Retraction notice to "PINK1 deficiency in gastric cancer compromises mitophagy, promotes the Warburg effect, and facilitates M2 polarization of macrophages" [Cancer Lett. 529 (2022) 19-36].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief and authors. Following the publication of the above article, the Editor was notified by a concerned reader that the authors supplied duplicated images. Specifically, that in Fig. 5 A, both FACS panels are identical and in Fig 5E, two different proteins (HK2 and PDK1) have the same western blot. After checking the data in relation with Fig. 5A and E, the authors have confirmed that the two pictures indeed have the problems of duplication. The authors reported that this problem came from the authors' unintentional behavior, which may be due to a copy and paste error in the manner of image processing. The authors sincerely apologize for the inconvenience caused to our Editors and readers. Due to this duplication error, the authors and Editor have made the decision to retract this paper.

PINK1 deficiency in gastric cancer compromises mitophagy, promotes the Warburg effect, and facilitates M2 polarization of macrophages.

Cancer cells are typically characterized by abnormal quality control of mitochondria, production of reactive oxygen species (ROS), dysregulation of the cell redox state, and the Warburg effect. Mutation or depletion of PTEN-induced kinase 1 (PINK1) or Parkin leads to mitophagy defects and accumulation of malfunctioning mitochondria, and is often detected in a variety of tumors. However, PINK1's role in the progression of gastric cancer (GC) remains unclear, with its main effect being on mitochondrial turnover, metabolic reprogramming, and tumor microenvironment (TME) alteration. To address these issues, we first assessed the expression levels of PINK1, mitophagy-associated molecules, ROS, HIF-1α, glycolysis-associated genes, and macrophage signatures in GC tissues and matched tumor-adjacent normal samples. In addition, GC cell lines (AGS and MKN-45) and xenograft mouse models were used to determine the mechanism by which PINK1 regulates mitophagy, metabolic reprogramming, tumor-associated macrophage (TAM) polarization, and GC progression. We found that PINK1 loss correlated with advanced stage GC and poorer overall survival. GC tissues with lower PINK1 levels showed compromised mitophagy signaling and enhanced glycolytic enzyme expression. In vitro experiments demonstrated that PINK1 deficiency promoted GC cell proliferation and migration through the inhibition of mitophagy, production of mitochondrial ROS, stabilization of HIF-1α, and facilitation of the Warburg effect under both normoxic and hypoxic conditions. Moreover, PINK1 deficiency in GC cells promoted TAM polarization toward the M2-like phenotype. Reintroduction of PINK1 or inhibition of HIF-1α effectively repressed PINK1 deficiency-mediated effects on GC cell growth, metabolic shift, and TAM polarization. Thus, mitophagy defects caused by PINK1 loss conferred a metabolic switch through accumulation of mtROS and stabilization of HIF-1α, thereby facilitating the M2 polarization of TAM to remodel an immunosuppressive microenvironment in GC. Our results clarify the mechanism between PINK1 and GC progression and may provide a novel strategy for the treatment of GC.

PINK1-mediated mitophagy protects against hepatic ischemia/reperfusion injury by restraining NLRP3 inflammasome activation.

Activation of nucleotide-binding domain leucine-rich repeat containing family pyrin domain containing 3 (NLRP3) inflammasome in Kupffer cells (KCs) contributes significantly to hepatic ischemia/reperfusion (I/R) injury, while the mechanism of how NLRP3 inflammasome is regulated remains less well defined. Recent evidence has showed that mitophagy acts as a central player for maintaining mitochondrial homeostatis through elimination of damaged mitochondria, leading to the prevention of hyperinflammation triggered by NLRP3 activation. In this study, we aimed at investigating the potential role of PTEN-induced kinase 1 (PINK1)-mediated mitophagy in hepatic I/R injury. C57BL/6 mice subjected to partial warm hepatic I/R or primary KCs exposed to anoxia/reoxygenation (A/R) was used as in vivo or in vitro model, respectively. Mitophagy was measured by protein levels of PINK1, Parkin, LC3B-II, TOMM20 and p62. NLRP3, caspase-1 and IL-1ß at mRNA and/or protein levels were used as indicators of inflammasome activation. Our results demonstrated remarkable hepatic inflammation and NLRP3 inflammasome activation during hepatic I/R, along with increased PINK1-mediated mitophagy. Notably, overexpression of PINK1 in vivo attenuated hepatic I/R injury, ROS production, NLRP3 activation and hepatic inflammation. In parallel, A/R challenge in vitro also triggered NLRP3 activation in KCs accompanied by increase in mitophagy. Enhanced mitophagy mediated by PINK1 overexpression further inhibited NLRP3 activation and reversed the KC-mediated inflammatory injury to hepatocytes. Kinase-dead mutation of PINK1 completely abolished the above protective effects by PINK1. Blocking of mitophagy/autophagy by silencing of PINK1/Parkin, ATG5, NDP52 or OPTN showed the totally opposite effects, respectively. Treatment with different autophagic inhibitors also consistently reversed the PINK1-mediated effects, suggesting that an intact PINK1-mediated mitophagy signaling was crucial for ablation of NLRP3 signaling in the presence of A/R. Together, these results support a critical role of PINK1-mediated mitophagy in mitochondrial quality control for KC activation and function in hepatic I/R.

Adenovirus-mediated OX40Ig gene transfer induces long-term survival of orthotopic liver allograft in rats.

BACKGROUND: To discuss the effect and mechanism of adenovirus-mediated OX40Ig gene transfer in inducing long-term survival of liver allografts in rats. METHODS: Orthotopic liver transplantation was performed from Lewis to Brown Norway (BN) rats through the modified two-cuffed technique, and all rats were randomly divided equally into four groups: control, AdEGFP, AdOX40Ig, and FK506. The survival times of the rats were recorded. The rats' liver function, serum cytokines, hepatocyte pathology, OX40Ig protein level, and mixed lymphocyte reaction (MLR) with or without recombinant interleukin-2 (rIL-2) were evaluated. RESULTS: Compared with the control and AdEGFP groups, the rats in the AdOX40Ig and FK506 groups survived longer (P < 0.05), experienced less damage to hepatic function (P < 0.05), and showed milder hepatic cellular rejection and less hepatic cellular apoptosis. Interferon (IFN)-γ and IL-2 content in the serum were lower after operation (P < .05) in the AdOX40Ig and FK506 groups. On the contrary, IL-4 and IL-10 content in the serum was higher after operation (P < 0.05) in the AdOX40Ig and FK506 groups. OX40Ig protein was significantly expressed in the AdOX40Ig group and reached the highest level on the 7th day after operation. With respect to the MLR between BN and Lewis rats, the AdOX40Ig group showed a lighter reaction for the same strain than the control and AdEGFP groups (P < 0.05), which is different from the MLR between BN and F344 rats. After adding rIL-2 to the MLR system between BN rats in the AdOX40Ig group and Lewis rats, MLR was aggravated. CONCLUSION: Through OX40/OX4OL pathways, OX40Ig created an immunosuppressive effect after liver transplantation in rats. This immunosuppressive effect is associated with reduced IL-2 and can be reversed by adding IL-2 with antigen specificity.

Asiatic acid protects against hepatic ischemia/reperfusion injury by inactivation of Kupffer cells via PPARγ/NLRP3 inflammasome signaling pathway.

Hepatic ischemia/reperfusion (I/R) contributes to major complications in clinical practice affecting perioperative morbidity and mortality. Recent evidence suggests the key role of nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammaosme activation on the pathogenesis of I/R injury. Asiatic acid (AA) is a pentacyclic triterpene derivative presented with versatile activities, including antioxidant, anti-inflammation and hepatoprotective effects. This study was designed to determine whether AA had potential hepatoprotective benefits against hepatic I/R injury, as well as to unveil the underlying mechanisms involved in the putative effects. Mice subjected to warm hepatic I/R, and Kupffer cells (KCs) or RAW264.7 cells challenged with lipopolysaccharide (LPS)/H2O2, were pretreated with AA. Administration of AA significantly attenuated hepatic histopathological damage, global inflammatory level, apoptotic signaling level, as well as NLRP3 inflammasome activation. These effects were correlated with increased expression of peroxisome proliferator-activated receptor gamma (PPARγ). Conversely, pharmacological inhibition of PPARγ by GW9662 abolished the protective effects of AA on hepatic I/R injury and in turn aggravated NLRP3 inflammasome activation. Activation of NLRP3 inflammasome was most significant in nonparenchymal cells (NPCs). Depletion of KCs by gadolinium chloride (GdCl3) further attenuated the detrimental effects of GW9662 on hepatic I/R as well as NLRP3 activation. In vitro, AA concentration-dependently inhibited LPS/H2O2-induced NLRP3 inflammaosome activation in KCs and RAW264.7 cells. Either GW9662 or genetic knockdown of PPARγ abolished the AA-mediated inactivation of NLRP3 inflammasome. Mechanistically, AA attenuated I/R or LPS/H2O2-induced ROS production and phosphorylation level of JNK, p38 MAPK and IκBα but not ERK, a mechanism dependent on PPARγ. Finally, AA blocked the deleterious effects of LPS/H2O2-induced macrophage activation on hepatocyte viability in vitro, and improved survival in a lethal hepatic I/R injury model in vivo. Collectively, these data suggest that AA is effective in mitigating hepatic I/R injury through attenuation of KCs activation via PPARγ/NLRP3 inflammasome signaling pathway.

Electron energy-loss safe-dose limits for manganese valence measurements in environmentally relevant manganese oxides.

Manganese (Mn) oxides are among the strongest mineral oxidants in the environment and impose significant influence on mobility and bioavailability of redox-active substances, such as arsenic, chromium, and pharmaceutical products, through oxidation processes. Oxidizing potentials of Mn oxides are determined by Mn valence states (2+, 3+, 4+). In this study, the effects of beam damage during electron energy-loss spectroscopy (EELS) in the transmission electron microscope have been investigated to determine the "safe dose" of electrons. Time series analyses determined the safe dose fluence (electrons/nm(2)) for todorokite (10(6) e/nm(2)), acid birnessite (10(5)), triclinic birnessite (10(4)), randomly stacked birnessite (10(3)), and δ-MnO(2) (<10(3)) at 200 kV. The results show that meaningful estimates of the mean Mn valence can be acquired by EELS if proper care is taken.

Mineralogy, morphology, and textural relationships in coatings on quartz grains in sediments in a quartz-sand aquifer.

Mineralogical studies of coatings on quartz grains and bulk sediments from an aquifer on Western Cape Cod, Massachusetts, USA were carried out using a variety of transmission electron microscopy (TEM) techniques. Previous studies demonstrated that coatings on quartz grains control the adsorption properties of these sediments. Samples for TEM characterization were made by a gentle mechanical grinding method and focused ion beam (FIB) milling. The former method can make abundant electron-transparent coating assemblages for comprehensive and quantitative X-ray analysis and the latter technique protects the coating texture from being destroyed. Characterization of the samples from both a pristine area and an area heavily impacted by wastewater discharge shows similar coating textures and chemical compositions. Major constituents of the coating include Al-substituted goethite and illite/chlorite clays. Goethite is aggregated into well-crystallized domains through oriented attachment resulting in increased porosity. Illite/chlorite clays with various chemical compositions were observed to be mixed with goethite aggregates and aligned sub-parallel to the associated quartz surface. The uniform spatial distribution of wastewater-derived phosphorus throughout the coating from the wastewater-contaminated site suggests that all of the coating constituents, including those adjacent to the quartz surface, are accessible to groundwater solutes. Both TEM characterization and chemical extraction results indicate there is a significantly greater amount of amorphous iron oxide in samples from wastewater discharge area compared to those from the pristine region, which might reflect the impact of redox cycling of iron under the wastewater-discharge area. Coating compositions are consistent with the moderate metal and oxy-metalloid adsorption capacities, low but significant cation exchange capacities, and control of iron(III) solubility by goethite observed in reactive transport experimental and modeling studies conducted at the site.

Presence, distribution, and diversity of iron-oxidizing bacteria at a landfill leachate-impacted groundwater surface water interface.

We examined the presence of iron-oxidizing bacteria (IOB) at a groundwater surface water interface (GSI) impacted by reduced groundwater originating as leachate from an upgradient landfill. IOB enrichments and quantifications were obtained, at high vertical resolution, by an iron/oxygen opposing gradient cultivation method. The depth-resolved soil distribution profiles of water content, Fe(2+), and total Fe indicated sharp gradients within the top 10 cm sediments of the GSI, where the IOB density was the highest. In addition, the vertical distribution of iron-reducing bacteria at the same sampling site mirrored the IOB distribution. Clone libraries from two separate IOB enrichments indicated a stratified IOB community with clear differences at short vertical distances. Alpha- and Betaproteobacteria were the dominant phylotypes. Clones from the near-surface sediment (1-2 cm below ground surface) were dominated by members of the Bradyrhizobiaceae and Comamonadaceae; clones from the deeper sediments were phylogenetically more diverse, dominated by members of the Rhodocyclaceae. The iron deposition profiles indicated that active iron oxidation occurred only within the near-to-surface GSI sediments. The match between the iron deposition profiles and the IOB abundance profiles strongly hints at the contribution of the IOB community to Fe oxidation in this Fe-rich GSI ecosystem.

Growth kinetics of disk-shaped copper islands in electrochemical deposition.

The ability to independently dictate the shape and crystal orientation of islands in electrocrystallization remains a significant challenge. The main reason for this is that the complex interplay between the substrate, nucleation, and surface chemistry is not fully understood. Here we report on the kinetics of island growth for copper on ruthenium oxide. The small nucleation overpotential leads to enhanced lateral growth and the formation of hexagonal disk-shaped islands. The amorphous substrate allows the nuclei to achieve the thermodynamically favorable orientation, i.e., a 111 surface normal. Island growth follows power law kinetics in both lateral and vertical directions. At shorter times, the two growth exponents are equal to 1/2 whereas at longer times lateral growth slows down while vertical growth speeds up. We propose a growth mechanism, wherein the lateral growth of disk-shaped islands is initiated by attachment of Cu adatoms on the ruthenium oxide surface onto the island periphery while vertical growth is initiated by two-dimensional nucleation on the top terrace and followed by lateral step propagation. These results indicate three criteria for enhanced lateral growth in electrodeposition: (i) a substrate that leads to a small nucleation overpotential, (ii) fast adatom surface diffusion on substrate to promote lateral growth, and (iii) preferential anion adsorption to stabilize the basal plane.

Enhanced cutinase production with Thermobifida fusca by two-stage pH control strategy.

A mutant of Thermobifida fusca ATCC 27730 was used for cutinase production. Acetate was the most suitable carbon source for cell growth and cutinase production compared with others. The pH was one of the most important factors affecting cutinase yield and productivity. Batch cutinase fermentations by mutant Thermobifida fusca WSH04 at various pH values ranging from 7.0 to 7.9 were studied. Based on the effects of different pH values on the specific cell growth rate and specific cutinase formation rate, a two-stage pH control strategy was developed, in which the pH was set at 7.3 for the first 20 h, and switched to 7.6 afterwards. By applying this two-stage pH control strategy for cutinase fermentation, the maximal cutinase activity reached 19.8 U/mL.