The vitexin/ICG liposome was fabricated via LOC and its physicochemical property and release in vitro were evaluated. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and live/dead staining were used to examine the enhanced antitumor effect of vitexin/ICG liposome in cooperation with PDT/PTT, while the related mechanism was explored by flow cytometry and western blot. The results were as follows: (1) The prepared vitexin/ICG liposome was smaller in size, homogenous in particle size distribution with significant low polydispersity index (PDI), and enhanced cumulative release in vitro. (2) We found that the formulated liposome presented strong cancer cell inhibition and suppression of its migration in a dose-dependent manner. (3) Further mechanistic studies showed that liposome combined with near-infrared irradiation could significantly upregulate levels of B cell lymphoma 2-associated X (Bax) protein and decrease B cell lymphoma 2 (Bcl-2) at protein levels. The vitexin/ICG liposomes prepared based on a simple LOC platform can effectively enhance the solubility of insoluble drugs, and the combined effect of PTT/PDT can effectively increase their antitumor effect, which provides a simple and valid method for the clinical translation of liposomes.

Enhancing Anticancer Efficacy of Formononetin Microspheres via Microfluidic Fabrication.

Formononetin is a flavonoid compound with anti-tumor and anti-inflammatory properties. However, its low solubility limits its clinical use. We employed microfluidic technology to prepare formononetin-loaded PLGA-PEGDA microspheres (Degradable polymer PLGA, Crosslinking agent PEGDA), which can encapsulate and release drugs in a controlled manner. We optimized and characterized the microspheres, and evaluated their antitumor effects. The microspheres had uniform size, high drug loading efficiency, high encapsulation efficiency, and stable release for 35 days. They also inhibited the proliferation, migration, and apoptosis. The antitumor mechanism involved the induction of reactive oxygen species and modulation of Bcl-2 family proteins. These findings suggested that formononetin-loaded PLGA-PEGDA microspheres, created using microfluidic technology, could be a novel drug delivery system that can overcome the limitations of formononetin and enhance its antitumor activity.

[Three-dimensional printed 316L stainless steel cardiovascular stent's electrolytic polishing and its mechanical properties].

The interventional therapy of vascular stent implantation is a popular treatment method for cardiovascular stenosis and blockage. However, traditional stent manufacturing methods such as laser cutting are complex and cannot easily manufacture complex structures such as bifurcated stents, while three-dimensional (3D) printing technology provides a new method for manufacturing stents with complex structure and personalized designs. In this paper, a cardiovascular stent was designed, and printed using selective laser melting technology and 316L stainless steel powder of 0-10 µm size. Electrolytic polishing was performed to improve the surface quality of the printed vascular stent, and the expansion behavior of the polished stent was assessed by balloon inflation. The results showed that the newly designed cardiovascular stent could be manufactured by 3D printing technology. Electrolytic polishing removed the attached powder and reduced the surface roughness Ra from 1.36 µm to 0.82 µm. The axial shortening rate of the polished bracket was 4.23% when the outside diameter was expanded from 2.42 mm to 3.63 mm under the pressure of the balloon, and the radial rebound rate was 2.48% after unloading. The radial force of polished stent was 8.32 N. The 3D printed vascular stent can remove the surface powder through electrolytic polishing to improve the surface quality, and show good dilatation performance and radial support performance, which provides a reference for the practical application of 3D printed vascular stent.

LRFN2 binding to NMDAR inhibits the progress of ESCC via regulating the Wnt/ß-Catenin and NF-κB signaling pathway.

As a neuronal transmembrane protein, leucine-rich repeat and fibronectin type-III domain-containing protein 2 (LRFN2) can recruit and combine with N-methyl-d-aspartate receptors (NMDARs) to promote nerve growth. Genetic studies suggest that mutations in LRFN2 are associated with various cancers. However, the role and mechanism of LRFN2 in the progression of ESCC have not been elucidated. In this study, we demonstrated that LRFN2 was significantly downregulated in ESCC tissues by qRT-PCR and immunohistochemistry. Low LRFN2 expression was an adverse prognostic factor in patients with ESCC. Overexpression of LRFN2 effectively suppressed the proliferation, migration, invasion, and epithelial-to-mesenchymal transition in vitro and tumor growth in vivo. Bioinformatics analysis indicated that Wnt/ß-catenin signaling regulation was one of the most potential mechanisms and studies confirmed that overexpression of LFRN2 obviously downregulated the expression of ß-catenin, c-Myc, and cyclin D1 in ESCC cells and tumor tissues. Further studies revealed that LRFN2 plays an anti-ESCC role by binding with NMDAR-GRIN2B and this effect can be weakened by NR2B-selective NMDA antagonist-NMDA-IN-1. Moreover, the bioinformatics analysis showed that the interaction of GRIN2B and GSK3ß affects the NF-κB pathway, which was demonstrated by western blot experiments. Collectively, our results indicate that LRFN2 binding to NMDARs inhibits the progression of ESCC by regulating the Wnt/ß-catenin and NF-κB pathway, which provides a new therapeutic target for improving the prognosis of patients with ESCC.