Association between aspartate aminotransferase to alanine aminotransferase ratio and mortality in critically ill patients with congestive heart failure.

Congestive heart failure (CHF) is a complex clinical syndrome that significantly impacts patient outcomes, especially in critically ill patients admitted to intensive care units (ICUs). The aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AST/ALT), has also been reported as a risk factor of cardiovascular diseases. However, few studies investigated the correlations between the AST/ALT ratio and ICU mortality in critically ill patients with CHF. This study investigates the association between the baseline AST/ALT ratio measured within the first 24 h of ICU admission and 28-day ICU all-cause mortality in critically ill patients with CHF. This retrospective cohort study included 4869 critically ill patients with CHF from the eICU Collaborative Research Database. Patients were categorized into tertiles based on their AST/ALT ratio: Tertile 1 (0.13-0.97), Tertile 2 (0.97-1.50), and Tertile 3 (1.50-5.89). Univariate and multivariate Cox proportional hazards regression models were used to evaluate the association between the AST/ALT ratio and 28-day ICU all-cause mortality. Nonlinear threshold effects and subgroup analyses were conducted to assess the robustness of the findings. Kaplan-Meier survival curves were generated to compare survival probabilities across tertiles. Participants with higher AST/ALT ratios were older, had higher illness severity, and experienced worse clinical outcomes. In univariate analysis, the AST/ALT ratio was significantly associated with 28-day ICU mortality (HR: 1.24, 95% CI 1.13-1.37, P < 0.0001). This association remained significant in the fully adjusted multivariate model. The highest tertile of AST/ALT ratio was associated with a significantly higher risk of mortality compared to the lowest tertile across all models (HR: 1.48, 95% CI 1.07-2.03, P = 0.0162 in Model 4). A nonlinear relationship was observed, with a threshold identified at an AST/ALT ratio of 2.08. Below this turning point, the association remained strong (HR: 1.47, 95% CI 1.13-1.91, P = 0.0036), while above it, the association was no longer significant. Subgroup analyses revealed no significant interactions, indicating that the association between AST/ALT ratio and mortality was consistent across various patient characteristics. Survival analysis showed that patients in the highest tertile had the poorest survival outcomes (P < 0.0001). An elevated AST/ALT ratio within the first 24 h of ICU admission is independently associated with increased 28-day ICU all-cause mortality in critically ill patients with CHF.

Antithermal-Quenching All-Inorganic Perovskite Crystals with Green Ultralong Persistent Luminescence for Advanced Anticounterfeiting Applications.

Long persistent luminescence (PersL) materials have revolutionized many fields of optoelectronics and photonics due to their applications in anticounterfeiting, information encryption, and in vivo bioimaging. Here, we reported a novel PersL crystal prepared by the heterovalent doping of Sb3+ into perovskite tetragonal phase RbCdCl3, comparing with the pristine non-perovskite orthorhombic phase analogue without PersL property. Surprisingly, under the UV light irradiation, the title crystals concurrently exhibit green ultralong PersL (>2400 s), high photoluminescence quantum yield (49.1%), and antithermal quenching in the range from 148 to 328 K. It was revealed by experimental results and theoretical analyses that green ultralong PersL and antithermal quenching of perovskite-phase RbCdCl3/Sb3+ crystals originate from the electron transition between the 5s2 level of the dopant Sb3+ and the electronic defect-induced trap states. Enlightened by the excellent optical properties, the tetragonal perovskite-phase RbCdCl3/Sb3+ PersL materials show promising application prospects in anticounterfeiting and encryption of information.

Radiological features on high-resolution MR imaging predicts successful recanalization in patients with symptomatic chronic intracranial large artery occlusion.

RATIONALE AND OBJECTIVES: Endovascular recanalization has been attempted in patients with symptomatic chronic intracranial large artery occlusion (CILAO), however, the heterogeneity of recanalization outcomes present challenges for the clinical application. OBJECTIVE: To determine the radiological features on high-resolution MR imaging (HR-MRI) for predicting successful recanalization of symptomatic CILAO. METHODS: Seventy-three patients with symptomatic CILAO who underwent endovascular recanalization at our center were retrospectively analyzed. Patients' clinical information, HR-MRI characteristics, procedural results, and outcomes were recorded. Factors related to successful recanalization were analyzed by univariate and multivariate analyses. RESULTS: Technical success was achieved in 61 (83.6%) patients, with a complication rate of 13.7% (10/73). Based on multivariate analysis, responsible occluded artery (middle cerebral artery (MCA) trunk versus intracranial internal carotid artery (ICA), P = 0.004; MCA trunk versus intracranial vertebrobasilar artery (VBA), P = 0.010), occlusion with residual lumen (P = 0.036), occlusion with marked plaque enhancement (P = 0.011), and shorter occlusion length (≤10.2 mm versus >10.2 mm, P = 0.008) were identified as independent positive predictors of successful recanalization. Patients were assigned score points according to the coefficients of the prediction model, and the technical success rates were 50.0%, 83.3%, 95.5%, and 100% in patients with score ≤ 2, 3, 4, and ≥ 5 points, respectively. CONCLUSIONS: The HR-MRI modality may be valuable in identifying candidates for endovascular recanalization of symptomatic CILAO. MCA trunk occlusion, occlusion with residual lumen, occlusion with marked plaque enhancement and shorter occlusion length on HR-MRI appear to be significantly associated with the success of recanalization.

Neuronal wiring diagram of an adult brain.

Connections between neurons can be mapped by acquiring and analysing electron microscopic brain images. In recent years, this approach has been applied to chunks of brains to reconstruct local connectivity maps that are highly informative1-6, but nevertheless inadequate for understanding brain function more globally. Here we present a neuronal wiring diagram of a whole brain containing 5 × 107 chemical synapses7 between 139,255 neurons reconstructed from an adult female Drosophila melanogaster8,9. The resource also incorporates annotations of cell classes and types, nerves, hemilineages and predictions of neurotransmitter identities10-12. Data products are available for download, programmatic access and interactive browsing and have been made interoperable with other fly data resources. We derive a projectome-a map of projections between regions-from the connectome and report on tracing of synaptic pathways and the analysis of information flow from inputs (sensory and ascending neurons) to outputs (motor, endocrine and descending neurons) across both hemispheres and between the central brain and the optic lobes. Tracing from a subset of photoreceptors to descending motor pathways illustrates how structure can uncover putative circuit mechanisms underlying sensorimotor behaviours. The technologies and open ecosystem reported here set the stage for future large-scale connectome projects in other species.

GDNF facilitates cognitive function recovery following neonatal surgical-induced learning and memory impairment via activation of the RET pathway and modulation of downstream effectors PKMζ and Kalirin in rats.

OBJECTIVE: The aim of this study is to elucidate the underlying mechanism through which glial cell line-derived neurotrophic factor (GDNF) improves cognitive deficits in adults resulting from neonatal surgical interventions. METHODS: Newborn Sprague-Dawley rats, regardless of gender, were randomly allocated into seven groups on postnatal day 7 as follows (n=15): (1) Control group (not subjected to anesthesia, surgery, or any pharmaceutical interventions); (2) GDNF group (received intracerebroventricular injection of GDNF); (3) Surgery group (underwent right carotid artery exposure under anesthesia with 3 % sevoflurane); (4) Surgery plus GDNF group; (5) Surgery plus GDNF and type II JAK inhibitor NVP-BBT594 (BBT594) group (administered intraperitoneal injection of BBT594); (6) BBT group; and (7) Surgery plus BBT group. Starting from postnatal day 33, all rats underwent Barnes maze and fear conditioning tests, followed by decapitation under sevoflurane anesthesia for subsequent analyses. The left hemibrains underwent Golgi staining, while the right hemibrains were used for hippocampal protein extraction to assess Protein kinase Mζ (PKMζ) and Kalirin expression through western blotting. RESULTS: GDNF demonstrated a mitigating effect on spatial learning and memory impairment, as well as context-related fear memory impairment, reductions in dendritic total lengths, and spinal density within the hippocampus induced by surgical intervention. Notably, all of these ameliorative effects of GDNF were reversed upon administration of the RET inhibitor BBT594. Additionally, GDNF alleviated the downregulation of protein expression of PKMζ and Kalirin in the hippocampus of rats subjected to surgery, subsequently reversed by BBT594. CONCLUSION: The effective impact of GDNF on learning and memory impairment caused by surgical intervention appears to be mediated through the RET pathway. Moreover, GDNF may exert its influence by upregulating the expression of PKMζ and Kalirin, consequently enhancing the development of dendrites and dendritic spines.

DBAII-Net with multiscale feature aggregation and cross-modal attention for enhancing infant brain injury classification in MRI.

Objectives.Magnetic resonance imaging (MRI) is pivotal in diagnosing brain injuries in infants. However, the dynamic development of the brain introduces variability in infant MRI characteristics, posing challenges for MRI-based classification in this population. Furthermore, manual data selection in large-scale studies is labor-intensive, and existing algorithms often underperform with thick-slice MRI data. To enhance research efficiency and classification accuracy in large datasets, we propose an advanced classification model.Approach.We introduce the Dual-Branch Attention Information Interactive Neural Network (DBAII-Net), a cutting-edge model inspired by radiologists' use of multiple MRI sequences. DBAII-Net features two innovative modules: (1) the convolutional enhancement module (CEM), which leverages advanced convolutional techniques to aggregate multi-scale features, significantly enhancing information representation; and (2) the cross-modal attention module (CMAM), which employs state-of-the-art attention mechanisms to fuse data across branches, dramatically improving positional and channel feature extraction. Performances (accuracy, sensitivity, specificity, area under the curve (AUC), etc) of DBAII-Net were compared with eight benchmark models for brain MRI classification in infants aged 6 months to 2 years.Main results.Utilizing a self-constructed dataset of 240 thick-slice brain MRI scans (122 with brain injuries, 118 without), DBAII-Net demonstrated superior performance. On a test set of approximately 50 cases, DBAII-Net achieved average performance metrics of 92.53% accuracy, 90.20% sensitivity, 94.93% specificity, and an AUC of 0.9603. Ablation studies confirmed the effectiveness of CEM and CMAM, with CMAM significantly boosting classification metrics.Significance.DBAII-Net with CEM and CMAM outperforms existing benchmarks in enhancing the precision of brain MRI classification in infants, significantly reducing manual effort in infant brain research. Our code is available athttps://github.com/jiazhen4585/DBAII-Net.

Association between TIMP1 polymorphism and female neuromyelitis optica spectrum disorder in Chinese population.

Aims: Earlier studies have indicated an association between the TIMP1 polymorphism and the risk of certain autoimmune diseases, as well as a link between higher TIMP1 levels and blood-brain barrier (BBB) disruption in neuromyelitis optica spectrum disorders (NMOSD). This study aimed to explore the correlation between TIMP1 polymorphism and NMOSD phenotypes. Methods: Genotyping of three loci (rs4898, rs2070584, rs6609533) in the TIMP1 gene was performed in 126 NMOSD patients and 213 healthy controls (HCs) from North China using the SNaPshot sequencing technique, and a correlation analysis was done between phenotypes and TIMP1 genotype. Results: The frequency of the rs4898-T, rs2070584-T, and rs6609533-G alleles was significantly higher in NMOSD patients than those in HCs (p < 0.05). Accordingly, the rs4898-TT, rs2070584-TT, and rs6609533-GG genotypes were found at a higher frequency in patients than in controls (p < 0.05). Haplotype analysis showed TIMP1 T-T-G (rs4898-rs2070584-rs6609533) frequency was higher in female NMOSD patients (p = 0.019), and the frequency of T-T-G haplotypes in the BBB disrupted group was higher compared with that in the BBB normal group (p = 0.04). Conclusions: TIMP1 rs4898-T, rs2070584-T, and rs6609533 polymorphism may contribute to the susceptibility of Female NMOSD patients in the Chinese Population. TIMP1 T-T-G (rs4898-rs2070584-rs6609533) haplotype is more common among female NMOSD patients and is linked to heightened disruption of the BBB.

Omega-3 fatty acids protect cartilage from acute injurie by reducing the mechanical sensitivity of chondrocytes.

Acute cartilage injuries, such as intra-articular fractures and blunt impacts, frequently result in chondrocyte death and extracellular matrix (ECM) degradation, significantly elevating the risk of post-traumatic osteoarthritis (PTOA). Despite advances in treatment, no effective therapies currently exist to fully cure PTOA or halt its progression. This study explores the protective effects of the dietary fatty acid eicosapentaenoic acid (EPA) on human primary chondrocytes (HPCs) and cartilage explants exposed to mechanical overload and blunt trauma. HPCs were isolated and subjected to mechanical stretching using BioFlex six-well culture plates, while cartilage explants were subjected to impact loading via a customized drop tower. EPA was incorporated into the culture medium, followed by assays to evaluate cell viability, calcium (Ca²âº) influx, apoptosis, reactive oxygen species (ROS) levels, and collagen type II alpha (Col-2a) expression. EPA treatment markedly decreased chondrocyte mechanical sensitivity, as demonstrated by enhanced cell viability and reduced lactate dehydrogenase (LDH) release. Furthermore, EPA inhibited Piezo1 activation, leading to lower intracellular Ca²âº concentrations, decreased apoptosis, and diminished ROS levels. In cartilage explants, EPA improved chondrocyte viability, minimized structural damage, and sustained higher Col-2a expression compared to the blunt trauma group. These results indicate that EPA effectively shields chondrocytes and cartilage explants from mechanical overload-induced damage by inhibiting Piezo1 activation and mitigating Ca²âº influx, apoptosis, and oxidative stress. The findings suggest that EPA supplementation could offer a promising strategy for preventing PTOA progression following acute cartilage injuries. Further research is warranted to assess the clinical applications of EPA and confirm its efficacy in larger animal models and human trials.

Perfusion deficit and vessel wall characteristics to predict recurrent ischemic events in medically treated patients with chronic symptomatic anterior circulation large vessel occlusion.

BACKGROUND: To investigate the association between perfusion deficit, vessel wall characteristics, and risk of recurrent ischemic events in medically treated patients with chronic symptomatic anterior circulation large vessel occlusion. METHODS: We retrospectively reviewed chronic symptomatic patients due to anterior circulation large vessel occlusion in our center. All patients received multiparametric magnetic resonance imaging (including perfusion-weighted imaging and high-resolution vessel wall imaging) within 4 weeks to 3 months after symptom onset. The association between baseline clinical or imaging variables and recurrent ischemic events was assessed in bivariate models and multivariable logistic regression to identify independent predictors of recurrence. RESULTS: Among 71 enrolled patients, 21.1% (15/71) patients had recurrent ischemic events (nine ischemic strokes and six transient ischemic attacks) during a 2-year follow-up. In bivariate models, hypertension, occlusion with hyperintense signals, the presence of intraluminal thrombus, Tmax >4 s volume, Tmax >6 s volume, Tmax >8 s volume, and Tmax >10 s volume were associated with recurrence (all p < 0.05). In multivariate analysis, hypertension (p = 0.039, OR 10.057 (95% CI, 1.123-90.048)), higher deficit volume of Tmax >4 s (p = 0.011, OR 1.012 (95% CI, 1.003-1.021)) and occlusion with hyperintense signal (p = 0.030, OR 6.732 (95% CI, 1.200-37.772)) were still independent predictors of recurrent ischemic events. CONCLUSIONS: Besides hypertension history, higher deficit volume of Tmax >4 s and occlusion with hyperintense signal determined using multiparametric MRI are strongly associated with risk for recurrent ischemic events in medically treated patients with chronic symptomatic anterior circulation large vessel occlusion. Future studies are needed to determine the utility of revascularization strategies in such high-risk patients.

Enhancement of gemcitabine sensitivity in intrahepatic cholangiocarcinoma through Saikosaponin-a mediated modulation of the p-AKT/BCL-6/ABCA1 axis.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) remains a significant challenge in cancer therapy, especially due to its resistance to established treatments like Gemcitabine, necessitating novel therapeutic approaches. METHODS: This study utilized Gemcitabine-resistant cell lines, patient-derived organotypic tumor spheroids (PDOTs), and patient-derived xenografts (PDX) to evaluate the effects of Saikosaponin-a (SSA) on ICC cellular proliferation, migration, apoptosis, and its potential synergistic interaction with Gemcitabine. Techniques such as transcriptome sequencing, Luciferase reporter assays, and molecular docking were employed to unravel the molecular mechanisms. RESULTS: SSA exhibited antitumor effects in both in vitro and PDX models, indicating its considerable potential for ICC treatment. SSA markedly inhibited ICC progression by reducing cellular proliferation, enhancing apoptosis, and decreasing migration and invasion. Crucially, it augmented Gemcitabine's efficacy by targeting the p-AKT/BCL6/ABCA1 signaling pathway. This modulation led to the downregulation of p-AKT and suppression of BCL6 transcriptional activity, ultimately reducing ABCA1 expression and enhancing chemosensitivity to Gemcitabine. Additionally, ABCA1 was validated as a predictive biomarker for drug resistance, with a direct correlation between ABCA1 expression levels and the IC50 values of various small molecule drugs in ICC gene profiles. CONCLUSION: This study highlights the synergistic potential of SSA combined with Gemcitabine in enhancing therapeutic efficacy against ICC and identifies ABCA1 as a key biomarker for drug responsiveness. Furthermore, the introduction of the novel PDOTs microfluidic model provides enhanced insights into ICC research. This combination strategy may provide a novel approach to overcoming treatment challenges in ICC.

[Role and mechanism of ginsenoside Rg1 in ameliorating sepsis-induced acute lung injury based on PERK/eIF2α/ATF4/CHOP-induced alveolar epithelial cell apoptosis].

The study investigates the therapeutic effects and mechanisms of ginsenoside Rg_1(GRg_1) on sepsis-induced acute lung injury(SALI). A murine model of SALI was created using cecal ligation and puncture(CLP) surgery, and mice were randomly assigned to groups for GRg_1 intervention. Survival and body weight changes were recorded, lung function was assessed with a non-invasive lung function test system, and lung tissue damage was evaluated through HE staining. The content and expression of inflammatory factors were measured by ELISA and qRT-PCR. Apoptosis was examined using flow cytometry and TUNEL staining. The activation and expression of apoptosis-related molecules cysteinyl aspartate specific proteinase 3(caspase-3), B-cell lymphoma-2(Bcl-2), Bcl-2 associated X protein(Bax), and endoplasmic reticulum stress-related molecules protein kinase R-like endoplasmic reticulum kinase(PERK), eukaryotic initiation factor 2α(eIF2α), activating transcription factor 4(ATF4), and C/EBP homologous protein(CHOP) were studied using Western blot and qRT-PCR. In addition, an in vitro model of lipopolysaccharide(LPS)-induced lung alveolar epithelial cell injury was used, with the application of the endoplasmic reticulum stress inducer tunicamycin to validate the action mechanism of GRg_1. RESULTS:: indicated that, when compared to the model group, GRg_1 intervention significantly enhanced the survival time of CLP mice, mitigated body weight loss, and improved impaired lung function indices. The GRg_1-treated mice also displayed reduced lung tissue pathological scores, a reduced lung tissue wet-to-dry weight ratio, and lower protein content in the bronchoalveolar lavage fluid. Serum levels of interleukin-6(IL-6), interleukin-1ß(IL-1ß), and tumor necrosis factor-α(TNF-α), as well as the mRNA expressions of these cytokines in lung tissues, were decreased. There was a notable decrease in the proportion of apopto-tic alveolar epithelial cells, and down-regulated expressions of caspase-3, Bax, PERK, eIF2α, ATF4, and CHOP and up-regulated expression of Bcl-2 were observed. In vitro findings showed that the apoptosis-lowering and apoptosis-related protein down-regulating effects of GRg_1 were significantly inhibited with the co-application of tunicamycin. Altogether, GRg_1 reduces apoptosis of alveolar epithelial cells, inhibits inflammation in the lungs, alleviates lung injury, and enhances lung function, possibly through the PERK/eIF2α/ATF4/CHOP pathway.

Genetic switch selectively kills hepatocellular carcinoma cell based on microRNA and tissue-specific promoter.

The clinical treatment of hepatocellular carcinoma (HCC) is still a heavy burden worldwide. Intracellular microRNAs (miRNAs) commonly express abnormally in cancers, thus they are potential therapeutic targets for cancer treatment. miR-21 is upregulated in HCC whereas miR-122 is enriched in normal hepatocyte but downregulated in HCC. In our study, we first generated a reporter genetic switch compromising of miR-21 and miR-122 sponges as sensor, green fluorescent protein (GFP) as reporter gene and L7Ae:K-turn as regulatory element. The reporter expression was turned up in miR-21 enriched environment while turned down in miR-122 enriched environment, indicating that the reporter switch is able to respond distinctly to different miRNA environment. Furthermore, an AAT promoter, which is hepatocyte-specific, is applied to increase the specificity to hepatocyte. A killing switch with AAT promoter and an apoptosis-inducing element, Bax, in addition to miR-21 and miR-122 significantly inhibited cell viability in Huh-7 by 70 % and in HepG2 by 60 %. By contrast, cell viability was not affected in five non-HCC cells. Thus, we provide a novel feasible strategy to improve the safety of miRNA-based therapeutic agent to cancer.

Molecular Insights into MpAGO1 and Its Regulatory miRNA, miR11707, in the High-Temperature Acclimation of Marchantia polymorpha.

As a model plant for bryophytes, Marchantia polymorpha offers insights into the role of RNA silencing in aiding early land plants navigate the challenges posed by high-temperature environments. Genomic analysis revealed unique ARGONAUTE1 ortholog gene (MpAGO1) in M. polymorpha, which is regulated by two species-specific microRNAs (miRNAs), miR11707.1 and miR11707.2. Comparative studies of small RNA profiles from M. polymorpha cellular and MpAGO1 immunoprecipitation (MpAGO1-IP) profiles at various temperatures, along with analyses of Arabidopsis AGO1 (AtAGO1), revealed that MpAGO1 has a low selectivity for a diverse range of small RNA species than AtAGO1. Protein structural comparisons revealed no discernible differences in the guide strand small RNA recognition middle domain, MID domain, of MpAGO1 and AtAGO1, suggesting the complexity of miRNA species specificity and necessitating further exploration. Small RNA profiling and size exclusion chromatography have pinpointed a subset of M. polymorpha miRNAs, notably miR11707, that remain in free form within the cell at 22°C but are loaded into MpAGO1 at 28°C to engage in RNA silencing. Investigations into the mir11707 gene editing (mir11707ge) mutants provided evidence of the regulation of miR11707 in MpAGO1. Notably, while MpAGO1 mRNA expression decreases at 28°C, the stability of the MpAGO1 protein and its associated miRNAs is essential for enhancing the RNA-inducing silencing complex (RISC) activity, revealing the importance of RNA silencing in enabling M. polymorpha to survive thermal stress. This study advances our understanding of RNA silencing in bryophytes and provides groundbreaking insights into the evolutionary resilience of land plants to climatic adversities.

Glycyrrhetinic acid blocks SARS-CoV-2 infection by activating the cGAS-STING signalling pathway.

BACKGROUND AND PURPOSE: Traditional Chinese medicine (TCM) played an important role in controlling the COVID-19 pandemic, but the scientific basis and its active ingredients are still weakly studied. This study aims to decipher the underlying anti-SARS-CoV-2 mechanisms of glycyrrhetinic acid (GA). EXPERIMENTAL APPROACH: GA's anti-SARS-CoV-2 effect was verified both in vitro and in vivo. Homogeneous time-resolved fluorescence assays, biolayer interferometry technology, and molecular docking were employed to examine interactions of GA with human stimulator of interferon genes (hSTING). Immunofluorescence staining, western blot, and RT-qPCR were used to investigate nuclear translocation of interferon regulatory factor 3 (IRF3) and levels of STING target genes. Pharmacokinetics of GA was studied in mice. KEY RESULTS: GA could directly bind to Ser162 and Tyr240 residues of hSTING, thus up-regulating downstream targets and activation of the STING signalling pathway. Such activation is crucial for limiting the replication of SARS-CoV-2 Omicron in Calu-3 cells and protecting against lung injury induced by SARS-CoV-2 Omicron infection in K18-ACE2 transgenic mice. Immunofluorescence staining and western blot indicated that GA increased levels of phosphorylated STING, phosphorylated TANK-binding kinase-1, and cyclic GMP-AMP synthase (cGAS). Importantly, GA increased nuclear translocation of IRF3. Pharmacokinetic analysis of GA in mice indicated it can be absorbed into circulation and detected in the lung at a stable level. CONCLUSION AND IMPLICATIONS: Activation of the cGAS-STING pathway through the GA-STING-IRF3 axis is essential for the antiviral activity of GA in mice, providing new insights into the potential translation of GA for treating SARS-CoV-2 in patients.

Hydroxyl-aluminum pillared bentonite enhanced Mn(II) removal by chlorine oxidation.

Al-PILC was used to catalyze the chlorine oxidation of Mn(II) in aqueous solution. The effects of various catalysts, catalyst dosage, chlorine dosage, pH value, temperature and organic content on the oxidation process were investigated. Results show that 1.5 mg/L chlorine can quickly oxidize Mn(II) from 0.5 mg/L to less than 0.04 mg/L with 10 mg/L Al-PILC. Using catalysts with higher porosity and higher SA, increase in chlorine concentration, increase in catalyst dosage, higher pH, and higher temperature can significantly enhance the rate of Mn(II) catalytic oxidation. The Mn(II) oxidation process includes the homogeneous oxidation, catalytic oxidation on the surface of the catalysts and self-catalytic oxidation produced by the newly produced MnOx. Al-PILC surface provides active sites for chlorine oxidation Mn(II) in the water, and also provides binding sites for the newly produced MnOx, which has higher catalytic activity and thus has an self-catalytic oxidation effect. The higher the porosity and SA of Al-PILC, the more catalytic oxidation active sites and loading sites, and the better the catalytic oxidation effect. The study promotes the understanding of chlorine catalyzed oxidation Mn(II) in aqueous solution, but also provide important guide to study newly efficient catalysts to oxidize Mn(II) with chlorine in aqueous solution.

Ruthenium-catalyzed C-H functionalization of indoles and indolines with 7-azabenzonorbornadienes: access to aminodihydronaphthyl indoles and indolines.

Indoles, indolines and hydronaphthylamines are ubiquitous structural motifs in natural products, pharmaceuticals, and biologically active molecules. In this paper, we report the synthesis of aminodihydronaphthyl-substituted indoles and indolines via a Ru-catalyzed carbamoyl-directed C-H functionalization of indoles and indolines with 7-azabenzonorbornadienes. In the presence of Cu(OAc)2 and AgSbF6, [Ru(p-cymene)Cl2]2 catalyzes the reaction of 1-carbamoylindoles with 7-azabenzonorbornadienes to produce 2-(1-amino-1,2-dihydronaphthalen-2-yl)indoles. Under the same conditions, the reaction of 1-carbamoylindolines with 7-azabenzonorbornadienes affords 7-(1-amino-1,2-dihydronaphthalen-2-yl)indolines. In both cases, the reactions yield cis-configured products.

Metabolomic-based analysis reveals bile acid-mediated ovarian failure induced by low temperature in zebrafish.

As ectotherms, fish are highly sensitive to temperature fluctuations, which can profoundly impact their reproductive cycles. In this study, we investigated the fertility and histological characteristics of zebrafish ( Danio rerio) ovaries exposed to a temperature gradient ranging from the thermopreferendum temperature of the species, 27°C, to lower temperatures of 22°C, 20°C, and 13°C over a period of two weeks. Comparative metabolomic (six biological replicates for each temperature) and transcriptomic (four biological replicates for each temperature) analyses were conducted under the four temperature conditions. Results indicated that lower temperatures inhibited oocyte development and differential metabolites were involved in steroid hormone production, antioxidant function, and lipid and protein catabolism. Disrupted reproductive hormones, increased proteolysis, and lipid degradation significantly impeded oocyte development and egg maturation. Notably, a significant increase in bile acid content was noted in the ovaries of the cold-treated fish, indicating that bile acids play a critical role in ovarian failure. Overall, these findings provide valuable insights into the mechanisms governing the reproductive response of fish to cold stress.

Realization of monolayer ZrTe5 topological insulators with wide band gaps.

Two-dimensional topological insulators hosting the quantum spin Hall effect have application potential in dissipationless electronics. To observe the quantum spin Hall effect at elevated temperatures, a wide band gap is indispensable to efficiently suppress bulk conduction. Yet, most candidate materials exhibit narrow or even negative band gaps. Here, via elegant control of van der Waals epitaxy, we have successfully grown monolayer ZrTe5 on a bilayer graphene/SiC substrate. The epitaxial ZrTe5 monolayer crystalizes in two allotrope isomers with different intralayer alignments of ZrTe3 prisms. Our scanning tunneling microscopy/spectroscopy characterization unveils an intrinsic full band gap as large as 254 meV and one-dimensional edge states localized along the periphery of the ZrTe5 monolayer. First-principles calculations further confirm that the large band gap originates from strong spin-orbit coupling, and the edge states are topologically nontrivial. These findings thus provide a highly desirable material platform for the exploration of the high-temperature quantum spin Hall effect.

Phage therapy combats pan drug-resistant Acinetobacter baumannii infection safely and efficiently.

Phage therapy offers a promising approach to combat the growing threat of antimicrobial resistance. Yet, key questions remain regarding dosage, administration routes, combination therapy, and the causes of therapeutic failure. In this study, we focused on a novel lytic phage, ФAb4B, which specifically targeted the Acinetobacter baumannii strains with KL160 capsular polysaccharide, including the pan-drug resistant A. baumannii YQ4. ФAb4B exhibited the ability to effectively inhibit biofilm formation and eradicate mature biofilms independently of dosage. Additionally, it demonstrated a wide spectrum of antibiotic-phage synergy and did not show any cytotoxic or haemolytic effects. Continuous phage injections, both intraperitoneally and intravenously over 7 d, showed no acute toxicity in vivo. Importantly, phage therapy significantly improved neutrophil counts, outperforming ciprofloxacin. However, excessive phage injections suppressed neutrophil levels. The combinatorial treatment of phage-ciprofloxacin rescued 91% of the mice, a superior outcome compared to phage alone (67%). The efficacy of the combinatorial treatment was independent of phage dosage. Notably, prophylactic administration of the combinatorial regimen provided no protection, but even when combined with a delayed therapeutic regimen, it saved all the mice. Bacterial resistance to the phage was not a contributing factor to treatment failure. Our preclinical study systematically describes the lytic phage's effectiveness in both in vitro and in vivo settings, filling in crucial details about phage treatment against bacteriemia caused by A. baumannii, which will provide a robust foundation for the future of phage therapy.