Bioactive triterpenoid compounds of Poria cocos (Schw.) Wolf in the treatment of diabetic ulcers via regulating the PI3K-AKT signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic ulcers represent a chronic condition characterized by prolonged hyperglycemia and delayed wound healing, accompanied by endocrine disorders, inflammatory responses, and microvascular damage in the epidermal tissue, demanding effective clinical treatment approaches. For thousands of years, ancient Chinese ethnopharmacological studies have documented the use of Poria cocos (Schw.) Wolf in treating diabetic ulcers. Recent research has substantiated the diverse pharmacological effects of Poria cocos (Schw.) Wolf, including its potential to alleviate hyperglycemia and exhibit anti-inflammatory, antioxidant, and immune regulatory properties, which could effectively mitigate diabetic ulcer symptoms. Furthermore, being a natural medicine, Poria cocos (Schw.) Wolf has demonstrated promising therapeutic effects and safety in the management of diabetic ulcers, holding significant clinical value. Despite its potential clinical efficacy and applications in diabetic ulcer treatment, the primary active components and underlying pharmacological mechanisms of Poria cocos (Schw.) Wolf remains unclear. Further investigations are imperative to establish a solid foundation for drug development in this domain. AIM OF THE STUDY AND MATERIALS AND METHODS: In this study, we aimed to identify the active compounds and potential targets of Poria cocos (Schw.) Wolf using UHPLC-Q-TOF-MS and TCMSP databases. Additionally, we attempt to identify targets related to diabetic ulcers. Following enrichment analysis, a network of protein-protein interactions was constructed to identify hub genes based on the common elements between the two datasets. To gain insights into the binding activities of the hub genes and active ingredients, molecular docking analysis was employed. Furthermore, to further validate the therapeutic effect of Poria cocos (Schw.) Wolf, we exerted in vitro experiments using human umbilical vein vascular endothelial cells and human myeloid leukemia monocytes (THP-1). The active ingredient of Poria cocos (Schw.) Wolf was applied in these experiments. Our investigations included various assays, such as CCK-8, scratch test, immunofluorescence, western blotting, RT-PCR, and flow cytometry, to explore the potential of Poria cocos (Schw.) Wolf triterpenoid extract (PTE) in treating diabetic ulcers. RESULTS: The findings here highlighted PTE as the primary active ingredient in Poria cocos (Schw.) Wolf. Utilizing network pharmacology, we identified 74 potential targets associated with diabetic ulcer treatment for Poria cocos (Schw.) Wolf, with five hub genes (JUN, MAPK1, STAT3, AKT1, and CTNNB1). Enrichment analysis revealed the involvement of multiple pathways in the therapeutic process, with the PI3K-AKT signaling pathway showing significant enrichment. Through molecular docking, we discovered that relevant targets within this pathway exhibited strong binding with the active components of Poria cocos (Schw.) Wolf. In vitro experiments unveiled that PTE (10 mg/L) facilitated the migration of human umbilical vein vascular endothelial cells (P < 0.05). PTE also increased the expression of CD31 and VEGF mRNA (P < 0.05) while activating the expressions of p-PI3K and p-AKT (P < 0.05). Moreover, PTE demonstrated its potential by reducing the expression of IL-1ß, IL-6, TNF-α, and NF-κB mRNA in THP-1 (P < 0.05) and fostering M2 macrophage polarization. These results signify the potential therapeutic effects of PTE in treating diabetic ulcers, with its beneficial actions mediated through the PI3K-AKT signaling pathway. CONCLUSIONS: PTE is the main active ingredient in Poria cocos (Schw.) Wolf that exerts therapeutic effects. Through PI3K-AKT signaling pathway activation and inflammatory response reduction, PTE promotes angiogenesis, thereby healing diabetic ulcers.

Undenatured type II collagen nanofibrils with sodium alginate coating: Structural characterization, physicochemical properties and capability to load curcumin.

In this study, the structural design and physicochemical property enhancement of undenatured type II collagen (UC-II) nanofibrils with sodium alginate (SA) coating induced by calcium ions (Ca2+) were investigated. The research aimed to elucidate the impact of Ca2+ concentration on the morphology, thermal stability, and digestive resistance, as well as to assess the potential of UC-II/SA nanofibrils as a delivery system for curcumin (Cur). A series of Ca2+ concentrations (1-9 mM) were methodically applied to optimize the condition that maintains the triple-helical structure of UC-II, thereby enhancing its functional properties. It was found that the Ca2+ level up to 5 mM effectively preserved the structural integrity and improved thermal stability of UC-II, with the added benefit of ensuring the substantial delivery of active fragment to small intestine (70.7 %), which was 3.43 times greater than that of uncoated UC-II. Moreover, incorporating Cur into the UC-II/SA nanofibrils resulted in a 300 times increase in Cur solubility and showcased the superior dispersion stability, antioxidant activity, and sustained release profile during simulated digestion. These findings underscored the dual functionality of the UC-II/SA system as both a stabilizing agent for UC-II nanofibrils and an efficient carrier for Cur delivery.

Effects of chitosan molecular weight and mass ratio with natural blue phycocyanin on physiochemical and structural stability of protein.

Phycocyanin (PC), an algae-extracted colorant, has extensive applications for its water-solubility and fresh blue shade. When PC is added to acidified media, dispersions are prone to aggregate and decolorize into cloudy systems. For palliating this matter, chitosan with high, medium, and low molecular weights (HMC, MMC, and LMC) were adopted in PC dispersions, and their protective effects were compared based on physiochemical stabilities. The optimal mass ratio between chitosan and PC was identified as 1:5 based on preliminary evaluations and was supported by the higher ζ-potential (31.0-32.1 mV), lower turbidity (39.6-43.6 NTU), and polyacrylamide gel electrophoresis results. Through interfacial and antioxidant capacity analyses, LMC was found to display a higher affinity to PC, which was also confirmed by SEM images and the maximum increase in transition temperature of their complex (155.70 °C) in DSC measurements. The mechanism of electrostatic interaction reinforced by hydrophobic effects and hydrogen bonding was elucidated by FT-IR and Raman spectroscopy. Further comprehensive stability evaluations revealed that, without light exposure, LMC kept PC from internal secondary structure to external blueness luster to the maximum extent. While with light exposure, LMC was not so flexible as HMC, to protect chromophores from attack of free radicals.

Anoikis patterns via machine learning strategy and experimental verification exhibit distinct prognostic and immune landscapes in melanoma.

BACKGROUND: Anoikis is a cell death programmed to eliminate dysfunctional or damaged cells induced by detachment from the extracellular matrix. Utilizing an anoikis-based risk stratification is anticipated to understand melanoma's prognostic and immune landscapes comprehensively. METHODS: Differential expression genes (DEGs) were analyzed between melanoma and normal skin tissues in The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression data sets. Next, least absolute shrinkage and selection operator, support vector machine-recursive feature elimination algorithm, and univariate and multivariate Cox analyses on the 308 DEGs were performed to build the prognostic signature in the TCGA-melanoma data set. Finally, the signature was validated in GSE65904 and GSE22155 data sets. NOTCH3, PIK3R2, and SOD2 were validated in our clinical samples by immunohistochemistry. RESULTS: The prognostic model for melanoma patients was developed utilizing ten hub anoikis-related genes. The overall survival (OS) of patients in the high-risk subgroup, which was classified by the optimal cutoff value, was remarkably shorter in the TCGA-melanoma, GSE65904, and GSE22155 data sets. Low-risk patients exhibited low immune cell infiltration and high expression of immunophenoscores and immune checkpoints. They also demonstrated increased sensitivity to various drugs, including dasatinib and dabrafenib. NOTCH3, PIK3R2, and SOD2 were notably associated with OS by univariate Cox analysis in the GSE65904 data set. The clinical melanoma samples showed remarkably higher protein expressions of NOTCH3 (P = 0.003) and PIK3R2 (P = 0.009) than the para-melanoma samples, while the SOD2 protein expression remained unchanged. CONCLUSIONS: In this study, we successfully established a prognostic anoikis-connected signature using machine learning. This model may aid in evaluating patient prognosis, clinical characteristics, and immune treatment modalities for melanoma.

Macrophage-Derived Cathepsin S Remodels the Extracellular Matrix to Promote Liver Fibrogenesis.

BACKGROUND & AIMS: Liver fibrosis is an intrinsic wound-healing response to chronic injury and the major cause of liver-related morbidity and mortality worldwide. However, no effective diagnostic or therapeutic strategies are available, owing to its poorly characterized molecular etiology. We aimed to elucidate the mechanisms underlying liver fibrogenesis. METHODS: We performed a quantitative proteomic analysis of clinical fibrotic liver samples to identify dysregulated proteins. Further analyses were performed on the sera of 164 patients with liver fibrosis. Two fibrosis mouse models and several biochemical experiments were used to elucidate liver fibrogenesis. RESULTS: We identified cathepsin S (CTSS) up-regulation as a central node for extracellular matrix remodeling in the human fibrotic liver by proteomic screening. Increased serum CTSS levels efficiently predicted liver fibrosis, even at an early stage. Secreted CTSS cleaved collagen 18A1 at its C-terminus, releasing endostatin peptide, which directly bound to and activated hepatic stellate cells via integrin α5ß1 signaling, whereas genetic ablation of Ctss remarkably suppressed liver fibrogenesis via endostatin reduction in vivo. Further studies identified macrophages as the main source of hepatic CTSS, and splenectomy effectively attenuated macrophage infiltration and CTSS expression in the fibrotic liver. Pharmacologic inhibition of CTSS ameliorated liver fibrosis progression in the mouse models. CONCLUSIONS: CTSS functions as a novel profibrotic factor by remodeling extracellular matrix proteins and may represent a promising target for the diagnosis and treatment of liver fibrosis.

Loading neural stem cells on hydrogel scaffold improves cell retention rate and promotes functional recovery in traumatic brain injury.

Neural stem cell (NSC) has gained considerable attention in traumatic brain injury (TBI) treatment because of their ability to replenish dysfunctional neurons and stimulate endogenous neurorestorative processes. However, their therapeutic effects are hindered by the low cell retention rate after transplantation into the dynamic brain. In this study, we found cerebrospinal fluid (CSF) flow after TBI is an important factor associated with cell loss following NSC transplantation. Recently, several studies have shown that hydrogels could serve as a beneficial carrier for stem cell transplantation, which provides a solution to prevent CSF flow-induced cell loss after TBI. For this purpose, we evaluated three different hydrogel scaffolds and found the gelatin methacrylate (GelMA)/sodium alginate (Alg) (GelMA/Alg) hydrogel scaffold showed the best capabilities for NSC adherence, growth, and differentiation. Additionally, we detected that pre-differentiated NSCs, which were loaded on the GelMA/Alg hydrogel and cultured for 7 days in neuronal differentiation medium (NSC [7d]), had the highest cell retention rate after CSF impact. Next, the neuroprotective effects of the NSC-loaded GelMA/Alg hydrogel scaffold were evaluated in a rat model of TBI. NSC [7d]-loaded GelMA/Alg markedly decreased microglial activation and neuronal death in the acute phase, reduced tissue loss, alleviated astrogliosis, promoted neurogenesis, and improved neurological recovery in the chronic phase. In summary, we demonstrated that the integration with the GelMA/Alg and modification of NSC differentiation could inhibit the influence of CSF flow on transplanted NSCs, leading to increased number of retained NSCs and improved neuroprotective effects, providing a promising alternative for TBI treatment.

Insight into the composite assembly process, nanofibril structure and stability of undenatured type II collagen in the presence of different types of nanocelluloses.

Four types of nanocelluloses (CNs), including cellulose nanocrystals (CNC), cellulose nanofibrils (CNF), cationic etherified nanocellulose (CCNF) and TEMPO-oxidized nanocellulose (TOCNF), were incorporated into the assembly process of undenatured type II collagen (UC-II). In the presence of CNs, the kinetics of UC-II composite assembly slightly fluctuated and the magnitude of UC-II assembly increased (from 59.93 to 66.83-85.06 %). CNC and CNF disrupted the triple helix structure of UC-II while CCNF and TOCNF had weak impact on it. Hydrogen bonding and hydrophobic interactions were dominant driving forces of UC-II/CNs, and electrostatic interactions were also involved in the fabrication of UC-II/CCNF and UC-II/TOCNF. UC-II/CNs exhibited distinct nanostructures due to the differences in shape, level, and surface group of CNs. CCNF and TOCNF contributed to the enhanced physical stability due to the increased surface charge. In addition, the thermal stability and rheological properties of UC-II/CNs were also improved. The composite assembly process, nanofibril structure and stability of UC-II in the presence of different types and levels of CNs, which was useful to develop the novel composite nanofibrils for the application in functional foods.

Damaged collagen detected by collagen hybridizing peptide as efficient diagnosis marker for early hepatic fibrosis.

Liver fibrosis is characterized by excessive synthesis and deposition of extracellular matrix (ECM) in liver tissues. However, it still has been lacking of early detection and diagnosis methods. The collagen hybridizing peptide (CHP) is a novel synthetic peptide that enables detection of collagen damage and tissue remodeling. Here, we showed that obvious CHP-positive staining could be detected in the liver while given CCl4 for only 3 days, which was significantly enhanced while given CCl4 for 7 days. However, H&E staining showed no significant changes in fibrous tissue, and sirius red-positive staining could only be observed while given CCl4 for 14 days. Moreover, CHP-positive staining enhanced initially at portal area which further extended into the hepatic lobule, which was increased more significantly than sirius red-positive staining in the model of 10 and 14 days. Further proteomic analysis of CHP-positive staining revealed that pathways associated with ECM remodeling were significantly increased, while retinol metabolism was downregulated. Meanwhile, proteins enriched in cellular gene transcription and signal transduction involved in fibrogenesis were also upregulated, suggesting that fibrosis occurred in CHP-positive staining. Our study provided evidence that CHP could detect the collagen damage in liver, which might be an efficient indicator for the diagnosis of liver fibrosis at a very early stage.

Rapid Preparation of Flame-Retardant Coatings Using Polyurethane Emulsion Mixed with Inorganic Fillers.

The traditional aqueous flame-retardant coating faces the problem of slow solvent evaporation rate in the preparation process. It is an urgent problem to ensure that the function of the membrane is not destroyed while accelerating the solvent volatilization. Herein, we fabricated films on the metal substrate surface by a totally novel method: demulsification-induced fast solidification to rapidly obtain the flame-retardant coating. The environmentally friendly flame retardants aluminum hydroxide and red phosphorus were mixed with the commercial water-based polyurethane 906 emulsion to explore the optimal mixing ratio, where the adhesion of the flame-retardant reached the Grade 3 standard, the sample remained intact after the 100 cm drop hammer test and the limiting oxygen index value reached 30.4%. In addition, compared with the traditional process, this method, with the advantages of rapidly drying, environmentally friendly, uniformly prepared coatings on the surface of any shape substrates, as well as accurate and controllable coating thickness, can be widely applied in the flame-retardant field.

Effects of different mechanical processes on the structural and powdery properties of insoluble undenatured type II collagen.

This study aimed to investigate the effects of dynamic high-pressure homogenization (DHPH), dynamic high-pressure microfluidization (DHPM), and wet media milling (WMM) processes on the particle size, microstructure, triple helix structure, wettability and suspension stability of insoluble undenatured type II collagen (IUC-II). The structural and powdery properties were regulated by different processes and parameters. By contrast, WMM-treated IUC-II showed smallest particle size (15.70 µm), highest wetting rate (216.94 mm/h) and best suspension stability. However, individual mechanical processes caused partial disruption of IUC-II triple helix structure. Low-acyl gellan gum (LAGG) could bind to IUC-II through hydrogen bonds and hydrophobic interactions, which protected the triple helix structure and further enhanced powdery properties of IUC-II treated by WMM process, but restrained the soluble transition during digestion. These results demonstrated that WMM process was more suitable for enhancing powdery properties of IUC-II, while the triple helix structure of IUC-II could be effectively protected by LAGG.

Nanostructured lipid carriers (NLCs) stabilized by natural or synthetic emulsifiers for lutein delivery: Improved physicochemical stability, antioxidant activity, and bioaccessibility.

This study investigated the impacts of individual emulsifiers on the physicochemical stability, antioxidant ability, and in vitro digestion behavior of lutein-loaded nanostructured lipid carriers (NLCs). NLCs particles stabilized by ethyl lauroyl arginate, rhamnolipid, or tea saponin were fabricated by high-pressure microfluidization method. Differential scanning calorimetry and X-ray diffraction results confirmed the regulatory effect of emulsifiers on the crystallization behavior of NLCs. NLCs stabilized by rhamnolipid presented higher encapsulation efficiency (94.73%) for lutein than those stabilized by tea saponin (90.39%) or ethyl lauroyl arginate (88.86%). Meanwhile, the stability of embedded lutein during storage or photothermal treatments was greatly enhanced. Individual emulsifiers, together with lutein, endowed NLCs with excellent antioxidant capacity. During in vitro digestion, rhamnolipid-stabilized NLCs showed the slowest release of free fatty acids (50.87%) and provided an optimal sustained release for lutein with relatively high bioaccessibility (23.01%).

Assessment of electroencephalography and event-related potentials in unresponsive patients with brain injury.

OBJECTIVE: To investigate the predictors of clinical outcomes in unresponsive patients with acquired brain injuries. METHODS: Patients with coma or disorders of consciousness were enrolled from August 2019 to March 2021. A retrospective analysis of demographics, etiology, clinical score, diagnosis, electroencephalography (EEG), and event-related potential (ERP) data from 1 week to 2 months after coma onset was conducted. Findings were assessed for predicting favorable outcomes at 6 months post-coma, and functional outcomes were determined using the Glasgow Outcome Scale-Extended (GOS-E). RESULTS: Of 68 patients, 22 patients had a good neurological outcome at 6 months, while 11 died. Univariate analysis showed that motor response (Motor-R; p < 0.001), EEG pattern (p = 0.015), sleep spindles (p = 0.018), EEG reactivity (EEG-R; p < 0.001), mismatch negativity (MMN) amplitude at electrode Fz (FzMMNA; p = 0.001), P3a latency (p = 0.044), and P3a amplitude at electrode Cz (CzP3aA; p < 0.001) were significantly correlated with patient prognosis. Multivariable logistic regression analysis showed that FzMMNA, CzP3aA, EEG-R, and Motor-R were significant independent predictors of a favorable outcome. The sensitivity and specificity of FzMMNA (dichotomized at 1.16 µV) were 86.4% and 58.5%, and of CzP3aA (cut-off value 2.76 µV) were 90.9% and 70.7%, respectively. ERP amplitude (ERP-A), a combination of FzMMNA and CzP3aA, improved prediction accuracy, with an area under the receiver operating characteristic curve (AUC) of 0.884. A model incorporating Motor-R, EEG-R, and ERP-A yielded an outstanding predictive performance (AUC=0.921) for a favorable outcome. CONCLUSION: ERP-A and the prognostic model resulted in the efficient prediction of a favorable outcome in unresponsive patients.

Chinese guideline on the application of anti-seizure medications in the perioperative period of supratentorial craniocerebral surgery.

Seizures are a common symptom of craniocerebral diseases, and epilepsy is one of the comorbidities of craniocerebral diseases. However, how to rationally use anti-seizure medications (ASMs) in the perioperative period of craniocerebral surgery to control or avoid seizures and reduce their associated harm is a problem. The China Association Against Epilepsy (CAAE) united with the Trauma Group of the Chinese Neurosurgery Society, Glioma Professional Committee of the Chinese Anti-Cancer Association, Neuro-Oncology Branch of the Chinese Neuroscience Society, and Neurotraumatic Group of Chinese Trauma Society, and selected experts for consultancy regarding outcomes from evidence-based medicine in domestic and foreign literature. These experts referred to the existing research evidence, drug characteristics, Chinese FDA-approved indications, and expert experience, and finished the current guideline on the application of ASMs during the perioperative period of craniocerebral surgery, aiming to guide relevant clinical practice. This guideline consists of six sections: application scope of guideline, concepts of craniocerebral surgery-related seizures and epilepsy, postoperative application of ASMs in patients without seizures before surgery, application of ASMs in patients with seizures associated with lesions before surgery, emergency treatment of postoperative seizures, and 16 recommendations.

The kinetic mechanism of cations induced protein nanotubes self-assembly and their application as delivery system.

The amphiphilic proteins can be used as building blocks (BBs) forming various self-assemblies. Understanding their self-assembly mechanism is important for designing novel nanomaterials. Herein, the BBs dimers were first prepared from carboxyl-abundant enzymolyzed α-lactalbumin (α-lac) at 50 °C. Then the unidentate coordination of Ca2+ between the BBs caused a ß-sheet stacking to further self-assemble into nanotubes (NTs). Compared with the traditional "one-pot" method, a step-wise new method was applied to study hydrolysis, aggregation and self-assembly processes separately. The α-lac was hydrolyzed into 11 kDa amphiphilic peptides independent of temperature while a BBs dimer was formed at 50 °C by hydrophobic interaction. Ca2+ induced a conformational change of BBs and promoted these BBs gradually aggregate into 10 strands of filaments, which twisted into helical ribbons by electrostatic repulsion. Ca2+ further induced the twisted helical ribbons closed into NTs driven by the reduction of line tension energy. Besides, the carboxyl-Ca2+ coordination dominated NTs elongation in the longitudinal direction and filaments aggregation in the lateral direction with the same binding stoichiometry of 1:1 respectively. Finally, NTs successfully encapsulated curcumin and improved the viscosity of liquid food. α-Lac NTs show a high potential as a delivery system for food applications.

Intracranial Pressure after Closure of Dura Predicts Decompressive Craniectomy in Patients with Head Trauma.

This study aimed to address the risk factors of second decompressive craniectomy (DC) in patients with traumatic brain injury (TBI) who initially underwent mass lesion evacuation, but no primary DC. Patients were enrolled if they had had a hospital visit to Xiangya Hospital, Central South University with acute closed TBI from January 1, 2017 to December 31, 2019 and had undergone craniotomic mass lesion evacuation. Sociodemographic information, computed tomography (CT) information, clinical profiles, and surgical information were obtained from an electronic database. Twenty-four patients who had undergone a second decompressive craniectomy (SDC) and 39 patients who had not (NSO) were included in the analysis. The prevailing lesions differed between the groups (p = 0.010). The SDC group had more compressed/obliterated basal cisterns than the NSO group (p = 0.028). After closure of the dura, the SDC group also had higher intracranial pressure (ICP) than the NSO group (10.9 mm Hg vs. 6.5 mm Hg, p = 0.005). Binary logistical regression indicated that ICP after dura closure was an independent predictor of second DC (odds ratio [OR] = 1.317, p = 0.011). A model using ICP after dura closure alone had an area under the curve value of 0.757 in its receiver operating characteristic curve. An ICP >10.5 mm Hg after closure of dura for the prediction of a second DC had a sensitivity of 56.3% and a specificity of 92.6%.

TFCP2, a binding protein of ATF3, promotes the progression of glioma by activating the synthesis of serine.

Glioma is one of the most common malignancies. De novo serine synthesis promotes glioma progression and therapeutic resistance. Therefore, clarifying the regulatory mechanism of serine synthesis is of great significance for glioma therapy. In this study, we found that the expression of TFCP2 was upregulated in glioma and that TFCP2 promoted glioma cell growth and sphere formation. Knockdown of TFCP2 expression inhibited glioma cell growth, sphere formation and tumorigenicity in nude mice. In terms of its molecular mechanism, TFCP2 was found to interact with ATF3 to cooperatively regulate the de novo synthesis of serine. Knockdown of TFCP2 expression significantly inhibited the binding of ATF3 to the promoter of PHGDH (a rate-limiting enzyme in the serine synthesis process). In conclusion, our studies proved that TFCP2 jointly regulates the de novo synthesis of serine through interaction with ATF3, thus promoting glioma progression. This study suggests that TFCP2 is a potential target for glioma therapy.

Immune Landscape and an RBM38-Associated Immune Prognostic Model with Laboratory Verification in Malignant Melanoma.

BACKGROUND: Current studies have revealed that RNA-binding protein RBM38 is closely related to tumor development, while its role in malignant melanoma remains unclear. Therefore, this research aimed to investigate the function of RBM38 in melanoma and the prognosis of the disease. METHODS: Functional experiments (CCK-8 assay, cell colony formation, transwell cell migration/invasion experiment, wound healing assay, nude mouse tumor formation, and immunohistochemical analysis) were applied to evaluate the role of RBM38 in malignant melanoma. Immune-associated differentially expressed genes (DEGs) on RBM38 related immune pathways were comprehensively analyzed based on RNA sequencing results. RESULTS: We found that high expression of RBM38 promoted melanoma cell proliferation, invasion, and migration, and RBM38 was associated with immune infiltration. Then, a five-gene (A2M, NAMPT, LIF, EBI3, and ERAP1) model of RBM38-associated immune DEGs was constructed and validated. Our signature showed superior prognosis capacity compared with other melanoma prognostic signatures. Moreover, the risk score of our signature was connected with the infiltration of immune cells, immune-regulatory proteins, and immunophenoscore in melanoma. CONCLUSIONS: We constructed an immune prognosis model using RBM38-related immune DEGs that may help evaluate melanoma patient prognosis and immunotherapy modalities.

Study of Vertebral Artery Dissection by Ultrasound Superb Microvascular Imaging Based on Deep Neural Network Model.

To assess the diagnostic value of ultrasound Superb Microvascular Imaging (SMI) and versus Doppler ultrasound (TCD) for microvascular structure and aerodynamic changes in vertebral artery dissection (VAD). In this paper, we firstly simulate the process of clinician recognition of vertebral artery dissection and propose a combination of a priori shape information of vertebral artery dissection and deep folly convolutional networks (DFCNs) for IVUS. In this paper, 15 patients with vertebral artery dissection confirmed by SMI, digital subtraction angiography (DSA), or computed tomography angiography (CTA) from 2020 to 2021 were selected, and the true and false lumen diameters, peak systolic flow velocity (PSV), end-diastolic flow velocity (EDV) and PSV, EDV, and plasticity index (PI) of the intracranial vertebral artery were measured. Among the 15 patients with VAD, 4 (27%, 4/15) had trauma-induced secondary vertebral artery entrapment and 11 (73%, 11/15) had spontaneous entrapment without a clear cause. According to the structural characteristics of the vessels, there were 11 cases (73%, 11/15) of double-lumen, intramural hematoma, and vertebral artery dissection aneurysm, and 11 cases (73%, 11/15) of V1 segment. SMI not only provides an objective assessment of the vascular morphology and aerodynamic changes in VAD but also, in combination with TCD, can further determine the opening of the traffic branches in the posterior circulation, providing reliable information for the early diagnosis and treatment of microvascular dissection of the vertebral artery.

Clinical Validation of BCI-Controlled Wheelchairs in Subjects With Severe Spinal Cord Injury.

Brain-controlled wheelchairs are one of the most promising applications that can help people gain mobility after their normal interaction pathways have been compromised by neuromuscular diseases. The feasibility of using brain signals to control wheelchairs has been well demonstrated by healthy people in previous studies. However, most potential users of brain-controlled wheelchairs are people suffering from severe physical disabilities or who are in a "locked-in" state. To further validate the clinical practicability of our previously proposed P300-based brain-controlled wheelchair, in this study, 10 subjects with severe spinal cord injuries participated in three experiments and completed ten predefined tasks in each experiment. The average accuracy and information transfer rate (ITR) were 94.8% and 4.2 bits/min, respectively. Moreover, we evaluated the physiological and cognitive burdens experienced by these individuals before and after the experiments. There were no significant changes in vital signs during the experiment, indicating minimal physiological and cognitive burden. The patients' average systolic blood pressure before and after the experiment was 113±13.7 mmHg and 114±11.9 mmHg, respectively (P = 0.122). The patients' average heart rates before and after the experiment were 79±8.4/min and 79±8.2/min, respectively (P = 0.147). The average task load, measured by the National Aeronautics and Space Administration task load index, ranged from 10.0 to 25.5. The results suggest that the proposed P300-based brain-controlled wheelchair is safe and reliable; additionally, it does not significantly increase the patient's physical and mental task burden, demonstrating its potential value in clinical applications. Our study promotes the development of a more practical brain-controlled wheelchair system.

Knockdown of NCK1-AS1 inhibits the development of atherosclerosis by targeting miR-1197/COX10 axis.

BACKGROUND: Although long non-coding RNA (lncRNA) NCK1-AS1 plays important roles in human cancer, its function in atherosclerosis (AS) remains unclear. METHOD: The expression of NCK1-AS1 in AS blood samples was detected by qRT-PCR. Oxidized low-density lipoprotein (ox-LDL) was used to construct the AS cell model, and quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to evaluate NCK1-AS1 level. Cell phenotypes including proliferation and apoptosis were assessed by Cell Counting Kit-8 (CCK-8) assay and flow cytometer, respectively. The malondialdehyde level was measured to evaluate oxidative stress. The expression of apoptosis-related proteins was evaluated by western blot. The expression of inflammatory cytokines (IL-1ß, IL-6 and TNK-α) was measured by qRT-PCR and ELISA assays. The relationship among NCK1-AS1, miR-1197 and COX10 was determined by bioinformatic analysis and luciferase reporter assay. RESULTS: NCK1-AS1 was significantly upregulated in AS blood samples and ox-LDL stimulated vascular smooth muscle cells (VSMCs). Knockdown of NCK1-AS1 increased cell viability, reduced cell apoptosis and MDA level, and also inhibited the expression of inflammatory cytokines (IL-1ß, IL-6 and TNK-α) in ox-LDL stimulated VSMCs. NCK1-AS1 could positively regulate COX10 expression by directly sponging miR-1197. Moreover, co-transfection of sh-NCK1-AS1 and miR-1197 inhibitor, or co-transfection of sh-NCK1-AS1 and pc-COX10 (COX10 overexpressing plasmid) obviously reduced cell viability, promoted cell apoptosis, and increased MDA level in VSMCs followed by ox-LDL treatment for 24 h compared to that in sh-NCK1-AS1 transfected VSMCs. CONCLUSION: Our study revealed that knockdown of NCK1-AS1 attenuated the development of AS by regulating miR-1197/COX10 axis, suggesting that this lncRNA might be a potential therapeutic target for AS.