An avian-origin internal backbone effectively increases the H5 subtype avian influenza vaccine candidate yield in both chicken embryonated eggs and MDCK cells.

Inactivated vaccines play an important role in preventing and controlling the epidemic caused by the H5 subtype avian influenza virus. The vaccine strains are updated in response to alterations in surface protein antigens, while an avian-derived vaccine internal backbone with a high replicative capacity in chicken embryonated eggs and MDCK cells is essential for vaccine development. In this study, we constructed recombinant viruses using the clade 2.3.4.4d A/chicken/Jiangsu/GY5/2017(H5N6, CkG) strain as the surface protein donor and the clade 2.3.4.4b A/duck/Jiangsu/84512/2017(H5N6, Dk8) strain with high replicative ability as an internal donor. After optimization, the integration of the M gene from the CkG into the internal genes from Dk8 (8GM) was selected as the high-yield vaccine internal backbone, as the combination improved the hemagglutinin1/nucleoprotein (HA1/NP) ratio in recombinant viruses. The r8GMΔG with attenuated hemagglutinin and neuraminidase from the CkG exhibited high-growth capacity in both chicken embryos and MDCK cell cultures. The inactivated r8GMΔG vaccine candidate also induced a higher hemagglutination inhibition antibody titer and microneutralization titer than the vaccine strain using PR8 as the internal backbone. Further, the inactivated r8GMΔG vaccine candidate provided complete protection against wild-type strain challenge. Therefore, our study provides a high-yield, easy-to-cultivate candidate donor as an internal gene backbone for vaccine development.

Validation of the Interaction Between Stress-Responsive LncRNAs and RNA-Binding Proteins In Vitro.

Plant long non-coding RNAs (lncRNAs) have been implicated in many biological processes, including responses to abiotic stresses, yet their detailed functions and especially their modes of action are still underexplored. lncRNAs often interact with proteins to participate in multiple levels of gene regulation. Therefore, identifying the RNA-binding proteins and validating their interaction with lncRNAs will be instrumental in revealing the functions of lncRNAs. Here, we describe two major methods to determine the interaction between lncRNA and proteins in vitro, RNA pull-down, and RNA EMSA.

Photodetector with a metalens packaging module for visible light communication based on RGBY illumination LED light source.

A novel, to the best of our knowledge, photodetector with a metalens packaging module used as the visible light communication (VLC) receiver is proposed and designed. An LED consisting of red, green, blue, and yellow chips (RGBY-LED) is adopted as the transmitter for intensity modulation direct detection VLC systems. A metalens array with a numerical aperture (NA) of 0.707 used as a polarization-insensitive planar lens of the VLC system receiver is designed at wavelengths of 457, 523, 592, and 623 nm corresponding to blue, green, yellow, and red for high efficiency. Compared with a traditional Fresnel lens positive-intrinsic-negative (PIN) photodetector module as the VLC receiver, the introduction of a metalens module can decrease the form factor of the VLC receiver module and, in particular, it is much thinner. The combination of the multi-color LED transmitter and photodetector metalens packaging module receiver can increase the modulation bandwidth due to four different wavelengths used for the VLC system. Finite-difference time domain (FDTD) simulations are performed to validate the performance of the photodetector with a metalens module. It is revealed that the corresponding efficiencies of 57.5%, 55.4%, 57%, and 56.3% were achieved at wavelengths of 623, 592, 523, and 457 nm, respectively, based on a metalens array with a 0.707 NA and 2.5 µm radius of the active area of the photodetector. It is a promising technology for indoor VLC systems such as those for smart phones and other Internet of Things devices due to the need for compact packaging for the receiver.

NIR triggered polydopamine coated cerium dioxide nanozyme for ameliorating acute lung injury via enhanced ROS scavenging.

Acute lung injury (ALI) is a life threatening disease in critically ill patients, and characterized by excessive reactive oxygen species (ROS) and inflammatory factors levels in the lung. Multiple evidences suggest that nanozyme with diversified catalytic capabilities plays a vital role in this fatal lung injury. At present, we developed a novel class of polydopamine (PDA) coated cerium dioxide (CeO2) nanozyme (Ce@P) that acts as the potent ROS scavenger for scavenging intracellular ROS and suppressing inflammatory responses against ALI. Herein, we aimed to identify that Ce@P combining with NIR irradiation could further strengthen its ROS scavenging capacity. Specifically, NIR triggered Ce@P exhibited the most potent antioxidant and anti-inflammatory behaviors in lipopolysaccharide (LPS) induced macrophages through decreasing the intracellular ROS levels, down-regulating the levels of TNF-α, IL-1ß and IL-6, up-regulating the level of antioxidant cytokine (SOD-2), inducing M2 directional polarization (CD206 up-regulation), and increasing the expression level of HSP70. Besides, we performed intravenous (IV) injection of Ce@P in LPS induced ALI rat model, and found that it significantly accumulated in the lung tissue for 6 h after injection. It was also observed that Ce@P + NIR presented the superior behaviors of decreasing lung inflammation, alleviating diffuse alveolar damage, as well as promoting lung tissue repair. All in all, it has developed the strategy of using Ce@P combining with NIR irradiation for the synergistic enhanced treatment of ALI, which can serve as a promising therapeutic strategy for the clinical treatment of ROS derived diseases as well.

Dual-circulation: influence mechanism of ETS's carbon reduction and its spatiotemporal characteristics based on intensity modified SDID model.

Traditional DID models overlook variations in policy intensity, causing estimation deviations from the actual situation and a limited understanding of the influence mechanism. In response, the Intensity Modified SDID Model is built to examine the influence mechanism of ETS's carbon reductions. Moreover, through model extensions, the study explores the spatiotemporal characteristics and heterogeneities of ETS's effects. Results show that: (1) "Dual-circulation" influence mechanism is confirmed, where ETS directly contributes to carbon reductions (2.70% to 10.0% impact) through external pathways, and internal pathways continuously strengthen reduction effects, comprehensive mechanisms are thereby formed and enhanced based on interaction among internal and external pathways. (2) Reasonable ETS levels are estimated and proposed to achieve "Dual Carbon Target", constraining nationwide carbon quotas by 20 billion tons/year, increasing carbon trading volumes by 80 thousand tons/year, and elevating the carbon trading prices by 100 RMB (14 USD) per ton. (3) ETS's carbon reduction effects are identified with temporal and spatial characteristics, temporally, effects peak in the 4th period (Event+4) but diminish in the 5th period (Event+5), spatially, effects peak in areas distancing around 1000 km but disappear beyond 1500 km. (4) ETS also has synergistic effects with atmospheric pollution reduction, including industrial emissions of sulfur dioxide and smoke (dust), but are insignificant to industrial emissions of wastewater and solid waste.

Intelligent fault detection strategy for knowledge entities in fault semantic networks of distribution network based on siamese networks.

The advent of smart grid technologies has brought about a paradigm shift in the management and operation of distribution networks, allowing for intricate system information to be encapsulated within semantic network models. These models, while robust, are not immune to faults within their knowledge entities, which can arise from a myriad of issues, potentially leading to verification failures and operational disruptions. Addressing this critical vulnerability, our research delves into the development of a novel fault detection methodology specifically tailored for the knowledge entity variables of semantic networks in distribution networks. In our approach, we first construct a state space equation that models the behavior of knowledge entity variables in the presence of faults. This foundational framework enables us to apply an unknown input observer strategy to effectively detect anomalies within the system. To bolster the fault identification process, we introduce the innovative use of a siamese network, a neural network architecture which is proficient in differentiating between similar datasets. Through simulation scenarios, we demonstrate the efficacy of our proposed fault detection method.

Reactive oxygen species in endothelial signaling in COVID-19: Protective role of the novel peptide PIP-2.

INTRODUCTION: Recent research suggests that endothelial activation plays a role in coronavirus disease 2019 (COVID-19) pathogenesis by promoting a pro-inflammatory state. However, the mechanism by which the endothelium is activated in COVID-19 remains unclear. OBJECTIVE: To investigate the mechanism by which COVID-19 activates the pulmonary endothelium and drives pro-inflammatory phenotypes. HYPOTHESIS: The "inflammatory load or burden" (cytokine storm) of the systemic circulation activates endothelial NADPH oxidase 2 (NOX2) which leads to the production of reactive oxygen species (ROS) by the pulmonary endothelium. Endothelial ROS subsequently activates pro-inflammatory pathways. METHODS: The inflammatory burden of COVID-19 on the endothelial network, was recreated in vitro, by exposing human pulmonary microvascular endothelial cells (HPMVEC) to media supplemented with serum from COVID-19 affected individuals (sera were acquired from patients with COVID-19 infection that eventually died. Sera was isolated from blood collected at admission to the Intensive Care Unit of the Hospital of the University of Pennsylvania). Endothelial activation, inflammation and cell death were assessed in HPMVEC treated with serum either from patients with COVID-19 or from healthy individuals. Activation was monitored by measuring NOX2 activation (Rac1 translocation) and ROS production; inflammation (or appearance of a pro-inflammatory phenotype) was monitored by measuring the induction of moieties such as intercellular adhesion molecule (ICAM-1), P-selectin and the NLRP3 inflammasome; cell death was measured via SYTOX™ Green assays. RESULTS: Endothelial activation (i.e., NOX2 activation and subsequent ROS production) and cell death were significantly higher in the COVID-19 model than in healthy samples. When HPMVEC were pre-treated with the novel peptide PIP-2, which blocks NOX2 activation (via inhibition of Ca2+-independent phospholipase A2, aiPLA2), significant abrogation of ROS was observed. Endothelial inflammation and cell death were also significantly blunted. CONCLUSIONS: The endothelium is activated during COVID-19 via cytokine storm-driven NOX2-ROS activation, which causes a pro-inflammatory phenotype. The concept of endothelial NOX2-ROS production as a unifying pathophysiological axis in COVID-19 raises the possibility of using PIP-2 to maintain vascular health.

Generalizable transcriptome-based tumor malignant level evaluation and molecular subtyping towards precision oncology.

In cancer treatment, therapeutic strategies that integrate tumor-specific characteristics (i.e., precision oncology) are widely implemented to provide clinical benefits for cancer patients. Here, through in-depth integration of tumor transcriptome and patients' prognoses across cancers, we investigated dysregulated and prognosis-associated genes and catalogued such important genes in a cancer type-dependent manner. Utilizing the expression matrices of these genes, we built models to quantitatively evaluate the malignant levels of tumors across cancers, which could add value to the clinical staging system for improved prediction of patients' survival. Furthermore, we performed a transcriptome-based molecular subtyping on hepatocellular carcinoma, which revealed three subtypes with significantly diversified clinical outcomes, mutation landscapes, immune microenvironment, and dysregulated pathways. As tumor transcriptome was commonly profiled in clinical practice with low experimental complexity and cost, this work proposed easy-to-perform approaches for practical clinical promotion towards better healthcare and precision oncology of cancer patients.

Research advances on molecular mechanism and natural product therapy of iron metabolism in heart failure.

The progression of heart failure (HF) is complex and involves multiple regulatory pathways. Iron ions play a crucial supportive role as a cofactor for important proteins such as hemoglobin, myoglobin, oxidative respiratory chain, and DNA synthetase, in the myocardial energy metabolism process. In recent years, numerous studies have shown that HF is associated with iron dysmetabolism, and deficiencies in iron and overload of iron can both lead to the development of various myocarditis diseases, which ultimately progress to HF. Iron toxicity and iron metabolism may be key targets for the diagnosis, treatment, and prevention of HF. Some iron chelators (such as desferrioxamine), antioxidants (such as ascorbate), Fer-1, and molecules that regulate iron levels (such as lactoferrin) have been shown to be effective in treating HF and protecting the myocardium in multiple studies. Additionally, certain natural compounds can play a significant role by mediating the imbalance of iron-related signaling pathways and expression levels. Therefore, this review not only summarizes the basic processes of iron metabolism in the body and the mechanisms by which they play a role in HF, with the aim of providing new clues and considerations for the treatment of HF, but also summarizes recent studies on natural chemical components that involve ferroptosis and its role in HF pathology, as well as the mechanisms by which naturally occurring products regulate ferroptosis in HF, with the aim of providing reference information for the development of new ferroptosis inhibitors and lead compounds for the treatment of HF in the future.

Recombinant hirudin suppresses angiogenesis of diffuse large B-cell lymphoma through regulation of the PAR-1-VEGF.

Hirudin is one of the specific inhibitors of thrombin, which has been confirmed to have strong bioactivities, including inhibiting tumors. However, the function and mechanism of hirudin and protease-activated receptor 1 (PAR-1) in diffuse large B-cell lymphoma (DLBCL) have not been clear. Detecting the expression PAR-1 in DLBCL tissues and cells by RT-qPCR and IHC. Transfected sh-NC, sh-PAR-1, or pcDNA3.1-PAR-1 in DLBCL cells or processed DLBCL cells through added thrombin, Vorapaxar, Recombinant hirudin (RH), or Na2S2O4 and co-culture with EA.hy926. And built DLBCL mice observed tumor growth. Detecting the expression of related genes by RT-qPCR, Western blot, IHC, and immunofluorescence, measured the cellular hypoxia with Hypoxyprobe-1 Kit, and estimated the cell inflammatory factors, proliferation, migration, invasion, and apoptosis by ELISA, CCK-8, flow cytometry, wound-healing and Transwell. Co-immunoprecipitation and pull-down measurement were used to verify the relationship. PAR-1 was highly expressed in DLBCL tissues and cells, especially in SUDHL2. Na2S2O4 induced SUDHL2 hypoxia, and PAR-1 did not influence thrombin-activated hypoxia. PAR-1 could promote SUDHL2 proliferation, migration, and invasion, and it was unrelated to cellular hypoxia. PAR-1 promoted proliferation, migration, and angiogenesis of EA.hy926 or SUDHL2 through up-regulation vascular endothelial growth factor (VEGF). RH inhibited tumor growth, cell proliferation, and migration, promoted apoptosis of DLBCL, and inhibited angiogenesis by down-regulating PAR-1-VEGF. RH inhibits proliferation, migration, and angiogenesis of DLBCL cells by down-regulating PAR-1-VEGF.

Matrix Metalloproteinase and Aortic Aneurysm: A Two-sample Mendelian Randomization Study.

BACKGROUND: Studies have linked matrix metalloproteinases (MMPs) to both thoracic aortic aneurysm and abdominal aortic aneurysm (TAA and AAA). The precise MMPs entailed in this procedure, however, were still unknown. This study used a two-sample Mendelian randomization (MR) analysis to look into the causal relationship between MMPs and the risk of TAA and AAA. METHODS: Eight MMPs, including MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-12, and MMP-13, were found among people of European ancestry with accessible Genome-Wide Association Studies (GWAS). We employed the findings from Genome-Wide Association Studies (GWAS) for 8 MMPs, and TAA and AAA from the FinnGen consortiums (3,201 cases and 317,899 controls, respectively) were used in a two-sample MR analysis. The primary method of analysis for MR was the inverse variance weighted (IVW) method, along with analyses of heterogeneity and horizontal pleiotropy. 31 single-nucleotide polymorphisms connected to MMP were retrieved. RESULTS: IVW demonstrated a negative causal association between TAA and AAA and serum MMP-12 levels. The incidence of TAA decreased by 1.031% for every 1 ng/mL increase in serum MMP-12 [odds ratio (OR) = 0.897, 95% confidence interval (CI): 0.831-0.968, P = 0.005]. The incidence of AAA fell by 1.653% (OR = 0.835, 95% CI: 0.752-0.926, P = 0.001) for every 1 ng/mL increase in serum MMP-12. There was no horizontal pleiotropy or heterogeneity in the MR data (P > 0.05). CONCLUSIONS: The levels of TAA and AAA and serum MMP-12 are causally related. MMP-12 is a factor that reduces the risk of AAA and TTA. Our study suggested that MMP-12 level is causally associated with a decreased risk of TAA and AAA.

Effect of CO2 fractional laser combined with recombinant human epidermal growth factor gel on skin barrier.

To evaluate the impact of CO2 fractional laser combined with recombinant human epidermal growth factor (rhEGF) gel on skin barrier in acne scar patients. In a retrospective analysis, we examined 105 acne scar patients admitted between July 2018 and August 2021. Of these, 51 received only CO2 fractional laser (control group), while 54 underwent a combination of CO2 fractional laser and rhEGF gel (observation group). We assessed treatment efficacy, symptom relief, skin barrier parameters, pre- and posttreatment inflammatory factors, adverse reactions, posttreatment quality of life, and patient satisfaction. The observation group exhibited a higher overall response rate, significantly shorter wound healing, scab formation, and scab detachment times. Additionally, this group showed increased stratum corneum water content, decreased pH, and transdermal water loss (TEWL), and reduced hypersensitive C-reactive protein and interleukin-6 expression posttreatment. Quality of life scores were higher, with fewer adverse reactions and greater treatment satisfaction. Combining CO2 fractional laser with rhEGF gel markedly improves acne scar treatment efficacy, enhances skin barrier function, reduces inflammation, and elevates quality of life. Its safety profile supports its broader clinical adoption.

A cyst-forming coccidian with large geographical range infecting forest and commensal rodents: Sarcocystis muricoelognathis sp. nov.

BACKGROUND: The geographic distribution and host-parasite interaction networks of Sarcocystis spp. in small mammals in eastern Asia remain incompletely known. METHODS: Experimental infections, morphological and molecular characterizations were used for discrimination of a new Sarcocystis species isolated from colubrid snakes and small mammals collected in Thailand, Borneo and China. RESULTS: We identified a new species, Sarcocystis muricoelognathis sp. nov., that features a relatively wide geographic distribution and infects both commensal and forest-inhabiting intermediate hosts. Sarcocystis sporocysts collected from rat snakes (Coelognathus radiatus, C. flavolineatus) in Thailand induced development of sarcocysts in experimental SD rats showing a type 10a cyst wall ultrastructure that was identical with those found in Rattus norvegicus from China and the forest rat Maxomys whiteheadi in Borneo. Its cystozoites had equal sizes in all intermediate hosts and locations, while sporocysts and cystozoites were distinct from other Sarcocystis species. Partial 28S rRNA sequences of S. muricoelognathis from M. whiteheadi were largely identical to those from R. norvegicus in China but distinct from newly sequenced Sarcocystis zuoi. The phylogeny of the nuclear 18S rRNA gene placed S. muricoelognathis within the so-called S. zuoi complex, including Sarcocystis attenuati, S. kani, S. scandentiborneensis and S. zuoi, while the latter clustered with the new species. However, the phylogeny of the ITS1-region confirmed the distinction between S. muricoelognathis and S. zuoi. Moreover, all three gene trees suggested that an isolate previously addressed as S. zuoi from Thailand (KU341120) is conspecific with S. muricoelognathis. Partial mitochondrial cox1 sequences of S. muricoelognathis were almost identical with those from other members of the group suggesting a shared, recent ancestry. Additionally, we isolated two partial 28S rRNA Sarcocystis sequences from Low's squirrel Sundasciurus lowii that clustered with those of S. scandentiborneensis from treeshews. CONCLUSIONS: Our results provide strong evidence of broad geographic distributions of rodent-associated Sarcocystis and host shifts between commensal and forest small mammal species, even if the known host associations remain likely only snapshots of the true associations.

Preparation and adjuvanticity against PCV2 of Viola philippica polysaccharide loaded in Chitosan-Gold nanoparticle.

The present Porcine circovirus type 2 virus (PCV2) vaccine adjuvants suffer from numerous limitations, such as adverse effects, deficient cell-mediated immune responses, and inadequate antibody production. In this study, we explored the potential of a novel nanoparticle (CS-Au NPs) based on gold nanoparticles (Au NPs) and chitosan (CS) that modified Viola philippica polysaccharide (VPP) as efficient adjuvants for PCV2 vaccine. The characterization demonstrated that CS-Au-VPP NPs had a mean particle size of 507.42 nm and a zeta potential value of -21.93 mV. CS-Au-VPP NPs also exhibited good dispersion and a stable structure, which did not alter the polysaccharide properties. Additionally, the CS-Au-VPP NPs showed easy absorption and utilization by the organism. To investigate their immune-enhancing potential, mice were immunized with a mixture of CS-Au-VPP NPs and PCV2 vaccine. The evaluation of relevant immunological indicators, including specific IgG antibodies and their subclasses, cytokines, and T cell subpopulations, confirmed their immune-boosting effects. The in vivo experiments revealed that the medium-dose CS-Au-VPP NPs significantly elevated the levels of specific IgG antibodies and their subclasses, cytokines, and T cell subpopulations in PCV2-immunized mice. These findings suggest that CS-Au-VPP NPs can serve as a promising vaccine adjuvant due to their stable structure and immunoenhancement capabilities.

Inhibition Effect of Pancreatic Exocrine Insufficiency on Immune Checkpoint Inhibitor Treatment in Pancreatic Cancer: A Retrospective Study.

Introduction: Chemotherapy combined with immune checkpoint inhibitors (ChIM) is used to treat advanced pancreatic ductal adenocarcinoma (PDAC). However, the efficacy of ChIM is similar to that of chemotherapy alone. Methods: To assess potential factors affecting the effectiveness of ChIM, we analyzed the clinical data of 359 patients with PDAC who visited the hospital during June 2017 to December 2022. Results: Surgical resection, diabetes, and ChIM were risk factors for pancreatic exocrine insufficiency (PEI). The adjusted odds ratio of ChIM was 2.63 (95% confidence interval (CI) 1.492-4.626) (P = 0.001). The incidence of PEI in the ChIM group (76.9%) was significantly higher than that of the chemotherapy group (60.2%) (P = 0.004). Survival analysis showed that ChIM did not improve the survival rate of patients with PDAC (hazard ratio (HR) 0.92, 0.707-1.197) (P = 0.534) in comparison with that of the chemotherapy group. However, in patients without PEI, those receiving ChIM showed a higher 1-year overall survival (OS) rate of 70.8% (two-sided, P = 0.045) and a median OS of 22.0 months (95% CI 11.5-32.5). Moreover, pancreatic enzyme replacement therapy significantly improved the OS of patients with PDAC (HR = 0.73, 95% CI = 0.561-0.956) (P = 0.022). Conclusion: Immune checkpoint inhibitors (ICIs) increased the incidence of PEI in patients with PDAC. The OS was not different between patients receiving chemotherapy and ChIM due to irregular PERT treatment. The finding show that pancreatic enzyme replacement therapy may improve the response rate of patients with PDAC to ICIs.

Randomness Regularization With Simple Consistency Training for Neural Networks.

Randomness is widely introduced in neural network training to simplify model optimization or avoid the over-fitting problem. Among them, dropout and its variations in different aspects (e.g., data, model structure) are prevalent in regularizing the training of deep neural networks. Though effective and performing well, the randomness introduced by these dropout-based methods causes nonnegligible inconsistency between training and inference. In this paper, we introduce a simple consistency training strategy to regularize such randomness, namely R-Drop, which forces two output distributions sampled by each type of randomness to be consistent. Specifically, R-Drop minimizes the bidirectional KL-divergence between two output distributions produced by dropout-based randomness for each training sample. Theoretical analysis reveals that R-Drop can reduce the above inconsistency by reducing the inconsistency among the sampled sub structures and bridging the gap between the loss calculated by the full model and sub structures. Experiments on 7 widely-used deep learning tasks ( 23 datasets in total) demonstrate that R-Drop is universally effective for different types of neural networks (i.e., feed-forward, recurrent, and graph neural networks) and different learning paradigms (supervised, parameter-efficient, and semi-supervised). In particular, it achieves state-of-the-art performances with the vanilla Transformer model on WMT14 English → German translation ( 30.91 BLEU) and WMT14 English → French translation ( 43.95 BLEU), even surpassing models trained with extra large-scale data and expert-designed advanced variants of Transformer models.

Water extract of moschus alleviates erastin-induced ferroptosis by regulating the Keap1/Nrf2 pathway in HT22 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Moschus, first described in the Shennong's Classic of the Materia medicine, is a scarce and precious animal medicine. Modern pharmacological researches have suggested that Moschus has neuroprotective actions, and its mechanism is related to anti-inflammatory, antioxidant, and anti-apoptosis effects. Ferroptosis is one of the major pathologies of Alzheimer's disease (AD) and is widely implicated in the pathogenesis and progression of AD. Although previous studies have suggested that Moschus possesses neuroprotective effect, whether Moschus could mitigate neuronal damages by inhibiting the onset of ferroptosis is unknown in model cells of AD. AIM OF THE STUDY: The aim of study was to explore the water extract of Moschus (WEM) on ferroptosis caused by erastin and the potential mechanism. MATERIALS AND METHODS: Erastin was used to stimulate HT22 cells to form ferroptosis model to evaluate the anti-ferroptosis effect of WEM by cell counting kit-8 and lactic dehydrogenase (LDH) tests. The malondialdehyde (MDA) and glutathione (GSH) kits are used for detection of MDA and GSH levels, and 2',7'-dichlorofluorescein diacetate and C11 BODIPY 581/591 fluorescence probe are used for evaluation of reactive oxygen species (ROS) and lipid peroxide (LOOH) levels. And Western blot was used to test nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase-1 (HO-1), and ferroptosis associated proteins including glutathione peroxidase 4 (GPX4), cystine/glutamate antiporter subunit (SLC7A11), ferritin heavy chain 1 (FTH1), ferroportin1 (FPN1), transferrin receptor (TFRC). In addition, the Nrf2 inhibitor ML385 was applied to verify whether WEM prevents erastin-induced ferroptosis by activating the Keap1/Nrf2 pathway. RESULTS: After WEM treatment, erastin-induced HT22 cell survival was significantly elevated, the accumulation of intracellular MDA, ROS, and LOOH were significantly reduced, the level of GSH and expressions of ferroptosis inhibitors GPX4 and SLC7A11 were significantly increased, and iron metabolism-related proteins TFRC, FPN1, and FTH1 were regulated. These effects of WEM are implemented by activating the Keap1/Nrf2 pathway. CONCLUSIONS: This study demonstrated that WEM could perform neuroprotective effects by alleviating ferroptosis, verified that WEM treatment of AD can be mediated by the Keap1/Nrf2 pathway, and provided theoretical support for the application of WEM in the treatment of AD.

An Electrochemiluminescent Sensor Based on Glycosyl Imprinting and Aptamer for the Detection of Cancer-Related Extracellular Vesicles.

Cancer-related extracellular vesicles (EVs) are considered important biomarkers for cancer diagnosis because they can convey a large amount of information about tumor cells. In order to detect cancer-related EVs efficiently, an electrochemiluminescence (ECL) sensor for the specific identification and highly sensitive detection of EVs in the plasma of cancer patients was constructed based on dual recognitions by glycosyl-imprinted polymer (GIP) and aptamer. The characteristic glycosyl Neu5Ac-α-(2,6)-Gal-ß-(1-4)-GlcNAc trisaccharide on the surface of EVs was used as a template molecule and 3-aminophenylboronic acid as a functional monomer to form a glycosyl-imprinted polymer by electropolymerization. After glycosyl elution, the imprinted film specifically recognized and adsorbed the EVs in the sample, and then the CD63 aptamer-bipyridine ruthenium (Aptamer-Ru(bpy)) was added to combine with the CD63 glycoprotein on the extracellular vesicle's surface, thus providing secondary recognition of the EVs. Finally, the EVs were quantitatively detected according to the ECL signal produced by the labeled bipyridine ruthenium. When more EVs were captured by the imprinted film, more probes were obtained after incubation, and the ECL signal was stronger. Under the optimized conditions, the ECL signal showed a good linear relationship with the concentration of EVs in the range of 9.5 × 102 to 9.5 × 107 particles/mL, and the limit of detection was 641 particles/mL. The GIP sensor can discriminate between the EV contents of cancer patients and healthy controls with high accuracy. Because of its affordability, high sensitivity, and ease of use, it is anticipated to be employed for cancer early detection and diagnosis.

Symmetrical Localized Built-in Electric Field by Induced Polarization Effect in Ionic Covalent Organic Frameworks for Selective Imaging and Killing Bacteria.

Photocatalytic materials are some of the most promising substitutes for antibiotics. However, the antibacterial efficiency is still inhibited by the rapid recombination of the photogenerated carriers. Herein, we design a cationic covalent organic framework (COF), which has a symmetrical localized built-in electric field due to the induced polarization effect caused by the electron-transfer reaction between the Zn-porphyrin unit and the guanidinium unit. Density functional theory calculations indicate that there is a symmetrical electrophilic/nucleophilic region in the COF structure, which results from increased electron density around the Zn-porphyrin unit. The formed local electric field can further inhibit the recombination of photogenerated carriers by driving rapid electron transfer from Zn-porphyrin to guanidinium under light irradiation, which greatly increases the yield of reactive oxygen species. This COF wrapped by DSPE-PEG2000 can selectively target the lipoteichoic acid of Gram-positive bacteria by electrostatic interaction, which can be used for selective discrimination and imaging of bacteria. Furthermore, this nanoparticle can rapidly kill Gram-positive bacteria including 99.75% of Staphylococcus aureus and 99.77% of Enterococcus faecalis at an abnormally low concentration (2.00 ppm) under light irradiation for 20 min. This work will provide insight into designing photoresponsive COFs through engineering charge behavior.

Market or regulation? The competition effect between green finance and environmental enforcement on environmental quality and its "dominate-follow" pattern.

Current research on environmental instruments often isolates the two mainstream types, market-based and regulation-based, overlooking their real-world interactions. In response, the intensity gap variable (EII_GAP) is constructed to link various instruments into a united system. Thus, based on the spatial econometrics of the spatial panel Durbin model (SPDM), the collective effects between market- and regulation-based environmental instruments on environmental quality are explored. Moreover, the political strategies for maximizing environmental benefits are discussed. Results show that the interaction pattern between market- and regulation-based environmental instruments on environmental quality is characterized by competition rather than cooperation. A unit widening in the intensity gap leads to 17 to 18% and 12 to 18% units of environmental quality improvement in local and adjacent areas, respectively. Furthermore, the "dominate-follow" approach as the most effective mode for maximizing environmental effects is proposed. This study recommends employing one type of instrument as the dominant while the other as the auxiliary. In provinces where one kind of environmental instrument takes domination, the environmental quality could be increased by around 8 to 113% after taking another contrary instrument as the auxiliary.