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.

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.

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.

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.

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.

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.

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.

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.

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. Our code is available at GitHub https://github.com/dropreg/R-Drop.

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.

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.

NaturalSpeech: End-to-End Text-to-Speech Synthesis With Human-Level Quality.

Text-to-speech (TTS) has made rapid progress in both academia and industry in recent years. Some questions naturally arise that whether a TTS system can achieve human-level quality, how to define/judge that quality, and how to achieve it. In this paper, we answer these questions by first defining the human-level quality based on the statistical significance of subjective measure and introducing appropriate guidelines to judge it, and then developing a TTS system called NaturalSpeech that achieves human-level quality on benchmark datasets. Specifically, we leverage a variational auto-encoder (VAE) for end-to-end text-to-waveform generation, with several key modules to enhance the capacity of the prior from text and reduce the complexity of the posterior from speech, including phoneme pre-training, differentiable duration modeling, bidirectional prior/posterior modeling, and a memory mechanism in VAE. Experimental evaluations on the popular LJSpeech dataset show that our proposed NaturalSpeech achieves -0.01 CMOS (comparative mean opinion score) to human recordings at the sentence level, with Wilcoxon signed rank test at p-level p >> 0.05, which demonstrates no statistically significant difference from human recordings for the first time.

Low-Temperature Adaptive Single-Atom Iron Nanozymes against Viruses in the Cold Chain.

Outbreaks of viral infectious diseases, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV), pose a great threat to human health. Viral spread is accelerated worldwide by the development of cold chain logistics; Therefore, an effective antiviral approach is required. In this study, it is aimed to develop a distinct antiviral strategy using nanozymes with low-temperature adaptability, suitable for cold chain logistics. Phosphorus (P) atoms are added to the remote counter position of Fe-N-C center to prepare FeN4P2-single-atom nanozymes (SAzymes), exhibiting lipid oxidase (OXD)-like activity at cold chain temperatures (-20, and 4 °C). This feature enables FeN4P2-SAzymes to disrupt multiple enveloped viruses (human, swine, and avian coronaviruses, and H1-H11 subtypes of IAV) by catalyzing lipid peroxidation of the viral lipid envelope. Under the simulated conditions of cold chain logistics, FeN4P2-SAzymes are successfully applied as antiviral coatings on outer packaging and personal protective equipment; Therefore, FeN4P2-SAzymes with low-temperature adaptability and broad-spectrum antiviral properties may serve as key materials for developing specific antiviral approaches to interrupt viral transmission through the cold chain.

Sequential regioselective arylation of pyrazolones with diaryliodonium salts.

The introduction of aromatic substituents into organic compounds significantly alters their physical and chemical characteristics. Yet, achieving precise control over the site-selectivity of arylation continues to pose a considerable challenge. We present here a controllable method for the site-selective mono-, di-, and triarylation of pyrazolone with diaryliodonium salts. The method showcases robustness, flexibility, and excellent compatibility with a broad range of functional groups. It enables control over both the site of arylation and the number of aryl additions. Specifically, three of the four substitutable positions in pyrazolone can be selectively arylated, effectively producing four products under controlled conditions. Additionally, the method supports one-pot sequential arylation, leading to an array of products with diverse aromatic substituents. Control experiments revealed the specific conditions of each reaction step.

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.

Associations of Serum Iron Status with MAFLD and Liver Fibrosis in the USA: a Nationwide Cross-Section Study.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new terminology characterized by liver steatosis. Iron status is related to many metabolic diseases. However, the researches on the associations of serum iron status with MAFLD are limited. The objective of this study was to investigate the associations of serum iron status biomarkers with MAFLD and liver fibrosis. A total of 5892 adults were enrolled in the current cross-sectional study using the 2017-March 2020 National Health and Nutrition Examination Survey. Liver steatosis and liver fibrosis were defined by the median values of controlled attenuation parameter ≥ 274 dB/m and liver stiffness measurement ≥ 8 kPa, respectively. The multivariable logistic/linear regression and restricted cubic spline analysis were conducted. After adjusting for potential confounders, higher ferritin levels were associated with higher odds of MAFLD (OR 4.655; 95% CI 2.301, 9.418) and liver fibrosis (OR 7.013; 95% CI 3.910, 12.577). Lower iron levels were associated with a higher prevalence of MAFLD (OR 0.622; 95% CI 0.458, 0.844) and liver fibrosis (OR 0.722; 95% CI 0.536, 0.974). Lower transferrin saturation (TSAT) was associated with a higher prevalence of MAFLD (OR 0.981; 95% CI 0.970, 0.991) and liver fibrosis (OR 0.988; 95% CI 0.979, 0.998). Higher ferritin levels, lower iron levels, and TSAT were associated with a higher prevalence of MAFLD and liver fibrosis. This study extended the knowledge of modifying iron status to prevent MAFLD and liver fibrosis. More prospective and mechanism studies were warranted to confirm the conclusions.

Preparation, characterization and immune response of chitosan­gold loaded Myricaria germanica polysaccharide.

In this study, a novel nano-drug delivery system (CS-Au NPs) based on gold nanoparticles (Au NPs) and chitosan (CS) that modified Myricaria germanica polysaccharide (MGP) was developed to enhance immune responses. At a MGP to CS Au ratio of 5:1, CS-Au-MGP NPs had a loading capacity of 78.27 %. The structure of CS-Au-MGP NPs were characterized by Transmission electron microscope, TEM-energy dispersive spectroscopy mapping, Fourier transform infrared spectroscopy, X-ray photoelectron spectrometer, particle size and zeta-potential distribution analysis. Under weakly acidic conditions, in vitro CS-Au-MGP NPs release was most effective. In vivo showed that co-immunization with CS-Au-MGP NPs and PCV2 significantly increased the organ index of the thymus, spleen, and liver in mice. Additionally, CS-Au-MGP NPs significantly increased the levels of IgG, IgG1, and IgG2a antibodies, as well as IFN-γ and IL-6 levels. Furthermore, the CS-Au-MGP NPs promoted proliferation of spleen T and B lymphocytes, increased the number of CD3+, CD4+, and CD8+ cells, and increased the CD4+/CD8+ T cell ratio. Meanwhile, CS-Au-MGP NPs remarkably TLR2/IRAK4 pathway activation and mRNA levels of cytokines (IFN-γ and IL-6). These results indicated that CS-Au-MGP NPs could enhance the immune activity, and it could be potentially used as an MGP delivery system for the induction of strong immune responses.

Pseudolaric acid B exerts an antifungal effect and targets SIRT1 to ameliorate inflammation by regulating Nrf2/NF-κB pathways in fungal keratitis.

Fungal keratitis (FK) is a vision-threatening infection. We aimed to explore the antifungal and anti-inflammatory effects of pseudolaric acid B (PAB) on FK and the underlying mechanisms involved. Network pharmacology utilized to acquire the potential target genes, and silent information regulator 1 (SIRT1) was consistently downregulated in Gene Expression Omnibus dataset and clinical samples. Molecular docking analysis showed that PAB and SIRT1 had good binding activity. No toxicity was observed in vivo and in vitro with a PAB concentration below 0.3 µM. PAB exerted its antifungal activity by destroying the integrity of hyphae, and alleviated the severity of FK in rats by decreasing clinical scores, fungal burden and inhibiting inflammatory cell infiltration. PAB increased SIRT1 to regulate the crosstalk between nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa-B (NF-κB), decreasing the levels of inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6; and pattern recognition receptors, C-type lectin domain containing 7A (Dectin-1), lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), toll like receptor (TLR)-2, and TLR4 both in vivo and in vitro. However, this anti-inflammatory effect of PAB was abolished by the SIRT1 inhibitor EX527. This study provides new evidence that PAB has antifungal and anti-inflammatory effects in FK and may provide a novel therapeutic strategy for the treatment of FK.