Mercury (Hg) is a toxic heavy-metal element, which can be enriched in fauna and flora and transformed into methylmercury (MeHg). MeHg is a widely distributed environmental pollutant that may be ...harmful to fish-eating populations through enrichment of aquatic food chains. The central nervous system is a primary target of MeHg. Embryos and infants are more sensitive to MeHg, and exposure to MeHg during gestational feeding can significantly impair the homeostasis of offspring, leading to long-term neurodevelopmental defects. At present, MeHg-induced neurodevelopmental toxicity has become a hotspot in the field of neurotoxicology, but its mechanisms are not fully understood. Some evidence point to oxidative damage, excitotoxicity, calcium ion imbalance, mitochondrial dysfunction, epigenetic changes, and other molecular mechanisms that play important roles in MeHg-induced neurodevelopmental toxicity. In this review, advances in the study of neurodevelopmental toxicity of MeHg exposure during pregnancy and the molecular mechanisms of related pathways are summarized, in order to provide more scientific basis for the study of neurodevelopmental toxicity of MeHg.
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•Transferrin (Tf) helped nanoplatform pinpoint tumor cells via Tf receptor mediated endocytosis process.•Acidic responsive Ca2+ and curcumin (CUR) release interfere Ca2+ homeostasis ...for Ca2+ overload, activating the apoptotic pathway.•Cascade catalytic reaction in CaO2/Tf induced ferroptosis.•The calcium and ferric ions interference strategy in this work offered synergistic combination of ferroptosis, Ca2+ overload therapy and chemotherapy.
Intracellular ions played prominent part in cell function and behavior. Disrupting intracellular ions homeostasis might switch ions signal from “regulating” to “destroying”. Inspired by this, we introduced the ions interference strategy for tumor therapy. Herein, curcumin (CUR) and transferrin (Tf) co-loaded calcium peroxide nanoparticles (CaO2 NPs) were formulated. With tumor targeting ability, CaO2/Tf/CUR pinpointed tumor cells and then instantaneously decomposed in acidic lysosomes, concurrently accompanying with the release of Ca2+ and CUR, as well as the production of H2O2. Then H2O2 not only damaged structure of Tf to release Fe3+, but also was converted to hydroxyl radicals via ferric ions mediated Fenton reaction for ferroptosis. In addition, the released Ca2+ and CUR induced Ca2+ overload via exogenous and endogenous calcium ions accumulation, respectively, further activating mitochondria apoptosis signaling pathway for cell injury. Therefore, based on calcium and ferric ions interference strategy, the cascade catalytic CaO2/Tf/CUR offered synergistic combination of ferroptosis, Ca2+ overload therapy and chemotherapy, which held a great promise in cancer treatment.
Programed cell death plays a key role in promoting human development and maintaining homeostasis. Ferroptosis is a recently identified pattern of programmed cell death that is closely associated with ...the onset and progression of neurodegenerative diseases. Ferroptosis is mainly caused by the intracellular accumulation of iron-dependent lipid peroxides. The cysteine/glutamate antibody Solute carrier family 7 member 11 (SLC7A11, also known as xCT) functions to import cysteine for glutathione biosynthesis and antioxidant defense. SLC7A11 has a significant impact on ferroptosis, and inhibition of SLC7A11 expression promotes ferroptosis. Moreover, SLC7A11 is also closely associated with neurodegenerative diseases. In this paper, we summarize the relationship between ferroptosis and neurodegenerative diseases and the role of SLC7A11 during this process. The various regulatory mechanisms of SLC7A11 are also discussed. In conclusion, we are looking forward to a theoretical basis for further understanding the occurrence and development of ferroptosis in SLC7A11 and neurodegenerative diseases, and to seek new clues for the treatment of neurodegenerative diseases.
Purpose
Although in recent years some randomized controlled trails (RCTs) have explored the analgesic effect of erector spinae plane block (ESPB) in spine surgery, their results are controversial. ...Our study aimed to examine the analgesic effect of preoperative ESPB in spine surgery by a meta-analysis of RCTs.
Methods
The articles of RCTs that compared preoperative ESPB with no block in terms of the analgesic effect in adult patients following spine surgery were eligible for inclusion. The primary outcome was the pain scores reported by Visual Analog Scale or Numerical Rating Scale of pain at different time intervals in 48 h after surgery. The secondary outcomes included postoperative opioid consumption, rescue analgesia requirement, opioid-related side effects and complications associated with ESPB.
Results
Twelve studies involving 828 patients were eligible for our study. Compared with no block, ESPB had a significant effect on reducing postoperative pain scores at rest and at movement at different time intervals except at movement at 48 h. ESPB significantly decreased opioid consumption in 24 h after surgery (SMD − 1.834; 95%CI − 2.752, − 0.915;
p
< 0.001;
I
2
= 89.0%), and reduced the incidence of rescue analgesia (RR 0.333; 95%CI 0.261, 0.425;
p
< 0.001;
I
2
= 0%) and postoperative nausea and vomiting (RR 0.380; 95%CI 0.272, 0.530;
p
< 0.001;
I
2
= 9.0%). Complications associated with ESPB were not reported in the included studies.
Conclusion
Our meta-analysis demonstrates that ESPB is effective in decreasing postoperative pain intensity and postoperative opioid consumption in spine surgery. Therefore, for the management of postoperative pain following spine surgery, preoperative ESPB is a good choice.
Oil bodies (OBs) are organelles for storing lipids, and they are composed of lipid cores and monolayer phospholipid protein membranes. During storage, membrane proteins anchored in the lipid core are ...often damaged by lipid oxidation products, leading to oxidative damage and a decreased quality of emulsified foods. Here, three natural antioxidants (gallic acid (GA), epigallocatechin gallate (EGCG), and tannic acid (TA)) were added to OB emulsions to study the effects of polyphenols on protein interfacial properties during oxidation and the lipid-protein co-oxidation behavior. Compared to GA, EGCG and TA with higher molecular weights and hydroxyl substitution showed better antioxidant activity, metal chelating activity, iron reduction ability, and affinity for OB. The polyphenols significantly reduced the contents of free amino and sulfhydryl groups in OB. Infrared spectroscopy analysis indicate that hydrogen bonding and hydrophobic interactions may exist between the polyphenols and OB. During storage, polyphenols inhibited >23% of the primary and secondary lipid oxidation products in the emulsions, whereas the formation of carbonyl groups and disappearance of sulfhydryl groups were only inhibited by 10.7% and 7.4%, respectively, indicating that polyphenols preferentially inhibited lipid oxidation over protein oxidation. Electrophoresis results showed that moderate oxidation (3 days of storage) disrupted the disulfide bonds of proteins. Note that moderate oxidation enhanced the interfacial properties of OB proteins, whereas excessive oxidation led to protein aggregation. This study offers new perspectives on using polyphenols to regulate the lipid-protein co-oxidation in OB, as well as the different properties of OB proteins after oxidation.
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•Three polyphenols increase the stability of oil body (OB) emulsions.•Tannic acid with a high hydroxyl content has the best affinity for OB.•Hydrogen bonding and hydrophobic interactions occur between the polyphenols and OB.•Polyphenols are more likely to inhibit lipid oxidation than protein oxidation.•Moderate oxidation enhances the interfacial properties of proteins.
Distribution lines are integral parts of the modern power system, which can affect the security and stability of power supply directly. An effective power system protection scheme should be able to ...detect all occurring faults as soon as possible. There are two tasks in fault diagnosis. One is the fault classification, where high accuracy rates have already achieved. Thus, this paper focuses on the other task, i.e. fault location. Enlightened by Fourier transform, this paper proposes an online data-driven method, which transforms signals from time domain to image domain through signal-to-image (SIG) algorithm and then process the transformed images with framework based on convolutional neural network (CNN). On the one hand, we can extract more crucial characteristic and information from image domain. On the other hand, the CNN-based structure is much smaller than others. It needs less memory space and would be easier to be transplanted to hardware platform. Moreover, the proposed algorithm does not require synchronous devices. The numerical comparison shows that the proposed SIG-CNN fault location model achieves robust and accurate results compared with other data-driven algorithms.
The construction of high-efficiency bifunctional electrocatalysts is still a main challenge for hydrogen production from water splitting, in which comprehensive structure regulation plays a key role ...for synergistically boosting the intrinsic activity and charge collection. Here, we used a two-step hydrothermal method for construction of an interjaculated CoSe/Ni3Se4 heterostructure from NiCo LDH nanosheets grown on stainless steel (SS) meshes as bifunctional electrocatalysts for overall water splitting. The SS meshes containing Fe and Ni act as an excellent 3D scaffold for catalyst growth and charge collection. The SS@CoSe/Ni3Se4 composite exhibits outstanding electrocatalytic performances with low overpotentials of 97 mV for hydrogen evolution and 230 mV for oxygen evolution to reach a current density of 10 mA cm−2, respectively. Moreover, by using SS@CoSe/Ni3Se4 as both the cathode and anode, the assembled electrolyze only required 1.55 V to reach 10 mA cm−2 for overall water splitting. The outstanding performance of SS@CoSe/Ni3Se4 benefits from the synergy between excellent charge collection capability of SS meshes and the abundant active sites at the CoSe/Ni3Se4 heterointerface formed with the in-situ conversion of NiCo LDH nanosheets. Electrochemical active surface area and impedance spectrum indicate that the CoSe/Ni3Se4 loaded on SS has the most abundant electrochemically active sites and the smallest electrochemical resistance, thereby exposing more active sites and enhancing the charge transfer to promote the catalytic activity. By integrating the delicate nanoscale heterostructure engineering with the microscale SS mesh scaffold, our work provides a new perspective for the preparation of high-performance and cheap electrocatalysts that are easy to be integrated with industrial applications.
•Interjaculated CoSe/Ni3Se4 heterostructure from NiCo LDH on stainless steel meshes as bifunctional electrocatalysts.•Require low overpotentials of 97 mV for hydrogen evolution and 230 mV for oxygen evolution to reach 10 mA cm−2.•The assembled electrolyzer only requires 1.55 V to reach 10 mA cm−2 for overall water splitting.•Synergy between SS with close interface for charge collection and CoSe/Ni3Se4 heterostructure with abundant active sites.
The unfolded protein response (UPR) is a cellular stress response mechanism induced by the accumulation of unfolded or misfolded proteins. Within the endoplasmic reticulum and mitochondria, a dynamic ...balance exists between protein folding mechanisms and unfolded protein levels under normal conditions. Disruption of this balance or an accumulation of unfolded proteins in these organelles can result in stress responses and UPR. The UPR restores organelle homeostasis and promotes cell survival by increasing the expression of chaperone proteins, regulating protein quality control systems, and enhancing the protein degradation pathway. However, prolonged or abnormal UPR can also have negative effects, including cell death. Therefore, many diseases, especially neurodegenerative diseases, are associated with UPR dysfunction. Neurodegenerative diseases are characterized by misfolded proteins accumulating and aggregating, and neuronal cells are particularly sensitive to misfolded proteins and are prone to degeneration. Many studies have shown that the UPR plays an important role in the pathogenesis of neurodegenerative diseases. Here, we will discuss the possible contributions of the endoplasmic reticulum unfolded protein response (UPR
er
) and the mitochondrial unfolded protein response (UPR
mt
) in the development of several neurodegenerative diseases.
Methylmercury (MeHg) is a widely distributed environmental pollutant that can easily cross the blood-brain barrier and accumulate in the brain, thereby damaging the central nervous system. Studies ...have shown that MeHg-induced mitochondrial damage and apoptosis play a crucial role in its neurotoxic effects. Mitochondrial unfolded protein response (UPR
) is indispensable to maintain mitochondrial protein homeostasis and ensure mitochondrial function, and the ATF4/CHOP axis is one of the signaling pathways to activate UPR
. In this study, the role of the ATF4/CHOP axis-mediated UPR
in the neurotoxicity of MeHg has been investigated by C57BL/6 mice and the HT22 cell line. We discovered that mice exposed to MeHg had abnormal neurobehavioral patterns. The pathological section showed a significant decrease in the number of neurons. MeHg also resulted in a reduction in mtDNA copy number and mitochondrial membrane potential (MMP). Additionally, the ATF4/CHOP axis and UPR
were found to be significantly activated. Subsequently, we used siRNA to knock down ATF4 or CHOP and observed that the expression of UPR
-related proteins and the apoptosis rate were significantly reduced. Our research showed that exposure to MeHg can over-activate the UPR
through the ATF4/CHOP axis, leading to mitochondrial damage and ultimately inducing neuronal apoptosis.
Methylmercury (MeHg) is a environmental contaminant, which can induce neurotoxic effects. So far, the exact molecular mechanisms of autophagy and its effect on apoptosis in MeHg-induced neurotoxicity ...have not been elucidated. Here, rats were exposed to MeHg (4, 8, or 12 μmol/kg) for 4 weeks to evaluate the dose-effect relationship between MeHg and apoptosis, or autophagy in cerebral cortex. On this basis, rapamycin (Rapa) or 3-methyladenine (3-MA) was administrated to further explore the regulatory mechanisms of autophagy on MeHg-induced neuronal apoptosis. The pathological changes, autophagy or apoptosis levels, expression of autophagic or apoptotic-associated factors such as mTOR, S6K1, 4EBP1, Vps34, Beclin1, p62, LC3, Bcl-2/Bax, caspase, or MAPKs were investigated. Results showed that MeHg dose-dependently induced pathological changes in cerebral cortex, and the levels of autophagy and apoptosis were increased. Furthermore, Rapa pretreatment antagonized MeHg-induced apoptosis, whereas 3-MA further aggravated apoptosis, which were supported by findings that Rapa activated mTOR-mediated autophagy while 3-MA inhibited Vps34-related autophagy, further affect neuronal apoptosis through regulation of apoptotic factors mentioned above. In conclusion, the findings indicated that MeHg dose-dependently induced autophagy or apoptosis, and mTOR or Vps34 may play important roles in mediating autophagy, which further regulated apoptosis through MAPKs or mitochondrial apoptosis pathways.
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•MeHg could induce autophagy and apoptosis in cerebral cortex.•The mTOR and Vps34 are involved in autophagy regulation.•The mitochondrial pathway and MAPKs are involved in apoptosis regulation.•Inhibition of mTOR could induce autophagy and antagonize the apoptosis.•Inhibition of Vps34 could decrease autophagy and aggravate the apoptosis.