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West Nile virus (WNV), a small, positive sense, single stranded RNA virus continues to encroach into new locales with emergence of new viral variants. Neurological disease in the equine can be moderate to severe in the face of low to undetectable virus loads. Physical methods of virus enrichment may increase sensitivity of virus detection and enhance analysis of viral diversity, especially for deep sequencing studies. However, the use of these techniques is limited mainly to non-neural tissues. We investigated the hypothesis that elimination of equine brain RNA enhances viral detection without limiting viral variation. Eight different WNV viral RNA enrichment and host RNA separation methods were evaluated to determine if elimination of host RNA enhanced detection of WNV and increase the repertoire of virus variants for sequencing. Archived brain tissue from 21 different horses was inoculated with WNV, homogenized, before enrichment and separation. The protocols utilized combinations of low-speed centrifugation, syringe filtration, and nuclease treatment. Viral and host RNA were analyzed using real-time PCR targeting the WNV Envelope (E) protein and equine G3PDH to determine relative sensitivity for WNV and host depletion, respectively. To determine the effect of these methods on viral variation, deep sequencing of the E protein was performed. Our results demonstrate that additional separation and enrichment methods resulted in loss of virus in the face of host RNA depletion. DNA sequencing showed no significant difference in total sequence variation between the RNA enrichment protocols. For equine brain infected with WNV, direct RNA extraction followed by host RNA depletion was most suitable. This study highlights the importance of evaluating viral enrichment and separation methods according to tissue type before embarking on studies where quantification of virus and viral variants is essential to the outcome of the study.

Cardiac biomarkers are being increasingly applied in pediatric populations, including those with cardiogenic and non-cardiogenic myocardial injury disease. The upper reference limits of biomarkers are an important reference for disease diagnosis and health evaluation. However, the upper reference limits of pediatric cardiac biomarkers remains unknown. A total of 1,797 serum samples were collected prospectively from healthy respondents aged 0 to 18 years old. These samples were analyzed using Roche cobas e411 to determine the concentrations of hs-cTnT, CK-MB mass, and NT-proBNP. The upper reference limits and 90% confidence interval were calculated according to Clinical and Laboratory Standards Institute C28- A3 guidelines. The study successfully established the upper reference limits for hs-cTnT, CK-MB mass, and NT-proBNP in healthy children and adolescents aged 0 to 18. The hs-cTnT, CK-MB mass, and NT-proBNP levels were visibly higher in neonatal serum. With the increase in age, hs-cTnT, CK-MB mass, and NT-proBNP decline gradually. They decrease quickly in the first year after birth and decrease slowly after 1 year old. Gender differences were observed in the concentrations of hs-cTnT and CK-MB mass among healthy children and teenagers aged 10 to 18 and 13 to 18. Specifically, boys had relatively higher concentrations of hs-cTnT and CK-MB mass. However, no gender difference was found in NT-proBNP concentration. The concentrations of hs-cTnT, CK-MB mass, and NT-proBNP were simultaneously tested in healthy Chinese children for the first time. The specific upper reference limits of age and gender in pediatrics were established. The results provide comprehensive references for medical institutions specializing in children's healthcare, which are conducive to preliminary screening, diagnosis, and treatment of pediatric cardiovascular diseases., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The tumor immunosuppressive microenvironment (TME) induced by incomplete radiofrequency ablation (iRFA) in hepatocellular carcinoma (HCC) is a critical driver of tumor progression and metastasis. Herein, we proposed a therapeutic strategy aimed at remodeling the post-iRFA TME by targeting exosome biogenesis, secretion, and PD-L1 expression, thereby rejuvenating cytotoxic T lymphocyte function to mitigate the progression and metastasis of HCC. Leveraging the versatile properties of polydopamine nanomodulators, we have engineered a tailored delivery platform for GW4869 and amlodipine (AM), enabling precise and tumor-specific release of these therapeutic agents. Initially, GW4869, a neutral sphingomyelinase inhibitor, synergized with AM, an intracellular calcium modulator, to suppress exosome biogenesis and secretion. Subsequently, AM triggered the autophagic degradation of PD-L1. In vitro and in vivo experiments demonstrated that this synergistic approach significantly enhanced the robust activation and proliferation of various functional T-cell subsets following iRFA, particularly CD8 + T cells, IFN-γ + CD8 + cytotoxic T cells, natural killer cells, and innate lymphoid cells. Concurrently, it effectively reduced the infiltration of immunosuppressive cell types, including regulatory T cells and myeloid-derived suppressor cells. This favorable remodeling of the TME substantially inhibited the progression and metastasis of HCC post-iRFA. Collectively, our study presented a promising paradigm for enhancing HCC treatment efficacy by integrating radiofrequency ablation with advanced immune modulation strategies.

Hematoma and secondary neuroinflammation continue to pose a significant challenge in the clinical treatment of intracerebral hemorrhage (ICH). This study describes a nanoregulator formed through the self-assembly of Mg 2+ and signal regulatory protein α (SIRPα) DNAzyme (SDz), aimed at enhancing hematoma resolution and inhibiting neuroinflammation in the treatment of ICH. The structure of SDz collapses in response to the acidic endo/lysosomal microenvironment of microglia, releasing Mg 2+ and the SIRPα DNAzyme. The Mg 2+ then acts as a cofactor to activate the SIRPα DNAzyme. By blocking the CD47-SIRPα signaling pathway, microglia can rapidly and effectively phagocytose red blood cells (RBCs), thereby promoting the clearance of the hematoma. Simultaneously, Mg 2+ reset the microglia to the M2 phenotype by inhibiting the MYD88/MAPK/NF-κB signaling pathway, thereby modulating the inflammatory microenvironment of ICH. This co-delivery and synergistic strategy resulted in a significant reduction in hematoma size, decreasing from 11.90 to 5.84 mm 3 , and promoted recovery from ICH with minimal systemic side effects. This simple yet highly effective nanoplatform, which involves complex synergistic mechanisms, proves to be effective for ICH therapy and holds great promise for introducing novel perspectives into clinical and translational approaches for ICH., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

With increasing life spans, breast cancer (BC) survivors may face the possibility of developing second primary cancer (SPC), which can considerably shorten survival. Lung cancer (LC) is a common SPC among BC survivors. This study explored the association between these two cancers through Mendelian randomization (MR) analysis. A bidirectional two-sample MR analysis was conducted with BC genome-wide association study (GWAS) data from the Breast Cancer Association Consortium (BCAC) included 228,951 individuals and the GWAS summary statistics from the Transdisciplinary Research in Cancer of the Lung (TRICL) of LC included 112,781 individuals. The IVW method and MR-RAPS method showed a causal effect of overall BC on lung adenocarcinoma (LUAD) (IVW: OR = 1.060, 95% CI = 1.008-1.116, P = 0.024; MR-RAPS: OR = 1.059, 95% CI = 1.005-1.116, P = 0.033), which indicated that patients with BC had an increased risk of LUAD. However, there is no strong evidence for a causal effect of LUAD on BC. Our study revealed a causal effect of BC on second primary LUAD, suggesting that we should intensify screening for second primary LC in BC survivors. Early intervention and treatment for patients with second primary LC are needed to reduce mortality in BC survivors., (© 2024. The Author(s).)

Radiofrequency ablation (RFA) therapy for hepatocellular carcinoma (HCC) suffers from incomplete ablation with tumor remnants, recurrence, and metastasis. To capture these matters, a calcium-based thermosensitizer (CBT) was constructed, which can swell the thermal ablation treatment. DMXAA was encapsulated within CaCO 3 nanoparticles and surface-modified using PEG. DMXAA @CBTNps emanates continuous cavitation to enhance the RFA effect, lower RFA power, and shorten the RFA time by responding to the acidic tumor microenvironment and releasing carbon dioxide bubbles. Ca 2+ deposition to form calcification instigates the calcium death of the tumor and strengthens the thermal conductivity, wherein CBT fortifies the immunogenic cell death (ICD) of RFA. The vascular disruptor DMXAA is administered to the tumor site to impair the blood and nutrient supply to the tumor tissue. Calcium carbonate nanoparticles generate persistent carbon dioxide bubbles within the acidic microenvironment, leading to a sustained cavitation effect that enhances magneto-thermal conversion. This synergistic approach facilitates tumor vascular occlusion, thereby improving thermal ablation therapy. This strategy is different from previous thermal ablation treatments in that the CBT-released product Ca 2+ , the continuous cavitation effect of CO 2 , and the vascular disrupting agent can accelerate the conversion of energy from electromagnetic energy to thermal energy and reduce the heat loss, which significantly amplifies the effect of thermal ablation treatment of HCC and intensifies ICD. Therefore, this research provides a promising avenue and therapeutic platform for clinical liver cancer treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Inclusion body hepatitis (IBH) induced by fowl adenovirus serotype 8b (FAdV-8b) infection is an important avian infectious disease circulating around the globe, posing significant losses to the poultry industry. In this study, a FAdV-8b strain, CH/SDQD/2021, was isolated from IBH-affected chickens in Shandong province, China and the genetic properties of CH/SDQD/2021 were characterized. The full genome length of CH/SDQD/2021 is 44,000 bp, with a G+C content of 58 % and 32 open reading frames (ORF). Sequencing alignment and phylogenetic analysis indicated that the genome identity of CH/SDQD/2021 compared to 30 other FAdV-E strains retrieved from GenBank ranges from 89.72 % to 96.71 %. Animal regression test indicated that CH/SDQD/2021 infection induced IBH in one-week-old SPF chickens. Subsequently, a reverse genetic system was developed to facilitate rapid genome manipulation of FAdV-8b for gene function study and vaccine development. To explore potential foreign gene insertion sites in FAdV-8b, ORF0-1-2, ORF11 and ORF19 of CH/SDQD/2021 were substituted by the green fluorescent gene ZsGreen, respectively, and the corresponding recombinant viruses were successfully rescued. The results showed that comparing with the parental FAdV-8b, the replication efficiency of the ORF0-1-2-substituted recombinant was reduced, while the replication efficiency of the ORF11-substituted recombinant was promoted. The findings of this study enrich the epidemiological data for the prevalent FAdV strains in China. Furthermore, the establishment of the FAdV-8b reverse genetic system will provide an efficient technique platform for FAdV-8b gene function research at the whole virus level and developing related multivalent vaccine candidates., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Streptococcus pneumoniae (S. pneumoniae) is a major cause of community-acquired pneumonia. Current standard clinical therapies mainly focus on combating S. pneumoniae through antibiotics. However, the limited delivery of antibiotics and the undetoxified hydrogen peroxide (H 2 O 2 ) virulence factor secreted by S. pneumoniae impede the therapeutic outcomes. Here we report an inhalable catalase (CAT)-tannic acid (TA) nanoassembly for local antibiotic (levofloxacin) delivery and simultaneously neutralizing the secreted H 2 O 2 virulence factors to treat pneumococcal pneumonia. After aerosol inhalation, the inhalable formulation (denoted as CT@LVX) effectively accumulates in lung tissues through TA-mediated mucoadhesion. CAT can reduce alveolar epithelial cells apoptosis by catalyzing the decomposition of accumulated H 2 O 2 in the infected lung tissues. In synergy with antibiotic LVX-mediated S. pneumoniae elimination, CT@LVX significantly decreases lung injury companied with reduced inflammatory, resulting in 100 % survival of mice with pneumonia. In a clinically isolated S. pneumoniae strain-induced pneumonia mouse model, CT@LVX also shows superior outcomes compared to the traditional antibiotic treatment, highlighting its potential clinical application prospects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

As the preferred anode material for sodium-ion batteries, hard carbon (HC) confronts significant obstacles in providing a long and dominant low-voltage plateau to boost the output energy density of full batteries. The critical challenge lies in precisely enhancing the local graphitization degree to minimize Na + ad-/chemisorption, while effectively controlling the growth of internal closed nanopores to maximize Na + filling. Unfortunately, traditional high-temperature preparation methods struggle to achieve both objectives simultaneously. Herein, a transient sintering-involved kinetically-controlled synthesis strategy is proposed that enables the creation of metastable HCs with precisely tunable carbon phases and low discharge/charge voltage plateaus. By optimizing the temperature and width of thermal pulses, the high-throughput screened HCs are characterized by short-range ordered graphitic micro-domains that possess accurate crystallite width and height, as well as appropriately-sized closed nanopores. This advancement realizes HC anodes with significantly prolonged low-voltage plateaus below 0.1 V, with the best sample exhibiting a high plateau capacity of up to 325 mAh g -1 . The energy density of the HC||Na 3 V 2 (PO 4 ) 3 full battery can therefore be increased by 20.7%. Machine learning study explicitly unveils the "carbon phase evolution-electrochemistry" relationship. This work promises disruptive changes to the synthesis, optimization, and commercialization of HC anodes for high-energy-density sodium-ion batteries., (© 2024 Wiley‐VCH GmbH.)

The misuse of antibiotics may contaminate the environment and cause harm to human health. Therefore, rapid and accurate detection of antibiotics is essential. In this study, a novel electrochemiluminescence resonance energy transfer (ECL-RET) pair was designed using a new ECL emitter (CPM, Ce-TBAPy) as the donor and Co-MOF@AuPt as the acceptor. Moreover, a highly sensitive and specific "on-off-on" ECL aptasensor was constructed for detecting sulfadiazine (SDZ). The aptasensor exhibited a broad linear range (from 10.0 fg mL -1 to 100 ng mL -1 ) for the SDZ concentration, with limit of detection and limit of quantification values of 1.14 fg mL -1 and 3.75 fg mL -1 , respectively. The aptasensor achieved good results in spiking experiments with milk and egg samples, and successfully quantified SDZ in fish meal quality control sample. The prepared aptasensor presents great potential for food and environmental safety by detecting antibiotics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Development of simple solid-phase electrochemiluminescence (ECL) immunosensor with convenient fabrication for high-performance detection of tumor biomarkers is crucial. Herein, a solid-phase ECL immunoassay was constructed based on a bipolar silica nanochannel film (bp-SNA) modified electrode for highly sensitive detection of carbohydrate antigen 125 (CA 125). Inexpensive and readily available indium tin oxide (ITO) electrode was used as the supporting electrode for the growth of bp-SNA. bp-SNA consists of a bilayer SNA film with different functional groups and charge properties, including negatively charged inner layer SNA (n-SNA) and positively charged outer layer SNA (p-SNA). The nanochannels of bp-SNA were used for the immobilization of ECL emitter tris(bipyridine)ruthenium(II), while the outer surface was utilized for constructing the immunorecognition interface. Due to the dual electrostatic interaction composed of electrostatic attraction from n-SNA and electrostatic repulsion from p-SNA, ECL emitter could be stably confined within bp-SNA, providing stable and high ECL signals to the modified electrode. After amino groups on the outer surface of bp-SNA were derivatized with aldehyde groups, recognition antibodies could be covalently immobilized, and an immunosensor was obtained after blocking nonspecific sites. When CA 125 binds to the antibodies on the recognition interface, the formed complex reduces the diffusion of the co-reactant tripropylamine (TPrA) to the supporting electrode, decreasing the ECL signal. Based on this mechanism, the constructed immunosensor can achieve sensitive ECL detection of CA 125. The linear detection range is from 0.01 to 100 U/mL, with a detection limit of 4.7 mU/mL. CA 125 detection in serum is also achieved. The construction immunosensor has advantages including simple and convenient fabrication, high stability of the immobilized emitter, and high selectivity, making it suitable for CA 125 detection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lu, Wu, Luo, Liu, Xi and Zhang.)

Background: In recent years, the incidence of pelvic fractures has been on the rise, predominantly affecting the elderly population. Deep vein thrombosis may lead to poor prognosis in patients. monocyte-to-lymphocyte ratio is novel biomarkers of inflammation, and this study aims to verify their predictive effect and construct the nomogram model., Method: This study used binary logistic regression analysis to predict the predictive effect of MLR on the occurrence of DVT in pelvic fractures patients. And use R studio to construct nomogram model., Result: The results showed that Age (1.04 [1.01, 1.07], p = 0.006), WBC (1.44 [1.28, 1.61], p < 0.001), and MLR (2.11 [1.08, 4.13], p = 0.029) were independent predictive factors. The nomogram demonstrated good predictive performance with small errors in both the training and validation groups, and most clinical patients could benefit from them., Conclusion: The nomogram constructed based on MLR can assist clinicians in early assessment of the probability of DVT occurrence., (© 2024. The Author(s).)

Background: Acute compartment syndrome(ACS) is a perilous consequence of trauma. Acute compartment syndrome's precise cause is yet unknown. We performed studies to confirm that acute compartment syndrome can be relieved by suppressing ferroptosis and activating the Nrf2/Hmox1 pathway., Methods: We generated an ACS rat model and we conducted next-generation sequencing(NGS) of skeletal muscle tissue and identified differentially expressed target genes. Ultimately, we performed in vivo experiments to validate the presence of ferroptosis and the Nrf2/Hmox1 pathway in ACS rats. After the minocycline intervention, the drug was evaluated for its effects on ACS by examining changes associated with ferroptosis., Results: The bioinformatics analysis identified that the genetic changes in the disease were mostly focused on ferroptosis, with noticeable modifications in Nrf2/Hmox1. Based on the in vivo results, it was observed that ACS rats exhibited significantly elevated levels of ferroptosis compared to the control rats. The suppression of the Nrf2/Hmox1 pathway mediated by minocycline improves outcomes in ACS and reduces tissue damage after intervention., Conclusion: Minocycline hinders ferroptosis via stimulating the Nrf2/Hmox1 pathway, which slows down the advancement of acute compartment syndrome., (© 2024. The Author(s).)

Long-term atmospheric nitrogen (N) deposition has been known to enhance plant productivity by increasing available N in terrestrial ecosystems. However, the response of carbon process to N deposition in terrestrial ecosystems remains unclear, particularly about different climate regions and biomes. In this study, we synthesized 1281 pairwise observations from 218 published articles on experimental N addition globally, aiming to quantify the responses of the carbon process and its mechanisms to N addition. Our results revealed a significant overall increase in net ecosystem productivity (NEP) by 31.42 % following N addition treatment, owing to increased aboveground net primary productivity (ANPP, 16.46 %), belowground net primary productivity (BNPP, 27.74 %), and reduced soil respiration (R s , -2.56 %), soil heterotrophic respiration (R h , -6.24 %). Furthermore, the effects of N addition on NEP varied with biomes and climate regions. The positive effect of N addition on NEP was more pronounced in arid regions (28.67 %) compared to humid regions (21.92 %), primarily driven by a higher increase in vegetation productivity. Additionally, N addition exhibited a higher increase in NEP (33.95 %) in forest compared to grassland (31.80 %), resulting from a more reduction in respiratory processes. However, the positive effects of N addition on NEP diminished with increasing experimental duration. Furthermore, ANPP and BNPP displayed a convex relationship with N addition rates, with the optimum BNPP addition rate exceeding that of ANPP. In contrast, R s exhibited a concave response to addition rates. These findings suggest that carbon sink in terrestrial ecosystems could be enhanced under future atmospheric N deposition, especially in arid regions and forest ecosystems. Our study provided insight for predicting how N deposition influences terrestrial ecosystem carbon process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Household air purifiers are widely used to enhance indoor air quality. However, limited information exists regarding the factors that influence their long-term performance. This study investigates the impact of various residential environments on the long-term efficacy of air purifiers. We deployed household air purifiers in three distinct environments: oily fumes (Group A), non-oily fumes (Group C), and a mixture of oily and non-oily fumes (Groups B-I and B-II). The selected air filter consisted of melt-blown polypropylene and activated carbon, materials commonly employed in commercial applications. The results demonstrated that the control efficiency of air purifiers in non-oily fume environments surpassed that in oily fume environments. After 12 months of operation, particulate matter (PM) concentrations rose by 92.7% and 76.5% in oily and non-oily fume environments, respectively. This increase was primarily attributed to the loss of electrostatic attraction in the polypropylene material due to the organic matter in oily particulate matter. After operating for 1000 h, the clean air delivery rate (CADR) attenuation rates for particulate matter were 70.6%, 19.9%, 16.7%, and 12.5% in Groups A, B-I, B-II, and C, respectively. The CADR attenuation rates for formaldehyde were 80.6%, 48.4%, 38.9%, and 37.3% in the same groups. Additionally, we developed a real-time prediction model for the service life of air purifiers using data from online sensors. When operated for 12 h daily at varying PM concentrations, the filters had an expected service life of 29-97 days in non-oily fume environments and 66-220 days in oily fume environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Accurate measurements are critical for timely early warning and effective prevention of epidemics due to the continuing impact of bioaerosols on human health. In recent years, researchers have been focused on developing and calibrating online monitoring instruments. However, there is still a lack of laboratory-generated standard aerosol samples suitable for calibration. Therefore, in this study, we utilized a self-developed Ink Jet Aerosol Generator (H-IJAG) to achieve controllable generation of monodisperse aerosol standard particles. The Aerosol Particle Size Spectrometer (APSS, TOPAS 323) was employed as the particle detector. The diameter of the droplet was calculated by measuring the projected area of the droplet in the same image using Image-J software. Experimental results demonstrated that under standardized inkjet parameters, H-IJAG exhibited good reliability and reproducibility, and generated solid particles within (0.4-15) μm. To better simulate the laser-induced fluorescence emission properties of ambient bioaerosol, tryptophan (Trp) and 7-hydroxycoumarin-4-acetic acid (7-HCA) were selected as solutes of the laboratory-generated aerosol samples, which are known bio-fluorescent materials. According to the law of propagation of uncertainty, the relative uncertainty of the volume equivalent diameter of Trp and 7-HCA solid particles by H-IJAG were 0.42 %, while the relative uncertainty of the particle number concentrations of Trp and 7-HCA solid particles generated by H-IJAG were 1.4 %. This optimized IJAG technique provides a promising solution for the accurate calibration of bioaerosol monitors., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our works, and there is no professional or other personal interest of any nature or kind in any product, service, and/or company that could be construed as influencing the position presented in, or the review of, the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Electron transfer flavoprotein (ETF) plays an important function in fatty acid beta oxidation and the amino acid metabolic pathway. It can provide pathogenicity to some opportunistic fungi via modulating cellular metabolite composition. Arthrobotrys oligospora is a typical invasion fungus to nematodes. Its ETF characterization is still unknown. Here, we showed that the mutations of A. oligospora ETF ( Aoetfα and Aoetfβ ) and its dehydrogenase ( Aoetfdh ) led to severe defects in mitochondrial integrity and blocked fatty acid metabolism. The pathogenicity-associated trap structures were completely suppressed when exposed to nematode-derived ascarosides and nutrition signals, including ammonia and urea. Compared to the wild-type strain, the nematode predatory activity was significantly reduced and delayed. But surprisingly, the rich nutrition could restore the massive trap and robust predatory activity in the mutant Aoetfβ beyond all induction cues. Moreover, the deletion of Aoetfβ has led to the accumulation of butyrate-like smell, which has a strong attraction to Caenorhabditis elegans nematodes. Ultimately, ETF and its dehydrogenase play a crucial role in nematode-trapping fungi, highlighting mitochondrial metabolite fluctuations that are connected to pathogenesis and further regulating the interactions between fungi and nematodes.

The restoration of alpine grasslands has garnered significant attention across various sectors. Historically, natural restoration has been the primary approach for grassland recovery, characterized by its prolonged duration. To expedite the recovery of degraded grasslands, it is essential to identify the limiting factors of restoration, enabling efficient and rapid recovery. Appropriate nitrogen (N) addition levels have been considered a potential strategy to enhance the recovery of grassland ecosystems and augment their ecological benefits. However, the effectiveness of N addition in alpine grassland restoration remains debated. This study investigated the impact of five N addition levels (CK: control [0 g/m 2 ]; LN: low N [5 g/m 2 ]; MN: medium N [10 g/m 2 ]; HN: high N [15 g/m 2 ]; SN: severe N [20 g/m 2 ]) and two experimental approaches (N addition once per year [NPY] and three times per year [NTY] at the same dosages) on plant and soil properties and the maximum restoration capacity of alpine meadows. Our findings reveal three key insights: The level of N addition was the primary factor influencing aboveground plant biomass and coverage. Plant diversity decreased under the NTY regime and increased with NPY in the Bayinbruck grassland. N addition significantly altered soil properties, including pH, salinity, soil organic carbon (SOC), soil-available phosphorus (AP), and soil total phosphorus (TP). Notably, soil TP, total nitrogen (TN), and AP substantially impacted plant community structure and diversity. Based on structural equation model (SEM) and analysis of variance (ANOVA), optimal grassland restoration was achieved with the HN (15 g/m 2 ) treatment under NPY and the MN and HN (10 and 15 g/m 2 ) treatments under NTY. Overall, our study offers crucial insights into the conservation, management, and restoration of grassland ecosystems on the Bayinbruck Plateau. It underscores the significance of N addition effects on plant communities, vegetation restoration, and soil properties., Competing Interests: All authors disclosed no relevant relationships., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Pollen development and germination are critical for successful generation of offspring in plants, yet they are highly susceptible to heat stress (HS). However, the molecular mechanism underlying this process has not been fully elucidated. In this study, we highlight the essential roles of two mRNA capping enzymes, named Arabidopsis mRNA capping phosphatase (ARCP) 1 and 2, in regulating male and female gamete development. The transmission efficiencies of gametes carrying arcp1 arcp2 from arcp1 +/- arcp2 -/- and arcp1 -/- arcp2 +/- mutants are 30% and zero, respectively. These mutants exhibited a significant increase in misshaped pollen, with germination rates approximately half of those in wild type. ARCP1/2 exhibit RNA triphosphatase and RNA guanylyltransferase activities, which are required for proper pollen development. Through RNA-seq analysis, genes involved in pollen development/germination and HS response were identified as downregulated genes in pollen from arcp1 +/- arcp2 -/- mutant. Furthermore, ARCP2 protein is degraded under HS condition, and inducing the expression of ARCP2 can increase the pollen germination rate under elevated temperature. We propose that HS triggers the degradation of mRNA capping enzymes, which in turn disrupts the transcriptome that required for pollen development and pollen germination and ultimately leads to male sterility., (© 2024 John Wiley & Sons Ltd.)

G-quadruplexs (G4s), four-stranded nucleic acid secondary structures, which formed by guanine-rich sequences play a vital role in human biological systems. Studies have shown that the formation of G4s is closely related to tumor development and apoptosis, which is considered as a new target for the development of anti-tumor drugs. Therefore, it is important to develop novel probes for G4s imaging. In this article, we engineered a near-infrared fluorescent probe (TOH) which can be activated by DNA G4s in living cells and tumor. TOH exhibits high selectivity to the structure of DNA G4s with the limit of detection for DNA G4s (Mito-0.5-2) is calculated to be 0.43 nM. Imaging studies of different cell lines revealed that the brighter fluorescence in cancer cell lines than in normal, indicating that DNA G4s maybe highly express in tumor cell lines. Simultaneously, TOH is also introduced into live tumor tissue imaging and found that the fluorescence intensity of tumor is the brightest relative to normal tissue, further validating the high expression of DNA G4s structures in tumor tissue. These features demonstrate TOH not only have the ability to image DNA G4 structures in real time, but also may have tumor diagnostic capabilities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: sarcopenia, typified by the progressive diminution of skeletal muscle mass and functionality, represents a substantial public health challenge, particularly among the geriatric population. Dietary intake, as a modifiable determinant, has elicited considerable interest due to its prospective role in preventing and alleviating sarcopenia., Methods: this investigation employed Mendelian randomization (MR) analysis, a robust statistical method, to investigate the causal associations between dietary consumption and sarcopenia-associated phenotypes, including appendicular lean mass (ALM), hand grip strength, and walking pace. Genetic variants extracted from the extensive UK Biobank cohort served as instrumental variables for a comprehensive set of 26 dietary elements., Results: our MR analysis unveiled that the ingestion of oily fish and cheese was significantly correlated with augmented ALM, diminished risk of low hand grip strength, and enhanced walking pace. In addition, cooked vegetables, fresh fruit, dried fruit, cereal, and raw vegetables were protective of one or both of the sarcopenia-associated phenotypes. These findings were robust to potential confounding influences owing to the sophisticated MR design., Conclusions: our results underscore that specific dietary constituents play a pivotal protective role against sarcopenia, underscoring the necessity for tailored nutritional strategies to bolster muscle health in the elderly. Further investigations are requisite to corroborate these findings across heterogeneous populations and to unravel the underlying biological mechanisms.

Benzophenone skeletons containing a carbonyl unit (O=C) have been widely used as electron acceptors in the thermally activated delayed fluorescence (TADF) materials. Herein, we present a novel molecular design concept for TADF materials by transitioning from a carbonyl to an amide (O=C-N) skeleton as the acceptor. The amide unit, compared to its carbonyl counterpart, offers a more stable electronic configuration. Leveraging this insight, we have developed a series of high-performance TADF molecules based on benzoyl carbazole and carbazoline acceptors. These molecules exhibit exceptionally small singlet-triplet energy gaps and pronounced aggregation-enhanced emission properties, achieving photoluminescence quantum yields in neat films as high as 99 %. Consequently, these materials serve as efficient emitters in non-doped organic light-eimtting diodes (OLEDs), reaching a maximum quantum efficiency (EQE max ) of up to 26.0 %, significantly higher than the 17.0 % obtained with benzophenone acceptor-based TADF molecules. Additionally, they have been used as TADF hosts in narrowband red fluorescent OLEDs, setting a record-high EQE max of 22.4 %., (© 2024 Wiley-VCH GmbH.)

Cancer poses a major threat to human health worldwide. The development of anti-tumor materials provides new modalities for cancer diagnosis and treatment. In this review, we comprehensively summarize the research progress and clinical applications of anti-tumor materials. First, we introduce the etiology and pathogenesis of cancer, and the significance and challenges of anti-tumor materials research. Then, we classify anti-tumor materials and discuss their mechanisms of action. After that, we elaborate the research advances and clinical applications of anti-tumor materials, including those targeting tumor cells and therapeutic instruments. Finally, we discuss the future perspectives and challenges in the field of anti-tumor materials. This review aims to provide an overview of the current status of anti-tumor materials research and application, and to offer insights into future directions in this rapidly evolving field, which holds promise for more precise, efficient and customized treatment of cancer., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Inflammatory bowel diseases (IBD) are often associated with dysregulated gut microbiota and excessive inflammatory microenvironment. Probiotic therapy combined with inflammation management is a promising approach to alleviate IBD, but the efficacy is hindered by the inferior colonization of probiotics in mucus-depleted inflammatory bowel segments. Here, we present modified montmorillonite armed probiotic Escherichia coli Nissle 1917 (MMT-Fe@EcN) with enhanced intestinal colonization and hydrogen sulfide (H 2 S) scavenging for synergistic alleviation of IBD. The montmorillonite layer that can protect EcN against environmental assaults in oral delivery and improve on-site colonization of EcN in the mucus-depleted intestinal segment due to its strong adhesive capability and electronegativity, with a 22.6-fold increase in colonization efficiency compared to EcN. Meanwhile, MMT-Fe@EcN can manage inflammation by scavenging H 2 S, which allows for enhancing probiotic viability and colonization for restoring the gut microbiota. As a result, MMT-Fe@EcN exhibits extraordinary therapeutic effects in the dextran sulfate sodium-induced mouse colitis models, including alleviating intestinal inflammation and restoring disrupted intestinal barrier function, and gut microbiota. These findings provide a promising strategy for clinical IBD treatment and potentially other mucus-depletion-related diseases., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Acenaphthylene-containing polycyclic aromatic hydrocarbons (AN-PAHs) are noteworthy structural motifs for organic functional materials due to their non-alternant electronic structure, which increases electron affinity. However, the synthesis of AN-PAHs has traditionally required multiple sequential synthetic steps, limiting structural diversity. Herein, we present a tandem C-H penta- and hexaannulation reaction of aryl alkyl ketone with acetylenedicarboxylate. This integrated approach enhances overall efficiency and selectivity, marking a significant advancement in AN-PAH synthesis. Mechanistic studies unveil an orchestrated extension of five- and six-membered rings through C-H activation-annulation and Diels-Alder reaction. Additionally, the tandem annulation reaction can be performed stepwise, further validating the proposed mechanism and increasing the structural diversity of AN-PAHs., (© 2024. The Author(s).)

Ischemic stroke is a devastating disease and one of the leading causes of mortality worldwide. Overproduction of reactive oxygen species and inflammatory response contribute to secondary damage following ischemic insult. Nanozymes with robust anti-oxidative stress properties possess therapeutic possibility for ischemic insult. However, insufficiency of nanozyme accumulation in the neuronal mitochondria hindered their application. Herein, we constructed polydopamine-coated Prussian blue nanoparticles (PB@PDA NPs) to realize the targeting neuronal mitochondria for ischemic stroke, with the properties of antioxidant and anti-inflammation. After administration, much higher accumulation of PB@PDA NPs in the brain was observed compared to that in the PB NP group. Moreover, PB@PDA NPs effectively attenuated brain infarct than that of PB NPs in neonatal mice following hypoxia-ischemia (HI) insult. PB@PDA NPs mainly colocated with neuronal mitochondria in vivo and in vitro. Apart from attenuating oxidative stress, PB@PDA NPs also suppressed neuronal apoptosis and counteracted inflammation, which effectively promote a short- and long-term functional recovery in HI mice. Further, the therapeutic efficacy of PB@PDA NPs was also found in adult ischemic mice via tail vein injection. Collectively, these findings illustrate that PB@PDA NPs via system injection accumulate in neuronal mitochondria and are beneficial for ischemic stroke., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Yijing Zhao et al.)

Background: Allergic rhinitis (AR) is an allergic reaction dominated by the Th2 immune response in the nasal mucosa. The bacterial infection process affects the balance between Th1 and Th2 immune responses, and the level of exposure to environmental flora is closely related to the development of AR. Hydrogen (H 2 ) is a medical molecule with anti-inflammatory and antioxidant properties. This study aimed to explore the possible mechanism of action of H 2 on AR through its ability to regulate the balance of nasal flora., Methods: Serum eosinophil count (EOS), immunoglobulin E (IgE) concentration, visual analog scale (VAS), total nasal symptom score (TNSS), and rhinoconjunctivitis quality of life questionnaire (RQLQ) were observed before and after hydrogen inhalation in AR patients. Skin prick test (SPT) was used to determine allergen sensitisation. Community composition and relative abundance of nasal flora were examined before and after hydrogen inhalation and in normal subjects using 16S rRNA gene sequencing., Results: There were no adverse reactions during and after hydrogen inhalation in AR patients, with a favorable safety profile and significant improvements in VAS, TNSS, EOS, and IgE (P < 0.05). Cavity flora 16S rRNA gene sequencing showed higher abundance of Ruminococcus and Erysipelotrichaceae flora in the nasal cavity of AR patients than in normal subjects, and their abundance could be down-regulated after H 2 inhalation. H 2 significantly increased the abundance of Blautia&#95;faecis and negatively correlated with VAS, TNSS, EOS, and IgE., Conclusions: H 2 may improve symptoms in AR patients by modulating the distribution of nasal flora. Trials with larger sample sizes are required to further test this hypothesis., Trial Registration: This trial was registered in the China Clinical Trial Registry (Registration No. ChiCTR2200062253)., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors.)

In recent years, advancements in retinal image analysis, driven by machine learning and deep learning techniques, have enhanced disease detection and diagnosis through automated feature extraction. However, challenges persist, including limited data set diversity due to privacy concerns and imbalanced sample pairs, hindering effective model training. To address these issues, we introduce the vessel and style guided generative adversarial network (VSG-GAN), an innovative algorithm building upon the foundational concept of GAN. In VSG-GAN, a generator and discriminator engage in an adversarial process to produce realistic retinal images. Our approach decouples retinal image generation into distinct modules: the vascular skeleton and background style. Leveraging style transformation and GAN inversion, our proposed hierarchical variational autoencoder module generates retinal images with diverse morphological traits. In addition, the spatially adaptive denormalization module ensures consistency between input and generated images. We evaluate our model on MESSIDOR and RITE data sets using various metrics, including structural similarity index measure, inception score, Fréchet inception distance, and kernel inception distance. Our results demonstrate the superiority of VSG-GAN, outperforming existing methods across all evaluation assessments. This underscores its effectiveness in addressing data set limitations and imbalances. Our algorithm provides a novel solution to challenges in retinal image analysis by offering diverse and realistic retinal image generation. Implementing the VSG-GAN augmentation approach on downstream diabetic retinopathy classification tasks has shown enhanced disease diagnosis accuracy, further advancing the utility of machine learning in this domain., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Benign prostatic hyperplasia (BPH) is one of the major chronic complications of type 2 diabetes mellitus (T2DM), and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH. The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients, including simple BPH patients, newly diagnosed T2DM patients, T2DM complicated with BPH patients and matched healthy individuals. The G protein-coupled estrogen receptor (GPER) inhibitor G15, GPER knockdown lentivirus, the YAP1 inhibitor verteporfin, YAP1 knockdown/overexpression lentivirus, targeted metabolomics analysis, and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH. The homeostasis of sex steroid hormone is disrupted in the serum of patients, accompanying with the proliferated prostatic epithelial cells (PECs). The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals. Elevated 17β-estradiol (E2) is the key contributor to the disrupted sex steroid hormone homeostasis, and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH. Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose (HG)-induced PECs proliferation through the formation of the YAP1-TEAD4 heterodimer. Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells. The anti-proliferative effects of verteporfin, an inhibitor of YAP1, are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells. Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Author(s).)

The 2023 Canadian forest fires have been extreme in scale and intensity with more than seven times the average annual area burned compared to the previous four decades 1 . Here, we quantify the carbon emissions from these fires from May to September 2023 on the basis of inverse modelling of satellite carbon monoxide observations. We find that the magnitude of the carbon emissions is 647 TgC (570-727 TgC), comparable to the annual fossil fuel emissions of large nations, with only India, China and the USA releasing more carbon per year 2 . We find that widespread hot-dry weather was a principal driver of fire spread, with 2023 being the warmest and driest year since at least 1980 3 . Although temperatures were extreme relative to the historical record, climate projections indicate that these temperatures are likely to be typical during the 2050s, even under a moderate climate mitigation scenario (shared socioeconomic pathway, SSP 2-4.5) 4 . Such conditions are likely to drive increased fire activity and suppress carbon uptake by Canadian forests, adding to concerns about the long-term durability of these forests as a carbon sink 5-8 ., (© 2024. The Author(s).)

Therapeutic cancer vaccines are among the first FDA-approved cancer immunotherapies. Among them, it remains a major challenge to achieve robust lymph-node (LN) accumulation. However, delivering cargo into LN is difficult owing to the unique structure of the lymphatics, and clinical responses have been largely disappointing. Herein, inspired by the Migrated-DCs homing from the periphery to the LNs, an injectable hydrogel-based polypeptide vaccine system is described for enhancing immunostimulatory efficacy, which could form a local niche of vaccine "hitchhiking" on DCs. The OVA peptide modified by lipophilic DSPE domains in the hydrogel is spontaneously inserted into the cell membrane to achieve "antigen anchoring" on DCs in vivo. Overall, OVA peptide achieves active access LNs through recruiting and "hitchhiking" subcutaneous Migrated-DCs. Remarkably, it is demonstrated that the composite hydrogel enhances LNs targeting efficacy by approximately six-fold compared to free OVA peptide. Then, OVA peptide can be removed from the cell surface under a typical acidic microenvironment within the LNs, further share them with LN-resident APCs via the "One-to-Many" strategy (One Migrated-DC corresponding to Many LN-resident APCs), thereby activating powerful immune stimulation. Moreover, the hydrogel vaccine exhibits significant tumor growth inhibition in melanoma and inhibits pulmonary metastatic nodule formation., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Core-shell tecto dendrimers (CSTDs) with excellent physicochemical properties and good tumor penetration and gene transfection efficiency have been demonstrated to have the potential to replace high-generation dendrimers in biomedical applications. However, their characterization and related biological properties of CSTDs for enhanced tumor penetration and gene delivery still lack in-depth investigation. Herein, three types of dual-responsive CSTDs are designed for thorough physicochemical characterization and investigation of their tumor penetration and gene delivery efficiency. Three types of CSTDs are prepared through phenylborate ester bonds of phenylboronic acid (PBA)-decorated generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers as cores and monose (galactose, glucose, or mannose)-conjugated G3 PAMAM dendrimers as shells and thoroughly characterized via NMR and other techniques. It is shown that the produced CSTDs display strong correlation signals between the PBA and monose protons, similar hydrodynamic diameters, and dual reactive oxygen species- and pH-responsivenesses. The dual-responsive CSTDs are proven to have structure-dependent tumor penetration property and gene delivery efficiency in terms of small interference RNA for gene silencing and plasmid DNA for gene editing, thus revealing a great potential for different biomedical applications., (© 2024 Wiley‐VCH GmbH.)

Alpha-fetoprotein (AFP) is a key marker for early cancer detection and assessment. However, the current detection methods struggle to balance accuracy with the need for decentralized medical treatment. To address this issue, a new AFP analysis platform utilizing digital image colorimetry has been developed. Functionalized gold nanoparticles act as colorimetric agents, changing from purple-red to light gray-blue when exposed to different AFP concentrations. A smartphone app captures these color changes and calculates the AFP concentration in the sample. To improve detection accuracy, a hardware device ensures uniform illumination. Testing has confirmed that this system can quantitatively analyze AFP using colorimetry. The limit of detection reached 0.083 ng/mL, and the average accuracy reached 90.81%. This innovative method enhances AFP testing by offering portability, precision, and low cost, making it particularly suitable for resource-limited areas.

Postoperative rehemorrhage following intracerebral hemorrhage surgery is intricately associated with a high mortality rate, yet there is now no effective clinical treatment. In this study, we developed a hemoglobin (Hb)-responsive in situ implantable DNA hydrogel comprising Hb aptamers cross-linked with two complementary chains and encapsulating deferoxamine mesylate (DFO). Functionally, the hydrogel generates signals upon postoperative rehemorrhage by capturing Hb, demonstrating a distinctive "self-diagnosis" capability. In addition, the ongoing capture of Hb mediates the gradual disintegration of the hydrogel, enabling the on-demand release of DFO without compromising physiological iron-dependent functions. This process achieves self-treatment by inhibiting the ferroptosis of neurocytes. In a collagenase and autologous blood injection model-induced mimic postoperative rehemorrhage model, the hydrogel exhibited a 5.58-fold increase in iron absorption efficiency, reducing hematoma size significantly (from 8.674 to 4.768 cubic millimeters). This innovative Hb-responsive DNA hydrogel not only offers a therapeutic intervention for postoperative rehemorrhage but also provides self-diagnosis feedback, holding notable promise for enhancing clinical outcomes.

Objective: This research aimed to investigate the association between the blood urea nitrogen-to-creatinine (BUN/Cr) ratio and the rate of in-hospital mortality in patients with acute ischemic stroke (AIS) and atrial fibrillation (AF), who are also receiving care in intensive care unit (ICU)., Methods: A retrospective study was conducted using the MIMIC-IV database. We collected data on BUN/Cr levels at admission for patients with AIS and concurrent AF. To assess the association between BUN/Cr and in-hospital mortality rate, statistical analysis was conducted employing multivariable logistic regression models and restricted cubic spline models. These models were utilized to investigate the potential relationship and provide insights into the impact of BUN/Cr on the likelihood of in-hospital mortality. Interaction and subgroup analyses were performed to evaluate the consistency of the correlation., Results: There were a total of 856 patients (age ≥ 18 years) with a median age of 78.0 years, of which 466 (54.4%) were female. Out of 856 patients, 182 (21.26%) died in the hospital. Upon controlling for confounding factors, the multivariable logistic regression analysis elucidated that patients falling within the third trisection (Q3 > 22.41 mg/dL) exhibited a noticeably increased susceptibility to in-hospital mortality when contrasted with their counterparts positioned in the second trisection (Q2: 17.2-22.41 mg/dL) (OR = 2.02, 95% CI: 1.26-3.26, p  = 0.004). A non-linear J-shaped relationship was observed between BUN/Cr at ICU admission and in-hospital mortality rate ( p  = 0.027), with a turning point at 19.63 mg/dL. In the threshold analysis, there was a 4% rise in in-hospital mortality for each 1 mg/dL increase in BUN/Cr (OR: 1.04, 95% CI: 1.01-1.06, p  = 0.012)., Conclusion: In patients with AIS complicated by AF, BUN/Cr at admission shows a J-shaped correlation with in-hospital mortality rate. When BUN/Cr exceeds 19.63 mg/dL, the in-hospital mortality rate increases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Li, Meng, Yang, Tian, Song and Liu.)

Innovative products entering the market will cause dynamic changes in market demand, and consumers' purchase regret and their return behavior make the market environment more and more complex, which in turn affects the dynamic decision-making in the supply chain. In this paper, under the situation of discrete decision time, combining with the objective reality, we make discrete modification to the classical Bass diffusion model (Bass model), construct a manufacturer-led, retailer-followed supply chain differential game model, analyze the optimal decision-making of the manufacturer and the retailer by combining with the theory of discrete optimal control, and then verify the conclusions by numerical simulation. The results show that: when retailers purchase directly from the manufacturer and sell in the market, the optimal pricing of the innovative product can make the supply chain as a whole, realizing Pareto optimality; consumer's purchase regret will increase the amount of returns, which will lead to the decrease of product sales and the profits of the manufacturer and the retailer; when the innovative product accounts for a different share of the market, the impact of purchase regret on the wholesale price and the retail price are also different. Therefore, manufacturers need to have an extensive comprehension of the market to minimize the negative effects of consumer regret and returns, and to formulate a reasonable pricing strategy for their products to gain as much profit as possible., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

An important concern is the availability of clean drinking water, which is an essential need for human survival. This issue arises due to the existence of hazardous micropollutants originating from various emission sources. Nanotechnology aids in the mitigation of micropollutants by assimilating and counteracting their effects, hence diminishing their influence on water and other ecosystems. The study investigates the relationship between nanotechnological progress, the adoption of renewable energy, environmental consequences, and economic growth in China, using the Environmental Kuznets Curve theory as a conceptual framework. The study employs panel cointegration tests to analyze structural breaks from 2000 to 2020. Nanotechnology is expected to reduce environmental degradation and the presence of micro-pollutants by increasing the use of renewable energy and promoting energy conservation. Nanotechnology is crucial for mitigating micro-pollutants and advancing sustainable development in this specific context. However, the literature also highlights the harmful consequences of nanoparticle emissions caused by nanotechnology on human and environmental health for a long duration, requiring more examination. This research is the first empirical inquiry into the relationship between improvements in nanotechnology, the use of renewable energy, economic growth, and ecological effect, all within the context of the Environmental Kuznets Curve theory. The results confirm the successful incorporation of all components with a focus on long-term outcomes. The findings suggest that the EKC hypothesis is relevant in China. In China, advancements in nanotechnology have a moderating effect on environmental degradation. The use of renewable energy sources in China enhances environmental circumstances. Given the offered empirical evidence, it is advisable for the government to have a leading role in the development of innovative nanotechnologies that have low emissions of nanoparticles. By using this approach, it will be possible to encourage the conservation of energy and the use of renewable sources in a more secure way, hence improving the effectiveness of sustainable development initiatives., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

An ultrasensitive immunosensor of Cys/Au@TiO 2 based on disposable screen-printed electrodes (SPE) for PIVKA-II detection for hepatocellular carcinoma (HCC) diagnosis was developed by utilizing Cystine (Cys) and nanocomposite Au@TiO 2 . Firstly, HAuCl 4 underwent a reduction reaction with NaBH 4 , then Au nanoparticles were coated onto TiO 2 nanoparticles. Followed, Cys/Au@TiO 2 was formed through self-assembly of cysteine to allow the monoclonal antibody of abnormal thrombospondin to bound to the amino group on the surface of the composite by covalent bonding. The mechanism is to determine the changes in the current of the sensor caused by the specific binding of the abnormal prothrombin monoclonal antibody adsorbed by the complex with its antigen. The Cys/Au@TiO 2 immunosensor was fully characterized by various analytical approaches and it showed a wide linear testing range of 1-10000 pg mL -1 (R 2  = 0.991) and the limit of detection down to 0.77 pg ml -1 , with highly sensitivity and specificity. The results showed that the developed immunosensor platform can effectively detect trace amounts of PIVKA-II protein and has potent clinical application for HCC diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: We found that the occurrence of hepatocellular carcinoma (HCC) has increased significantly in non-cirrhotic individuals, with HCC being frequently overlooked or misdiagnosed. Contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) is known to have a high diagnostic quality in high-risk HCC patients. Therefore, we aimed to compare the detection accuracy of CEUS LI-RADS for HCC between low- and high-risk individuals, to confirm its value in low-risk patients at increased risk of HCC, but not yet included in the high-risk groups of LI-RADS. In addition, since CEUS LR-4 and LR-M categories contain a relatively high proportion of HCC, and serum alpha-fetoprotein (AFP) is the most commonly used biomarker for HCC, and the clinically valid, we attempted to further improve the early diagnostic capability of CEUS LI-RADS for HCC in the low-risk and high-risk patients by combining CEUS LR-4 and LR-M categories with AFP., Methods: We defined high-risk groups (HR)-included in the high-risk patients of LI-RADS, low-risk groups (LR)-not included in the high-risk patients of LI-RADS and enrolled 189 HCC patients with LR and HR settings in a retrospective study. All lesions were confirmed histopathologically. The CEUS LI-RADS accuracy for detecting HCC in these two patients was compared. In addition, the diagnostic algorithm in our study was proposed (for CEUS LR-4 and LR-M patients with AFP>20 ng/ml). we analyzed the ability of CEUS LI-RADS as a valid method of establishing the early diagnosis of HCC in LR and HR patients by combining LR-4 and LR-M categories with AFP., Results: Through comparative analysis, the specificity of the CEUS LR-5 category for HCC in the HR group was 78.4%, whereas in the LR group, it was 94.2%. Meanwhile, the sensitivity (63.2% vs. 63.0%) and positive predictive value (PPV) (75.0% vs. 88.7%) did not differ between the LR and HR groups ( P = 0.990, P = 0.299). It is noteworthy that there were the high proportion of HCC in CEUS LR-4 and LR-M categories in our cases and when we combined CEUS LR-4 and LR-M categories with AFP significantly improved the sensitivity by 21.0% (84.2%) in the LR group, and by 16.0% (79.0%) in the HR group, with statistically difference in sensitivity after combination in the HR group ( P = 0.014)., Conclusions: The CEUS LR-5 category has real meaningful utility in the diagnosis of HCC in both LR and HR patients. The early detection power of the CEUS LI-RADS category for HCC patients was further increased when the CEUS LR-4 and LR-M categories were combined with elevated AFP., (Copyright © 2024 Copyright: © 2024 Journal of Cancer Research and Therapeutics.)

The increasing atmospheric CO 2 concentration (e[CO 2 ]) has mixed effects on soybean most varieties' yield. This study elucidated the effect of e[CO 2 ] on soybean yield and the underlying mechanisms related to photosynthetic capacity, non-structural carbohydrate (NSC) accumulation, and remobilisation. Four soybean cultivars were cultivated in open-top chambers at two CO 2 levels. Photosynthesis rates were determined from R2 to R6. Plants were sampled at R5 and R8 to determine carbohydrate concentrations. There were significant variations in yield responses among the soybean cultivars under e[CO 2 ], from no change in DS1 to a 22% increase in SN14. DS1 and SN14 had the smallest and largest increase, respectively, in daily carbon assimilation capacity. Under e[CO 2 ], DS1, MF5, and XHJ had an increase in Ci, at which point the transition from Rubisco-limited to ribulose-1,5-bisphosphate regeneration-limited photosynthesis occurred, in contrast with SN14. Thus, the cultivars might have distinct mechanisms that enhance photosynthesis under e[CO 2 ] conditions. A positive correlation was between daily carbon assimilation response to e[CO 2 ] and soybean yield, emphasising the importance of enhanced photosynthate accumulation before the R5 stage in determining yield response to e[CO 2 ]. E[CO 2 ] significantly influenced NSC accumulation in vegetative organs at R5, with variation among cultivars. There was enhanced NSC remobilisation during seed filling, indicating cultivar-specific responses to the remobilisation of sucrose and soluble sugars, excluding sucrose and starch. A positive correlation was between leaf and stem NSC remobilisation and yield response to e[CO 2 ], emphasising the role of genetic differences in carbohydrate remobilisation mechanisms in determining soybean yield variation under elevated CO 2 levels., Competing Interests: Declaration of competing interest All the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The development of efficient and multifunctional sonosensitizers is crucial for enhancing the efficacy of sonodynamic therapy (SDT). Herein, we have successfully constructed a CoO x -loaded amorphous metal-organic framework (MOF) UIO-66 (A-UIO-66-CoO x ) sonosensitizer with excellent catalase (CAT)- and glutathione-oxidase (GSH-OXD)-like activities. The A-UIO-66-CoO x exhibits a 2.6-fold increase in singlet oxygen ( 1 O 2 ) generation under ultrasound (US) exposure compared to crystalline UIO-66 sonosensitizer, which is attributed to its superior charge transfer efficiency and consistent oxygen (O 2 ) supply. Additionally, the A-UIO-66-CoO x composite reduces the expression of glutathione peroxidase (GPX4) by depleting glutathione (GSH) through Co 3+ and Co 2+ valence changes. The high levels of highly cytotoxic 1 O 2 and deactivation of GPX4 can lead to lethal lipid peroxidation, resulting in concurrent apoptosis and ferroptosis. Both in vitro and vivo tumor models comprehensively confirmed the enhanced SDT antitumor effect using A-UIO-66-CoO x sonosensitizer. Overall, this study emphasizes the possibility of utilizing amorphization engineering to improve the effectiveness of MOFs-based sonosensitizers for combined cancer therapies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

To protect occupants in vehicle cabin environments from the health risks of high concentrations of particulate matter (PM), it is important to install vehicle cabin air filter (VCAF) to eliminate PM. In this study, we investigated the filtration performance of 22 VCAFs. Results showed that the minimum average filtration efficiency was 56.1 % for particles with a diameter of 0.1-0.3 μm, a pressure drop of 33.2-250 Pa at air velocity of 2.5 m/s, and the dust-holding capacity ranged from 5.8 to 19.4 g. In addition, as the filter area increased from 0.23 m 2 to 0.50 m 2 , the filtration efficiency for particles with a diameter of 0.1-0.3 μm increased from 56.7 % to 77.5 %, the pressure drop decreased from 96.1 to 62.5 Pa, and the dust holding capacity increased 2.7 times. Furthermore, we compared the service life of VCAF from 31 major Chinese cities and found that the service life varied greatly from maximum of 1730 h for Haikou to minimum of 352 h for Shijiazhuang. Considering occupant health risks, Beijing requires that VCAFs have PM 2.5 filtration efficiency at least 88.1 %, and Liaoning requires minimum of 97.5 %. Hence, choosing the appropriate VCAF based on the atmospheric environment of different cities deserves our attention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Antitumor agents often lack effective penetration and accumulation to achieve high therapeutic efficacy in treating solid tumors. Nanomotor-based nanomaterials offer a potential solution to address this obstacle. Among them, nitric oxide (NO) based nanomotors have garnered attention for their potential applications in nanomedicine. However, there widespread clinical adoption has been hindered by their complex preparation processes. To address this limitation, we have developed a NO-driven nanomotor utilizing a convenient and scalable nanogel preparation procedure. These nanomotors, loaded with the fluorescent probe / sonosensitizer chlorin e6 (Ce6), were specifically engineered for sonodynamic therapy. Through comprehensive in vitro investigations using both 2D and 3D cell models, as well as in vivo analysis of Ce6 fluorescent signal distribution in solid tumor models, we observed that the self-propulsion of these nanomotors significantly enhances cellular uptake and tumor penetration, particularly in solid tumors. This phenomenon enables efficient access to challenging tumor regions and, in some cases, results in complete tumor coverage. Notably, our nanomotors have demonstrated long-term in vivo biosafety. This study presents an effective approach to enhancing drug penetration and improving therapeutic efficacy in tumor treatment, with potential clinical relevance for future applications., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Neoadjuvant therapy (NT) has increased survival rates for patients with locally advanced esophageal cancer (EC), but estimating the impact of NT treatment prior to surgery is still very difficult., Methods: A retrospective study of the clinical information of 150 patients with locally advanced EC who got NT at Qilu Hospital of Shandong University between June 2018 and June 2023. Patients were randomized into training and internal validation groups at a 3:1 ratio. Furthermore, an external validation cohort comprised 38 patients who underwent neoadjuvant therapy at Qianfoshan Hospital in the Shandong Province between June 2021 and June 2023. Independent risk factors were identified using univariate and multivariate logistic regression (forward stepwise regression). Predictive models and dynamic web nomograms were developed by integrating these risk factors., Results: A total of 188 patients with locally advanced EC were enrolled, of whom 118 achieved stage I of neoadjuvant pathologic TNM (ypTNM) after receiving NT and 129 achieved grades 0-1 in the tumor regression grade (TRG). Logistic regression analysis identified five independent predictors of TRG grades 0-1: pulmonary function tests (PFT), prognostic nutritional index (PNI), triglyceride (TG) levels, squamous cell carcinoma antigen (SCC-Ag) levels, and combination immunotherapy. The areas under the receiver operating characteristic (ROC) curves for the training, internal validation, and external validation groups were 0.87, 0.75, and 0.80, respectively. Meanwhile, two independent predictors of stage I of ypTNM were identified: prealbumin (PA) and SCC antigen. The areas under the ROC curves for the training, internal validation, and external validation groups were 0.78, 0.67, and 0.70, respectively. The Hosmer-Lemeshow test for both predictive models showed excellent calibration, with well-fitted calibration curves. Decision curve analysis (DCA) and clinical impact curves (CIC) have demonstrated that nomograms are of clinical utility., Conclusion: The nomograms performed well in predicting the likelihood of stage I of ypTNM and TRG grade 0-1 after NT in patients with locally advanced EC. It helps thoracic surgeons to predict the sensitivity of patients to NT before surgery, which enables precise treatment of patients with locally advanced EC., (© 2024. The Author(s).)

Reactive astrocytes are important pathophysiologically and synthesize neurosteroids. We observed that LPS increased immunoreactive TLR4 and key steroidogenic enzymes in cortical astrocytes of rats and investigated whether corticosteroids are produced and mediate astrocytic TLR4-dependent innate immune responses. We found that LPS increased steroidogenic acute regulatory protein (StAR) and StAR-dependent aldosterone production in purified astrocytes. Both increases were blocked by the TLR4 antagonist TAK242. LPS also increased 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and corticosterone production, and both were prevented by TAK242 and by siRNAs against 11β-HSD1, StAR, or aldosterone synthase (CYP11B2). Knockdown of 11β-HSD1, StAR, or CYP11B2 or blocking either mineralocorticoid receptors (MR) or glucocorticoid receptors (GR) prevented dephosphorylation of p-Ser 9 GSK-3β, activation of NF-κB, and the GSK-3β-dependent increases of C3, IL-1β, and TNF-α caused by LPS. Exogenous aldosterone mimicked the MR- and GSK-3β-dependent pro-inflammatory effects of LPS in astrocytes, but corticosterone did not. Supernatants from astrocytes treated with LPS reduced MAP2 and viability of cultured neurons except when astrocytic StAR or MR was inhibited. In adrenalectomized rats, intracerebroventricular injection of LPS increased astrocytic TLR4, StAR, CYP11B2, and 11β-HSD1, NF-κB, C3 and IL-1β, decreased astrocytic p-Ser 9 GSK-3β in the cortex and was neurotoxic, except when spironolactone was co-injected, consistent with the in vitro results. LPS also activated NF-κB in some NeuN + and CD11b + cells in the cortex, and these effects were prevented by spironolactone. We conclude that intracrine aldosterone may be involved in the TLR4-dependent innate immune responses of astrocytes and can trigger paracrine effects by activating astrocytic MR/GSK-3β/NF-κB signaling., (© 2024 Federation of American Societies for Experimental Biology.)

In semi-supervised learning (SSL), many approaches follow the effective self-training paradigm with consistency regularization, utilizing threshold heuristics to alleviate label noise. However, such threshold heuristics lead to the underutilization of crucial discriminative information from the excluded data. In this paper, we present OTAMatch, a novel SSL framework that reformulates pseudo-labeling as an optimal transport (OT) assignment problem and simultaneously exploits data with high confidence to mitigate the confirmation bias. Firstly, OTAMatch models the pseudo-label allocation task as a convex minimization problem, facilitating end-to-end optimization with all pseudo-labels and employing the Sinkhorn-Knopp algorithm for efficient approximation. Meanwhile, we incorporate epsilon-greedy posterior regularization and curriculum bias correction strategies to constrain the distribution of OT assignments, improving the robustness with noisy pseudo-labels. Secondly, we propose PseudoNCE, which explicitly exploits pseudo-label consistency with threshold heuristics to maximize mutual information within self-training, significantly boosting the balance of convergence speed and performance. Consequently, our proposed approach achieves competitive performance on various SSL benchmarks. Specifically, OTAMatch substantially outperforms the previous state-of-the-art SSL algorithms in realistic and challenging scenarios, exemplified by a notable 9.45% error rate reduction over SoftMatch on ImageNet with 100K-label split, underlining its robustness and effectiveness.

The combination of ferroptosis, cuproptosis, and chemodynamic therapy (CDT) would be a potential strategy for tumor diagnosis and enhanced treatment. However, the therapeutic effect was severely limited by the lack of specific delivery of catalytic ions and the low Fenton reaction efficiency in tumor microenvironment (TME) with excess glutathione, limited acidity and insufficient endogenous hydrogen peroxide. In this work, p-carboxybenzenesulfonamide (BS), a carbonic anhydrase IX (CA IX) inhibitor, was modified on the surface of generation-5 poly(amidoamine) dendrimer to load copper peroxide nanoparticles, which were complexed with iron (Fe)-tannic acid (TF) networks for targeted magnetic resonance (MR) imaging and enhanced ferroptosis/cuproptosis/CDT by regulating TME. The formed CuO 2 @G5-BS/TF nanocomplexes with an average size of 39.4 nm could be specifically accumulated at tumor site and effectively internalized by metastatic 4T1 cells via the specific interaction between BS and CA IX over-expressed on tumor cells. Meanwhile, the inhibition of CA IX activity could not only decrease the intracellular pH to accelerate Fe 3+ /Cu 2+ release, H 2 O 2 self-supply and Fenton reaction, but also suppress tumor metastasis by alleviating the extracellular acidity in TME. Moreover, the reduction of Fe 3+ /Cu 2+ by intracellular glutathione (GSH) could further amplify ROS generation and enhance CDT efficacy, and the GSH depletion could in turn inhibit GPX-4 mediated antioxidant reaction to induce ferroptosis, resulting in effective therapeutic efficacy. In vivo experimental results demonstrated that CuO 2 @G5-BS/TF could provide better tumor MR imaging, effectively inhibit the growth and metastasis of 4T1 breast tumors, and be metabolized without significant systemic toxicity. Thus, CuO 2 @G5-BS/TF nanocomplexes provided a new approach for targeted MR imaging and enhanced ferroptosis/cuproptosis/CDT of triple-negative breast cancer. STATEMENT OF SIGNIFICANCE: Taking the advantage of dendrimer and metal-phenolic system, stable CuO 2 @G5-BS/TF nanocomplexes with an average size of 39.4 nm were synthesized to efficiently load Fe 3+ and CuO 2 nanoparticles for TNBC treatment and MR imaging. CuO 2 @G5-BS/TF nanocomplexes could target tumor cells overexpressing CAIX via the specific binding with BS, and the inhibition of CAIX activity could not only decrease the intracellular pH to accelerate Fe 3+ /Cu 2+ release, H 2 O 2 self-supply and Fenton reaction, but also suppress tumor metastasis by alleviating the extracellular acidity. The reduction of Fe 3+ /Cu 2+ by intracellular GSH could further amplify ·OH generation, and the GSH depletion could in turn inhibit GPX-4 mediated antioxidant reaction to induce ferroptosis, resulting in effective therapeutic efficacy by enhanced ferroptosis/cuproptosis/CDT via tumor microenvironment regulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Outstanding overall mechanical properties are essential for the successful utilization of hydrogels in advanced applications such as human-machine interfaces and soft robotics. However, conventional hydrogels suffer from fracture toughness-stiffness conflict and fatigue threshold-stiffness conflict, limiting their applicability. Simultaneously enhancing the fracture toughness, fatigue threshold, and stiffness of hydrogels, especially within a homogeneous single network structure, has proven to be a formidable challenge. In this work, we overcome this challenge through the design of a loosely cross-linked hydrogel with slight dehydration. Experimental results reveal that the slightly-dehydrated, loosely cross-linked polyacrylamide hydrogel, with an original/current water content of 87%/70%, exhibits improved mechanical properties, which is primarily attributed to the synergy between the long-chain structure and the dense dehydration-induced entanglements. Importantly, the creation of these microstructures does not require intricate design or processing. This simple approach holds significant potential for hydrogel applications where excellent anti-fracture and fatigue-resistant properties are necessary., (© 2024. The Author(s).)