The major hurdle in glioblastoma therapy is the low efficacy of drugs crossing the blood–brain barrier (BBB). Neisseria meningitidis is known to specifically enrich in the central nervous system ...through the guidance of an outer membrane invasion protein named Opca. Here, by loading a chemotherapeutic drug methotrexate (MTX) in hollow manganese dioxide (MnO2) nanoparticles with surface modification of the Opca protein of Neisseria meningitidis, a bionic nanotherapeutic system (MTX@MnO2‐Opca) is demonstrated to effectively overcome the BBB. The presence of the Opca protein enables the drug to cross the BBB and penetrate into tumor tissues. After accumulating in glioblastoma, the nanotherapeutic system catalyzes the decomposition of excess H2O2 in the tumor tissue and thereby generates O2, which alleviates tumor hypoxia and enhances the effect of chemotherapy in the treatment of glioblastoma. This bionic nanotherapeutic system may exhibit great potential in the treatment of glioblastoma.
By loading the chemotherapeutic drug methotrexate in hollow manganese dioxide nanoparticles with surface modification of Opca protein of Neisseria meningitidis, a bionic nanotherapeutic system is constructed to effectively overcome the blood–brain barrier for improved glioblastoma therapy.
Glioblastoma is the most common lethal malignant intracranial tumor with a low 5‐year survival rate. Currently, the maximal safe surgical resection, followed by high‐dose radiotherapy (RT), is a ...standard treatment for glioblastoma. However, high‐dose radiation to the brain is associated with brain injury and results in a high fatality rate. Here, integrated pharmaceutics (named D‐iGSNPs) composed of gold sub‐nanometer particles (GSNPs), blood‐brain barrier (BBB) penetration peptide iRGD, and cell cycle regulator α‐difluoromethylornithine is designed. In both simulated BBB and orthotopic murine GL261 glioblastoma models, D‐iGSNPs are proved to have a beneficial effect on the BBB penetration and tumor targeting. Meanwhile, data from cell and animal experiments reveal that D‐iGSNPs are able to sensitize RT. More importantly, the synergy of D‐iGSNPs with low‐dose RT can exhibit an almost equal therapeutic effect with that of high‐dose RT. This study demonstrates the therapeutic advantages of D‐iGSNPs in boosting RT, and may provide a facile approach to update the current treatment of glioblastoma.
Multifunctionalized gold sub‐nanometer particles (D‐iGSNPs) are designed to sensitize radiotherapy against glioblastoma, which is modified with cyclopeptide iRGD and cell cycle regulator α‐difluoromethylornithine. With small size and iRGD modification, the D‐iGSNPs can easily penetrate through the blood‐brain barrier and target the glioma, which make radiotherapy more effective toward glioblastoma.
Surfactant flooding as a potential enhanced oil recovery technology in depleted reservoirs after water flooding has attracted extensive attention. In this study, 12 surfactants belonging to five ...different types of surfactants and their compounded formulations were investigated for surfactant flooding under 90–120 °C and 20 × 104 mg/L salinity. Two surfactant formulations obtained a stable ultralow interfacial tension (IFT) level (≤10–3 mN/m) with crude oil after aging for 125 days. The surfactant formulations were used to further investigate the effects of the initial IFT values, the dynamic reduction rate of IFT, and the surfactant concentration and emulsification on oil recovery through core flooding experiments. The results indicated that oil recovery increased with the decrease of the initial IFT values and the increase of the dynamic reduction rate of IFT. The 10–3 mN/m IFT level yielded an additional oil recovery of approximately 7% compared with the 10–1 mN/m IFT level. However, under the same IFT level (10–4 mN/m), it was not the bigger the surfactant concentration that resulted in a higher additional oil recovery. In four surfactant concentrations (0.2%, 0.5%, 1%, and 3%), the 0.5% surfactant formulation obtained the highest oil recovery of 36.65%. Further study manifested that emulsification has important effects on oil recovery. When surfactant concentrations were increased to 1% and 3%, the emulsification was too strong, which makes it more difficult to displace oil. The two selected surfactant formulations could successfully yield additional oil recovery of 20–26%, which indicates these two formulations have great potential for improving oil recovery in high temperature and high salinity oil reservoirs.
A newly discovered iridescent virus that causes severe disease and high mortality in farmed Litopenaeus vannamei in Zhejiang, China, has been verified and temporarily specified as shrimp hemocyte ...iridescent virus (SHIV). Histopathological examination revealed basophilic inclusions and pyknosis in hematopoietic tissue and hemocytes in gills, hepatopancreas, periopods and muscle. Using viral metagenomics sequencing, we obtained partial sequences annotated as potential iridoviridae. Phylogenetic analyses using amino acid sequences of major capsid protein (MCP) and ATPase revealed that it is a new iridescent virus but does not belong to the five known genera of Iridoviridae. Transmission electron microscopy showed that the virus exhibited a typical icosahedral structure with a mean diameter of 158.6 ± 12.5 nm (n = 30)(v-v) and 143.6 ± 10.8 nm (n = 30)(f-f), and an 85.8 ± 6.0 nm (n = 30) nucleoid. Challenge tests of L. vannamei via intermuscular injection, per os and reverse gavage all exhibited 100% cumulative mortality rates. The in situ hybridization showed that hemopoietic tissue, gills, and hepatopancreatic sinus were the positively reacting tissues. Additionally, a specific nested PCR assay was developed. PCR results revealed that L. vannamei, Fenneropenaeus chinensis, and Macrobrachium rosenbergii were SHIV-positive, indicating a new threat existing in the shrimp farming industry in China.
Nicotinamide mononucleotide (NMN) or Nicotinamide-1-ium-1-β-D-ribofuranoside 5′-phosphate is a nucleotide that can be converted into nicotinamide adenine dinucleotide (NAD) in human cells. NMN has ...recently attracted great attention because of its potential as an anti-aging drug, leading to great efforts for its effective manufacture. The chemical synthesis of NMN is a challenging task since it is an isomeric compound with a complicated structure. The majority of biological synthetic routes for NMN is through the intermediate phosphoribosyl diphosphate (PRPP), which is further converted to NMN by nicotinamide phosphoribosyltransferase (Nampt). There are various routes for the synthesis of PRPP from simple starting materials such as ribose, adenosine, and xylose, but all of these require the expensive phosphate donor adenosine triphosphate (ATP). Thus, an ATP regeneration system can be included, leading to diminished ATP consumption during the catalytic process. The regulations of enzymes that are not directly involved in the synthesis of NMN are also critical for the production of NMN. The aim of this review is to present an overview of the biological production of NMN with respect to the critical enzymes, reaction conditions, and productivity.
The basal forebrain is a group of nerve nuclei on the ventral side of the ventral ganglion, composed of γ‐aminobutyric acid neurons, glutamatergic neurons, cholinergic neurons, and orexigenic ...neurons. Previous studies have focused on the involvement of the basal forebrain in regulating reward, learning, movement, sleep–awakening, and other neurobiological behaviors, but its role in the regulation of general anesthesia has not been systematically elucidated. Therefore, the different neuronal subtypes in the basal forebrain and projection pathways in general anesthesia will be discussed in this paper. In this paper, we aim to determine and elaborate on the role of the basal forebrain in general anesthesia and the development of theoretical research and provide a new theory.
General anesthesia has been widely used in clinical practice for many years, but its underlying mechanism remains unclear. The basal forebrain (BF) is a major component in the ascending reticular activation system, which plays a key role in anesthesia. On the one hand, BF is classified into the following anatomical structures: The medial septum (MS), the nucleus basalis magnocellularis (NBM), the ventral pallidum (VP), the substantia innominate (SI), the level of division of diagonal band (HDB), and the magnocellular preoptic nucleus (MCPO). On the other hand, BF is made up of four types of neurons: cholinergic neurons, γ‐aminobutyric acid neurons, glutamatergic neurons, and orexigenic neurons. However, different types of cells in BF and different substructures of BF play different roles in regulating anesthesia and the mechanism is still unclear. In this review, we focus mainly on the role of BF in general anesthesia. Thus, the investigations of the BF will contribute toward understanding the mechanism of general anesthesia.
How general anesthesia causes loss of consciousness has been a mystery for decades. It is generally thought that arousal-related brain nuclei, including the locus coeruleus (LC), are involved. Here, ...by monitoring locomotion behaviors and neural activities, we developed a larval zebrafish model for studying general anesthesia induced by propofol and etomidate, two commonly used intravenous anesthetics. Local lesion of LC neurons via two-photon laser-based ablation or genetic depletion of norepinephrine (NE; a neuromodulator released by LC neurons) via CRISPR/Cas9-based mutation of dopamine-β-hydroxylase (dbh) accelerates induction into and retards emergence from general anesthesia. Mechanistically, in vivo whole-cell recording revealed that both anesthetics suppress LC neurons’ activity through a cooperative mechanism, inhibiting presynaptic excitatory inputs and inducing GABAA receptor-mediated hyperpolarization of these neurons. Thus, our study indicates that the LC-NE system plays a modulatory role in both induction of and emergence from intravenous general anesthesia.
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•Intravenous anesthetics induce general anesthesia in larval zebrafish•Impairment of the locus coeruleus (LC)-norepinephrine system affects anesthesia•Anesthetics suppress LC neuronal activities via pre- and postsynaptic mechanisms•Larval zebrafish is an ideal model for investigation of general anesthesia
The locus coeruleus (LC)-norepinephrine (NE) system is involved in general anesthesia. Here, Du et al. show that the LC-NE system plays a modulatory role in the induction and emergence of intravenous general anesthesia induced by propofol and etomidate, both of which suppress LC neuronal activities through a cooperative mechanism.
Dopamine (DA), a monoamine neurotransmitter, is synthesized and released mainly by neurons in the ventral tegmental area and the substantia nigra (SN) pars compacta of the midbrain. DA and its ...receptors are essential for the regulation of arousal, movement, cognition, reward, and other neurobiological behaviors. Arousal, locomotion, cognition, reward, and other neurobiological functions are all regulated by dopamine and its receptors. Dopamine receptors can be divided into D1‐like receptors (including D1 and D5) or D2‐like receptors (containing D2, D3, and D4), with D1 and D2 receptors (D1Rs, and D2Rs) being the most important. Currently, studies indicated that D1Rs and D2Rs are tightly involved with the process of sleep‐wake and general anesthesia, but the specific mechanism remains unclear. In this review, we compiled the most recent findings, mainly focusing on the structure, distribution, and signal pathway of D1Rs and D2Rs in the central nervous system, as well as the involvement of D1Rs and D2Rs in sleep‐wake and general anesthesia. Thus, the investigations of the D1Rs and D2Rs will benefit not only better knowledge for how sleep‐wake control works but also the mechanism of general anesthesia.
The distribution of dopamine D1 and D2 receptors in the central nervous system is shown here. Activation of D1R in NAc, DRN, and NB promotes awakening from natural sleep and general anesthesia. D2R acts in a brain area‐dependent manner, with D2R in NAc playing a sleep‐promoting role and D2R in DRN and ventral tegmental area a awakening‐promoting role, and the function of both receptors in other brain areas remains to be further investigated.
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