Exploring Appropriate Reference Intervals and Clinical Decision Limits for Glucose-6-Phosphate Dehydrogenase Activity in Individuals From Guangzhou, China.

Background: Quantitative detection of glucose-6-phosphate dehydrogenase (G6PD) is commonly done to screen for G6PD deficiency. However, current reference intervals (RIs) of G6PD are unsuitable for evaluating G6PD-activity levels with local populations or associating G6PD variants with hemolysis risk to aid clinical decision-making. We explored appropriate RIs and clinical decision limits (CDLs) for G6PD activity in individuals from Guangzhou, China. Methods: We enrolled 5,852 unrelated individuals between 2020 and 2022 and screened their samples in quantitative assays for G6PD activity. We conducted further investigations, including G6PD genotyping, thalassemia genotyping, follow-up analysis, and statistical analysis, for different groups. Results: In Guangzhou, the RIs for the G6PD activities were 11.20-20.04 U/g Hb in male and 12.29-23.16 U/g Hb in female. The adjusted male median and normal male median (NMM) values were 15.47 U/g Hb and 15.51 U/g Hb, respectively. A threshold of 45% of the NMM could be used as a CDL to estimate the probability of G6PD variants. Our results revealed high hemolysis-risk CDLs (male: <10% of the NMM, female: <30% of the NMM), medium hemolysis-risk CDLs (male: 10%-45% of the NMM, female: 30%-79% of the NMM), and low hemolysis-risk CDLs (male: ≥ 45% of the NMM, female: ≥ 79% of the NMM). Conclusions: Collectively, our findings contribute to a more accurate evaluation of G6PD-activity levels within the local population and provide valuable insights for clinical decision-making. Specifically, identifying threshold values for G6PD variants and hemolysis risk enables improved prediction and management of G6PD deficiency, ultimately enhancing patient care and treatment outcomes.

Chinese organic rice transition spatial econometrics empirical analysis.

Based on the integrated model of Super-SBM model, spatial Durbin model (SDM) and Grey neural network model, this paper analyzes the panel data of various provinces in China from multiple angles and dimensions. It was found that there were significant differences in eco-efficiency between organic rice production and conventional rice production. The response of organic rice to climate change, the spatial distribution of ecological and economic benefits and the impact on carbon emission were analyzed. The results showed that organic rice planting not only had higher economic benefits, but also showed a rising trend of ecological benefits and a positive feedback effect. This finding highlights the importance of organic rice farming in reducing carbon emissions. Organic rice farming effectively reduces greenhouse gas emissions, especially carbon dioxide and methane, by improving soil management and reducing the use of fertilizers and pesticides. This has important implications for mitigating climate change and promoting soil health and biodiversity. With the acceleration of urbanization, the increase of organic rice planting area shows the trend of organic rice gradually replacing traditional rice cultivation, further highlighting the potential of organic agriculture in emission reduction, environmental protection and sustainable agricultural production. To this end, it is recommended that the Government implement a diversified support strategy to encourage technological innovation, provide guidance and training, and raise public awareness and demand for organic products. At the same time, private sector participation is stimulated to support the development of organic rice cultivation through a public-private partnership model. Through these measures, further promote organic rice cultivation, achieve the dual goals of economic benefits and environmental benefits, and effectively promote the realization of double carbon emission reduction targets.

Amphipathic Phenylalanine-Induced Nucleophilic-Hydrophobic Interface Toward Highly Reversible Zn Anode.

Aqueous Zn2+-ion batteries (AZIBs), recognized for their high security, reliability, and cost efficiency, have garnered considerable attention. However, the prevalent issues of dendrite growth and parasitic reactions at the Zn electrode interface significantly impede their practical application. In this study, we introduced a ubiquitous biomolecule of phenylalanine (Phe) into the electrolyte as a multifunctional additive to improve the reversibility of the Zn anode. Leveraging its exceptional nucleophilic characteristics, Phe molecules tend to coordinate with Zn2+ ions for optimizing the solvation environment. Simultaneously, the distinctive lipophilicity of aromatic amino acids empowers Phe with a higher adsorption energy, enabling the construction of a multifunctional protective interphase. The hydrophobic benzene ring ligands act as cleaners for repelling H2O molecules, while the hydrophilic hydroxyl and carboxyl groups attract Zn2+ ions for homogenizing Zn2+ flux. Moreover, the preferential reduction of Phe molecules prior to H2O facilitates the in situ formation of an organic-inorganic hybrid solid electrolyte interphase, enhancing the interfacial stability of the Zn anode. Consequently, Zn||Zn cells display improved reversibility, achieving an extended cycle life of 5250 h. Additionally, Zn||LMO full cells exhibit enhanced cyclability of retaining 77.3% capacity after 300 cycles, demonstrating substantial potential in advancing the commercialization of AZIBs.

Toward Simultaneous Dense Zinc Deposition and Broken Side-Reaction Loops in the Zn//V2 O5 System.

The Zn//V2 O5 system not only faces the incontrollable growth of zinc (Zn) dendrites, but also withstands the cross-talk effect of by-products produced from the cathode side to the Zn anode, inducing interelectrode talk and aggravating battery failure. To tackle these issues, we construct a rapid Zn2+ -conducting hydrogel electrolyte (R-ZSO) to achieve Zn deposition modulation and side reaction inhibition in Zn//V2 O5 full cells. The polymer matrix and BN exhibit a robust anchoring effect on SO4 2- , accelerating Zn2+ migration and enabling dense Zn deposition behavior. Therefore, the Zn//Zn symmetric cells based on the R-ZSO electrolyte can operate stably for more than 1500 h, which is six times higher than that of cells employing the blank electrolyte. More importantly, the R-ZSO hydrogel electrolyte effectively decouples the cross-talk effects, thus breaking the infinite loop of side reactions. As a result, the Zn//V2 O5 cells using this modified hydrogel electrolyte demonstrate stable operation over 1,000 cycles, with a capacity loss rate of only 0.028 % per cycle. Our study provides a promising gel chemistry, which offers a valuable guide for the construction of high-performance and multifunctional aqueous Zn-ion batteries.

Activation of the CD200/CD200R1 axis improves cognitive impairment by enhancing hippocampal neurogenesis via suppression of M1 microglial polarization and neuroinflammation in hypoxic-ischemic neonatal rats.

Following hypoxic-ischemic brain damage (HIBD), there is a decline in cognitive function; however, there are no effective treatment strategies for this condition in neonates. This study aimed to evaluate the role of the cluster of differentiation 200 (CD200)/CD200R1 axis in cognitive function following HIBD using an established model of HIBD in postnatal day 7 rats. Western blotting analysis was conducted to evaluate the protein expression levels of CD200, CD200R1, proteins associated with the PI3K/Akt-NF-κB pathway, and inflammatory factors such as TNF-α, IL-1ß, and IL-6 in the hippocampus. Additionally, double-immunofluorescence labeling was utilized to evaluate M1 microglial polarization and neurogenesis in the hippocampus. To assess the learning and memory function of the experimental rats, the Morris water maze (MWM) test was conducted. HIBDleads to a decrease in the expression of CD200 and CD200R1 proteins in the neonatal rat hippocampus, while simultaneously increasing the expression of TNF-α, IL-6, and IL-1ß proteins, ultimately resulting in cognitive impairment. The administration of CD200Fc, a fusion protein of CD200, was found to enhance the expression of p-PI3K and p-Akt, but reduce the expression of p-NF-κB. Additionally, CD200Fc inhibited M1 polarization of microglia, reduced neuroinflammation, improved hippocampal neurogenesis, and mitigated cognitive impairment caused by HIBD in neonatal rats. In contrast, blocking the interaction between CD200 and CD200R1 with the anti-CD200R1 antibody (CD200R1 Ab) exerted the opposite effect. Furthermore, the PI3K specific activator, 740Y-P, significantly increased the expression of p-PI3K and p-Akt, but reduced p-NF-κB expression. It also inhibited M1 polarization of microglia, reduced neuroinflammation, and improved hippocampal neurogenesis and cognitive function in neonatal rats with HIBD. Our findings illustrate that activation of the CD200/CD200R1 axis inhibits the NF-κB-mediated M1 polarization of microglia to improve HIBD-induced cognitive impairment and hippocampal neurogenesis disorder via the PI3K/Akt signaling pathway.

Organic Intercalation Induced Kinetic Enhancement of Vanadium Oxide Cathodes for Ultrahigh-Loading Aqueous Zinc-Ion Batteries.

Vanadium-based oxides have attracted much attention because of their rich valences and adjustable structures. The high theoretical specific capacity contributed by the two-electron-transfer process (V5+ /V3+ ) makes it an ideal cathode material for aqueous zinc-ion batteries. However, slow diffusion kinetics and poor structural stability limit the application of vanadium-based oxides. Herein, a strategy for intercalating organic matter between vanadium-based oxide layers is proposed to attain high rate performance and long cycling life. The V3 O7 ·H2 O is synthesized in situ on the carbon cloth to form an open porous structure, which provides sufficient contact areas with electrolyte and facilitates zinc ion transport. On the molecular level, the added organic matter p-aminophenol (pAP) not only plays a supporting role in the V3 O7 ·H2 O layer, but also shows a regulatory effect on the V5+ /V4+ redox process due to the reducing functional group on pAP. The novel composite electrode with porous structure exhibits outstanding reversible specific capacity (386.7 mAh g-1 , 0.1 A g-1 ) at a high load of 6.5 mg cm-2 , and superior capacity retention of 80% at 3 A g-1 for 2100 cycles.

Dexmedetomidine alleviates cognitive impairment by promoting hippocampal neurogenesis via BDNF/TrkB/CREB signaling pathway in hypoxic-ischemic neonatal rats.

AIMS: Dexmedetomidine (DEX) has been reported to alleviate hypoxic-ischemic brain damage (HIBD) in neonates. This study aimed to investigate whether DEX improves cognitive impairment by promoting hippocampal neurogenesis via the BDNF/TrkB/CREB signaling pathway in neonatal rats with HIBD. METHODS: HIBD was induced in postnatal day 7 rats using the Rice-Vannucci method, and DEX (25 µg/kg) was administered intraperitoneally immediately after the HIBD induction. The BDNF/TrkB/CREB pathway was regulated by administering the TrkB receptor antagonist ANA-12 through intraperitoneal injection or by delivering adeno-associated virus (AAV)-shRNA-BDNF via intrahippocampal injection. Western blot was performed to measure the levels of BDNF, TrkB, and CREB. Immunofluorescence staining was utilized to identify the polarization of astrocytes and evaluate the levels of neurogenesis in the dentate gyrus of the hippocampus. Nissl and TTC staining were performed to evaluate the extent of neuronal damage. The MWM test was conducted to evaluate spatial learning and memory ability. RESULTS: The levels of BDNF and neurogenesis exhibited a notable decrease in the hippocampus of neonatal rats after HIBD, as determined by RNA-sequencing technology. Our results demonstrated that treatment with DEX effectively increased the protein expression of BDNF and the phosphorylation of TrkB and CREB, promoting neurogenesis in the dentate gyrus of the hippocampus in neonatal rats with HIBD. Specifically, DEX treatment significantly augmented the expression of BDNF in hippocampal astrocytes, while decreasing the proportion of detrimental A1 astrocytes and increasing the proportion of beneficial A2 astrocytes in neonatal rats with HIBD. Furthermore, inhibiting the BDNF/TrkB/CREB pathway using either ANA-12 or AAV-shRNA-BDNF significantly counteracted the advantageous outcomes of DEX on hippocampal neurogenesis, neuronal survival, and cognitive improvement. CONCLUSIONS: DEX promoted neurogenesis in the hippocampus by activating the BDNF/TrkB/CREB pathway through the induction of polarization of A1 astrocytes toward A2 astrocytes, subsequently mitigating neuronal damage and cognitive impairment in neonates with HIBD.

N6-methyladenosine demethylase FTO regulates synaptic and cognitive impairment by destabilizing PTEN mRNA in hypoxic-ischemic neonatal rats.

Hypoxic-ischemic brain damage (HIBD) can result in significant global rates of neonatal death or permanent neurological disability. N6-methyladenosine (m6A) modification of RNA influences fundamental aspects of RNA metabolism, and m6A dysregulation is implicated in various neurological diseases. However, the biological roles and clinical significance of m6A in HIBD remain unclear. We currently evaluated the effect of HIBD on cerebral m6A methylation in RNAs in neonatal rats. The m6A dot blot assay showed a global augmentation in RNA m6A methylation post-HI. Herein, we also report on demethylase FTO, which is markedly downregulated in the hippocampus and is the main factor involved with aberrant m6A modification following HI. By conducting a comprehensive analysis of RNA-seq data and m6A microarray results, we found that transcripts with m6A modifications were more highly expressed overall than transcripts without m6A modifications. The overexpression of FTO resulted in the promotion of Akt/mTOR pathway hyperactivation, while simultaneously inhibiting autophagic function. This is carried out by the demethylation activity of FTO, which selectively demethylates transcripts of phosphatase and tensin homolog (PTEN), thus promoting its degradation and reduced protein expression after HI. Moreover, the synaptic and neurocognitive disorders induced by HI were effectively reversed through the overexpression of FTO in the hippocampus. Cumulatively, these findings demonstrate the functional importance of FTO-dependent hippocampal m6A methylome in cognitive function and provides novel mechanistic insights into the therapeutic potentials of FTO in neonatal HIBD.

Research on the performance of a valveless piezoelectric pump with a herringbone bluffbody.

Aiming to improve the output performance of a valveless piezoelectric pump, this article presents a valveless piezoelectric pump with a herringbone bluffbody. The bluffbody is herringbone shaped and distributed in a tapered chamber. The tapered chamber and the bluffbody create a large reverse resistance in the chamber, thus effectively mitigating the backflow problem of the valveless pump. The theoretical analysis determined the relationship between the flow rate and the flow resistance coefficient as well as the variation of the pump chamber volume. It was also concluded that the piezoelectric pump has the best output flow at intrinsic frequencies. Through simulation calculations, the effectiveness of the bluffbody structure in mitigating backflow in piezoelectric pumps is analyzed to provide a reference for experimental prototype design parameters. Finally, a range of prototypes is produced for experimentation. The experimental results show that the designed bluffbody shape can increase the return energy loss to effectively mitigate the return flow issues of the valveless piezoelectric pump, thus improving the output performance. The optimum output flow rate is 158.5 ml/min at 200 V and 52.5 Hz and the tapered chamber angle of 6°, and the bluffbody height, angle, and quantities are 2 mm, 40°, and 2, respectively. The construction of the valveless piezoelectric pump proposed in this research can be used as a reference for subsequent improvements in the performance of valveless piezoelectric pumps, and due to the high output performance, experimental studies can be carried out in applications such as dispensing and heat dissipation in electronic products.

Interface Engineering with Dynamics-Mechanics Coupling for Highly Reactive and Reversible Aqueous Zinc-Ion Batteries.

The practical application of AZIBs is hindered by problems such as dendrites and hydrogen evolution reactions caused by the thermodynamic instability of Zinc (Zn) metal. Modification of the Zn surface through interface engineering can effectively solve the above problems. Here, sulfonate-derivatized graphene-boronene nanosheets (G&B-S) composite interfacial layer is prepared to modulate the Zn plating/stripping and mitigates the side reactions with electrolyte through a simple and green electroplating method. Thanks to the electronegativity of the sulfonate groups, the G&B-S interface promotes a dendrite-free deposition behavior through a fast desolvation process and a uniform interfacial electric field mitigating the tip effect. Theoretical calculations and QCM-D experiments confirmed the fast dynamic mechanism and excellent mechanical properties of the G&B-S interfacial layer. By coupling the dynamics-mechanics action, the G&B-S@Zn symmetric battery is cycled for a long-term of 1900 h at a high current density of 5 mA cm-2 , with a low overpotential of ≈30 mV. Furthermore, when coupled with the LMO cathode, the LMO//G&B-S@Zn cell also exhibits excellent performance, indicating the durability of the G&B-S@Zn anode. Accordingly, this novel multifunctional interfacial layer offers a promising approach to significantly enhance the electrochemical performance of AZIBs.

Activation of the CD200/CD200R1 axis attenuates neuroinflammation and improves postoperative cognitive dysfunction via the PI3K/Akt/NF-κB signaling pathway in aged mice.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a neurological complication occurring after anesthesia and surgery. Neuroinflammation plays a critical role in the pathogenesis of POCD, and the activation of the cluster of differentiation 200 (CD200)/CD200R1 axis improves neurological recovery in various neurological disorders by modulating inflammation. The aim of this study was to investigate the impact and underlying mechanism of CD200/CD200R1 axis on POCD in aged mice. METHODS: The model of POCD was established in aged mice. To assess the learning and memory abilities of model mice, the Morris water maze test was implemented. CD200Fc (CD200 fusion protein), CD200R1 Ab (anti-CD200R1 antibody), and 740Y-P (a specific PI3K activator) were used to evaluate the effects of the CD200/CD200R1/PI3K/Akt/NF-κB signaling pathway on hippocampal microglial polarization, neuroinflammation, synaptic activity, and cognition in mice. RESULTS: It was observed that anesthesia/surgery induced cognitive decline in aged mice, increased the levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1 ß and decreased the levels of postsynaptic density protein 95 (PSD-95), synaptophysin (SYN) in the hippocampus. Moreover, CD200Fc and 740Y-P attenuated neuroinflammation and synaptic deficits and reversed cognitive impairment via the phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (Akt)/nuclear factor-kappa B (NF-κB) signaling pathway, whereas CD200R1 Ab administration exerted the opposite effects. Our results further show that the CD200/CD200R1 axis modulates M1/M2 polarization in hippocampal microglia via the PI3K/Akt/NF-κB signaling pathway. CONCLUSIONS: Our findings indicate that the activation of the CD200/CD200R1 axis reduces neuroinflammation, synaptic deficits, and cognitive impairment in the hippocampus of aged mice by regulating microglial M1/M2 polarization via the PI3K/Akt/NF-κB signaling pathway.

Molecular recognition effect enabled by novel crown ether as macrocyclic host towards highly reversible Zn anode.

Aqueous Zn2+ ion batteries present notable advantages, including high abundance, low toxicity, and intrinsic nonflammability. However, they exhibit severe irreversibility due to uncontrolled dendrite growth and corrosion reactions, which limit their practical applications. Inspired by their distinct molecular recognition characteristics, supramolecular crown ethers featuring interior cavity sizes identical to the diameter of Zn2+ ions were screened as macrocyclic hosts to optimize the Zn2+ coordination environment, facilitating the suppression of the reactivity of H2O molecules and inducing the in-situ formation of organic-inorganic hybrid dual-protective interphase. The in-situ assembled interphase confers the system with an "ion-sieving" effect to repel H2O molecules and facilitate rapid Zn2+ transport, enabling the suppression of side reactions and uniform deposition of Zn2+ ions. Consequently, we were able to achieve dendrite-free Zn2+ plating/stripping at 98.4% Coulombic efficiency for approximately 300 cycles in Zn||Cu cell, steady charge-discharge for 1360 h in Zn||Zn symmetric cell, and improved cyclability of 70% retention for 200 cycles in Zn||LMO full cell, outlining a promising strategy to challenge lithium-ion batteries in low-cost, and large-scale applications.

Zinc-Bromine Rechargeable Batteries: From Device Configuration, Electrochemistry, Material to Performance Evaluation.

Zinc-bromine rechargeable batteries (ZBRBs) are one of the most powerful candidates for next-generation energy storage due to their potentially lower material cost, deep discharge capability, non-flammable electrolytes, relatively long lifetime and good reversibility. However, many opportunities remain to improve the efficiency and stability of these batteries for long-life operation. Here, we discuss the device configurations, working mechanisms and performance evaluation of ZBRBs. Both non-flow (static) and flow-type cells are highlighted in detail in this review. The fundamental electrochemical aspects, including the key challenges and promising solutions, are discussed, with particular attention paid to zinc and bromine half-cells, as their performance plays a critical role in determining the electrochemical performance of the battery system. The following sections examine the key performance metrics of ZBRBs and assessment methods using various ex situ and in situ/operando techniques. The review concludes with insights into future developments and prospects for high-performance ZBRBs.

Large Interlayer Distance and Heteroatom-Doping of Graphite Provide New Insights into the Dual-Ion Storage Mechanism in Dual-Carbon Batteries.

Dual-ion batteries (DIBs) is a promising technology for large-scale energy storage. However, it is still questionable how material structures affect the anion storage behavior. In this paper, we synthesis graphite with an ultra-large interlayer distance and heteroatomic doping to systematically investigate the combined effects on DIBs. The large interlayer distance of 0.51 nm provides more space for anion storage, while the doping of the heteroatoms reduces the energy barriers for anion intercalation and migration and enhances rapid ionic storage at interfaces simultaneously. Based on the synergistic effects, the DIBs composed of carbon cathode and lithium anode afford ultra-high capacity of 240 mAh g-1 at current density of 100 mA g-1 . Dual-carbon batteries (DCBs) using the graphite as both of cathode and anode steadily cycle 2400 times at current density of 1 A g-1 . Hence, this work provides a reference to the strategy of material designs of DIBs and DCBs.

Bifunctional Dynamic Adaptive Interphase Reconfiguration for Zinc Deposition Modulation and Side Reaction Suppression in Aqueous Zinc Ion Batteries.

Dendrite growth and electrode/electrolyte interface side reactions in aqueous zinc-ion batteries (AZIBs) not only impair the battery lifetime but also pose serious safety concerns for the battery system, hindering its application in large-scale energy storage systems. Herein, by introducing positively charged chlorinated graphene quantum dot (Cl-GQD) additives into the electrolyte, a bifunctional dynamic adaptive interphase is proposed to achieve Zn deposition regulation and side reaction suppression in AZIBs. During the charging process, the positively charged Cl-GQDs are adsorbed onto the Zn surface, acting as an electrostatic shield layer that facilitates smooth Zn deposition. In addition, the relative hydrophobic properties of chlorinated groups also build a hydrophobic protective interface for the Zn anode, mitigating the corrosion of the Zn anode by water molecules. More importantly, the Cl-GQDs are not consumed throughout the cell operation and exhibit a dynamic reconfiguration behavior, which ensures the stability and sustainability of this dynamic adaptive interphase. Consequently, the cells mediated by the dynamic adaptive interphase enable dendrite-free Zn plating/stripping for more than 2000 h. Particularly, even at 45.5% depth of discharge, the modified Zn//LiMn2O4 hybrid cells still retain 86% capacity retention after 100 cycles, confirming the feasibility of this simple approach for application with limited Zn sources.

Structure of a highly branched galacturonoglucan from fruits of Schisandra chinensis (Turcz.) Baill.

A novel galacturonoglucan, named SCP-1, is isolated and purified from Schisandra chinensis fruits. The structure of SCP-1 is systematically investigated by a combination of monosaccharide compositions, absolute Mw, methylation analysis, partial acid hydrolysis, isoamylase degradations, and nuclear magnetic resonance spectroscopy. The structure of SCP-1 is theoretically described as follows: (i) Glc and GalA in a molar ratio of 17:3; (ii) â†’ 4)-α-Glcp-(1→, →4,6)-α-Glcp-(1→, →3,4,6)-α-Glcp-(1→, α-Glcp-(1→, →4)-α-GalAp-6-OMe-(1→, α-GalAp-6-OMe-(1→, ß-Glcp-(1→, →6-)-ß-Glcp-(1 â†’ and →3,4)-ß-Glcp-(1 â†’ in a molar ratio of 48:5:3:3:10:5:12:5:9; (iii) a repeating unit of →4)-α-Glcp-(1 â†’ as a backbone with branched points at C-3 and C-6, substituted by different types of acidic and neutral side chains to form multiple branches; and (iv) a rigid rod configuration deduced from α value of 1.26 in Mark-Houwink equation ([η] = kMα). Anti-tumor assay investigated the effects of SCP-1 on human HepG2 cancer cell lines in vitro. This is for the first time to report a galacturonoglucan in S. chinensis fruits.

HRG inhibits liver cancer lung metastasis by suppressing neutrophil extracellular trap formation.

BACKGROUND: Distant metastasis is a sign of poor prognosis for cancer patients. Extrahepatic liver cancer metastases commonly spread to the lung. Remodelling of the metastatic microenvironment is essential for tumour metastasis. Neutrophil-associated metastatic microenvironment contributes to the early metastatic colonisation of cancer cells in the lung. METHOD: The lung metastasis models were constructed via treated cancer cells by tail vein injection into mice. And samples of lung were harvested at the indicated time to analyze tumor growth and immune cells in the microenvironment. Tumors and lung metastasis specimens were obtained via surgical operations for research purposes. Neutrophils were obtained from peripheral blood of patients with liver cancer or healthy donors (HD). RESULTS: Hepatocellular carcinoma cells reduce the secretion of histidine-rich glycoprotein (HRG), regulate the recruitment and activation of neutrophils in the metastatic microenvironment and promote the production of neutrophil extracellular traps (NETs), thereby promoting liver cancer lung metastasis. HRG binds to FCγR1 on the neutrophil membrane while inhibiting PI3K and NF-κB activation, thereby reducing IL-8 secretion to reduce neutrophil recruitment. Meanwhile, HRG inhibited IL8-MAPK and NF-κB pathway activation and ROS production, resulting in reduced NETs formation. CONCLUSIONS: Our study reveals that liver cancer regulates neutrophil recruitment and NETs formation in the metastatic microenvironment by reducing HRG secretion, thereby promoting tumour lung metastasis. The results of this study will contribute to the development of possible strategies for treating metastases.

PINK1-Mediated Mitophagy Promotes Oxidative Phosphorylation and Redox Homeostasis to Induce Drug-Tolerant Persister Cancer Cells.

The drug-tolerant persister (DTP) state enables cancer cells to evade cytotoxic stress from anticancer therapy. However, the mechanisms governing DTP generation remain poorly understood. Here, we observed that lung adenocarcinoma (LUAD) cells and organoids entered a quiescent DTP state to survive MAPK inhibitor treatment. DTP cells following MAPK inhibition underwent a metabolic switch from glycolysis to oxidative phosphorylation (OXPHOS). PTEN-induced kinase 1 (PINK1), a serine/threonine kinase that initiates mitophagy, was upregulated to maintain mitochondrial homeostasis during DTP generation. PINK1-mediated mitophagy supported DTP cell survival and contributed to poor prognosis. Mechanistically, MAPK pathway inhibition resulted in MYC-dependent transcriptional upregulation of PINK1, leading to mitophagy activation. Mitophagy inhibition using either clinically applicable chloroquine or depletion of PINK1 eradicated drug tolerance and allowed complete response to MAPK inhibitors. This study uncovers PINK1-mediated mitophagy as a novel tumor protective mechanism for DTP generation, providing a therapeutic opportunity to eradicate DTP and achieve complete responses. SIGNIFICANCE: DTP cancer cells that cause relapse after anticancer therapy critically depend on PINK1-mediated mitophagy and metabolic reprogramming, providing a therapeutic opportunity to eradicate persister cells to prolong treatment efficacy.

Scientific issues of zinc-bromine flow batteries and mitigation strategies.

Zinc-bromine flow batteries (ZBFBs) are promising candidates for the large-scale stationary energy storage application due to their inherent scalability and flexibility, low cost, green, and environmentally friendly characteristics. ZBFBs have been commercially available for several years in both grid scale and residential energy storage applications. Nevertheless, their continued development still presents challenges associated with electrodes, separators, electrolyte, as well as their operational chemistry. Therefore, rational design of these components in ZBFBs is of utmost importance to further improve the overall device performance. In this review, the focus is on the scientific understanding of the fundamental electrochemistry and functional components of ZBFBs, with an emphasis on the technical challenges of reaction chemistry, development of functional materials, and their application in ZBFBs. Current limitations of ZBFBs with future research directions in the development of high performance ZBFBs are suggested.