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Abstract Increasing attention has been given to the utilization of swarm intelligent optimization algorithms to facilitate cooperative target search of unmanned aerial vehicle swarm (UAVs). However, there exist common issues associated with swarm intelligent optimization algorithms, which are low search efficiency and easy to trap in local optima. Simultaneously, the concentrated initial positioning of UAVs increase the probability of collisions between UAVs. To address these issues, this paper proposes a reinforced robotic bean optimization algorithm (RRBOA) aimed at enhancing the efficiency of UAVs for cooperative target search in unknown environments. Firstly, the algorithm employs a region segmentation exploration strategy to enhance the initialization of UAVs, ensuring a uniform distribution of UAVs to avoid collisions and the coverage capability of UAVs search. Subsequently, a neutral evolution strategy is incorporated based on the spatial distribution pattern of population, which aims to enhance cooperative search by enabling UAVs to freely explore the search space, thus improving the global exploration capability of UAVs. Finally, an adaptive Levy flight strategy is introduced to expand the search range of UAVs, enhancing the diversity of UAVs search and then preventing the UAVs search from converging to local optima. Experimental results demonstrate that RRBOA has significant advantages over other methods on nine benchmark simulations. Furthermore, the extension testing, which focuses on simulating pollution source search, confirms the effectiveness and applicability of RRBOA

Abstract Objective Glioblastoma (GBM) is one of the most aggressive brain tumors and often leads to poor outcomes. Studies have indicated that glycan levels are significantly correlated with the pathogenesis and development of cancers. However, whether glycan levels can serve as diagnostic or prognostic biomarkers in GBM remains unclear. Methods We obtained glycomic profiles in tissue and serum samples from 55 individuals with GBM using a well‐established lectin biochip platform probing with 11 specific lectins. Results Our univariate analysis showed that 5 out of the 11 lectin‐probed glycans (LPGs) were significantly higher in GBM tissues than in peri‐tumoral tissues. After logistic regression analyses, only the Jacalin‐probed T‐antigen difference between the two groups remained significant (p = 0.037). Moreover, survival‐related analyses showed that the level of Jacalin‐probed T‐antigen was significantly associated with the progression‐free survival (p = 0.038) of patients. However, none of the LPG levels were correlated with the overall survival or the chemosensitivity to temozolomide therapy. The correlation coefficient analysis showed a moderate‐to‐strong correlation in the Jacalin‐probed T‐antigen levels between GBM tissues and serum samples, indicating its potential usefulness as a non‐invasive GBM progression biomarker. Interpretation Glycomics analyses can be helpful in the prediction of GBM recurrences and may provide information useful for GBM glycan‐based target therapies or vaccine development.

Abstract Background Olfactory dysfunction occurs frequently in Parkinson’s disease (PD). In this study, we aimed to explore the potential biomarkers and underlying molecular pathways of nicotine for the treatment of olfactory dysfunction in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice. Methods MPTP was introduced into C57BL/6 male mice to generate a PD model. Regarding in vivo experiments, we performed behavioral tests to estimate the protective effects of nicotine in MPTP-induced PD mice. RNA sequencing and traditional molecular methods were used to identify molecules, pathways, and biological processes in the olfactory bulb of PD mouse models. Then, in vitro experiments were conducted to evaluate whether nicotine can activate the prok2R/Akt/FoxO3a signaling pathway in both HEK293T cell lines and primary olfactory neurons treated with 1-methyl-4-phenylpyridinium (MPP+). Next, prok2R overexpression (prok2R+) and knockdown (prok2R−) were introduced with lentivirus, and the Akt/FoxO3a signaling pathway was further explored. Finally, the damaging effects of MPP+ were evaluated in prok2R overexpression (prok2R+) HEK293T cell lines. Results Nicotine intervention significantly alleviated olfactory and motor dysfunctions in mice with PD. The prok2R/Akt/FoxO3a signaling pathway was activated after nicotine treatment. Consequently, apoptosis of olfactory sensory neurons was significantly reduced. Furthermore, prok2R+ and prok2R− HEK293T cell lines exhibited upregulation and downregulation of the Akt/FoxO3a signaling pathway, respectively. Additionally, prok2R+ HEK293T cells were resistant to MPP+-induced apoptosis. Conclusions This study showed the effectiveness and underlying mechanisms of nicotine in improving hyposmia in PD mice. These improvements were correlated with reduced apoptosis of olfactory sensory neurons via activated prok2R/Akt/FoxO3a axis. These results explained the potential protective functions of nicotine in PD patients.

Alpha beta hydrolase domain containing 5 (ABHD5) is an essential coactivator of adipose triglyceride lipase (ATGL), a rate-limiting enzyme in various cell types that promotes the hydrolysis of triacylglycerol (TG) into diacylglycerol (DG) and fatty acid (FA). It acts as a critical regulatory factor in cellular lipid metabolism. The reprogramming of lipid metabolism is one of the hallmarks of cancer, suggesting that altering lipid metabolism could become a new strategy for tumor treatment. Research has revealed a close association between ABHD5 and the development and progression of malignancies. This review summarizes the role of ABHD5 in various malignant tumors and explores the different signaling pathways and metabolic routes that may be involved, providing a comprehensive mechanistic understanding of ABHD5.

Identification of potential cerebrovascular disorder in the patient with traumatic subarachnoid hemorrhage (tSAH) is a key element to decrease the complication occurrence and mortality rate. In this study, we aim to compare the diagnostic values between dual-source computed tomography angiography (DSCTA) and traditional tomography angiography (CTA) in identification of potential cerebrovascular disorder among tSAH patients. A total of 113 tSAH patients with the hemorrhage involving more than 2 cisterns were recruited. Among that, 42 patients received DSCTA scans, and another 71 patients received traditional CTA scans. Subsequently, all patients received digital subtraction angiography (DSA) tests to confirm the presence of the cerebrovascular disorder. In DSCTA scan group, 21.4 % (9/42) patients were reported to have cerebrovascular disorders: seven patients had intracranial aneurysms; a patient had pseudoaneurysm with carotid artery cavernous sinus fistula; and a patient had Moyamoya disease. DSA tests had the same results with that with DSCTA scans. In the cohort receiving CTA scans, 19.7 % (14/71) patients were reported to had intracranial aneurysms. However, the positive results of DSA tests for this cohort were 22.5 % (16/71). Two inconsistent results between the CTA scan and DSA test were found, including an arteriovenous malformation and an arteriovenous fistula. In summary, DSCTA and CTA had similar positive rates but differ in diagnostic accuracy for identification of cerebrovascular disorders in tSAH patients.

DLAT has been recognized as a cuproptosis-related gene that is crucial for cuproptosis in earlier research. The study is to look at how DLAT affects individuals with low-grade glioma's prognosis and immune infiltration. The Genotype-Tissue Expression (GTEx) database and the TCGA database were used in this work to download RNAseq data in TPM format. DLAT was found to be overexpressed in LGG by comparing DLAT expression levels between LGG and normal brain tissue, and the expression of DLAT was verified by immunohistochemistry and semi-quantitative analysis. Then, the functional enrichment analysis revealed that the biological functional pathways and possible signal transduction pathways involved were primarily focused on extracellular matrix organization, transmembrane transporter complex, ion channel complex, channel activity, neuroactive ligand-receptor interaction, complement and coagulation cascades, and channel activity. The level of immune cell infiltration by plasmacytoid dendritic cells and CD8 T cells was subsequently evaluated using single-sample gene set enrichment analysis, which showed that high DLAT expression was inversely connected with that level of infiltration. The link between the methylation and mRNA transcription of DLAT was then further investigated via the MethSurv database, and the results showed that DLAT's hypomethylation status was linked to a poor outcome. Finally, by evaluating the prognostic value of DLAT using the Cox regression analysis and Kaplan-Meier technique, a column line graph was created to forecast the overall survival (OS) rate at 1, 3, and 5 years after LGG identification. The aforementioned results demonstrated that high DLAT expression significantly decreased OS and DSS, and that overexpression of DLAT in LGG was significantly linked with WHO grade, IDH status, primary therapy outcome, overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) events. DLAT was discovered as a separate predictive sign of OS in the end. DLAT might thus represent a brand-new predictive biomarker.

The atrioventricular node (AVN) is a key component of the cardiac conduction system and takes over pacemaking of the ventricles if the sinoatrial node fails. IP3 (inositol 1,4,5 trisphosphate) can modulate excitability of myocytes from other regions of the heart, but it is not known whether IP3 receptor (IP3-R) activation modulates AVN cell pacemaking. Consequently, this study investigated effects of IP3 on spontaneous action potentials (APs) from AVN cells isolated from rabbit hearts. Immunohistochemistry and confocal imaging demonstrated the presence of IP3-R2 in isolated AVN cells, with partial overlap with RyR2 ryanodine receptors seen in co-labelling experiments. In whole-cell recordings at physiological temperature, application of 10 µM membrane-permeant Bt3-(1,4,5)IP3-AM accelerated spontaneous AP rate and increased diastolic depolarization rate, without direct effects on ICa,L, IKr, If or INCX. By contrast, application via the patch pipette of 5 µM of the IP3-R inhibitor xestospongin C led to a slowing in spontaneous AP rate and prevented 10 µM Bt3-(1,4,5)IP3-AM application from increasing the AP rate. UV excitation of AVN cells loaded with caged-IP3 led to an acceleration in AP rate, the magnitude of which increased with the extent of UV excitation. 2-APB slowed spontaneous AP rate, consistent with a role for constitutive IP3-R activity; however, it was also found to inhibit ICa,L and IKr, confounding its use for studying IP3-R. Under AP voltage clamp, UV excitation of AVN cells loaded with caged IP3 activated an inward current during diastolic depolarization. Collectively, these results demonstrate that IP3 can modulate AVN cell pacemaking rate.

Nanotechnology plays a pivotal role in the biomedical field, especially in the synthesis and regulation of drug particle size. Reducing drug particles to the micron or nanometer scale can enhance bioavailability. Supercritical fluid technology, as a green drug development strategy, is expected to resolve the challenges of thermal degradation, uneven particle size, and organic solvent residue faced by traditional methods such as milling and crystallization. This paper provides an insight into the application of super-stable homogeneous intermix formulating technology (SHIFT) and super-table pure-nanomedicine formulation technology (SPFT) developed based on supercritical fluids for drug dispersion and micronization. These technologies significantly enhance the solubility and permeability of hydrophobic drugs by controlling the particle size and morphology, and the modified drugs show excellent therapeutic efficacy in the treatment of hepatocellular carcinoma, pathological scarring, and corneal neovascularization, and their performance and efficacy are highlighted when administered through multiple routes of administration. Overall, supercritical fluids have opened a green and efficient pathway for clinical drug development, which is expected to reduce side effects and enhance therapeutic efficacy.

Abstract Lymph nodes play a pivotal role in tumor progression as key components of the lymphatic system. However, the unique physiological structure of lymph nodes has traditionally constrained the drug delivery efficiency. Excitingly, nanomedicines have shown tremendous advantages in lymph node-specific delivery, enabling distinct recognition and diagnosis of lymph nodes, and hence laying the foundation for efficient tumor therapies. In this review, we comprehensively discuss the key factors affecting the specific enrichment of nanomedicines in lymph nodes, and systematically summarize nanomedicines for precise lymph node drug delivery and therapeutic application, including the lymphatic diagnosis and treatment nanodrugs and lymph node specific imaging and identification system. Notably, we delve into the critical challenges and considerations currently facing lymphatic nanomedicines, and futher propose effective strategies to address these issues. This review encapsulates recent findings, clinical applications, and future prospects for designing effective nanocarriers for lymphatic system targeting, with potential implications for improving cancer treatment strategies.

Abstract Glioma is the most prevalent type of primary brain tumor, and glioblastoma multiforme (GBM) is the highest and most deadly type of primary central nervous system (CNS) tumor, affecting a significant number of patients each year, with a median overall survival of approximately 14.6 months after diagnosis. Despite intensive treatment, nearly all GBM patients experience recurrence, with a 5-year survival rate of about 5%. The protective BBB and high tumor heterogeneity prevent the effective delivery of drugs, resulting in the treatment failure of various drugs. The emergence of nanometer-scale diagnosis and treatment methods has provided new promising approaches to overcome these difficulties. Thus, our review focuses on the development of BBB-crossing nanomedicine-enhanced chemotherapy and combined therapy applications for glioma. Meanwhile, we also reviewed the strategies to overcome the blood–brain barrier. Additionally, we discuss recent achievements in the area of brain tumor treatment with nanomedicine and the rational design approach, which will offer recommendations for anti-GBM nanomedicine development.

ABSTRACT Pituitary adenomas (PAs) are common benign brain tumors. Although associations between the gastrointestinal microbiome and PA have been reported previously, studies on the distributions of salivary microbial species in PA patients and among their different clinical phenotypes are currently lacking. In this study, saliva samples from 42 patients and 20 healthy individuals were selected for third-generation sequencing. The PA group included four clinical phenotypes: adrenocorticotropic hormone-secreting PA (n = 6), growth hormone-secreting PA (n = 9), prolactin-secreting PA (n = 18), and nonfunctioning PA (n = 9). All samples were sequenced, and the data were clustered and de-chimerized to obtain information regarding the abundance of operational taxonomic units. We found that the species distributions in the saliva of PA patients were more abundant than those of healthy individuals. A total of 82 genera were identified across all samples, of which 14 and 17 genera were more abundant in the saliva samples of patients with PA and healthy individuals, respectively. In the phenotypic functional prediction, the phenotypes of anaerobic and Gram-positive organisms were more commonly seen in patients with PA than in healthy individuals. The bioinformatics prediction indicated that multiple metabolic pathways were involved in the pathogenesis of PA. In conclusion, this study highlighted the associations of salivary microbiome profiles with PA, which may improve the existing understanding of the pathogenesis of PA and provide diagnostic and therapeutic targets for PA. IMPORTANCE The gut and salivary microbiomes have been widely reported to be significantly associated with a number of neurological disorders. The stability of the microbiome in the oral cavity makes it a potentially ideal sample that can be conveniently obtained for the investigation of microbiome-based pathogenesis in diseases. In the present study, we used a single-molecule long-read sequencing technique to study the distribution of the salivary microbiota in patients with pituitary adenoma (PA) and healthy individuals, as well as among four clinical phenotypes of PA. We found that the diversity of salivary microbes was more abundant in PA patients than in healthy individuals. We also observed some unique genera in different PA phenotypes. The bioinformatics-based functional predictions identified potential links between microbes and different clinical phenotypes of PA. This study improves the existing understanding of the pathogenesis of PA and may provide diagnostic and therapeutic targets for PA.

Gene therapy has shown remarkable effectiveness in the management of disease like cancer and inflammation as a revolutionary therapeutic. Nonetheless, therapeutic drug target discovery, efficient gene delivery, and gene delivery vehicles continue to be significant obstacles. Due to their effective gene transport capabilities and low immunogenicity, supramolecular polymers have garnered significant interest. Herein, ABHD5 is identified as a potential therapeutic target since it is dysregulated in hepatocellular carcinoma (HCC). Interestingly, the downregulation of ABHD5 could induce programmed death-ligand 1 (PD-L1) expression in liver cancer, which may contribute to the immunosuppression. To overcome the immunosuppression caused by PD-L1, an injectable hydrogel is designed to achieve efficient abhydrolase domain containing 5 (ABHD5) gene delivery via the host-guest interaction with branched polyethyleneimine-g-poly (ethylene glycol), poly (ethylene oxide) and poly (propylene oxide) block copolymers and α-CD (PPA/CD), demonstrating the capability for sustained gene release. The co-assembly hydrogel demonstrates good biocompatibility and enhanced gene transfection efficiency, efficiently triggering tumor cell apoptosis. Overall, the results of this study suggest that ABHD5 is a potential therapeutic target, and that a host-guest-based supramolecular hydrogel could serve as a promising platform for the inhibition of HCC.

Background: Metal-responsive transcription factor-1 performs a necessary position in a range of cancers. It is unknown, though, how the prognosis of patients with low-grade gliomas is related to immune infiltration. Method: The Cancer Genome Atlas database was used in this investigation to evaluate MTF-1 transcription in low-grade glioma and healthy brain tissues, and immunohistochemistry was used to confirm MTF-1 levels. By using functional enrichment analysis and R software, the putative biological roles and signaling pathways connected to MTF-1 in LGG as well as its prognostic significance were investigated. Further research was done on the connection involving MTF-1 and tumor mutational burden in LGG. Finally, the research evaluated how MTF-1 and immune cell infiltration are related. Results: We noticed that the WHO grade, 1p/19q codeletion, and older age were all substantially linked with MTF-1 overexpression in low-grade gliomas. OS and disease-specific survival were significantly lowered as a result of MTF-1 transcription. MTF-1 was recognized as an independent OS prognostic predictor with a poor prognosis by multifactorial Cox analysis. Functional enrichment analysis revealed that the primary enrichment pathways were chemical carcinogenesis—receptor activation and the generation of miRNAs implicated in gene suppression by miRNA. Additionally, there was a negative correlation between MTF-1 overexpression and the degree of immune cell infiltration in neutrophils and DC. Conclusion: MTF-1 may be a novel prognostic biomarker.

The fabrication of freestanding 3D lattice structures with beam diameters less than 100 nm is a considerable challenge. Here, the authors report quasi-BCC nanolattices of gold and copper, featuring beam diameters as low as 34 nm, that demonstrate an exceptionally high capacity for energy absorption.

Abstract. Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations. The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), published in 2021, introduces major changes that advance the role of molecular diagnostics in meningiomas. To follow the revision of WHO CNS5, this expert consensus statement was formed jointly by the Group of Neuro-Oncology, Society of Neurosurgery, Chinese Medical Association together with neuropathologists and evidence-based experts. The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients. Registration:. Practice guideline REgistration for transPAREncy (PREPARE), IPGRP-2022CN234

Abstract As the indispensable second cellular messenger, calcium signaling is involved in the regulation of almost all physiological processes by activating specific target proteins. The importance of calcium ions (Ca2+) makes its “Janus nature” strictly regulated by its concentration. Abnormal regulation of calcium signals may cause some diseases; however, artificial regulation of calcium homeostasis in local lesions may also play a therapeutic role. “Calcium overload,” for example, is characterized by excessive enrichment of intracellular Ca2+, which irreversibly switches calcium signaling from “positive regulation” to “reverse destruction,” leading to cell death. However, this undesirable death could be defined as “calcicoptosis” to offer a novel approach for cancer treatment. Indeed, Ca2+ is involved in various cancer diagnostic and therapeutic events, including calcium overload-induced calcium homeostasis disorder, calcium channels dysregulation, mitochondrial dysfunction, calcium-associated immunoregulation, cell/vascular/tumor calcification, and calcification-mediated CT imaging. In parallel, the development of multifunctional calcium-based nanomaterials (e.g., calcium phosphate, calcium carbonate, calcium peroxide, and hydroxyapatite) is becoming abundantly available. This review will highlight the latest insights of the calcium-based nanomaterials, explain their application, and provide novel perspective. Identifying and characterizing new patterns of calcium-dependent signaling and exploiting the disease element linkage offer additional translational opportunities for cancer theranostics.

Abstract Background Melatonin (MEL), an endogenous hormone, has been widely investigated in neurological diseases. Microglia (MG), a resident immunocyte localizing in central nervous system is reported to play important functions in the animal model of temporal lobe epilepsy (TLE). Some evidence showed that MEL influenced activation of MG, but the detailed model of action that MEL plays in remains uncertain. Methods In this study, we established a model of TLE in mice by stereotactic injection of kainic acid (KA). We treated the mice with MEL. Lipopolysaccharide, ROCK2‐knockdown (ROCK‐KD) and ‐overexpression (ROCK‐OE) of lentivirus‐treated cells were used in cell experiments to simulate an in vitro inflammatory model. Results The results of electrophysiological tests showed that MEL reduced frequency and severity of seizure. The results of behavioral tests indicated MEL improved cognition, learning, and memory ability. Histological evidences demonstrated a significant reduction of neuronal death in the hippocampus. In vivo study showed that MEL changed the polarization status of MG from a proinflammatory M1 phenotype to an anti‐inflammatory M2 phenotype by inversely regulating the RhoA/ROCK signaling pathway. In cytological study, we found that MEL had a significant protective effect in LPS‐treated BV‐2 cells and ROCK‐KD cells, while the protective effect of MEL was significantly attenuated in ROCK‐OE cells. Conclusion MEL played an antiepileptic role in the KA‐induced TLE modeling mice both in behavioral and histological levels, and changed MG polarization status by regulating the RhoA/ROCK signaling pathway.

IntroductionPost-neurosurgical bacterial meningitis (PNBM) is a serious complication for patients who receive neurosurgical treatment, but the diagnosis is difficult given the complicated microenvironment orchestrated by sterile brain injury and pathogenic infection. In this study, we explored potential diagnostic biomarkers and immunological features using a proteomics platform.MethodsA total of 31 patients with aneurysmal subarachnoid hemorrhage (aSAH) who received neurosurgical treatment were recruited for this study. Among them, 15 were diagnosed with PNBM. The remaining 16 patients were categorized into the non-PNBM group. Proteomics analysis of the cerebrospinal fluid (CSF) was conducted on the Olink platform, which contained 92 immunity-related molecules.ResultsWe found that the expressions of 27 CSF proteins were significantly different between the PNBM and non-PNBM groups. Of those 27 proteins, 15 proteins were upregulated and 12 were downregulated in the CSF of the PNBM group. The receiver operating characteristic curve analysis indicated that three proteins (pleiotrophin, CD27, and angiopoietin 1) had high diagnostic accuracy for PNBM. Furthermore, we also performed bioinformatics analysis to explore potential pathways and the subcellular localization of the proteins.ConclusionIn summary, we found a cohort of immunity-related molecules that can serve as potential diagnostic biomarkers for PNBM in patients with aSAH. These molecules also provide an immunological profile of PNBM.

The sinoatrial node (SAN) and subsidiary pacemakers in the cardiac conduction system generate spontaneous electrical activity which is indispensable for electrical and therefore contractile function of the heart. The hyperpolarisation-activated cyclic nucleotide-gated channel HCN4 is responsible for genesis of the pacemaker “funny” current during diastolic depolarisation. S-palmitoylation, the reversible conjugation of the fatty acid palmitate to protein cysteine sulfhydryls, regulates the activity of key cardiac Na+ and Ca2+ handling proteins, influencing their membrane microdomain localisation and function. We investigated HCN4 palmitoylation and its functional consequences in engineered human embryonic kidney 293T cells as well as endogenous HCN4 in neonatal rat ventricular myocytes. HCN4 was palmitoylated in all experimental systems investigated. We mapped the HCN4 palmitoylation sites to a pair of cysteines in the HCN4 intracellular amino terminus. A double cysteine-to-alanine mutation CC93A/179AA of full length HCN4 caused a ∼67% reduction in palmitoylation in comparison to wild type HCN4. We used whole-cell patch clamp to evaluate HCN4 current (IHCN4) in stably transfected 293T cells. Removal of the two N-terminal palmitoylation sites did not significantly alter half maximal activation voltage of IHCN4 or the activation slope factor. IHCN4 was significantly larger in cells expressing wild type compared to non-palmitoylated HCN4 across a range of voltages. Phylogenetic analysis revealed that although cysteine 93 is widely conserved across all classes of HCN4 vertebrate orthologs, conservation of cysteine 179 is restricted to placental mammals. Collectively, we provide evidence for functional regulation of HCN4 via palmitoylation of its amino terminus in vertebrates. We suggest that by recruiting the amino terminus to the bilayer, palmitoylation enhances the magnitude of HCN4-mediated currents, but does not significantly affect the kinetics.

Abstract Background Applying traditional fluorescence navigation technologies in hepatocellular carcinoma is severely restricted by high false-positive rates, variable tumor differentiation, and unstable fluorescence performance. Results In this study, a green, economical and safe nanomedicine formulation technology was developed to construct carrier-free indocyanine green nanoparticles (nanoICG) with a small uniform size and better fluorescent properties without any molecular structure changes compared to the ICG molecule. Subsequently, nanoICG dispersed into lipiodol via a super-stable homogeneous intermixed formulation technology (SHIFT&nanoICG) for transhepatic arterial embolization combined with fluorescent laparoscopic hepatectomy to eliminate the existing shortcomings. A 52-year-old liver cancer patient was recruited for the clinical trial of SHIFT&nanoICG. We demonstrate that SHIFT&nanoICG could accurately identify and mark the lesion with excellent stability, embolism, optical imaging performance, and higher tumor-to-normal tissue ratio, especially in the detection of the microsatellite lesions (0.4 × 0.3 cm), which could not be detected by preoperative imaging, to realize a complete resection of hepatocellular carcinoma under fluorescence laparoscopy in a shorter period (within 2 h) and with less intraoperative blood loss (50 mL). Conclusions This simple and effective strategy integrates the diagnosis and treatment of hepatocellular carcinoma, and thus, it has great potential in various clinical applications.

Abstract The clinical applications of transcatheter arterial embolization (TAE) conversion therapy combined with hepatectomy have been severely restricted by ill‐defined tumoral boundaries and miniscule hidden lesions. Fluorescent surgical navigation is a promising method for overcoming these barriers. However, sufficient delivery of the fluorescent probe into the tumor region after long‐term TAE is challenging due to blockade of the tumor‐supplying artery. Here, a super‐stable homogeneous intermix formulating technology (SHIFT) to physically mix lipiodol and indocyanine green (ICG) formulation (SHIFT and ICG) for fluorescent surgical navigation after long‐term TAE conversion therapy is provided. Through the retrospective study of 45 clinical liver cancer patients, it is found that SHIFT and ICG formulation have excellent tumor deposition effect and safety. During surgical resection after long‐term TAE conversion therapy, SHIFT and ICG could clearly identify in real time the full tumor regions and boundaries and had a high signal‐to‐normal tissues ratio—even the indistinguishable satellite lesions could be identified with a strong fluorescence intensity. Meanwhile, SHIFT and ICG could improve operative, anesthetic, and postoperative variables associated with postoperative complications. This simple and effective SHIFT could provide precise fluorescent navigation for surgical resection following long‐term embolization therapy in clinical practice and has great potential for a translational pipeline.

The discrepancy between the number of patients awaiting liver transplantation and the number of available donors has become a key issue in the transplant setting. There is a limited access to liver transplantation, as a result, it is increasingly dependent on the use of extended criteria donors (ECD) to increase the organ donor pool and address rising demand. However, there are still many unknown risks associated with the use of ECD, among which preservation before liver transplantation is important in determining whether patients would experience complications survive after liver transplantation. In contrast to traditional static cold preservation of donor livers, normothermic machine perfusion (NMP) may reduce preservation injury, improve graft viability, and potentially ex vivo assessment of graft viability before transplantation. Data seem to suggest that NMP can enhance the preservation of liver transplantation to some extent and improve the early outcome after transplantation. In this review, we provided an overview of NMP and its application in ex vivo liver preservation and pre-transplantation, and we summarized the data from current clinical trials of normothermic liver perfusion.

As an independent characteristic of electromagnetic radiation, the polarization of light is sensitive to the scattering and absorption characteristics of the mineral particles. The combination of polarization and infrared absorption spectroscopy is conducive to rapidly and accurately detecting the SiO2 content of metallurgical sandstone deposits. In this study, the 8–14 μm polarized infrared absorption spectra and the grade of the sandstone ore samples were used to analyse the spectral characteristics of the sandstone powder samples. Principal component analysis (PCA) and the successive projection algorithm (SPA) were used to reduce the dimension of the original data, first-order derivative, reciprocal logarithm, and multivariate scattering correction (MSC) data. Then, generalized regression neural network (GRNN), partial least squares regression (PLSR), and convolutional neural network (CNN) were employed to establish a hyperspectral prediction model of SiO2 grade. The results show that the quantitative model by the PCA-CNN algorithm has the better prediction precision for the reciprocal logarithm data, with a coefficient of determination (R2), root mean square error (RMSE), and ratio of performance to interquartile range (RPIQ) of 0.907, 0.023, and 5.11, respectively. This method indicates that the polarized infrared absorption spectra and the PCA-CNN model can provide a more robust and significant spectral interpretation than single infrared spectra, and it is expected to be applied to any high-purity quartz deposit type for in situ and rapid analysis.

Abstract Background Photoimmunotherapy is one of the most promising strategies in tumor immunotherapies, but targeted delivery of photosensitizers and adjuvants to tumors remains a major challenge. Here, as a proof of concept, we describe bone marrow mesenchymal stem cell-derived nanovesicles (NVs) displaying anti-PD-L1 antibodies (aPD-L1) that were genetically engineered for targeted drug delivery. Results The high affinity and specificity between aPD-L1 and tumor cells allow aPD-L1 NVs to selectively deliver photosensitizers to cancer tissues and exert potent directed photothermal ablation. The tumor immune microenvironment was programmed via ablation, and the model antigen ovalbumin (OVA) was designed to fuse with aPD-L1. The corresponding membrane vesicles were then extracted as an antigen–antibody integrator (AAI). AAI can work as a nanovaccine with the immune adjuvant R837 encapsulated. This in turn can directly stimulate dendritic cells (DCs) to boast the body's immune response to residual lesions. Conclusions aPD-L1 NV-based photoimmunotherapy significantly improves the efficacy of photothermal ablation and synergistically enhances subsequent immune activation. This study describes a promising strategy for developing ligand-targeted and personalized cancer photoimmunotherapy. Graphic Abstract

Soil reflectance spectra and hyperspectral images have great potential to monitor and evaluate soil texture in large-scale scenarios. In hilly areas, sand, clay, and silt have similar spectral characteristics in visible, near-infrared, and short-wave infrared (VNIR-SWIR) reflection spectra. Soil texture spectra belong to mixed spectra despite some differences in particle size, mineral composition, and water content, making their distinction difficult. The accurate identification of the content within different particle sizes is difficult as it involves capturing spectral reflection features. Therefore, this study aimed to predict soil texture content through machine learning and unmixing the soil texture’s spectra while also comparing their respective modelling performances. Taking typical cultivated land in the Jianghuai hills as an example, the GaoFen-5 Advanced Hyperspectral Imaging (GF-5 AHSI) laboratory spectra of soil samples were used to predict sand, silt, and clay particle contents using partial least squares regression (PLSR) and convolutional neural networks (CNNs). The entire spectra of VNIR-SWIR regions were smoothed, and the dimensions were reduced via principal component analysis (PCA). The prediction models of sand, silt, and clay particle content were constructed, and inversion maps were generated using AHSI. The results showed that the PCA-CNN model achieved a higher prediction precision than the PCA-PLSR in both ASD and GF-5 data. Clay content exhibited the highest predictive performance with a coefficient of determination (R2) of 0.948 and 0.908 and a root mean square error (RMSE) of 26.51 g/kg and 31.24 g/kg, respectively, which represented a 39.0% and 79.8% increase in R2 and a 57% and 57.1% decrease in RMSE compared to that of the PCA-PLSR. This method indicates that the PCA-CNN model can effectively achieve nonlinear interactions between multiple spectral components and better model and fit spectral mixing processes; moreover, it provides an alternative method for investigating the spatial distribution of soil texture.

Ni/CaO, a low-cost dual-functional material (DFM), has been widely studied for integrated CO2 capture and hydrogenation. The core of this dual-functional material should possess both good CO2 capture–conversion performance and structural stability. Here, we synthesized Ni/CaO DFMs modified with alkali metals (Na, K, and Li) through a combination of precipitation and combustion methods. It was found that Na-modified Ni/CaO (Na-Ni/CaO) DFM offered stable CO2 capture–conversion activity over 20 cycles, with a high CO2 capture capacity of 10.8 mmol/g and a high CO2 conversion rate of 60.5% at the same temperature of 650 °C. The enhanced CO2 capture capacity was attributed to the improved surface basicity of Na-Ni/CaO. In addition, the incorporation of Na into DFMs had a favorable effect on the formation of double salts, which shorten the CO2 capture and release process and promoted DFM stability by hindering their aggregation and the sintering of DFMs.

Abstract Rett Syndrome (RTT) is a congenital, X‐chromosome‐linked developmental disorder characterized by developmental delay, dysautonomia, and breathing irregularities. RTT is also associated with sudden death and QT intervals are prolonged in some RTT patients. Most individuals with RTT have mutations in the MECP2 gene. Whilst there is some evidence for QT prolongation in mouse models of RTT, there is comparatively little information on how loss of Mecp2 function affects ventricular action potentials (APs) and, to‐date, none on ventricular APs from female RTT mice. Accordingly, the present study was conducted to determine ECG and ventricular AP characteristics of Mecp2Null/+ female mice. ECG recordings from 12–13 month old female Mecp2Null/+ mice showed prolonged rate corrected QT (QTc) intervals compared to wild‐type (WT) controls. Although Mecp2Null/+ animals exhibited longer periods of apnoea than did controls, no correlation between apnoea length and QTc interval was observed. Action potentials (APs) from Mecp2Null/+ myocytes had longer APD90 values than those from WT myocytes and showed augmented triangulation. Application of the investigational INa,Late inhibitor GS‐6615 (eleclazine; 10 μM) reduced both APD90 and AP triangulation in Mecp2Null/+ and WT myocytes. These results constitute the first direct demonstration of delayed repolarization in Mecp2Null/+ myocytes and provide further evidence that GS‐6615 may have potential as an intervention against QT prolongation in RTT.

Metabolic Syndrome (MS) remains the leading cause of mortality and morbidity globally. Adipose tissue releases adipokines that play key roles in metabolic and cardio-cerebro-vascular homeostasis. Subfatin, induced after exercise or upon cold exposure in adipose tissue, is a novel secreted protein homologous to Metrn, a neutrophic factor with angiogenic properties. The protein was proved to be of great significance in the browning of white adipose tissue (BWT) and insulin resistance (IR). It affected insulin sensitivity at least via its local autocrine/paracrine action through AMP-activated protein kinase (AMPK) or peroxisome proliferator-activated receptor δ (PPAR-δ) dependent signaling. Subfatin blocked the release of inflammatory mediators, improved intracellular insulin signal transduction and reversed IR. It also improved glucose tolerance and played a key role in metabolism and cardiovascular and cerebrovascular homeostasis. It was reported that the level of serum subfatin was significantly correlated with the occurrence and severity of coronary heart disease, which might be a new target for the treatment of coronary heart disease. In addition, exercise increased the level of subfatin in circulation and adipose tissue, promoted energy consumption, improved glucose and lipid metabolism, increased the heat production of brown fat, and strengthened the anti-inflammatory mechanism. Given its role in metabolic disorders, subfatin is considered as a candidate biomarker of MS. However, the clinical significance of subfatin remains largely unclear. The purpose of this article is to review the research on the effect of subfatin on MS in recent years.

Immunoglobulin A (IgA) is the most abundant immunoglobulin synthesized in the human body. It has the highest concentration in the mucosa and is second only to IgG in serum. IgA plays an important role in mucosal immunity, and is the predominant antibody used to protect the mucosal surface from pathogens invasion and to maintain the homeostasis of intestinal flora. Moreover, The binding IgA to the FcαRI (Fc alpha Receptor I) in soluble or aggregated form can mediate anti- or pro- inflammatory responses, respectively. IgA is also known as one of the most heavily glycosylated antibodies among human immunoglobulins. The glycosylation of IgA has been shown to have a significant effect on its immune function. Variation in the glycoform of IgA is often the main characteration of autoimmune diseases such as IgA nephropathy (IgAN), IgA vasculitis (IgAV), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). However, compared with the confirmed glycosylation function of IgG, the pathogenic mechanism of IgA glycosylation involved in related diseases is still unclear. This paper mainly summarizes the recent reports on IgA’s glycan structure, its function, its relationship with the occurrence and development of diseases, and the potential application of glycoengineered IgA in clinical antibody therapeutics, in order to provide a potential reference for future research in this field.

The coupling between optically active substances of algae particles and inorganic suspended solids of water makes the characteristics of reflection spectra of water complex and changeable. This makes modeling and inversion of polarization remote sensing in class II water difficult. In our study, considering the influence of the mixing ratio of algae particles and inorganic suspended solids, the sensor incidence angle, and the solar zenith angle on the polarization reflection spectrum, we analyzed the coupling characteristics of the polarized bidirectional reflectance of particulate matter through control experiments of mixed components of water particles in the laboratory. With Chaohu Lake in China as an example, the polarized reflectance coupling characteristics of water particles was investigated by the water-leaving radiation. The results showed that in the characteristic bands of 570, 675, and 705 nm, the degree of linear polarization (DOLP) was sensitive to the water-leaving radiation of the particles rather than to the reflectance. With the variation of observation angle, the reflection spectra were strongly interfered with by solar flare when the sensor zenith angle was close to 50° on the meridian plane with an azimuth angle of 180°, but DOLP was less affected, while also having a low correlation in the high concentration region. Combined with the coupling characteristics of particles at 675 and 705 nm, the model of DOLP ratio was established by partial least squares regression (PLSR) with a determination coefficient (R2) of 0.91, root mean square error (RMSE) 0.035, and a verification accuracy of 0.959. This shows that the model has better prediction ability for the coupling characteristics of water particles by the polarization reflection spectra and provides good support for mixed spectral unmixing of class II water.

Although immunotherapy has paved a new avenue for cancer treatment, inadequate immune response often executes suboptimal therapeutic effects. In general, an effective immune response undergoes presentation of antigen by antigen-presenting cells, proliferation and differentiation of lymphocytes, and attack of cancer cells by cytotoxic T lymphocytes (CTLs). The antigen self-presentation and immunosuppression reversal (ASPIRE) nanovaccine derived from dendritic cells provides a simplified and immune deregulated procedure for immunotherapy profiting from its orientable peculiarity. By integrating major histocompatibility complex class I (MHC-I) molecules into present specific epitopes and co-delivering anti-PD-1 antibody and B7 costimulatory molecules through the programmed biomimetic synthesis, the ASPIRE nanovaccine demonstrates a milestone in personalized cancer immunotherapy.

Background: Atrial-ventricular differences in voltage-gated Na+ currents might be exploited for atrial-selective antiarrhythmic drug action for the suppression of atrial fibrillation without risk of ventricular tachyarrhythmia. Eleclazine (GS-6615) is a putative antiarrhythmic drug with properties similar to the prototypical atrial-selective Na+ channel blocker ranolazine that has been shown to be safe and well tolerated in patients. Objective: The present study investigated atrial-ventricular differences in the biophysical properties and inhibition by eleclazine of voltage-gated Na+ currents. Methods: The fast and late components of whole-cell voltage-gated Na+ currents (respectively, INa and INaL) were recorded at room temperature (∼22°C) from rat isolated atrial and ventricular myocytes. Results: Atrial INa activated at command potentials ∼5.5 mV more negative and inactivated at conditioning potentials ∼7 mV more negative than ventricular INa. There was no difference between atrial and ventricular myocytes in the eleclazine inhibition of INaL activated by 3 nM ATX-II (IC50s ∼200 nM). Eleclazine (10 μM) inhibited INa in atrial and ventricular myocytes in a use-dependent manner consistent with preferential activated state block. Eleclazine produced voltage-dependent instantaneous inhibition in atrial and ventricular myocytes; it caused a negative shift in voltage of half-maximal inactivation and slowed the recovery of INa from inactivation in both cell types. Conclusions: Differences exist between rat atrial and ventricular myocytes in the biophysical properties of INa. The more negative voltage dependence of INa activation/inactivation in atrial myocytes underlies differences between the 2 cell types in the voltage dependence of instantaneous inhibition by eleclazine. Eleclazine warrants further investigation as an atrial-selective antiarrhythmic drug.

Drug resistance is the most significant causes of cancer chemotherapy failure. Various mechanisms of drug resistance include tumor heterogeneity, tumor microenvironment, changes at cellular levels, genetic factors, and other mechanisms. In recent years, more attention has been paid to tumor resistance mechanisms and countermeasures. Nanomedicine is an emerging treatment platform, focusing on alternative drug delivery and improved therapeutic effectiveness while reducing side effects on normal tissues. Here, we reviewed the principal forms of drug resistance and the new possibilities that nanomaterials offer for overcoming these therapeutic barriers. Novel nanomaterials based on tumor types are an excellent modality to equalize drug resistance that enables gain more rational and flexible drug selectivity for individual patient treatment. With the emergence of advanced designs and alternative drug delivery strategies with different nanomaterials, overcome of multidrug resistance shows promising and opens new horizons for cancer therapy. This review discussed different mechanisms of drug resistance and recent advances in nanotechnology-based therapeutic strategies to improve the sensitivity and effectiveness of chemotherapeutic drugs, aiming to show the advantages of nanomaterials in overcoming of drug resistance for tumor chemotherapy, which could accelerate the development of personalized medicine.

The anodic dissolution of the high-grade nickel matte in the sulfuric acid solution was investigated at the dynamic potential and potentiostatic polarizations, and the solid products on the surface of the matte at various polarized potentials were characterized by optical microscope, scanning electron microscope and Raman spectroscopy in order to understand the passivation mechanism for the anodic dissolution of nickel matte. The results show that the oxidation dissolution activity of nickel and copper sulfides existing in the matte during the anodic dissolution decreases in the order Cu2S ​> ​Ni3S2 ​> ​NiS ​> ​CuS. When the anodic polarization potential is increasing to 1.2 ​V vs. SCE, the solid product for the oxidation of Cu2S is composed of CuS, which forms a compact layer with fine cracks covering the surface and hinders the anodic dissolution further of Cu2S underneath. While, at the same polarization potential, Ni3S2 in the matte can be anodically dissolved to form Ni2+ and elemental sulfur, and the solid product layer composing of sulfur and NiS is porous with coarse cracks, and has adverse effect on the anodic dissolution of Ni3S2 in the nickel matte.

Sodium silicate, a new type of CO2 sorbent, has a relatively low cost, but its sorption reactivity is not yet good enough. Alkali carbonate doping is commonly used as an effective means to improve the CO2 uptake reactivity of solid sorbents. In this study, sodium orthosilicate, Na4SiO4, was synthesized and mixed with 5, 10, and 20 mol% of Li2CO3–Na2CO3 or Li2CO3–Na2CO3–K2CO3 as CO2 sorbents. The promotion of alkali carbonates on Na4SiO4 in CO2 capture was characterized using thermal analyses in an 80 vol% CO2–20 vol% N2 atmosphere. The phase evolution and structural transformations during CO2 capture were characterized by in situ XRD and Raman, and the results showed that the intermediate pyrocarbonate, C2O52−, which emerged from alkali carbonates, enhanced the CO2 capture of Na4SiO4 to form Na2CO3 and Na2SiO3 from 100 °C. Isothermal analyses showed that 10 mol% of Li2CO3–Na2CO3 was the optimal additive for Na4SiO4 to attain better CO2 uptake performance. The alkali carbonates were effective in reducing the activation energy for both chemisorption and bulk diffusion, improving the cycle stability of Na4SiO4.

The verification efficiency and precision of copper ore grade has a great influence on copper ore mining. At present, the common method for the exploration of reserves often uses chemical analysis and identification, which have high costs, long cycles, and pollution risks but cannot realize the in situ determination of the copper grade. The existing scalar spectrometric techniques generally have limited accuracy. As a vector spectrum, polarization state information is sensitive to mineral particle distribution and composition, which is conducive to high-precision detection. Taking the visible-near infrared parallel polarization reflectance spectrum data and grade data of a copper mine in Xiaoyuan village, Huaining County, Anhui Province, China, as an example, the characteristics of the parallel polarization spectra of the copper mine were analyzed. The spectra were pretreated by first-order derivative transform and wavelet denoising, and the dimensions of wavelet denoising spectra, parallel polarization spectra, and first-order derivative spectra were also reduced by principal component analysis (PCA). Three, four, and eight principal components of the three types of spectra were selected as variables. Four machine learning models, the radial basis function (RBF), support vector machine (SVM), generalized regression neural network (GRNN), and partial least squares regression (PLSR), were selected to establish the PCA parallel polarization reflectance spectrum and copper grade prediction model. The accuracy of the model was evaluated by the determination coefficient (R2) and root mean square error (RMSE). The results show that, for parallel polarization spectra, first-order derivative spectra, and wavelet denoising spectra, the PCA-SVM model has better results, with R2 values of 0.911, 0.942, and 0.953 and RMSE values of 0.022, 0.019, and 0.017, respectively. This method can effectively reduce the redundancy of polarized hyperspectral data, has better model prediction ability, and provides a useful exploration for the grade analysis of hydrothermal copper deposits at meso-low temperatures.

In this work, an innovative method was utilized to determine the AgCl(1% mol)/Ag reference electrode potential versus Cl2/Cl− at 673 K. Instead of directly measuring the chlorine electrode potential, the AgCl(1% mol)/Ag electrode potential versus Cl2/Cl− was calculated from the decomposition voltage of LiCl and the equilibrium potential of Li+/Li versus AgCl(1% mol)/Ag in a LiCl-KCl melt. The decomposition voltage of LiCl in the LiCl-KCl melt was calculated using the Nernst equation and the equilibrium potential of Li+/Li was determined by chronopotentiometry, open circuit chronopotentiometry and potentiodynamic scan techniques, and the deviation is within 5 mV. The AgCl(1% mol)/Ag electrode potential was determined to be −1.130 V vs Cl2/Cl− at 673 K. Since it does not involve direct injection of chlorine gas, this method is more convenient and safer than existing approaches. Furthermore, it also has the potential to be used to calibrate reference electrodes in a variety of melts.

Terminal sialic acids (Sia) on soluble glycoprotein of saliva play an important role in the clearance of influenza virus. The aim of this study is to investigate the alteration of sialylation on the salivary proteins of women during the lactation period and its effect on the saliva binding ability to virus. In total, 210 saliva samples from postpartum women with and without breastfeeding were collected, and the expression level of α2-3/6-linked Sia on the whole salivary proteins and specific glycoproteins of IgA and MUC5B from different groups were tested and verified using lectin microarray, blotting analysis and ELISA based method. The H1N1 vaccine and three strains of Avian influenza virus (AIV) were used for the saliva binding assay. Results showed that the variation in salivary expression level of α2-3-linked Sia was much more obvious than the α2-6-linked Sia, which was up-regulated significantly in the breastfeeding groups compared to the non-breastfeeding groups at the same postpartum stage. Furthermore, the binding abilities of salivary glycoproteins to AIV strains and H1N1 vaccine were increased in breastfeeding groups accordingly. This finding adds new evidence for the maternal benefit of breastfeeding and provides new thinking to protect postpartum women from AIV infection.

The prognosis of glioma is significantly correlated with the pathological grades; however, the correlations between the prognostic biomarkers with pathological grades have not been elucidated. S100A11 is involved in a variety of malignant biological processes of tumor, whereas its biological and clinicopathological features on glioma remain unclear. In this study, the S100A11 expression and clinical information were obtained from the public databases (TCGA, GEPIA2) to analyze its correlations with the pathological grade and the prognosis of glioma patients. We then verified the expression of S100A11 by immunohistochemistry staining. The effects of S100A11 on the proliferation of glioma cells were confirmed by cytological function assays (CCK-8, Flow cytometry, Clone formation assay) in vitro , the role of S100A11 in regulation of glioma growth was determined by xenograft model assay. We observed that S100A11 expression positively correlated with the pathological grades, while negatively correlated with the survival time of patients. In cytological analysis, we found the proliferations of glioma cell lines were significantly inhibited in vitro ( P < 0.05) after interfering S100A11 expression via shRNAs. The cell cycle was blocked at G0/G1 stage. The ability of clone formation was significantly decreased, and the tumorigenicity in vivo was weakened ( P < 0.05). In summary, S100A11 was over-expressed in gliomas and positively correlated with the pathological grades. Interfering the expression of S100A11 significantly inhibited the proliferation of glioma in vitro and the tumorigenicity in vivo ( P < 0.05). In conclusion, S100A11 might be considered as a potential biomarker in glioma.

Rett syndrome (RTT) is a severe developmental disorder that is strongly linked to mutations in the MECP2 gene. RTT has been associated with sudden unexplained death and ECG QT interval prolongation. There are mixed reports regarding QT prolongation in mouse models of RTT, with some evidence that loss of Mecp2 function enhances cardiac late Na current, INa,Late. The present study was undertaken in order to investigate both ECG and ventricular AP characteristics in the Mecp2Null/Y male murine RTT model and to interrogate both fast INa and INa,Late in myocytes from the model. ECG recordings from 8–10-week-old Mecp2Null/Y male mice revealed prolongation of the QT and rate corrected QT (QTc) intervals and QRS widening compared to wild-type (WT) controls. Action potentials (APs) from Mecp2Null/Y myocytes exhibited longer APD75 and APD90 values, increased triangulation and instability. INa,Late was also significantly larger in Mecp2Null/Y than WT myocytes and was insensitive to the Nav1.8 inhibitor A-803467. Selective recordings of fast INa revealed a decrease in peak current amplitude without significant voltage shifts in activation or inactivation V0.5. Fast INa ‘window current’ was reduced in RTT myocytes; small but significant alterations of inactivation and reactivation time-courses were detected. Effects of two INa,Late inhibitors, ranolazine and GS-6615 (eleclazine), were investigated. Treatment with 30 µM ranolazine produced similar levels of inhibition of INa,Late in WT and Mecp2Null/Y myocytes, but produced ventricular AP prolongation not abbreviation. In contrast, 10 µM GS-6615 both inhibited INa,Late and shortened ventricular AP duration. The observed changes in INa and INa,Late can account for the corresponding ECG changes in this RTT model. GS-6615 merits further investigation as a potential treatment for QT prolongation in RTT.

In order to rationally develop and utilize a Ta–Nb–Li–Rb rare metal deposit in Jiangxi Province, the mineralogical characteristics of the ore, such as chemical composition, mineral composition, modes of occurrence of major elements, and dissemination characteristics of major minerals, were investigated in detail based on optical microscopy analysis, chemical analysis, X-ray diffraction analysis, artificial panning, mineral liberation analysis, and electron probe microanalysis. The results reveal that the main useful elements in the ore are tantalum, niobium, lithium, and rubidium. Niobium and tantalum are mainly found in the mineral form of columbite. Columbite has particle sizes ranging from 0.5 mm to 0.012 mm, with the most common sizes being 0.3 to 0.044 mm. Intergranular dispersion accounts for 73.92% of the embedding in columbite, whereas inclusions account for 26.08%. Lithium is found mostly in zinnwaldite, while rubidium is found primarily in feldspar and zinnwaldite, both in a homogenous distribution. The beneficiation evaluation of this ore was conducted based on the mineralogical characteristic, and it indicates that the tantalum-niobium–lithium–rubidium rare metal resources, as well as the feldspar and quartz non-metallic resources in the ore, can be effectively and comprehensively recovered using gravity, magnetic, and flotation separation methods. A staged grinding and separating process was adopted which could produce tantalum–niobium mineral concentrates (18.34% Ta2O5 at a recovery of 47.65% and 41.33% Nb2O5 at a recovery of 69.96%), zinnwaldite concentrate (2.41% Li2O and 0.80% Rb2O at a recovery of 81.82%) and other concentrates such as cassiterite, topaz, galena, sphalerite, and feldspar. This study provides suggestions for the rational development and utilization of the deposit and provides a reasonable level of recovery prediction.

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the recent global COVID-19 outbreak, which led to a public health emergency. Entry of SARS-CoV-2 into human cells is dependent on the SARS-CoV receptor, angiotensin converting enzyme 2 (ACE2) receptor, and cathepsin. Cathepsin degrades the spike protein (S protein), which results in the entry of viral nucleic acid into the human host cell.MethodsWe explored the susceptibility of the central nervous system (CNS) to SARS-CoV-2 infection using single-cell transcriptome analysis of glioblastoma.ResultsThe results showed that ACE2 expression is relatively high in endothelial cells (ECs), bone marrow mesenchymal stem cells (BMSCs), and neural precursor cells (NPCs). Cathepsin B (Cat B) and cathepsin (Cat L) were also strongly expressed in various cell clusters within the glioblastoma microenvironment. Immunofluorescence staining of glioma and normal brain tissue chips further confirmed that ACE2 expression co-localized with CD31, CD73, and nestin, which confirmed the susceptibility to SARS-CoV-2 of nervous system cells, including ECs, BMSCs, and NPCs, from clinical specimens.ConclusionsThese findings reveal the mechanism of SARS-CoV-2 neural invasion and suggest that special attention should be paid to SARS-CoV-2–infected patients with neural symptoms, especially those who suffered a glioma.

Statins have been reported to suppress CD40 expression and nuclear factor (NF)-κB activation, which are both up-regulated in the intestines following traumatic brain injury (TBI)-induced intestinal injury. In this study, we aimed to investigate the effects of the statin rosuvastatin on post-TBI jejunal injury in rats, focusing on potential mechanisms involving the CD40/NF-κB signaling pathway. The jejunal CD40 expression was determined by western blotting. The DNA-binding activity of NF-κB was assessed by electrophoretic mobility shift assays (EMSAs). The tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels were assessed by enzyme-linked immunosorbent assays (ELISAs). The severity of the jejunal mucosal injury was assessed by hematoxylin and eosin (HE) staining and histopathological evaluation. We found that the post-TBI upregulation of both CD40 expression and NF-κB activity in the jejunal tissues were significantly inhibited by rosuvastatin, while the post-TBI expression of TNF-α and IL-1β was significantly suppressed by rosuvastatin. In addition, rosuvastatin significantly ameliorated TBI-induced effects on the villus height, crypt depth, and villous surface area. Rosuvastatin suppressed TBI-induced intestinal injury in rats, which may be associated with the blockade of the CD40/NF-κB pathway.

Background: Intracranial vertebral artery dissection aneurysms (VADAs) may cause acute ischemia or hemorrhage, in which case urgent endovascular treatment will be needed. Although the majority of patients obtain a good functional outcome after surgery, a surprising finding has been a poor quality of life (QOL) in follow-up. The purpose of this study was to evaluate clinical efficacy in reconstructive endovascular therapy for acute intracranial VADAs and to analyze the factors contributing to subsequent QOL.Methods: In this prospective study, 33 consecutive VADA patients with subarachnoid hemorrhage were recruited for comparison with 37 VADA patients with posterior circulation cerebral ischemia. All VADA patients were treated using a reconstructive strategy. Clinical, radiological, neurological, and cognitive data, as well as QOL, were assessed at admission and 6 months after surgery. Stoke Specific Quality of Life (SS-QOL) was evaluated for patients with good functional outcome [modified Ranking Scale (mRS) scoring 0-2] for subgroup analysis. Predictors for QOL at follow-up were analyzed by regression model.Results: Immediate angiography after surgery showed complete VADA obliteration in 57 (81.4%) patients and partial obliteration in 13 (18.6%) patients. Three (4.3%) cases suffered from perioperative complications, comprising two cases of stent thrombosis in the hemorrhagic group and one case of posterior inferior cerebellar artery occlusion in the ischemic group. Twenty-five (75.8%) patients in the hemorrhagic group and 30 (81.1%) patients in the ischemic group had a favorable outcome (mRS scoring 0-2) at 6-month follow-up. Follow-up angiography displayed that one case of recurrence occurred separately in both groups. Fifteen of the 33 hemorrhagic patients (45.5%) and 19 of the 37 ischemic patients (51.4%) rated QOL at follow-up as bad (SS-QOL score ≤ 3.9) despite a good functional outcome. Severity of neurological disorder and impaired neurocognition at baseline in VADA patients are proved to be independent predictors for the decline of QOL according to regression analysis.Conclusion: Reconstructive endovascular therapy for acute intracranial VADAs is a safe and effective method with a low complication rate. VADAs lead to impaired QOL at 6-month follow-up, which is attributable to multiple factors. This study demonstrated that neurological and cognitive status at baseline is of significant importance for QOL after VADAs.

Using ferric chloride as an oxidant, here, we investigated the leaching effect of low-nickel matte in a flow field produced by mechanical agitation. The factors affecting a leaching reaction, such as stirring speed, leaching time, low-nickel matte particle size, and inert abrasive quartz sand, were studied. X-ray diffraction (XRD), X-ray fluorescence spectroscopy (XRF), a laser particle size analyzer, optical microscopy (OM), a scanning electron microscopy (SEM) with an energy dispersive X-ray detector (EDS), and a Raman spectrometer were used to characterize the materials before and after the leaching reaction. The contents of the main metal ions such as Ni, Cu, and Co in the leaching solution were analyzed by inductively coupled plasma atomic emission spectroscopy (ICP-AES). Using the control variable method, the optimal experimental conditions were as follows: 2 mol/L FeCl3—0.5 mol/L HCl-H2O system with low-nickel matte and quartz sand (mass ratio is 1:5) and leaching at 90 °C for 8 h. The results showed that the blocking effect of the solid product sulfur layer was effectively removed and continuous leaching was realized. The leaching efficiencies of Ni, Cu, and Co were 98.9%, 99.3%, and 98.1%, respectively.