Electrochemical water splitting enhancement by introducing mesoporous NiCoFe-trimetallic phosphide nanosheets as catalysts for the oxygen evolution reaction.

Transition metal-based catalysts are widely used in electrocatalysis, especially in the field of water splitting, due to their excellent electrochemical performance, which focuses on improving the efficiency of the complex oxygen evolution reaction (OER) that occurs at the anode. Transition metal-based catalysts will undergo electrochemical surface reconstruction and form (oxy)hydroxide-based hybrids, which consider the actual active sites for OER. So many efforts have been made to know the origin of the effect of electrochemical surface reconstruction on the performance of the OER. Herein, NiCoFe-phosphide catalyst nanosheets were constructed by a simple one-step hydrothermal reaction by adding oleylamine and ethanol to water solvent during the preparation of the catalyst precursor and high-temperature gas-phase phosphating and significantly showed high effectiveness catalytic activity and conductivity in comparison to normal and traditional preparation methods. Electrochemical analysis, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and high-resolution transmission electron microscopy (HRTEM) demonstrate that the surface was constructed during the electrochemical reaction and formed an amorphous layer of MOx(OH)y active sites, which increased the electrochemical surface area and promoted charge transfer. As well, the synthesized NiCoFePx-PNSs catalyst nanosheets exhibit excellent catalytic activity with a low overpotential equal to 259 mV to achieve the OER at a current density of 10 mA cm-2 and a low Tafel slope of 50.47 mV dec-1 which is better than for most reported transition metal-based electrocatalysts. This work provides a new design for a transition metal-based catalyst for OER as well as further insights into the effect of electrochemical surface reconstruction on intrinsic activity and OER performance.

Mapping and candidate gene analysis of QTLs for grain shape in a rice chromosome segment substitution line Z485 and breeding of SSSLs.

Grain shape is one of the most important factors that affects rice yield. Cloning novel grain shape genes and analyzing their genetic mechanisms are crucial for high yield breeding. In this study, a slender grain CSSL-Z485 with 3-segments substitution in the genetic background of Nipponbare was constructed in rice. Cytological analysis showed that the longer grain length of Z485 was related to the increase in glume cell numbers, while the narrower grain width was associated with the decrease in cell width. Three grain shape-related quantitative trait locus (QTLs), including qGL12, qGW12, and qRLW12, were identified through the F2 population constructed from a cross between Nipponbare and Z485. Furthermore, four single segment substitution lines (SSSLs, S1-S4) carrying the target QTLs were dissected from Z485 by MAS. Finally, three candidate genes of qGL12 for grain length and qGW12 for grain width located in S3 were confirmed by DNA sequencing, RT-qPCR, and protein structure prediction. Specifically, candidate gene 1 encodes a ubiquitin family protein, while candidate genes 2 and 3 encode zinc finger proteins. The results provide valuable germplasm resources for cloning novel grain shape genes and molecular breeding by design. Supplementary information: The online version contains supplementary material available at 10.1007/s11032-024-01480-x.

Peripheral CX3CR1+ T cells combined with PD-1 blockade therapy potentiates the anti-tumor efficacy for lung cancer.

Identifying tumor-relevant T cell subsets in the peripheral blood (PB) has become a potential strategy for cancer treatment. However, the subset of PB that could be used to treat cancer remains poorly defined. Here, we found that the CX3CR1+ T cell subset in the blood of patients with lung cancer exhibited effector properties and had a higher TCR matching ratio with tumor-infiltrating lymphocytes (TILs) compared to CX3CR1- T cells, as determined by paired single-cell RNA and TCR sequencing. Meanwhile, the anti-tumor activities, effector cytokine production, and mitochondrial function were enhanced in CX3CR1+ T cells both in vitro and in vivo. However, in the co-culture system of H322 cells with T cells, the percentages of apoptotic cells and Fas were substantially higher in CX3CR1+ T cells than those in CX3CR1- T cells. Fas-mediated apoptosis was rescued by treatment with an anti-PD-1 antibody. Accordingly, the combination of adoptive transfer of CX3CR1+ T cells and anti-PD-1 treatment considerably decreased Fas expression and improved the survival of lung xenograft mice. Moreover, an increased frequency of CX3CR1+ T cells in the PB correlated with a better response and prolonged survival of patients with lung cancer who received anti-PD-1 therapy. These findings indicate the promising potential of adoptive transfer of peripheral CX3CR1+ T cells as an individual cancer immunotherapy.

High Frequency of Prior SARS-CoV-2 Infection by Sensitive Nucleocapsid Assays.

Prior infection with SARS-CoV-2 is typically measured by nucleocapsid serology assays. In this study, we show that the Simoa serology assays and T cell intracellular cytokine staining assays are more sensitive than the clinical Elecsys assay for detection of nucleocapsid-specific immune responses. These data suggest that the prevalence of prior SARS-CoV-2 infection in the population may be higher than currently appreciated.

A progress update on the biological effects of biodegradable microplastics on soil and ocean environment: A perfect substitute or new threat?

Conventional plastics are inherently difficult to degrade, causing serious plastic pollution. With the development of society, biodegradable plastics (BPs) are considered as an alternative to traditional plastics. However, current research indicated that BPs do not undergo complete degradation in natural environments. Instead, they may convert into biodegradable microplastics (BMPs) at an accelerated rate, thereby posing a significant threat to environment. In this paper, the definition, application, distribution, degradation behaviors, bioaccumulation and biomagnification of BPs were reviewed. And the impacts of BMPs on soil and marine ecosystems, in terms of physicochemical property, nutrient cycling, microorganisms, plants and animals were comprehensively summarized. The effects of combined exposure of BMPs with other pollutants, and the mechanism of ecotoxicity induced by BMPs were also addressed. It was found that BMPs reduced pH, increased DOC content, and disrupted the nitrification of nitrogen cycle in soil ecosystem. The shoot dry weight, pod number and root growth of soil plants, and reproduction and body length of soil animals were inhibited by BMPs. Furthermore, the growth of marine plants, and locomotion, body length and survival of marine animals were suppressed by BMPs. Additionally, the ecotoxicity of combined exposure of BMPs with other pollutants has not been uniformly concluded. Exposure to BMPs induced several types of toxicity, including neurotoxicity, gastrointestinal toxicity, reproductive toxicity, immunotoxicity and genotoxicity. The future calls for heightened attention towards the regulation of the degradation of BPs in the environment, and pursuit of interventions aimed at mitigating their ecotoxicity and potential health risks to human.

NOX4 promotes tumor progression through the MAPK-MEK1/2-ERK1/2 axis in colorectal cancer.

BACKGROUND: Metabolic reprogramming plays a key role in cancer progression and clinical outcomes; however, the patterns and primary regulators of metabolic reprogramming in colorectal cancer (CRC) are not well understood. AIM: To explore the role of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in promoting progression of CRC. METHODS: We evaluated the expression and function of dysregulated and survival-related metabolic genes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Consensus clustering was used to cluster CRC based on dysregulated metabolic genes. A prediction model was constructed based on survival-related metabolic genes. Sphere formation, migration, invasion, proliferation, apoptosis and clone formation was used to evaluate the biological function of NOX4 in CRC. mRNA sequencing was utilized to explore the alterations of gene expression NOX4 over-expression tumor cells. In vivo subcutaneous and lung metastasis mouse tumor model was used to explore the effect of NOX4 on tumor growth. RESULTS: We comprehensively analyzed 3341 metabolic genes in CRC and identified three clusters based on dysregulated metabolic genes. Among these genes, NOX4 was highly expressed in tumor tissues and correlated with worse survival. In vitro, NOX4 overexpression induced clone formation, migration, invasion, and stemness in CRC cells. Furthermore, RNA-sequencing analysis revealed that NOX4 overexpression activated the mitogen-activated protein kinase-MEK1/2-ERK1/2 signaling pathway. Trametinib, a MEK1/2 inhibitor, abolished the NOX4-mediated tumor progression. In vivo, NOX4 overexpression promoted subcutaneous tumor growth and lung metastasis, whereas trametinib treatment can reversed the metastasis. CONCLUSION: Our study comprehensively analyzed metabolic gene expression and highlighted the importance of NOX4 in promoting CRC metastasis, suggesting that trametinib could be a potential therapeutic drugs of CRC clinical therapy targeting NOX4.

Comparison of the immunogenicity and protective efficacy of ACAM2000, MVA, and vectored subunit vaccines for Mpox in rhesus macaques.

The 2022-2023 mpox outbreak triggered vaccination efforts using smallpox vaccines that were approved for mpox, including modified vaccinia Ankara (MVA; JYNNEOS), which is a safer alternative to live replicating vaccinia virus (ACAM2000). Here, we compare the immunogenicity and protective efficacy of JYNNEOS by the subcutaneous or intradermal routes, ACAM2000 by the percutaneous route, and subunit Ad35 vector-based L1R/B5R or L1R/B5R/A27L/A33R vaccines by the intramuscular route in rhesus macaques. All vaccines provided robust protection against high-dose intravenous mpox virus challenge with the current outbreak strain, with ACAM2000 providing near complete protection and JYNNEOS and Ad35 vaccines providing robust but incomplete protection. Protection correlated with neutralizing antibody responses as well as L1R/M1R- and B5R/B6R-specific binding antibody responses, although additional immune responses likely also contributed to protection. This study demonstrates the protective efficacy of multiple vaccine platforms against mpox virus challenge, including both current clinical vaccines and vectored subunit vaccines.

Boosting oxygen evolution reaction rates with mesoporous Fe-doped MoCo-phosphide nanosheets.

Transition metal-based catalysts are commonly used for water electrolysis and cost-effective hydrogen fuel production due to their exceptional electrochemical performance, particularly in enhancing the efficiency of the oxygen evolution reaction (OER) at the anode. In this study, a novel approach was developed for the preparation of catalysts with abundant active sites and defects. The MoCoFe-phosphide catalyst nanosheets were synthesized using a simple one-step hydrothermal reaction and chemical vapor deposition-based phosphorization. The resulting MoCoFe-phosphide catalyst nanosheets displayed excellent electrical conductivity and a high number of electrochemically active sites, leading to high electrocatalytic activities and efficient kinetics for the OER. The MoCoFe-phosphide catalyst nanosheets demonstrated remarkable catalytic activity, achieving a low overpotential of only 250 mV to achieve the OER at a current density of 10 mA cm-2. The catalyst also exhibited a low Tafel slope of 43.38 mV dec-1 and maintained high stability for OER in alkaline media, surpassing the performance of most other transition metal-based electrocatalysts. The outstanding OER performance can be attributed to the effects of Mo and Fe, which modulate the electronic properties and structures of CoP. The results showed a surface with abundant defects and active sites with a higher proportion of Co2+ active sites, a larger specific surface area, and improved interfacial charge transfer. X-ray photoelectron spectroscopy (XPS) analysis revealed that the catalyst's high activity originates from the presence of Mo6+/Mo4+ and Co2+/Co3+ redox couples, as well as the formation of active metal (oxy)hydroxide species on its surface.

A novel CD8+ T cell-related gene signature as a prognostic biomarker in hepatocellular carcinoma.

CD8+ T cells have great roles in tumor suppression and elimination of various tumors including hepatocellular carcinoma (HCC). Nonetheless, potential prognostic roles of CD8+ T cell-related genes (CD8Gs) in HCC remains unknown. In our study, 416 CD8Gs were identified in HCC, which were enriched in inflammatory and immune signaling pathways. Using The Cancer Genome Atlas dataset, a 5-CD8Gs risk model (KLRB1, FYN, IL2RG, FCER1G, and DGKZ) was constructed, which was verified in International Cancer Genome Consortium and gene expression omnibus datasets. Furthermore, we found that overall survival was independently correlated with the CD8Gs signature, and it was associated with immune- and cancer-related signaling pathways and immune cells infiltration. Finally, drug sensitivity data indicated that 10 chemotherapeutic drugs held promise as therapeutics for HCC patients with high-risk. In conclusion, multi-databases analysis showed that 5-CD8Gs and their signature could be an indicator to predict candidate drugs for HCC therapy.

Cycloalkane degradation by an uncultivated novel genus of Gammaproteobacteria derived from China's marginal seas.

The consumption of cycloalkanes is prevalent in low-temperature marine environments, likely influenced by psychrophilic microorganisms. Despite their significance, the primary active species responsible for marine cycloalkane degradation remain largely unidentified due to cultivation challenges. In this study, we provide compelling evidence indicating that the uncultured genus C1-B045 of Gammaproteobacteria is a pivotal participant in cycloalkane decomposition within China's marginal seas. Notably, the relative abundance of C1-B045 surged from 15.9% in the methylcyclohexane (MCH)-consuming starter culture to as high as 97.5% in MCH-utilizing extinction cultures following successive dilution-to-extinction and incubation cycles. We used stable isotope probing, Raman-activated gravity-driven encapsulation, and 16 S rRNA gene sequencing to link cycloalkane-metabolizing phenotype to genotype at the single-cell level. By annotating key enzymes (e.g., alkane monooxygenase, cyclohexanone monooxygenase, and 6-hexanolactone hydrolase) involved in MCH metabolism within C1-B045's representative metagenome-assembled genome, we developed a putative MCH degradation pathway.

Waning immunity and IgG4 responses following bivalent mRNA boosting.

Messenger RNA (mRNA) vaccines were highly effective against the ancestral SARS-CoV-2 strain, but the efficacy of bivalent mRNA boosters against XBB variants was substantially lower. Here, we show limited durability of neutralizing antibody (NAb) responses against XBB variants and isotype switching to immunoglobulin G4 (IgG4) responses following bivalent mRNA boosting. Bivalent mRNA boosting elicited modest XBB.1-, XBB.1.5-, and XBB.1.16-specific NAbs that waned rapidly within 3 months. In contrast, bivalent mRNA boosting induced more robust and sustained NAbs against the ancestral WA1/2020 strain, suggesting immune imprinting. Following bivalent mRNA boosting, serum antibody responses were primarily IgG2 and IgG4 responses with poor Fc functional activity. In contrast, a third monovalent mRNA immunization boosted all isotypes including IgG1 and IgG3 with robust Fc functional activity. These data show substantial immune imprinting for the ancestral spike and isotype switching to IgG4 responses following bivalent mRNA boosting, with important implications for future booster designs and boosting strategies.

Cytotoxic Compounds from Marine Fungi: Sources, Structures, and Bioactivity.

Marine fungi, such as species from the Penicillium and Aspergillus genera, are prolific producers of a diversity of natural products with cytotoxic properties. These fungi have been successfully isolated and identified from various marine sources, including sponges, coral, algae, mangroves, sediment, and seawater. The cytotoxic compounds derived from marine fungi can be categorized into five distinct classes: polyketides, peptides, terpenoids and sterols, hybrids, and other miscellaneous compounds. Notably, the pre-eminent group among these compounds comprises polyketides, accounting for 307 out of 642 identified compounds. Particularly, within this collection, 23 out of the 642 compounds exhibit remarkable cytotoxic potency, with IC50 values measured at the nanomolar (nM) or nanogram per milliliter (ng/mL) levels. This review elucidates the originating fungal strains, the sources of isolation, chemical structures, and the noteworthy antitumor activity of the 642 novel natural products isolated from marine fungi. The scope of this review encompasses the period from 1991 to 2023.

Novel Polystyrene-Binding Nanobody for Enhancing Immunoassays: Insights into Affinity, Immobilization, and Application Potential.

Nanobodies, which represent the next generation of antibodies due to their unique properties, face a significant limitation in their poor physical adsorption on solid supports. In this study, we successfully discovered polystyrene binding nanobodies from a synthetic nanobody library. Notably, bivalent nanobody B2 exhibited high affinity for polystyrene (0.7 nM for ELISA saturation binding analysis and 15.6 nM for isothermal titration calorimetry), displaying a pH-dependent behavior. Remarkably, hydrophobic and electrostatic interactions contribute minimally to the binding process. Molecular modeling provided insights into the interaction between B2 and polystyrene, revealing that the Trp51 residue within the CDR2 loop formed an aromatic H-bond with polystyrene at a distance of 2.74 Å, thus explaining the observed reduction in B2 affinity caused by Trp51 mutations. To explore B2's potential in protein immobilization, we constructed a bispecific nanobody by fusing B2 to an anticarcinoembryonic antigen nanobody 11C12, which cannot be immobilized on polystyrene through passive adsorption. Remarkably, the fusion construct achieved effective immobilization on polystyrene within 5 min by passing the need for periplasmic protein purification despite its low expression level. Moreover, the fusion construct demonstrated excellent linearity in the chemiluminescent enzyme immunoassay. For the first time, this study reports a simplified and seamless platform for the oriented immobilization of nanobody. Importantly, the entire process eliminated the need for protein purification, enabling efficient and rapid immobilization of fusion proteins directly from crude cell extracts, even when the expression level was low. Our developed process dramatically reduced the processing time from 2.5 days to just 5 min.

Sulforaphane activates CD8+ T cells antitumor response through IL-12RB2/MMP3/FasL-induced MDSCs apoptosis'.

BACKGROUND: Extensive attention has been given to the role of myeloid-derived suppressor cells (MDSCs) in driving tumor progression and treatment failure. Preclinical studies have identified multiple agents that eliminate MDSCs. However, none have been authorized in the cliniccal ues due to the safety reasons. In the present study, we investigated the efficacy and mechanism of sulforaphane (SFN) to eliminate MDSCs in the tumor microenvironment (TME). METHODS: We monitored SFN effect on tumor growth and the percents or apoptosis of immune cell subsets in mice models bearing LLC or B16 cells. Flow cytometry, quantitative reverse transcription-PCR, immunohistochemistry, ELISA, immunofluorescence, imaging flow cytometry and western blot were performed to validate the role of SFN on MDSCs function in vivo and in vitro. RNA sequencing was then used to interrogate the mechanisms of how SFN regulated MDSCs function. Tumor xenograft models were established to evaluate the involvement of IL-12RB2/MMP3/FasL induced MDSCs apoptosis in vivo. We verified the effect of SFN on MDSCs and CD8+ T cells in the blood samples from a phase I clinical trial (KY-2021-0350). RESULTS: In this study, we elucidated that SFN liberated CD8+ T-cell antitumor ability by reducing MDSCs abundance, leading to repressed tumor growth. SFN treatment suppressed MDSCs accumulation in the peripheral blood and tumor sites of mice, but had no effect on the bone marrow. Mechanistically, SFN activates IL-12RB2, which stimulates the MMP3/FasL signaling cascade to trigger caspase 3 cleavage and induce apoptosis in MDSCs. Clinically, SFN treatment eliminates peripheral MDSCs and increases the percentage and activation of CD8+ T cells. CONCLUSIONS: Collectively, we uncovered the role of SFN in eliminating MDSCs to emancipate CD8+ T cells through IL-12RB2/MMP3/FasL induced apoptosis, thus providing a strategy for targeting MDSCs to control tumors and improve clinical efficacy.

Melatonin improves cholestatic liver disease via the gut-liver axis.

Cholestatic liver disease is characterized by disturbances in the intestinal microbiota and excessive accumulation of toxic bile acids (BA) in the liver. Melatonin (MT) can improve liver diseases. However, the underlying mechanism remains unclear. This study aimed to explore the mechanism of MT on hepatic BA synthesis, liver injury, and fibrosis in 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-fed and Mdr2-/- mice. MT significantly improved hepatic injury and fibrosis with a significant decrease in hepatic BA accumulation in DDC-fed and Mdr2-/- mice. MT reprogramed gut microbiota and augmented fecal bile salt hydrolase activity, which was related to increasing intestinal BA deconjugation and fecal BA excretion in both DDC-fed and Mdr2-/- mice. MT significantly activated the intestinal farnesoid X receptor (FXR)/fibroblast growth factor 15 (FGF-15) axis and subsequently inhibited hepatic BA synthesis in DDC-fed and Mdr2-/- mice. MT failed to improve DDC-induced liver fibrosis and BA synthesis in antibiotic-treated mice. Furthermore, MT provided protection against DDC-induced liver injury and fibrosis in fecal microbiota transplantation mice. MT did not decrease liver injury and fibrosis in DDC-fed intestinal epithelial cell-specific FXR knockout mice, suggesting that the intestinal FXR mediated the anti-fibrosis effect of MT. In conclusion, MT ameliorates cholestatic liver diseases by remodeling gut microbiota and activating intestinal FXR/FGF-15 axis-mediated inhibition of hepatic BA synthesis and promotion of BA excretion in mice.

Surface Reconstruction Facilitated by Fluorine Migration and Bimetallic Center in NiCo Bimetallic Fluoride Toward Oxygen Evolution Reaction.

Oxygen evolution reaction (OER) is a critical anodic reaction of electrochemical water splitting, developing a high-efficiency electrocatalyst is essential. Transition metal-based catalysts are much more cost-effective if comparable activities can be achieved. Among them, fluorides are rarely reported due to their low aqueous stability of coordination and low electric conductivity. Herein, a NiCo bimetallic fluoride with good crystallinity is designed and constructed, and significantly enhanced catalytic activity and conductivity are observed. The inevitable oxidation of transition metal ions at high potential and the dissociation of F- are attributed to the low aqueous stability of coordination. The theoretical researches predicte that transition metal fluorides should have a strong tendency to electrochemical reconstruction. Therefore, based on the observations on their electrochemical behavior, high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, and bode plots, it is further demonstrated that surface reconstruction occurred during the electrochemical process, meanwhile a significant increase of electrochemically active area, which is created by F migration, are also directly observed. Additionally, DFT calculation results show that the electronic structure of the catalysts is modulated by the bimetallic centers, and this reconstruction helps optimizing the adsorption energy of oxygen-containing species and improves OER activity.

Mucosal boosting enhances vaccine protection against SARS-CoV-2 in macaques.

A limitation of current SARS-CoV-2 vaccines is that they provide minimal protection against infection with current Omicron subvariants1,2, although they still provide protection against severe disease. Enhanced mucosal immunity may be required to block infection and onward transmission. Intranasal administration of current vaccines has proven inconsistent3-7, suggesting that alternative immunization strategies may be required. Here we show that intratracheal boosting with a bivalent Ad26-based SARS-CoV-2 vaccine results in substantial induction of mucosal humoral and cellular immunity and near-complete protection against SARS-CoV-2 BQ.1.1 challenge. A total of 40 previously immunized rhesus macaques were boosted with a bivalent Ad26 vaccine by the intramuscular, intranasal and intratracheal routes, or with a bivalent mRNA vaccine by the intranasal route. Ad26 boosting by the intratracheal route led to a substantial expansion of mucosal neutralizing antibodies, IgG and IgA binding antibodies, and CD8+ and CD4+ T cell responses, which exceeded those induced by Ad26 boosting by the intramuscular and intranasal routes. Intratracheal Ad26 boosting also led to robust upregulation of cytokine, natural killer, and T and B cell pathways in the lungs. After challenge with a high dose of SARS-CoV-2 BQ.1.1, intratracheal Ad26 boosting provided near-complete protection, whereas the other boosting strategies proved less effective. Protective efficacy correlated best with mucosal humoral and cellular immune responses. These data demonstrate that these immunization strategies induce robust mucosal immunity, suggesting the feasibility of developing vaccines that block respiratory viral infections.

[Retracted] Downregulation of let­7b promotes COL1A1 and COL1A2 expression in dermis and skin fibroblasts during heat wound repair.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the western blotting data shown in Figs. 4B and 5 and the H&E immunostaining data shown in Fig 1A were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published, or were submitted for publication at around the same time.  Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 13: 2683-2688, 2016; DOI: 10.3892/mmr.2016.4877].

Polystyrene micro- and nanoplastics induce gastric toxicity through ROS mediated oxidative stress and P62/Keap1/Nrf2 pathway.

Microplastics (MPs) exist widely in the environment and can enter the human body indirectly through the food chain or directly through inhalation or ingestion. The primary organ that MPs contaminated food or water enters the human body through the digestive tract is the stomach. However, at present, the effects of MPs on the stomach and the related mechanism remain unclear. In this study, our results indicated that 50 nm and 250 nm polystyrene MPs (PS-MPs) at environmental related dose significantly decreased stomach organ coefficient, inhibited gastric juice secretion and mucus secretion, disrupted gastric barrier function and suppressed antioxidant ability in mice. In vitro experiments showed that PS-MPs inhibited cell viability, increased ROS generation, and induced apoptosis through mitochondria-dependent pathway. Simultaneously, PS-MPs also decreased mitochondrial membrane potential, ATP level, disrupted mitochondrial kinetic homeostasis, and activated P62 / Nrf2 / Keap1 pathway. Furthermore, blocking ROS (NAC) partially alleviated ROS and apoptosis caused by PS-MPs. Based on above findings, the potential adverse outcome pathway (AOP) of PS-MPs-caused gastric toxicity was proposed which provides a new insight into the risk assessment of MP related gastric damage. Our study unveils the gastric injury induced by PS MPs is dependent on ROS - mediated P62 / Nrf2 / Keap1 signaling pathway, and provides scientific basis for further exploration the mechanism of gastric toxicity of PS MPs.

Current advances in bacteria-based cancer immunotherapy.

As the understanding of the tumor microenvironment has deepened, immunotherapy has become a promising strategy for cancer treatment. In contrast to traditional therapies, immunotherapy is more precise and induces fewer adverse effects. In this field, some bacteria have attracted increased attention because of their natural ability to preferentially colonize and proliferate inside tumor sites and exert antitumor effects. Moreover, bacterial components may activate innate and adaptive immunity to resist tumor progression. However, the application of bacteria-based cancer immunotherapy is hampered by potential infection-associated toxicity and unpredictable behavior in vivo. Owing to modern developments in genetic engineering, bacteria can be modified to weaken their toxicity and enhance their ability to eliminate tumor cells or activate the antitumor immune response. This review summarizes the roles of bacteria in the tumor microenvironment, current strategies for bacterial engineering, and the synergistic efficiency of bacteria with other immunotherapies. In addition, the prospects and challenges of the clinical translation of engineered bacteria are summarized.