Dual effects of serum urate on stroke risk and prognosis: insights from Mendelian randomization.

Background: To investigate the causal associations of serum urate (SUA) with stroke risk and prognosis using Mendelian randomization (MR) and the potential mediating role of stroke risk factors in the causal pathways. Methods: We used the random-effects inverse variance weighting (IVW) as our primary method. We initially performed two-sample univariable MR (UVMR) to identify the causal associations of SUA (n = 437,354) with any stroke (AS, FinnGen: n = 311,635; MEGASTROKE: n = 446,696), ischemic stroke (IS, FinnGen: n = 212,774; MEGASTROKE: n = 440,328), intracranial hemorrhage (ICH, FinnGen: n = 343,663; ISGC: n = 3,026), functional outcome after ischemic stroke at 90d (n = 4,363), and motor recovery within 24 months after stroke (n = 488), and then multivariable MR (MVMR) to estimate the direct causal effects of SUA on these outcomes, adjusting for potential confounders. Finally, we further conducted a two-step MR to investigate the potential mediating role of body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and estimated glomerular filtration rate (eGFR) in the identified causal pathways. Results: Genetically predicted elevated SUA levels were significantly associated with increased risk of AS (meta-analysis: OR = 1.09, 95% CI [1.04-1.13], p = 3.69e-05) and IS (meta-analysis: OR = 1.10, 95% CI [1.01-1.19], p = 0.021) and with improved poor functional outcome after ischemic stroke at 90d (OR = 0.81, 95% CI [0.72-0.90], p = 1.79e-04) and motor recovery within 24 months after stroke (OR = 1.42, 95% CI [1.23-1.64], p = 2.15e-06). In MVMR, SBP and DBP significantly attenuated the causal effects of SUA on AS, IS, and functional outcome after ischemic stroke at 90d and motor recovery within 24 months after stroke. Further mediation analyses showed that SBP mediated 52.4 and 34.5% of the effects of SUA on AS and IS, while DBP mediated 28.5 and 23.4% of the causal effects, respectively. Conclusion: This study supports the dual role of genetically predicted SUA in increasing stroke risk, especially ischemic stroke risk, and in improving functional outcome and motor recovery. SBP and DBP are key mediators lying on the causal pathways of SUA with AS and IS.

Substrate and functional characterization of the lysine acetyltransferase MsKat and deacetylase MsCobB in Mycobacterium smegmatis.

Tuberculosis (TB) is a serious cause of infectious death worldwide. Recent studies have reported that about 30% of the Mtb proteome was modified post-translationally, indicating that their functions are essential for drug resistance, mycobacterial survival, and pathogenicity. Among them, lysine acetylation, reversibly regulated by acetyltransferase and deacetylase, has important roles involved in energy metabolism, cellular adaptation, and protein interactions. However, the substrate and biological functions of these two important regulatory enzymes remain unclear. Herein, we utilized the non-pathogenic M. smegmatis strain as a model and systematically investigated the dynamic proteome changes in response to the overexpressing of MsKat/MsCobB in mycobacteria. A total of 4179 proteins and 1236 acetylated sites were identified in our data. Further analysis of the dynamic changes involved in proteome and acetylome showed that MsKat/MsCobB played a regulatory role in various metabolic pathways and nucleic acid processes. After that, the quantitative mass spectrometric method was utilized and proved that the AMP-dependent synthetase, Citrate synthase, ATP-dependent specificity component of the Clp protease, and ATP-dependent DNA/RNA helicases were identified to be the substrates of MsKat. Overall, our study provided an important resource underlying the substrates and functions of the acetylation regulatory enzymes in mycobacteria. SIGNIFICANCE: In this study, we systematically analyzed the dynamic molecular changes in response to the MsKat/MsCobB overexpression in mycobacteria at proteome and lysine acetylation level by using a TMT-based quantitative proteomic approach. Pathways related with glycolysis, degradation of branched chain amino acids, phosphotransferase system were affected after disturbance of the two regulates enzymes involved in lysine acetylation. We also proved that AMP-dependent synthetase Clp protease, ATP-dependent DNA/RNA helicases and citrate synthase was the substrate of MsKat according to our proteomic data and biological validation. Together, our study underlined the substrates and functions of the acetylation regulatory enzymes in mycobacteria.

Anti-intercellular adhesion molecule 1 monomaintenance therapy induced long-term liver allograft survival without chronic rejection.

Calcineurin inhibitors (CNIs) are essential in liver transplantation (LT); however, their long-term use leads to various adverse effects. The anti-intercellular adhesion molecule (ICAM)-1 monoclonal antibody MD3 is a potential alternative to CNI. Despite its promising results with short-term therapy, overcoming the challenge of chronic rejection remains important. Thus, we aimed to investigate the outcomes of long-term MD3 therapy with monthly MD3 monomaintenance in nonhuman primate LT models. Rhesus macaques underwent major histocompatibility complex-mismatched allogeneic LT. The conventional immunosuppression group (Con-IS, n = 4) received steroid, tacrolimus, and sirolimus by 4 months posttransplantation. The induction MD3 group (IN-MD3, n = 5) received short-term MD3 therapy for 3 months with Con-IS. The maintenance MD3 group (MA-MD3, n = 4) received MD3 for 3 months, monthly doses by 2 years, and then quarterly. The MA-MD3 group exhibited stable liver function without overt infection and had significantly better liver allograft survival than the IN-MD3 group. Development of donor-specific antibody and chronic rejection were suppressed in the MA-MD3 group but not in the IN-MD3 group. Donor-specific T cell responses were attenuated in the MA-MD3 group. In conclusion, MD3 monomaintenance therapy without maintenance CNI provides long-term liver allograft survival by suppressing chronic rejection, offering a potential breakthrough for future human trials.

A Shape Memory Polymeric Shield for Protecting Corneal Endothelium During Phacoemulsification.

Background: The purpose of this study was to explore the protective effect of a shape memory polymeric shield on corneal endothelium during phacoemulsification in rabbits. Methods: Poly-(glycerol dodecanedioate) (PGD) with a transition temperature of 24.416°C was prepared to make a shape memory shield with a thickness of 100 µm, an arc length of 14 mm, and a radius of curvature of 8.8 mm. In the control group, a phaco-tip with bevel-down was used to simulate injury to the corneal endothelium by phacoemulsification in rabbits. In the experimental group, the pre-cooled and curled shape memory shield was injected into and removed from the anterior chamber before and after phaco-power release. Anterior segment optical coherence tomography (AS-OCT), confocal microscope, trypan blue/alizarin red staining, and scanning electron microscope were performed to measure endothelial damage after surgery. Results: One day postoperatively, the lost cell ratio of the control group and the experimental group were 28.08 ± 5.21% and 3.50 ± 1.43%, respectively (P < 0.0001), the damaged cell ratios were 11.83 ± 2.30% and 2.55 ± 0.52%, respectively (P < 0.0001), and the central corneal thicknesses (CCT) were 406.75 ± 16.74 µm and 340. 5 ±13.48 µm, respectively (P < 0.0001). Seven days postoperatively, the endothelial cell density (ECD) of the control group and the experimental group were 1674 ± 285/mm2 and 2561 ± 554/mm2, respectively (P < 0.05). The above differences were all statistically significant. Conclusions: This PGD based shape memory shield has a protective effect on corneal endothelium during phacoemulsification. It reduces postoperative corneal edema and ECD decrease in the short term after surgery. Translational Relevance: The shape memory PGD "shield" in this study may have a use in certain human patients with vulnerable corneas of low endothelial cell count or shallow anterior chambers.

Atox1 protects hippocampal neurons after traumatic brain injury via DJ-1 mediated anti-oxidative stress and mitophagy.

Regulation of the oxidative stress response is crucial for the management and prognosis of traumatic brain injury (TBI). The copper chaperone Antioxidant 1 (Atox1) plays a crucial role in regulating intracellular copper ion balance and impacting the antioxidant capacity of mitochondria, as well as the oxidative stress state of cells. However, it remains unknown whether Atox1 is involved in modulating oxidative stress following TBI. Here, we investigated the regulatory role of Atox1 in oxidative stress on neurons both in vivo and in vitro, and elucidated the underlying mechanism through culturing hippocampal HT-22 cells with Atox1 mutation. The expression of Atox1 was significantly diminished following TBI, while mice with overexpressed Atox1 exhibited a more preserved hippocampal structure and reduced levels of oxidative stress post-TBI. Furthermore, the mice displayed notable impairments in learning and memory functions after TBI, which were ameliorated by the overexpression of Atox1. In the stretch injury model of HT-22 cells, overexpression of Atox1 mitigated oxidative stress by preserving the normal morphology and network connectivity of mitochondria, as well as facilitating the elimination of damaged mitochondria. Mechanistically, co-immunoprecipitation and mass spectrometry revealed the binding of Atox1 to DJ-1. Knockdown of DJ-1 in HT-22 cells significantly impaired the antioxidant capacity of Atox1. Mutations in the copper-binding motif or sequestration of free copper led to a substantial decrease in the interaction between Atox1 and DJ-1, with overexpression of DJ-1 failing to restore the antioxidant capacity of Atox1 mutants. The findings suggest that DJ-1 mediates the ability of Atox1 to withstand oxidative stress. And targeting Atox1 could be a potential therapeutic approach for addressing post-traumatic neurological dysfunction.

Persistent metabolic toxicities following developmental exposure to hexafluoropropylene oxide trimer acid (HFPO-TA): Roles of peroxisome proliferator activated receptor gamma.

BACKGROUND: Hexafluoropropylene oxide trimer acid (HFPO-TA), a perfluorooctanoic acid (PFOA) substitute, exhibited strong affinity and capability to activate peroxisome proliferator activated receptor gamma (PPARγ), a lipid metabolism regulator, suggesting potential to induce metabolic toxicities. METHODS: Fertile chicken eggs were exposed to 0, 0.5, 1 or 2 mg/kg (egg weight) HFPO-TA and incubated until hatch. Serum from 0- and 3- month-old chickens were subjected to liquid chromatography ultra-high resolution mass spectrometry for HFPO-TA concentration, while liver, pancreas and adipose tissue samples were collected for histopathological assessments. In ovo PPARγ reporter and silencing system were established with lentivirus microinjection. qRT-PCR and immunohistochemistry were utilized to evaluate the expression levels of PPARγ downstream genes. RESULTS: In 3-month-old animals developmentally exposed to HFPO-TA, adipose tissue hyperplasia, hepatic steatosis, pancreas islet hypertrophy and elevated serum free fatty acid / insulin levels were observed. Results of reporter assay and qRT-PCR indicated HFPO-TA-mediated PPARγ transactivation in chicken embryo. Silencing of PPARγ alleviated HFPO-TA-induced changes, while PPARγ agonist rosiglitazone mimicked HFPO-TA-induced effects. qRT-PCR and immunohistochemistry revealed that FASN and GPD1 were upregulated following developmental exposure to HFPO-TA in 3-month-old animals. CONCLUSIONS: Developmental exposure to HFPO-TA induced persistent metabolic toxicities in chickens, in which PPARγ played a central role.

Meningioma achieves malignancy and erastin-induced ferroptosis resistance through FOXM1-AURKA-NRF2 axis.

The oncogene Aurora kinase A (AURKA) has been implicated in various tumor, yet its role in meningioma remains unexplored. Recent studies have suggested a potential link between AURKA and ferroptosis, although the underlying mechanisms are unclear. This study presented evidence of AURKA upregulation in high grade meningioma and its ability to enhance malignant characteristics. We identified AURKA as a suppressor of erastin-induced ferroptosis in meningioma. Mechanistically, AURKA directly interacted with and phosphorylated kelch-like ECH-associated protein 1 (KEAP1), thereby activating nuclear factor erythroid 2 related factor 2 (NFE2L2/NRF2) and target genes transcription. Additionally, forkhead box protein M1 (FOXM1) facilitated the transcription of AURKA. Suppression of AURKA, in conjunction with erastin, yields significant enhancements in the prognosis of a murine model of meningioma. Our study elucidates an unidentified mechanism by which AURKA governs ferroptosis, and strongly suggests that the combination of AURKA inhibition and ferroptosis-inducing agents could potentially provide therapeutic benefits for meningioma treatment.

CXXC5 drove inflammation and ovarian cancer proliferation via transcriptional activation of ZNF143 and EGR1.

CXXC5, a zinc-finger protein, is known for its role in epigenetic regulation via binding to unmethylated CpG islands in gene promoters. As a transcription factor and epigenetic regulator, CXXC5 modulates various signaling processes and acts as a key coordinator. Altered expression or activity of CXXC5 has been linked to various pathological conditions, including tumorigenesis. Despite its known role in cancer, CXXC5's function and mechanism in ovarian cancer are unclear. We analyzed multiple public databases and found that CXXC5 is highly expressed in ovarian cancer, with high expression correlating with poor patient prognosis. We show that CXXC5 expression is regulated by oxygen concentration and is a direct target of HIF1A. CXXC5 is critical for maintaining the proliferative potential of ovarian cancer cells, with knockdown decreasing and overexpression increasing cell proliferation. Loss of CXXC5 led to inactivation of multiple inflammatory signaling pathways, while overexpression activated these pathways. Through in vitro and in vivo experiments, we confirmed ZNF143 and EGR1 as downstream transcription factors of CXXC5, mediating its proliferative potential in ovarian cancer. Our findings suggest that the CXXC5-ZNF143/EGR1 axis forms a network driving ovarian cell proliferation and tumorigenesis, and highlight CXXC5 as a potential therapeutic target for ovarian cancer treatment.

Characteristics of spatial and temporal variability in the distribution of biological soil crusts on the Loess Plateau, China.

Biological soil crust (biocrust) is widely distributed on the Loess Plateau and plays multiple roles in regulating ecosystem stability and multifunctionality. Few reports are available on the distribution characteristics of biocrust in this region, which limits the assessment of its ecological functions. Based on 388 sampling points in different precipitation zones on the Loess Plateau from 2009 to 2020, we analyzed the coverage, composition, and influencing factors of biocrust across different durations since land abandonment, precipitation levels, topography (slope aspect and position), and utilization of abandoned slopelands (shrubland, forest, and grassland). On this base, with the assistance of machine learning and spatial modeling methods, we generated a distribution map of biocrust and its composition at a resolution of 250 m × 250 m, and analyzed the spatial distribution of biocrust on the Loess Plateau. The results showed that the average biocrust coverage in the woodlands and grasslands was 47.3%, of which cyanobacterial crust accounted for 25.5%, moss crust 19.7%, and lichen crust 2.1%. There were significant temporal and spatial variations. Temporally, the coverage of biocrust in specific regions fluctuated with the extension of the abandoned durations and coverage of cyanobacterial crust, while moss crust showed a reverse pattern. In addition, the coverage of biocrust in the wet season was slightly higher than that in the dry season within a year. Spatially, the coverage of biocrusts on the sandy lands area on the Loess Plateau was higher and dominated by cyanobacterial crusts, while the coverage was lower in the hilly and gully area. Precipitation and utilization of abandoned land were the major factors driving biocrust coverage and composition, while slope direction and position did not show obvious effect. In addition, soil organic carbon content, pH, and texture were related to the distribution of biocrust. This study uncovered the spatial and temporal variability of biocrust distribution, which might provide important data support for the research and management of biocrust in the Loess Plateau region.

Interleukin-2/anti-interleukin-2 immune complex attenuates cold ischemia-reperfusion injury after kidney transplantation by increasing renal regulatory T cells.

BACKGROUND: Cold ischemia-reperfusion injury (IRI) is an unavoidable complication of kidney transplantation. We investigated the role of regulatory T cells (Treg) in cold IRI and whether the interleukin (IL)-2/anti-IL-2 antibody complex (IL-2C) can ameliorate cold IRI. METHODS: We developed a cold IRI mouse model using kidney transplantation and analyzed the IL-2C impact on cold IRI in acute, subacute and chronic phases. RESULTS: Treg transfer attenuated cold IRI, while Treg depletion aggravated cold IRI. Next, IL-2C administration prior to IRI mitigated acute renal function decline, renal tissue damage and apoptosis and inhibited infiltration of effector cells into kidneys and pro-inflammatory cytokine expression on day 1 after IRI. On day 7 after IRI, IL-2C promoted renal regeneration and reduced subacute renal damage. Furthermore, on day 28 following IRI, IL-2C inhibited chronic fibrosis. IL-2C decreased reactive oxygen species-mediated injury and improved antioxidant function. When IL-2C was administered following IRI, it also increased renal regeneration with Treg infiltration and suppressed renal fibrosis. In contrast, Treg depletion in the presence of IL-2C eliminated the positive effects of IL-2C on IRI. CONCLUSION: Tregs protect kidneys from cold IRI and IL-2C inhibited cold IRI by increasing the renal Tregs, suggesting a potential of IL-2C in treating cold IRI. KEY POINTS: Interleukin (IL)-2/anti-IL-2 antibody complex attenuated acute renal injury, facilitated subacute renal regeneration and suppressed chronic renal fibrosis after cold ischemia-reperfusion injury (IRI) by increasing the renal Tregs. IL-2/anti-IL-2 antibody complex decreased reactive oxygen species-mediated injury and improved antioxidant function. This study suggests the therapeutic potential of the IL-2/anti-IL-2 antibody complex in kidney transplantation-associated cold IR.

First Report of the Rust Fungus Melampsora ferrinii on Salix babylonica in China and a New Spermogonial and Aecial Host, Corydalis bungeana.

The occurrence of rust fungi on Corydalis bungeana Turcz. and Salix babylonica L. were found in same area of Hebei Province, China from 2022 to 2023. The life cycle connection of these rust fungi was suspected because Peng et al. (2022) reported the life cycle of Melampsora ferrinii Toome & Aime by inoculations, producing spermogonia and aecia on Corydalis species, and uredinia on S. babylonica. The morphology of the uredinial and telial stages on S. babylonica collected in the field was identical with the description of M. ferrinii by Toome and Aime (2015), and its identity was confirmed by phylogenetic analyses using the method of Ji et al. (2020) (LSU-PP087777, ITS-PP091274; Similarity with M. ferrinii: LSU-100%, ITS-99.85%). To confirm the life cycle of this rust fungus, inoculations were conducted on C. bungeana with basidiospores obtained from the teliospores on fallen leaves of Salix babylonica. The fallen leaves producing basidiospores were cut into small pieces (ca. 5 mm2) and placed on healthy leaves of C. bungeana. The inoculated plants were kept in a moist plastic box in darkness at 15-20℃ for 2 days and then transferred to the floor near windows at about 15-20℃ for observations. Ten days after inoculations small yellow spots of spermogonia appeared on the upper surface of the leaves of C. bungeana. About 7 days later, pale yellow aecia with aeciospores were produced mainly on the under surface of the leaves and petioles. The morphology of rust fungus on C. bungeana collected from the fields and obtained by inoculations was identical with the description by Peng et al. (2022). Phylogenetic analyses also showed that a specimen on C. bungeana collected from the field (LSU-OR607838, ITS-OR612063) were included into the same clade of M. ferrinii (Similarity: LSU-100 %, ITS-99.85). Based on morphology, inoculations and DNA sequence analyses, the rust fungi on C. bungeana and S. babylonica are identified as different stages of life cycle of M. ferrinii. This rust fungus has been reported to produce spermogonia and aecia on C. acuminata Franch., C. edulis Maxim. and C. racemosa (Thunb.) Pers. in China (Peng et al. 2022), and uredinia and telia on S. babylonica in USA, Argentina and Iran (Toome and Aime 2015, Abbasi et al. 2024), and on Salix sp. in Chile (Zapata 2016). Therefore, C. bungeana is a new host for M. ferrinii, and its field occurrence on S. babylonica is reported for the first time in China although Peng et al. (2022) reported successful results in its inoculations to S. babylonica in China. This report contributes to the control of rust diseases caused by this species. Specimens used in this experiment were deposited in the Fungal Herbarium of the Jilin Agricultural University, Changchun, China (HMJAU) and sequences newly analyzed were deposited in GenBank.

Reactivating PTEN to impair glioma stem cells by inhibiting cytosolic iron-sulfur assembly.

Glioblastoma, the most lethal primary brain tumor, harbors glioma stem cells (GSCs) that not only initiate and maintain malignant phenotypes but also enhance therapeutic resistance. Although frequently mutated in glioblastomas, the function and regulation of PTEN in PTEN-intact GSCs are unknown. Here, we found that PTEN directly interacted with MMS19 and competitively disrupted MMS19-based cytosolic iron-sulfur (Fe-S) cluster assembly (CIA) machinery in differentiated glioma cells. PTEN was specifically succinated at cysteine (C) 211 in GSCs compared with matched differentiated glioma cells. Isotope tracing coupled with mass spectrometry analysis confirmed that fumarate, generated by adenylosuccinate lyase (ADSL) in the de novo purine synthesis pathway that is highly activated in GSCs, promoted PTEN C211 succination. This modification abrogated the interaction between PTEN and MMS19, reactivating the CIA machinery pathway in GSCs. Functionally, inhibiting PTEN C211 succination by reexpressing a PTEN C211S mutant, depleting ADSL by shRNAs, or consuming fumarate by the US Food and Drug Administration-approved prescription drug N-acetylcysteine (NAC) impaired GSC maintenance. Reexpressing PTEN C211S or treating with NAC sensitized GSC-derived brain tumors to temozolomide and irradiation, the standard-of-care treatments for patients with glioblastoma, by slowing CIA machinery-mediated DNA damage repair. These findings reveal an immediately practicable strategy to target GSCs to treat glioblastoma by combination therapy with repurposed NAC.

Resistant Dextrin Protects Rats Against Streptozotocin Induced Gestational Diabetes Mellitus via Alteration of TLR4/MyD88/NF-κB Signaling Pathway.

Objective: Gestational diabetes mellitus (GDM) is a metabolic disorder that occurs in 3-5% of pregnancies. The inflammatory response is essential to the development of GDM. Resistant dextrin is a natural fiber and exhibits an antidiabetic effect against diabetes. We investigate resistant dextrin's preventive role and underlying mechanism against STZ-induced GDM. Material and method: Female Wistar rats were utilized, and GDM was induced in pregnant rats using STZ. The levels of glycated hemoglobin (HbA1c), resistin, serum-c-peptide, free fatty acid, antioxidant, hepatic glycogen, lipid, inflammatory cytokines, apoptosis, and inflammatory parameters were estimated. mRNA expression of Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor kappa B (NF-κB) and NOD-like receptor protein 3 (NLRP3) was estimated. We also estimated the histopathology of pancreatic and liver tissue. Result: Body weight, plasma insulin, fetal body weight, and blood glucose levels were all considerably (P < .001) improved by resistant dextrin, while placental weight and blood sugar levels were also decreased. Resistant dextrin significantly (P < .001) suppressed the levels of HbA1c, resistin, serum-c-peptide, and hepatic glycogen and improved the free fatty acid (FFA) level. Resistant dextrin significantly (P < .001) altered the level of adiponectin, leptin, intercellular Adhesion Molecule 1 (ICAM-1), and visfatin; antioxidant parameters such as malonaldehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), glutathione S-transferase GST, inflammatory cytokines like tumor necrosis factor- α (TNF-α), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-2 (IL-2), interferon- γ (INF-γ), interleukin-10 (IL-10); apoptosis parameters include Bcl-2, caspase-3, and Bax, respectively. Resistant dextrin significantly (P < .001) suppressed the mRNA expression of NF-κB, MyD88, NLRP3, and TLR4. Resistant dextrin altered the histopathological changes in the pancreas and hepatic tissue. Discussion and Conclusion: In short, resistant dextrin demonstrated a protective effect against STZ-induced GDM by modulating the TLR4/MyD88/NF-κB signaling pathway.

An evaluation of microplastic contamination in the marine waters and species in the coastal region of the South Yellow Sea, China.

Microplastics (MPs) contamination of marine environments poses a significant ecological risk, although impacts on species' realized niche spaces remain unclear. The current study investigates MPs distribution across pelagic habitats, benthic sediments, and key biota in the South Yellow Sea, China. Samples were collected via trawling across estuarine transects, and tissues were digested to extract MPs. Density gradient separations and vacuum-filtrations prepared particle extracts for ATR-FTIR and Micro-Raman spectroscopic characterization. Sampling along industrialized river transects reveals ubiquitous plastic particle presence, with concentrations ranging from 0 to 51.68 item/L seawater. Contamination levels reach their peak at station estuaries before dispersing offshore, indicating significant waste stream inputs. Importantly, MPs detected in demersal and pelagic fish species, as well as in bivalves, confirm exposure across trophic niches. Gastrointestinal tract and gill concentrations reached 0.6 items/g fresh tissue, reflecting significant biological uptake and in vivo retention. The greatest population of organisms occurred adjacent to polluted areas. Overall, distribution of MPs from polluted rivers to coastal food webs was evident, suggesting potential negative impacts on key ecological functions in this system. These findings underscore the need to develop upstream mitigation efforts so as to minimize MPs contamination in areas where nearshore and offshore niches intersect.

Reversible Carbon Dioxide/Lithium Oxalate Regulation toward Advanced Aprotic Lithium Carbon Dioxide Battery.

Li-CO2 batteries have received significant attention owing to their advantages of combining greenhouse gas utilization and energy storage. However, the high kinetic barrier between gaseous CO2 and the Li2CO3 product leads to a low operating voltage (<2.5 V) and poor energy efficiency. In addition, the reversibility of Li2CO3 has always been questioned owing to the introduction of more decomposition paths caused by its higher charging plateau. Here, a novel "trinity" Li-CO2 battery system was developed by synergizing CO2, soluble redox mediator (2,2,6,6-tetramethylpiperidoxyl, as TEM RM), and reduced graphene oxide electrode to enable selective conversion of CO2 to Li2C2O4. The designed Li-CO2 battery exhibited an output plateau reaching up to 2.97 V, higher than the equilibrium potential of 2.80 V for Li2CO3, and an ultrahigh round-trip efficiency of 97.1 %. The superior performance of Li-CO2 batteries is attributed to the TEM RM-mediated preferential growth mechanism of Li2C2O4, which enhances the reaction kinetics and rechargeability. Such a unique design enables batteries to cope with sudden CO2-deficient environments, which provides an avenue for the rationally design of CO2 conversion reactions and a feasible guide for next-generation Li-CO2 batteries.

Sodium sulfite-driven Helicobacter pylori eradication: Unraveling oxygen dynamics through multi-omics investigation.

Due to the emergence and spread of multidrug resistance in Helicobacter pylori (H. pylori), its eradication has become difficult. Sodium sulfite (SS), a widely used food additive for ensuring food safety and storage, has been recognized as an effective nonbactericidal agent for H. pylori eradication. However, the mechanism by which H. pylori adapts and eventually succumbs under low- or no-oxygen conditions remains unknown. In this study, we aimed to evaluate the anti-H. pylori effect of SS and investigated the multiomics mechanism by which SS kills H. pylori. The results demonstrated that SS effectively eradicated H. pylori both in vitro and in vivo. H. pylori responds to the oxygen changes regulated by SS, downregulates the HcpE gene, which is responsible for redox homeostasis in bacteria, decreases the activities of enzymes related to oxidative stress, and disrupts the outer membrane structure, increasing susceptibility to oxidative stress. Furthermore, SS downregulates the content of cytochrome C in the microaerobic respiratory chain, leading to a sharp decrease in ATP synthesis. Consequently, the accumulation of triglycerides (TGs) in bacteria due to oxidative stress supports anaerobic respiration, meeting their energy requirements. The multifaceted death of H. pylori caused by SS does not result in drug resistance. Thus, screening of the redox homeostasis of HcpE as a new target for H. pylori infection treatment could lead to the development of a novel approach for H. pylori eradication therapy.

Modifiable risk factors mediate the effect of gastroesophageal reflux disease on stroke and subtypes: A Mendelian randomization study.

OBJECTIVES: Previous observational studies have suggested that gastroesophageal reflux disease (GERD) increases the risk of stroke, but the specific underlying mechanisms are unclear. We investigated the causal associations of GERD with stroke and its subtypes using Mendelian randomization (MR), and evaluated the potential mediating effects of modifiable stroke risk factors in the causal pathway. METHODS: Genetic instrumental variables for GERD were extracted from the latest genome-wide association study (GWAS) summary level data. We initially performed two-sample MR to examine the association of GERD with stroke and its subtypes, including ischemic stroke, intracranial hemorrhage, and the major subtypes of ischemic stroke. Two-step MR was further employed to investigate the mediating effect of 15 risk factors in the causal pathway. RESULTS: We found significant causal associations of genetically predicted GERD with increased risk of stroke (OR: 1.22 95% CI: 1.126-1.322), ischemic stroke (OR: 1.19 95% CI: 1.098-1.299), and large-artery stroke (OR: 1.49 95% CI: 1.214-1.836). Replication and sensitivity analyses yielded consistent effect directions and similar estimates. Further mediation analyses indicated that hypertension (HTN), systolic blood pressure (SBP), and type 2 diabetes (T2D) mediated 36.0%, 9.0%, and 15.8% of the effect of GERD on stroke; 42.9%, 10.8%, and 21.4% for ischemic stroke, and 23.3%; 7.9%, and 18.7% for large-artery stroke, respectively. CONCLUSIONS: This study supports that GERD increases susceptibility to stroke, ischemic stroke, and large-artery stroke, and is partially mediated by HTN, SBP, and T2D.

JHD205, A Novel Abemaciclib Derivative, Exerts Antitumor Effects on Breast Cancer by CDK4/6.

BACKGROUND: Efficient targeted molecular therapeutics are needed for the treatment of triple-negative breast cancer (TNBC), a highly invasive and difficult-to-treat form of breast cancer associated with a poor prognosis. OBJECTIVES: This study aims to evaluate the potential of selective CDK4/6 inhibitors as a therapeutic option for TNBC by impairing the cell cycle G1 phase through the inhibition of retinoblastoma protein (Rb) phosphorylation. METHODS: In this study, we synthesized a compound called JHD205, derived from the chemical structure of Abemaciclib, and examined its inhibitory effects on the malignant characteristics of TNBC cells. RESULTS: Our results demonstrated that JHD205 exhibited superior tumor growth inhibition compared to Abemaciclib in breast cancer xenograft chicken embryo models. Western blot analysis revealed that JHD205 could dosedependently degrade CDK4 and CDK6 while also causing abnormal changes in other proteins associated with CDK4/6, such as p-Rb, Rb, and E2F1. Moreover, JHD205 induced apoptosis and DNA damage and inhibited DNA repair by upregulating Caspase3 and p-H2AX protein levels. CONCLUSION: Collectively, our findings suggest that JHD205 holds promise as a potential treatment for breast carcinoma.

The Relationship Between Negative Coping Styles, Psychological Resilience, and Positive Coping Styles in Military Personnel: A Cross-Lagged Analysis.

Background: Military personnel experience prolonged exposure to high-stress environments. Positive coping styles can assist in maintaining their mental and behavioral well-being, whereas negative coping styles cannot. Health behavior change theory specifies that an individual can transition from a negative to a positive coping style. The psychological resilience concept may prove vital in this transition. Methods: In a longitudinal study design, two questionnaires were administered to 233 military personnel twice, the first at T1 in April 2023 and the second at T2 in July 2023. The questionnaire measured individual negative coping style, positive coping style and psychological resilience. Results: The data showed that the negative coping style at T1 negatively predicted the level of psychological resilience at T2 (γ= - 0.26, p < 0.001) and the positive coping style at T2 (γ= - 0.16, p < 0.001). The level of psychological resilience at T1 positively predicted the positive coping style at T2 (γ= 0.22, p < 0.01). Psychological resilience played a mediating role between negative coping style and positive coping style. In addition, there was an interaction between psychological resilience and positive coping style in military personnel at the two time points. Conclusion: The negative coping styles that presently exist among military personnel have the potential to diminish their future positive coping styles by lowering their psychological resilience. This highlights the need to focus on the development and training of psychological resilience for military personnel, as it can effectively counteract negative coping styles and promote positive coping styles.