Electronic Structure Modification of MnO2 Nanosheet Arrays with Enhanced Water Oxidation Activity and Stability by Nitrogen Plasma.

The strategic design of catalysts for the oxygen evolution reaction (OER) is crucial in tackling the substantial energy demands associated with hydrogen production in electrolytic water splitting. Despite extensive research on birnessite (δ-MnO2) manganese oxides to enhance catalytic activity by modulating Mn3+ species, the ongoing challenge is to simultaneously stabilize Mn3+ while improving overall activity. Herein, oxygen (O) vacancies and nitrogen (N) doping have been simultaneously introduced into the MnO2 through a simple nitrogen plasma approach, resulting in efficient OER performance. The optimized N-MnO2v electrocatalyst exhibits outstanding OER activity in alkaline electrolyte, reducing the overpotential by nearly 160 mV compared to pure pristine MnO2 (from 476 to 312 mV) at 10 mA cm-2, and a small Tafel slope of 89 mV dec-1. Moreover, it demonstrates excellent durability over a 122 h stability test. The introduction of O vacancies and incorporation of N not only fine-tune the electronic structure of MnO2, increasing the Mn3+ content to enhance overall activity, but also play a crucial role in stabilizing Mn3+, thereby leading to exceptional stability over time. Subsequently, density functional theory calculations validate the optimized electronic structure of MnO2 achieved through the two engineering methods, effectively lowering the intermediate adsorption free energy barrier. Our synergistic approach, utilizing nitrogen plasma treatment, opens a pathway to concurrently enhance the activity and stability of OER electrocatalysts, applicable not only to Mn-based but also to other transition metal oxides.

Xeno Nucleic Acids as Functional Materials: From Biophysical Properties to Application.

Xeno nucleic acid (XNA) are artificial nucleic acids, in which the chemical composition of the sugar moiety is changed. These modifications impart distinct physical and chemical properties to XNAs, leading to changes in their biological, chemical, and physical stability. Additionally, these alterations influence the binding dynamics of XNAs to their target molecules. Consequently, XNAs find expanded applications as functional materials in diverse fields. This review provides a comprehensive summary of the distinctive biophysical properties exhibited by various modified XNAs and explores their applications as innovative functional materials in expanded fields.

Glutathione-Coated Gold Nanoparticles Enabling Bifunctional Therapy at the Buried Interface for Efficient and UV-Resistant Perovskite Solar Cells.

Very recently, the poor contact between the perovskite and carrier selective layer has been regarded as a critical issue for improving the performance and stability of perovskite solar cells (PSCs). In this study, the buried interface of regularly structured PSCs has been targeted. Glutathione-coated gold nanoparticles (GSH-AuNPs) are used as double-sided passivating agents to improve the quality of the perovskite films. It has been demonstrated that the GSH-AuNPs interact strongly with the SnO2 underlayer and the upper perovskite layer, significantly reducing the defect densities of this interface. Thus, the power conversion efficiency (PCE) of the PSCs can be increased from 20.46% (control, 19.38%, IPCE corrected) to 22.22% (GSH-AuNPs modified, 21.10%, IPCE corrected) with notable enhancement in Voc and FF. Moreover, the strong interaction between the C═O groups of GSH-AuNPs and the undercoordinated Pb2+ species of the perovskite films inhibits the formation of metallic Pb0. As a result, the unencapsulated GSH-AuNPs-modified devices retained 80% of their initial PCEs after 1000 h at ambient conditions, with a relative humidity (RH) of 60 ± 5%. UV-resistant PSCs have also been demonstrated after introducing GSH-AuNPs. Therefore, our findings demonstrate the bidirectional therapy strategy as a feasible approach for achieving efficient and UV-resistant PSCs.

PIM1-HDAC2 axis modulates intestinal homeostasis through epigenetic modification.

The mucosal barrier is crucial for intestinal homeostasis, and goblet cells are essential for maintaining the mucosal barrier integrity. The proviral integration site for Moloney murine leukemia virus-1 (PIM1) kinase regulates multiple cellular functions, but its role in intestinal homeostasis during colitis is unknown. Here, we demonstrate that PIM1 is prominently elevated in the colonic epithelia of both ulcerative colitis patients and murine models, in the presence of intestinal microbiota. Epithelial PIM1 leads to decreased goblet cells, thus impairing resistance to colitis and colitis-associated colorectal cancer (CAC) in mice. Mechanistically, PIM1 modulates goblet cell differentiation through the Wnt and Notch signaling pathways. Interestingly, PIM1 interacts with histone deacetylase 2 (HDAC2) and downregulates its level via phosphorylation, thereby altering the epigenetic profiles of Wnt signaling pathway genes. Collectively, these findings investigate the unknown function of the PIM1-HDAC2 axis in goblet cell differentiation and ulcerative colitis/CAC pathogenesis, which points to the potential for PIM1-targeted therapies of ulcerative colitis and CAC.

Timing determines zooplankton community responses to multiple stressors.

Human activities and climate change cause abiotic factors to fluctuate through time, sometimes passing thresholds for organismal reproduction and survival. Multiple stressors can independently or interactively impact organisms; however, few studies have examined how they interact when they overlap spatially but occur asynchronously. Fluctuations in salinity have been found in freshwater habitats worldwide. Meanwhile, heatwaves have become more frequent and extreme. High salinity pulses and heatwaves are often decoupled in time but can still collectively impact freshwater zooplankton. The time intervals between them, during which population growth and community recovery could happen, can influence combined effects, but no one has examined these effects. We conducted a mesocosm experiment to examine how different recovery times (0-, 3-, 6-week) between salt treatment and heatwave exposure influence their combined effects. We hypothesized that antagonistic effects would appear when having short recovery time, because previous study found that similar species were affected by the two stressors, but effects would become additive with longer recovery time since fully recovered communities would respond to heatwave similar to undisturbed communities. Our findings showed that, when combined, the two-stressor joint impacts changed from antagonistic to additive with increased recovery time between stressors. Surprisingly, full compositional recovery was not achieved despite a recovery period that was long enough for population growth, suggesting legacy effects from earlier treatment. The recovery was mainly driven by small organisms, such as rotifers and small cladocerans. As a result, communities recovering from previous salt exposure responded differently to heatwaves than undisturbed communities, leading to similar zooplankton communities regardless of the recovery time between stressors. Our research bolsters the understanding and management of multiple-stressor issues by revealing that prior exposure to one stressor has long-lasting impacts on community recovery that can lead to unexpected joint effects of multiple stressors.

Manipulating the tumour immune microenvironment by N6-methyladenosine RNA modification.

N6-methyladenosine (m6A), a posttranscriptional regulatory mechanism, is the most common epigenetic modification in mammalian mRNA. M6A modifications play a crucial role in the developmental network of immune cells. The expression of m6A-related regulators often affects carcinogenesis and tumour suppression networks. In the tumour microenvironment, m6A-modified enzymes can affect the occurrence and progression of tumours by regulating the activation and invasion of tumour-associated immune cells. Immunotherapy, which utilises immune cells, has been demonstrated to be a powerful weapon in tumour treatment and is increasingly being used in the clinic. Here, we provide an updated and comprehensive overview of how m6A modifications affect invasive immune cells and their potential role in immune regulation. In addition, we summarise the regulation of epigenetic regulators associated with m6A modifications in tumour cells on the antitumour response of immune cells in the tumour immune microenvironment. These findings provide new insights into the role of m6A modifications in the immune response and tumour development, leading to the development of novel immunotherapies for cancer treatment.

Metabolic transformation of cyclopiazonic acid in liver microsomes from different species based on UPLC-Q/TOF-MS.

To investigate the metabolic transformation of cyclopiazonic acid (CPA) in the liver of different species and to supplement accurate risk assessment information, the metabolism of CPA in liver microsomes from four animals and humans was studied using the ultra-high-performance liquid chromatography-quadrupole/time-of-flight method. The results showed that a total of four metabolites were obtained, and dehydrogenation, hydroxylation, methylation, and glucuronidation were identified as the main metabolic pathways of CPA. Rat liver microsomes exhibited the highest metabolic capacity for CPA, with dehydrogenated (C20H18N2O3) and glucuronic acid-conjugated (C26H28N2O10) metabolites identified in all liver microsomes except chicken, indicating significant species metabolic differences. Moreover, C20H18N2O3 was only detected in the incubation system with cytochromes P450 3A4 (CYP3A4). The hydroxylated (C20H20N2O4) and methylated (C21H22N2O3) metabolites were detected in all incubation systems except for the CYP2C9, with CYP3A4 demonstrating the strongest metabolic capacity. The "cocktail" probe drug method showed that CPA exhibited a moderate inhibitory effect on the CYP3A4 (IC50 value = 8.658 µM), indicating that the substrate had a negative effect on enzyme activity. Our results provide new insights to understand the biotransformation profile of CPA in animals and humans.

Bending skyrmion strings under two-dimensional thermal gradients.

Magnetic skyrmions are topologically protected magnetization vortices that form three-dimensional strings in chiral magnets. With the manipulation of skyrmions being key to their application in devices, the focus has been on their dynamics within the vortex plane, while the dynamical control of skyrmion strings remained uncharted territory. Here, we report the effective bending of three-dimensional skyrmion strings in the chiral magnet MnSi in orthogonal thermal gradients using small angle neutron scattering. This dynamical behavior is achieved by exploiting the temperature-dependent skyrmion Hall effect, which is unexpected in the framework of skyrmion dynamics. We thus provide experimental evidence for the existence of magnon friction, which was recently proposed to be a key ingredient for capturing skyrmion dynamics, requiring a modification of Thiele's equation. Our work therefore suggests the existence of an extra degree of freedom for the manipulation of three-dimensional skyrmions.

Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical trial.

OBJECTIVE: To determine whether a single low dose of esketamine administered after childbirth reduces postpartum depression in mothers with prenatal depression. DESIGN: Randomised, double blind, placebo controlled trial with two parallel arms. SETTING: Five tertiary care hospitals in China, 19 June 2020 to 3 August 2022. PARTICIPANTS: 364 mothers aged ≥18 years who had at least mild prenatal depression as indicated by Edinburgh postnatal depression scale scores of ≥10 (range 0-30, with higher scores indicating worse depression) and who were admitted to hospital for delivery. INTERVENTIONS: Participants were randomly assigned 1:1 to receive either 0.2 mg/kg esketamine or placebo infused intravenously over 40 minutes after childbirth once the umbilical cord had been clamped. MAIN OUTCOME MEASURES: The primary outcome was prevalence of a major depressive episode at 42 days post partum, diagnosed using the mini-international neuropsychiatric interview. Secondary outcomes included the Edinburgh postnatal depression scale score at seven and 42 days post partum and the 17 item Hamilton depression rating scale score at 42 days post partum (range 0-52, with higher scores indicating worse depression). Adverse events were monitored until 24 hours after childbirth. RESULTS: A total of 364 mothers (mean age 31.8 (standard deviation 4.1) years) were enrolled and randomised. At 42 days post partum, a major depressive episode was observed in 6.7% (12/180) of participants in the esketamine group compared with 25.4% (46/181) in the placebo group (relative risk 0.26, 95% confidence interval (CI) 0.14 to 0.48; P<0.001). Edinburgh postnatal depression scale scores were lower in the esketamine group at seven days (median difference -3, 95% CI -4 to -2; P<0.001) and 42 days (-3, -4 to -2; P<0.001). Hamilton depression rating scale scores at 42 days post partum were also lower in the esketamine group (-4, -6 to -3; P<0.001). The overall incidence of neuropsychiatric adverse events was higher in the esketamine group (45.1% (82/182) v 22.0% (40/182); P<0.001); however, symptoms lasted less than a day and none required drug treatment. CONCLUSIONS: For mothers with prenatal depression, a single low dose of esketamine after childbirth decreases major depressive episodes at 42 days post partum by about three quarters. Neuropsychiatric symptoms were more frequent but transient and did not require drug intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT04414943.

Identification and classification of the genomes of novel microviruses in poultry slaughterhouse.

Microviridae is a family of phages with circular ssDNA genomes and they are widely found in various environments and organisms. In this study, virome techniques were employed to explore potential members of Microviridae in a poultry slaughterhouse, leading to the identification of 98 novel and complete microvirus genomes. Using a similarity clustering network classification approach, these viruses were found to belong to at least 6 new subfamilies within Microviridae and 3 higher-level taxonomic units. Genome size, GC content and genome structure of these new taxa showed evident regularities, validating the rationality of our classification method. Our method can divide microviruses into about 45 additional detailed clusters, which may serve as a new standard for classifying Microviridae members. Furthermore, by addressing the scarcity of host information for microviruses, the current study significantly broadened their host range and discovered over 20 possible new hosts, including important pathogenic bacteria such as Helicobacter pylori and Vibrio cholerae, as well as different taxa demonstrated different host specificities. The findings of this study effectively expand the diversity of the Microviridae family, providing new insights for their classification and identification. Additionally, it offers a novel perspective for monitoring and controlling pathogenic microorganisms in poultry slaughterhouse environments.

Establishment and validation of an artificial intelligence web application for predicting postoperative in-hospital mortality in patients with hip fracture: a National cohort study of 52,707 cases.

BACKGROUND: In-hospital mortality following hip fractures is a significant concern, and accurate prediction of this outcome is crucial for appropriate clinical management. Nonetheless, there is a lack of effective prediction tools in clinical practice. By utilizing artificial intelligence and machine learning techniques, this study aims to develop a predictive model that can assist clinicians in identifying geriatric hip fracture patients at a higher risk of in-hospital mortality. METHODS: A total of 52,707 geriatric hip fracture patients treated with surgery from 90 hospitals were included in this study. The primary outcome was postoperative in-hospital mortality. The patients were randomly divided into two groups, with a ratio of 7:3. The majority of patients, assigned to the training cohort, were used to develop the AI models. The remaining patients, assigned to the validation cohort, were used to validate the models. Various machine learning algorithms, including logistic regression (LR), decision tree (DT), naïve Bayesian (NB), neural network (NN), eXGBoosting machine (eXGBM), and random forest (RF), were employed for model development. A comprehensive scoring system, incorporating 10 evaluation metrics, was developed to assess the prediction performance, with higher scores indicating superior predictive capability. Based on the best machine learning-based model, an AI application was developed on the Internet. In addition, a comparative testing of prediction performance between doctors and the AI application. FINDINGS: The eXGBM model exhibited the best prediction performance, with an AUC of 0.908 (95% CI: 0.881-0.932), as well as the highest accuracy (0.820), precision (0.817), specificity (0.814), and F1 score (0.822), and the lowest Brier score (0.120) and log loss (0.374). Additionally, the model showed favorable calibration, with a slope of 0.999 and an intercept of 0.028. According to the scoring system incorporating 10 evaluation metrics, the eXGBM model achieved the highest score (56), followed by the RF model (48) and NN model (41). The LR, DT, and NB models had total scores of 27, 30, and 13, respectively. The AI application has been deployed online at https://in-hospitaldeathinhipfracture-l9vhqo3l55fy8dkdvuskvu.streamlit.app/ , based on the eXGBM model. The comparative testing revealed that the AI application's predictive capabilities significantly outperformed those of the doctors in terms of AUC values (0.908 vs. 0.682, P <0.001). CONCLUSIONS: The eXGBM model demonstrates promising predictive performance in assessing the risk of postoperative in-hospital mortality among geriatric hip fracture patients. The developed AI model serves as a valuable tool to enhance clinical decision-making.

Suspected duloxetine-induced restless legs syndrome phenotypic variant: a case report.

BACKGROUND: Restless arms syndrome (RAS) is the most common variant of restless legs syndrome (RLS), which is easy to be ignored in clinical practice due to the lack of specific diagnostic criteria. When effective therapeutic agents induced RAS and symptoms persisted after briefly observation, clinicians will face the challenge of weighing efficacy against side effects. CASE PRESENTATION: A 67-year-old woman was admitted to a geriatric psychiatric ward with depression. Upon admission, the escitalopram dose was reduced from 15 mg to 10 mg per day, and the duloxetine dose was increased from 60 mg to 80 mg per day. The next night before bedtime, she developed itching and creeping sensations deep inside bilateral shoulders and arms, with the urge to move, worsening at rest, and alleviation after hammering. The symptoms persisted when escitalopram was discontinued. A history of RLS was confirmed. Treatment with 40 mg of duloxetine and 0.125 mg of pramipexole significantly improved depression, and the paresthesia disappeared, with no recurrence occurring 6 months after discharge. DISCUSSION AND CONCLUSIONS: This case suggests that psychiatrists should pay attention to RLS variants when increasing doses of duloxetine. Long-term improvement can be achieved through dosage reduction combined with dopaminergic drugs instead of immediate discontinuation.

Cryogenic Electron-Beam Writing for Perovskite Metasurface.

Halide perovskites (HPs) metasurfaces have recently attracted significant interest due to their potential to not only further enhance device performance but also reveal the unprecedented functionalities and novel photophysical properties of HPs. However, nanopatterning on HPs is critically challenging as they are readily destructed by the organic solvents in the standard lithographic processes. Here, we present a novel, subtle, and fully nondestructive HPs metasurface fabrication strategy based on cryogenic electron-beam writing. This technique allows for high-precision patterning and in situ imaging of HPs with excellent compatibility. As a proof-of-concept, broadband absorption enhanced metasurfaces were realized by patterning nanopillar arrays on CH3NH3PbI3 film, which results in photodetectors with approximately 14-times improvement on responsivity and excellent stability. Our findings highlight the great feasibility of cryogenic electron-beam writing for producing perovskite metasurface and unlocking the unprecedented photoelectronic properties of HPs.

Targeted Drug Nanodelivery and Immunotherapy for Combating Tumor Resistance.

Chemotherapy resistance is a common cause of tumor treatment failure. Various molecular responses, such as increased expression of efflux transporter proteins, including Pglycoprotein (P-gp), changes in the tumor microenvironment (TME), the role of platelets, and the effects of cancer stem cells (CSCs), can lead to drug resistance. Through extensive research on the mechanisms of drug resistance, more effective anti-resistance drugs and therapeutic approaches are being developed. This review explores drug resistance mechanisms and summarizes relevant anti-resistance drugs. In addition, due to the therapeutic limitations of the aforementioned treatments, new advances in nanocarrier-based combination immunotherapy to address the challenge of drug resistance have been described. Nanocarriers combined with immunotherapy can not only target tumor sites for targeted drug release but also modulate the autoimmune system and enhance immune efficacy, thereby overcoming tumor drug resistance. This review suggests new strategies for overcoming tumor drug resistance and is expected to inform tumor treatment and prognosis.

What makes a cyanobacterial bloom disappear? A review of the abiotic and biotic cyanobacterial bloom loss factors.

Cyanobacterial blooms present substantial challenges to managers and threaten ecological and public health. Although the majority of cyanobacterial bloom research and management focuses on factors that control bloom initiation, duration, toxicity, and geographical extent, relatively little research focuses on the role of loss processes in blooms and how these processes are regulated. Here, we define a loss process in terms of population dynamics as any process that removes cells from a population, thereby decelerating or reducing the development and extent of blooms. We review abiotic (e.g., hydraulic flushing and oxidative stress/UV light) and biotic factors (e.g., allelopathic compounds, infections, grazing, and resting cells/programmed cell death) known to govern bloom loss. We found that the dominant loss processes depend on several system specific factors including cyanobacterial genera-specific traits, in situ physicochemical conditions, and the microbial, phytoplankton, and consumer community composition. We also address loss processes in the context of bloom management and discuss perspectives and challenges in predicting how a changing climate may directly and indirectly affect loss processes on blooms. A deeper understanding of bloom loss processes and their underlying mechanisms may help to mitigate the negative consequences of cyanobacterial blooms and improve current management strategies.

Cholestyramine alleviates bone and muscle loss in irritable bowel syndrome via regulating bile acid metabolism.

Irritable bowel syndrome (IBS) is a widespread gastrointestinal disorder known for its multifaceted pathogenesis and varied extraintestinal manifestations, yet its implications for bone and muscle health are underexplored. Recent studies suggest a link between IBS and musculoskeletal disorders, but a comprehensive understanding remains elusive, especially concerning the role of bile acids (BAs) in this context. This study aimed to elucidate the potential contribution of IBS to bone and muscle deterioration via alterations in gut microbiota and BA profiles, hypothesizing that cholestyramine could counteract these adverse effects. We employed a mouse model to characterize IBS and analysed its impact on bone and muscle health. Our results revealed that IBS promotes bone and muscle loss, accompanied by microbial dysbiosis and elevated BAs. Administering cholestyramine significantly mitigated these effects, highlighting its therapeutic potential. This research not only confirms the critical role of BAs and gut microbiota in IBS-associated bone and muscle loss but also demonstrates the efficacy of cholestyramine in ameliorating these conditions, thereby contributing significantly to the field's understanding and offering a promising avenue for treatment.

Extracellular vesicles produced by 3D cultured MSCs promote wound healing by regulating macrophage activation through ANXA1.

The conundrum of wound healing has transformed into an imminent medical challenge. Presently, cell-free therapy centered around extracellular vesicles (EVs) has become a pivotal and promising research avenue. EVs generated from three-dimensional (3D) cell cultures have been previously established to possess enhanced tissue regeneration potential, although the underlying mechanisms remain elusive. In this study, we observed higher expression of annexin ANXA1 in 3D-cultured EVs. Remarkably, 3D-EVs with elevated ANXA1 expression demonstrated a more potent capacity to promote macrophage polarization from the M1 phenotype to the M2 phenotype. Concurrently, they exhibited superior abilities to enhance cell migration and tube formation, facilitating expedited wound healing in animal experiments. Conversely, the application of an ANXA1 inhibitor counteracted the positive effects of 3D-EVs. Taken together, our data validate that extracellular vesicles derived from 3D-cultured MSCs regulate macrophage polarization via ANXA1, thereby fostering wound healing.

Decoding the complexity of on-target integration: characterizing DNA insertions at the CRISPR-Cas9 targeted locus using nanopore sequencing.

BACKGROUND: CRISPR-Cas9 technology has advanced in vivo gene therapy for disorders like hemophilia A, notably through the successful targeted incorporation of the F8 gene into the Alb locus in hepatocytes, effectively curing this disorder in mice. However, thoroughly evaluating the safety and specificity of this therapy is essential. Our study introduces a novel methodology to analyze complex insertion sequences at the on-target edited locus, utilizing barcoded long-range PCR, CRISPR RNP-mediated deletion of unedited alleles, magnetic bead-based long amplicon enrichment, and nanopore sequencing. RESULTS: We identified the expected F8 insertions and various fragment combinations resulting from the in vivo linearization of the double-cut plasmid donor. Notably, our research is the first to document insertions exceeding ten kbp. We also found that a small proportion of these insertions were derived from sources other than donor plasmids, including Cas9-sgRNA plasmids, genomic DNA fragments, and LINE-1 elements. CONCLUSIONS: Our study presents a robust method for analyzing the complexity of on-target editing, particularly for in vivo long insertions, where donor template integration can be challenging. This work offers a new tool for quality control in gene editing outcomes and underscores the importance of detailed characterization of edited genomic sequences. Our findings have significant implications for enhancing the safety and effectiveness of CRISPR-Cas9 gene therapy in treating various disorders, including hemophilia A.

USP18 Stabilized FTO Protein to Activate Mitophagy in Ischemic Stroke Through Repressing m6A Modification of SIRT6.

Ischemic stroke (IS) is a dangerous cerebrovascular disorder with a significant incidence and death rate. Ubiquitin-specific peptidase 18 (USP18) has been proven to mitigate ischemic brain damage; however, its potential regulatory mechanisms remain unclear. In vivo and in vitro models of IS were established by middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R). Neurocyte injury was detected by MTT, LDH, ROS level, mitochondrial membrane potential (Δψm), and flow cytometry. Molecular expression was evaluated by qPCR, Western blotting, and immunofluorescence staining. Molecular mechanisms were determined by Co-IP, RIP, and MeRIP. IS injury was determined by neurological behavior score and TTC staining. Mitophagy was observed by TEM. USP18 and fat mass and obesity-associated protein (FTO) expression declined after OGD/R. Dysfunctional mitochondrial and apoptosis in OGD/R-stimulated neurocytes were eliminated by USP18/FTO overexpression via mitophagy activation. USP18-mediated de-ubiquitination was responsible for increasing FTO protein stability. Up-regulation of FTO protein restrained m6A modification of sirtuin6 (SIRT6) in a YTHDF2-dependent manner to enhance SIRT6 expression and subsequent activation of AMPK/PGC-1α/AKT signaling. FTO induced mitophagy to ameliorate nerve cell damage through SIRT6/AMPK/PGC-1α/AKT pathway. Finally, USP18/FTO overexpression relieved IS in rats via triggering SIRT6/AMPK/PGC-1α/AKT axis-mediated mitophagy. USP18 increased FTO protein stability to trigger SIRT6-induced mitophagy, thus mitigating IS. Our data unravel the novel neuroprotective mechanism of USP18 and suggest its potential as a promising treatment target for IS.

Impacts of sequential salinity and heat stress are recovery time-specific in freshwater crustacean, Daphnia pulicaria.

Stressors can interact to affect animal fitness, but we have limited knowledge about how temporal variation in stressors may impact their combined effect. This limits our ability to predict the outcomes of pollutants and future dynamic environmental changes. Elevated salinity in freshwater ecosystems has been observed worldwide. Meanwhile, heatwaves have become more frequent and intensified as an outcome of climate change. These two stressors can jointly affect organisms; however, their interaction has rarely been explored in the context of freshwater ecosystems. We conducted lab experiments using Daphnia pulicaria, a key species in lakes, to investigate how elevated salinity and heatwave conditions collectively affect freshwater organisms. We also monitored the impacts of various recovery times between the two stressors. Daphnia physiological conditions (metabolic rate, Na+-K+-ATPase (NKA) activity, and lipid peroxidation level) and life history traits (survival, fecundity, and growth) in response to salt stress as well as mortality in heat treatment were examined. We found that Daphnia responded to elevated salinity by upregulating NKA activity and increasing metabolic rate, causing a high lipid peroxidation level. Survival, fecundity, and growth were all negatively affected by this stressor. These impacts on physiological conditions and life history traits persisted for a few days after the end of the exposure. Heat treatments caused mortality in Daphnia, which increased with rising temperature. Results also showed that individuals that experienced salt exposure were more susceptible to subsequent heat stress, but this effect decreased with increasing recovery time between stressors. Findings from this work suggest that the legacy effects from a previous stressor can reduce individual resistance to a subsequent stressor, adding great difficulties to the prediction of outcomes of multiple stressors. Our work also demonstrates that cross-tolerance/susceptibility and the associated mechanisms remain unclear, necessitating further investigation.