Enhancing the Antitumor Efficacy of Oncolytic Adenovirus Through Sonodynamic Therapy-Augmented Virus Replication.

The therapeutic efficacy of oncolytic adenoviruses (OAs) relies on efficient viral transduction and replication. However, the limited expression of coxsackie-adenovirus receptors in many tumors, along with the intracellular antiviral signaling, poses significant obstacles to OA infection and oncolysis. Here, we present sonosensitizer-armed OAs (saOAs) that potentiate the antitumor efficacy of oncolytic virotherapy through sonodynamic therapy-augmented virus replication. The saOAs could not only efficiently infect tumor cells via transferrin receptor-mediated endocytosis but also exhibit enhanced viral replication and tumor oncolysis under ultrasound irradiation. We revealed that the sonosensitizer loaded on the viruses induced the generation of ROS within tumor cells, which triggered JNK-mediated autophagy, ultimately leading to the enhanced viral replication. In mouse models of malignant melanoma, the combination of saOAs and sonodynamic therapy elicited a robust antitumor immune response, resulting in significant inhibition of melanoma growth and improved host survival. This work highlights the potential of sonodynamic therapy in enhancing the effectiveness of OAs and provides a promising platform for fully exploiting the antitumor efficacy of oncolytic virotherapy.

Human biomonitoring of serum polycyclic aromatic hydrocarbons and oxygenated derivatives by gas chromatography coupled with tandem mass spectrometry.

While polycyclic aromatic hydrocarbons (PAHs) are well-known for their potential carcinogenic and mutagenic effects, the health implications of exposure to oxygenated PAHs (OPAHs), which are significant substitutes with increased persistence and bioaccumulation, are less understood. In this work, we compared the background levels of liquid-liquid, solid-phase, and supported-liquid extraction for the determination of serum PAHs and OPAHs. Liquid-liquid extraction demonstrated minimal background interference and was validated and used for human biomonitoring of PAHs and OPAHs in 240 participants using gas chromatography coupled with tandem mass spectrometry. We observed significant positive correlations between these compounds using Spearman correlation analysis. Furthermore, we investigated the concentration levels and compositions of PAHs and OPAHs among different demographic characteristics, including gender, age, and body mass index. Linear regression analysis demonstrated a weak but significant correlation between total concentrations of PAHs and OPAHs and age and body mass index. A multivariate linear regression analysis was then conducted to examine the association of exposure to individual PAHs and OPAHs with the body mass index. Naphthalene exposure and body mass index showed a statistically significant positive correlation, suggesting that higher levels of naphthalene exposure are associated with higher body mass index values. This study establishes a robust method for biomonitoring PAHs and OPAHs in serum, evaluating the exposure levels of these compounds in healthy adults and highlighting their associations with demographic characteristics.

MT1E in AML: A Gateway to Understanding Regulatory Cell Death and Immunotherapeutic Responses.

Regulated cell death (RCD) plays a crucial role in the initiation and progression of tumors, particularly in acute myeloid leukemia (AML). This study investigates the prognostic importance of RCD-related genes in AML and their correlation with immune infiltration.We combined TCGA and GTEx data, analyzing 1488 RCD-related genes, to develop a predictive model using LASSO regression and survival analysis. The model's accuracy was validated against multiple databases, examining immune cell infiltration, therapy responses, and drug sensitivity among risk groups. RT-qPCR confirmed MT1E expression in AML patients and healthy bone marrow. CCK8 and Transwell assays measured cell proliferation, adhesion, migration, and invasion, while flow cytometry and Western blotting assessed apoptosis and protein expression.We developed a prognostic model using 10 RCD methods, which demonstrated strong predictive ability, showing an inverse correlation between age and risk scores with survival in AML patients. Functional enrichment analysis of the model is linked to immune modulation pathways. RT-qPCR revealed significantly lower MT1E expression in AML versus healthy bone marrow (p<0.05). Consequently, experiments were designed to assess the function of MT1E overexpression.Findings indicated that MT1E overexpression showed it significantly reduced THP-1 cell proliferation and adhesion(p<0.001), decreased migration(p<0.001) and invasiveness(p<0.05), and increased apoptosis(p<0.05), with a notable rise in Caspase3 expression.A novel AML RCD risk model was developed, showing promise as a prognostic marker for evaluating outcomes and immune therapy effectiveness. Insights into MT1E's impact on AML cell proliferation and apoptosis open possibilities for improving patient outcomes and devising personalized treatment strategies.

Correlation between hearing loss and mild cognitive impairment in the elderly population: Mendelian randomization and cross-sectional study.

Background: Hearing loss and tinnitus have been linked to mild cognitive impairment (MCI); however, the evidence is constrained by ethical and temporal constraints, and few prospective studies have definitively established causation. This study aims to utilize Mendelian randomization (MR) and cross-sectional studies to validate and analyze this association. Methods: This study employs a two-step approach. Initially, the genetic data of the European population from the Genome-wide association studies (GWAS) database is utilized to establish the causal relationship between hearing loss and cognitive impairment through Mendelian randomization using the inverse variance weighted (IVW) method. This is achieved by identifying strongly correlated single nucleotide polymorphisms (SNPs), eliminating linkage disequilibrium, and excluding weak instrumental variables. In the second step, 363 elderly individuals from 10 communities in Qingdao, China are assessed and examined using methods questionnaire survey and pure tone audiology (PTA). Logistic regression and multiple linear regression were used to analyze the risk factors of MCI in the elderly and to calculate the cutoff values. Results: Mendelian randomization studies have shown that hearing loss is a risk factor for MCI in European populations, with a risk ratio of hearing loss to MCI loss of 1. 23. The findings of this cross-sectional study indicate that age, tinnitus, and hearing loss emerged as significant risk factors for MCI in univariate logistic regression analysis. Furthermore, multivariate logistic regression analysis identified hearing loss and tinnitus as potential risk factors for MCI. Consistent results were observed in multiple linear regression analysis, revealing that hearing loss and age significantly influenced the development of MCI. Additionally, a notable finding was that the likelihood of MCI occurrence increased by 9% when the hearing threshold exceeded 20 decibels. Conclusion: This study provides evidence from genomic and epidemiological investigations indicating that hearing loss may serve as a risk factor for cognitive impairment. While our epidemiological study has found both hearing loss and tinnitus as potential risk factors for cognitive decline, additional research is required to establish a causal relationship, particularly given that tinnitus can manifest as a symptom of various underlying medical conditions.

Short Didysprosium Covalent Bond Enables High Magnetization Blocking Temperature of a Direct 4f-4f Coupled Dinuclear Single-Molecule Magnet.

Coupling two magnetic anisotropic lanthanide ions via a direct covalent bond is an effective way to realize high magnetization blocking temperature of single-molecule magnets (SMMs) by suppressing quantum tunneling of magnetization (QTM), whereas so far only single-electron lanthanide-lanthanide bonds with relatively large bond distances are stabilized in which coupling between lanthanide and the single electron dominates over weak direct 4f-4f coupling. Herein, we report for the first time synthesis of short Dy(II)-Dy(II) single bond (3.61 Å) confined inside a carbon cage in the form of an endohedral metallofullerene Dy2@C82. Such a direct Dy(II)-Dy(II) covalent bond renders a strong Dy-Dy antiferromagnetic coupling that effectively quenches QTM at zero magnetic field, thus opening up magnetic hysteresis up to 25 K using a field sweep rate of 25 Oe/s, concomitant with a high 100 s magnetization blocking temperature (TB,100s) of 27.2 K.

Evaluating the necessity of lymph node sampling in lung adenocarcinoma with ground glass opacities.

BACKGROUND: Ground glass opacity is observed frequently in the early stages of lung adenocarcinoma and is associated with a favorable prognosis and a low incidence of lymph node metastasis. However, the necessity of lymph node sampling in these patients is questionable, although current guidelines still recommend it. METHODS: Radiologic and clinical data were retrospectively collected and analyzed for 2,298 patients with lung cancer who underwent surgical resection for lesions ≤15 mm during 2022. Based on the consolidation tumor ratios, patients were categorized into 4 groups (pure ground glass opacity, ground glass opacity-predominant, solid-predominant, and pure solid). The incidence of lymph node metastasis in each group was examined. RESULTS: A total of 2,298 patients with a median age of 54.0 years were enrolled in this study. Tumors were categorized into 4 types: 1,427 (62.1%) were pure ground glass opacity, which constituted the majority, while 421 (18.3%) were ground glass opacity-predominant, 330 (14.4%) were solid-predominant, and the remaining 120 (5.2%) were pure solid. Significant positive correlations were revealed between the consolidation tumor ratio group and pathologic grade (P < .001, ρ = 0.307), T stage (P < .001, ρ = 0.270), and N stage (P < .001, ρ = 0.105). Among the included cases, only 7 cases with metastasis were in the pure solid group. Within this group, 113 cases (94.2%) were N0, 5 cases (4.2%) were N1, and 2 cases (1.7%) were N2. CONCLUSION: Lymph node metastasis exclusively occurred in the pure solid group, suggesting that for nodules <15 mm, lymph node sampling may be crucial for pure solid nodules but less so for those containing ground glass opacities.

Exploring the mechanisms of glycolytic genes involvement in pulmonary arterial hypertension through integrative bioinformatics analysis.

The purpose of this study was to identify the mechanisms underlying the involvement of glycolytic genes in pulmonary arterial hypertension (PAH). This study involved downloading 3 datasets from the GEO database at the National Center for Biotechnology Information. The datasets were processed to obtain expression matrices for analysis. Genes involved in glycolysis-related pathways were obtained, and genes related to glycolysis were selected based on significant differences in expression. Gene Ontology functional annotation analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and GSEA enrichment analysis were performed on the DEGs. Combining LASSO regression with SVM-RFE machine learning technology, a PAH risk prediction model based on glycolysis related gene expression was constructed, and CIBERSORTx technology was used to analyse the immune cell composition of PAH patients. Gene enrichment analysis revealed that the DEGs work synergistically across multiple biological pathways. A total of 6 key glycolysis-related genes were selected using LASSO regression and SVM. A bar plot was constructed to evaluate the weights of the key genes and predict the risk of PAH. The clinical application value and predictive accuracy of the model were assessed. Immunological feature analysis revealed significant correlations between key glycolysis-related genes and the abundances of different immune cell types. The glycolysis genes (ACSS2, ALAS2, ALDH3A1, ADOC3, NT5E, and TALDO1) identified in this study play important roles in the development of pulmonary arterial hypertension, providing new evidence for the involvement of glycolysis in PAH.

A Phase IIa Multicenter, Randomized, Vehicle-Controlled, Dose Escalating Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of CBT-001 Ophthalmic Solution in Patients With Primary or Recurrent Pterygium.

Purpose: To evaluate the safety and efficacy of CBT-001, a multitarget tyrosine kinase inhibitor eyedrop, for pterygia. Design: Phase II clinical trial. Stage 1 was a single center, open-labeled, vehicle-controlled study. Stage 2 was a multicenter, randomized, double-masked, vehicle-controlled trial. Participants: Patients with primary or recurrent pterygia. Main Outcome Measures: The primary efficacy end point was lesion vascularity based on masked grading of photographs by an independent reading center. Other end points included dimensions of pterygia and safety. Methods: In stage 1, 24 eyes of 24 patients received 1 drop of CBT-001 in a dose escalation fashion (0.02%, 0.05%, and 0.2%) to determine the maximally tolerated dose based on adverse events (AEs) and blood drug levels. In stage 2, subjects were randomly assigned to receive the maximally tolerated dose of CBT-001 or vehicle dosed 3 times a day for 4 weeks with a 20-week follow-up. Results: In stage 1, the plasma maximum concentration values for all doses of CBT-001 were at or below the limit of detection (0.01 ng/ml). The most commonly reported AEs were mild foreign body sensation and irritation. CBT-001 0.2% was evaluated in stage 2. Baseline demographic characteristics were similar between patients receiving CBT-001 (n = 25) and vehicle (n = 23). After 4 weeks of dosing, the mean change from baseline in pterygium vascularity scores was -0.8 ± 0.7 (mean ± standard deviation) in subjects receiving CBT-001 0.2% and 0.0 ± 0.5 in subjects receiving vehicle (P < 0.001; 95% confidence interval: -1.12, -0.40). Pterygium vascularity scores remained significantly decreased, after the 4-week dosing period, at weeks 8 and 16, but not at week 24. The mean changes from baseline in the length of the pterygia were also significantly lower in subjects receiving CBT-001 compared with vehicle at weeks 2, 4, and 8 (P ≤ 0.014). The most commonly reported AEs were ocular, mild in severity, resolved after therapy, and did not result in discontinuation. Conclusions: CBT-001 0.2% decreased pterygia vascularity and lesion length after 4 weeks of dosing with a prolonged effect after dosing. The drug was well tolerated with minimal detected systemic drug levels. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Spinocerebellar ataxias: from pathogenesis to recent therapeutic advances.

Spinocerebellar ataxia is a phenotypically and genetically heterogeneous group of autosomal dominant-inherited degenerative disorders. The gene mutation spectrum includes dynamic expansions, point mutations, duplications, insertions, and deletions of varying lengths. Dynamic expansion is the most common form of mutation. Mutations often result in indistinguishable clinical phenotypes, thus requiring validation using multiple genetic testing techniques. Depending on the type of mutation, the pathogenesis may involve proteotoxicity, RNA toxicity, or protein loss-of-function. All of which may disrupt a range of cellular processes, such as impaired protein quality control pathways, ion channel dysfunction, mitochondrial dysfunction, transcriptional dysregulation, DNA damage, loss of nuclear integrity, and ultimately, impairment of neuronal function and integrity which causes diseases. Many disease-modifying therapies, such as gene editing technology, RNA interference, antisense oligonucleotides, stem cell technology, and pharmacological therapies are currently under clinical trials. However, the development of curative approaches for genetic diseases remains a global challenge, beset by technical, ethical, and other challenges. Therefore, the study of the pathogenesis of spinocerebellar ataxia is of great importance for the sustained development of disease-modifying molecular therapies.

Quantification of urinary podocyte-derived migrasomes for the diagnosis of kidney disease.

Migrasomes represent a recently uncovered category of extracellular microvesicles, spanning a diameter range of 500 to 3000 nm. They are emitted by migrating cells and harbour a diverse array of RNAs and proteins. Migrasomes can be readily identified in bodily fluids like serum and urine, rendering them a valuable non-invasive source for disease diagnosis through liquid biopsy. In this investigation, we introduce a streamlined and effective approach for the capture and quantitative assessment of migrasomes, employing wheat germ agglutinin (WGA)-coated magnetic beads and flow cytometry (referred to as WBFC). Subsequently, we examined the levels of migrasomes in the urine of kidney disease (KD) patients with podocyte injury and healthy volunteers using WBFC. The outcomes unveiled a substantial increase in urinary podocyte-derived migrasome concentrations among individuals with KD with podocyte injury compared to the healthy counterparts. Notably, the urinary podocyte-derived migrasomes were found to express an abundant quantity of phospholipase A2 receptor (PLA2R) proteins. The presence of PLA2R proteins in these migrasomes holds promise for serving as a natural antigen for the quantification of autoantibodies against PLA2R in the serum of patients afflicted by membranous nephropathy. Consequently, our study not only pioneers a novel technique for the isolation and quantification of migrasomes but also underscores the potential of urinary migrasomes as a promising biomarker for the early diagnosis of KD with podocyte injury.

ß-arrestin2 is indispensable for the antidepressant effects of fluoxetine via inhibiting astrocytic pyroptosis in chronic mild stress mouse model for depression.

ß-arrestin2 is a versatile protein for signaling transduction in brain physiology and pathology. Herein, we investigated the involvement of ß-arrestin2 in pharmacological effects of fluoxetine for depression. A chronic mild stress (CMS) model was established using wild-type (WT) and ß-arrestin2-/- mice. Behavioral results demonstrated that CMS mice showed increased immobility time in the tail suspension test and forced swimming test, elevated concentrations of pro-inflammatory factors in peripheral blood, increased expression of pyroptosis-related proteins, and increased co-labeling of glial fibrillary acidic protein and Caspase1 p10 in the hippocampus compared to the CON group. Treatment with fluoxetine (FLX) ameliorated these conditions. However, compared with the ß-arrestin2-/- CMS group, these results of the ß-arrestin2-/- CMS + FLX group showed no significant changes. These results suggested that the above effects of FLX could be eliminated by knocking out ß-arrestin2. Mass spectrometry implying that FLX promoted the binding of ß-arrestin2 to the NLRP2 inflammasome of depressed mice. Subsequently, the results of the cellular experiments suggested that the 5HT2B receptor antagonist may attenuate L-kynurenine + ATP-induced cell pyroptosis by attenuating NLRP2 binding to ß-arrestin2. We further found that the lack of ß-arrestin2 eliminated the anti-pyroptosis effect of fluoxetine. In conclusion, ß-arrestin2 is an essential protein for fluoxetine to alleviate pyroptosis in the hippocampal astrocytes of CMS mice. Mechanistically, we found that the 5-HT2BR-ß-arrestin2-NLRP2 axis is vital for maintaining the antidepressant effects of fluoxetine.

The influence of music performance anxiety on career expectations of early musical career students: self-efficacy as a moderator.

Music performance anxiety (MPA) is recognized as a distinct emotional behavior rather than merely a motor control disorder and is influenced by specific conditioning experiences. This study investigates the interrelationships between MPA, self-efficacy, and future career expectations among music students within the Chinese context. The participants of this study were 340 high school students majoring in music education and performance, drawn from three music schools in China. Data were collected using several questionnaires: the MPA Inventory for Adolescents (MPAI-A), the Self-Efficacy Formative Questionnaire, and the Career Futures Inventory (CFI). The findings indicate that MPA is negatively associated with self-efficacy and future career expectations. Additionally, self-efficacy acts as a partial moderator between MPA and career expectations, suggesting that enhancing the self-efficacy of music students can boost their future career aspirations and mitigate the adverse effects of MPA. This research explores the complex relationships among MPA, self-efficacy, and future career expectations, emphasizing the importance of curriculum and pedagogical strategies in music schools. Music students with high levels of self-efficacy may exhibit more confidence and stable performances before audiences. According to the panel regression analysis, self-efficacy significantly positively influences career expectations. An appropriate educational environment and supportive pedagogical approaches to MPA can foster the early career development of musicians.

GHS-R1a deficiency protects against lipopolysaccharide-induced spatial memory impairment in mice.

Neuroinflammation has been implicated in cognitive deficits of neurological and neurodegenerative diseases. There is abundant evidence that the application of ghrelin, an orexigenic hormone regulating appetite and energy balance, abrogates neuroinflammation and rescues associated memory impairment. However, the underlying mechanism is uncertain. In this study, we find that both intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of lipopolysaccharide (LPS) impairs spatial memory in mice. LPS treatment causes neuroinflammation and microglial activation in the hippocampus. Ghsr1a deletion suppresses LPS-induced microglial activation and neuroinflammation, and rescued LPS-induced memory impairment. Our findings thus suggest that GHS-R1a signaling may promote microglial immunoactivation and contribute to LPS-induced neuroinflammation. GHS-R1a may be a new therapeutic target for cognitive dysfunction associated with inflammatory conditions.

Peptide-TLR7/8a-Coordinated DNA Vaccines Elicit Enhanced Immune Responses against Infectious Diseases.

DNA vaccines represent an innovative approach for the immunization of diverse diseases. However, their clinical trial outcomes are constrained by suboptimal transfection efficiency and immunogenicity. In this work, we present a universal methodology involving the codelivery of Toll-like receptor 7/8 agonists (TLR7/8a) and antigen gene using TLR7/8a-conjugated peptide-coated poly(ß-amino ester) (PBAE) nanoparticles (NPs) to augment delivery efficiency and immune response. Peptide-TLR7/8a-coated PBAE NPs exhibit advantageous biophysical attributes, encompassing diminutive particle dimensions, nearly neutral ζ potential, and stability in the physiological environment. This synergistic approach not only ameliorates the stability of plasmid DNA (pDNA) and gene delivery efficacy but also facilitates subsequent antigen production. Furthermore, under optimal formulation conditions, the TLR7/8a-conjugated peptide coated PBAE NPs exhibit a potent capacity to induce robust immune responses. Collectively, this nanoparticulate gene delivery system demonstrates heightened transfection efficacy, stability, biodegradability, immunostimulatory effect, and low toxicity, making it a promising platform for the clinical advancement of DNA vaccines.

Extracellular cold-inducible RNA-binding protein mediated neuroinflammation and neuronal apoptosis after traumatic brain injury.

Background: Extracellular cold-inducible RNA-binding protein (eCIRP) plays a vital role in the inflammatory response during cerebral ischaemia. However, the potential role and regulatory mechanism of eCIRP in traumatic brain injury (TBI) remain unclear. Here, we explored the effect of eCIRP on the development of TBI using a neural-specific CIRP knockout (KO) mouse model to determine the contribution of eCIRP to TBI-induced neuronal injury and to discover novel therapeutic targets for TBI. Methods: TBI animal models were generated in mice using the fluid percussion injury method. Microglia or neuron lines were subjected to different drug interventions. Histological and functional changes were observed by immunofluorescence and neurobehavioural testing. Apoptosis was examined by a TdT-mediated dUTP nick end labelling assay in vivo or by an annexin-V assay in vitro. Ultrastructural alterations in the cells were examined via electron microscopy. Tissue acetylation alterations were identified by non-labelled quantitative acetylation via proteomics. Protein or mRNA expression in cells and tissues was determined by western blot analysis or real-time quantitative polymerase chain reaction. The levels of inflammatory cytokines and mediators in the serum and supernatants were measured via enzyme-linked immunoassay. Results: There were closely positive correlations between eCIRP and inflammatory mediators, and between eCIRP and TBI markers in human and mouse serum. Neural-specific eCIRP KO decreased hemispheric volume loss and neuronal apoptosis and alleviated glial cell activation and neurological function damage after TBI. In contrast, eCIRP treatment resulted in endoplasmic reticulum disruption and ER stress (ERS)-related death of neurons and enhanced inflammatory mediators by glial cells. Mechanistically, we noted that eCIRP-induced neural apoptosis was associated with the activation of the protein kinase RNA-like ER kinase-activating transcription factor 4 (ATF4)-C/EBP homologous protein signalling pathway, and that eCIRP-induced microglial inflammation was associated with histone H3 acetylation and the α7 nicotinic acetylcholine receptor. Conclusions: These results suggest that TBI obviously enhances the secretion of eCIRP, thereby resulting in neural damage and inflammation in TBI. eCIRP may be a biomarker of TBI that can mediate the apoptosis of neuronal cells through the ERS apoptotic pathway and regulate the inflammatory response of microglia via histone modification.

Dihydroquercetin alleviates dopamine neuron loss via regulating TREM2 activation.

BACKGROUND: Parkinson's disease (PD) is a prevalent neurodegenerative disorder, marked by the degeneration of dopamine (DA) neurons in the substantia nigra (SN). Current evidence strongly suggests that neuroinflammation, primarily mediated by microglia, contributes to PD pathogenesis. Triggering receptor expressed on myeloid cells 2 (TREM2) might serve as a promising therapeutic target for PD due to its ability to suppress neuroinflammation. Dihydroquercetin (DHQ) is an important natural dihydroflavone and confers apparent anti-inflammatory, antioxidant and anti-fibrotic effects. Recently, DHQ-mediated neuroprotection was exhibited. However, the specific mechanisms of its neuroprotective effects remain incompletely elucidated. METHODS: In this study, rat models were utilized to induce damage to DA neurons using lipopolysaccharide (LPS) and 6-hydroxydopamine (6-OHDA) to assess the impacts of DHQ on the loss of DA neurons. Furthermore, DA neuronal MN9D cells and microglial BV2 cells were employed to investigate the function of TREM2 in DHQ-mediated DA neuroprotection. Finally, TREM2 knockout mice were used to investigate whether the neuroprotective effects mediated by DHQ through a mechanism dependent on TREM2. RESULTS: The main findings demonstrated that DHQ effectively protected DA neurons against neurotoxicity induced by LPS and 6-OHDA and inhibited microglia-elicited neuroinflammation. Meanwhile, DHQ promoted microglial TREM2 signaling activation. Notably, DHQ failed to reduce inflammatory cytokines release and further present neuroprotection from DA neurotoxicity upon TREM2 silencing. Similarly, DHQ didn't exert DA neuroprotection in TREM2 knockout mice. CONCLUSIONS: These findings suggest that DHQ exerted DA neuroprotection by regulating microglia TREM2 activation.

Progress and Challenges in Polystyrene Recycling and Upcycling.

Polystyrene is a staple plastic in the packaging and insulation market. Despite its good recyclability, the willingness of PS recycling remains low, largely due to the high recycling cost and limited profitability. This review examines the research progresses, gaps, and challenges in areas that affect the recycling costs, including but not limited to logistics, packaging design, and policymaking. We critically evaluate the recent developments in upcycling strategies, and we particularly focus on tandem and hydrogen-atom transfer (HAT) upcycling strategies. We conclude that future upcycling studies should focus on not only reaction chemistry and mechanisms but also economic viability of the processes. The goal of this review is to stimulate the development of innovative recycling strategies with low recycling costs and high economic output values. We hope to stimulate the economic and technological momentum of PS recycling towards a sustainable and circular economy.

Bridging Nickel-MOF and Copper Single Atoms/Clusters with H-Substituted Graphdiyne for the Tandem Catalysis of Nitrate to Ammonia.

Interfacial engineering of synergistic catalysts is one of the keys to achieving multiple proton-coupled electron transfer processes in nitrate-to-ammonia conversion. Herein, by joining ultrathin nickel-based metal-organic framework (denoted Ni-MOF) nanosheets with few-layered hydrogen-substituted graphdiyne-supported copper single atoms and clusters (denoted HsGDY@Cu), a tandem catalyst of Ni-MOFs@HsGDY@Cu with dual-active interfaces was developed for the concerted catalysis of nitrate-to-ammonia. In such a system, the sandwiched HsGDY layer could serve as a bridge to connect the coordinated unsaturated Ni2+ sites with Cu single atoms/clusters in a limited range of 0 to 3.6 nm. From Ni2+ to Cu, via the hydrogen spillover process, the hydrogen radicals (H⋅) generated at the unsaturated Ni2+ sites could migrate across HsGDY to the Cu sites to participate in the transformation of *HNO3 to NH3. From Cu to Ni2+, bypassing the higher reaction energy for *HNO3 formation on the Ni2+ sites, the NO2 - detached from the Cu sites could diffuse onto the unsaturated Ni2+ sites to form NH3 as well. The combined results make this hybrid a tandem catalyst with dual active sites for the catalysis of nitrate-to-ammonia conversion with improved Faradaic efficiency at lower overpotentials.

Optimization of the fermentation media and growth conditions of Bacillus velezensis BHZ-29 using a Plackett-Burman design experiment combined with response surface methodology.

Introduction: Bacillus velezensis occurs extensively in the soil environment. It produces a range of antimicrobial compounds that play an important role in the field of biological control. However, during the actual application process it is often affected by factors such as the medium formulation and fermentation conditions, and therefore biocontrol measures often do not achieve their expected outcomes. Methods: In this study, the B. velezensis BHZ-29 strain was used as the research object. The carbon and nitrogen sources, and inorganic salts that affect the number of viable bacteria and antibacterial potency of B. velezensis BHZ-29, were screened by a single factor test. A Plackett-Burman design experiment was conducted to determine the significant factors affecting the number of viable bacteria and antibacterial potency, and a Box-Behnken design experiment was used to obtain the optimal growth of B. velezensis BHZ-29. The medium formula that produced the highest number of viable bacteria and most antibacterial substances was determined. The initial pH, temperature, amount of inoculant, liquid volume, shaking speed, and culture time were determined by a single factor test. The factors that had a significant influence on the number of viable bacteria of B. velezensis BHZ-29 were selected by an orthogonal test. A Box-Behnken design experiment was conducted to obtain the optimal fermentation conditions, and highest number of viable bacteria and antibacterial titer. Results: Molasses, peptone, and magnesium sulfate had significant effects on the viable count and antibacterial titer of B. velezensis BHZ-29. The viable count of B. velezensis BHZ-29 increased from 7.83 × 109 to 2.17 × 1010 CFU/mL, and the antibacterial titer increased from 111.67 to 153.13 mm/mL when the optimal media were used. The optimal fermentation conditions for B. velezensis BHZ-29 were as follows: temperature 25.57°C, pH 7.23, culture time 95.90 h, rotation speed 160 rpm, amount of inoculant 2%, and liquid volume 100 ml. After the optimization of fermentation conditions, the number of viable bacteria increased to 3.39 × 1010 CFU/mL, and the bacteriostatic titer increased to 158.85 mm/ml.The plant height and leaf number of cotton plants treated with BHZ-29 fermentation broth were higher than those of cotton inoculated with Verticillium dahliae. The number of bacteria was 1.15 × 107 CFU/g, and the number of fungi was 1.60 × 105 spores/g. The disease index of the cotton seedlings treated with the optimized fermentation broth was 2.2, and a control effect of 93.8% was achieved. B. velezensis BHZ-29 could reduce the disease index of cotton Verticillium wilt and had a controlling effect on the disease. The best effect was achieved in the treatment group with an inoculation concentration of 2 × 108 CFU/ml, the disease index was 14.50, and a control effect of 84.18% was achieved. Discussion: The fermentation process parameters of the number of viable bacteria and antibacterial titer by strain B. velezensis BHZ-29 were optimized to lay a foundation for the practical production and application of strain B. velezensis BHZ-29 in agriculture.