Profiling of Early Immune Responses to Vaccination Using THP-1-Derived Dendritic Cells.

The COVID-19 pandemic has made assessing vaccine efficacy more challenging. Besides neutralizing antibody assays, systems vaccinology studies use omics technology to reveal immune response mechanisms and identify gene signatures in human peripheral blood mononuclear cells (PBMCs). However, due to their low proportion in PBMCs, profiling the immune response signatures of dendritic cells (DCs) is difficult. Here, we develop a predictive model for evaluating early immune responses in dendritic cells. We establish a THP-1-derived dendritic cell (TDDC) model and stimulate their maturation in vitro with an optimal dose of attenuated yellow fever 17D (YF-17D). Transcriptomic analysis reveals that type I interferon (IFN-I)-induced immunity plays a key role in dendritic cells. IFN-I regulatory biomarkers (IRF7, SIGLEC1) and IFN-I-inducible biomarkers (IFI27, IFI44, IFIT1, IFIT3, ISG15, MX1, OAS2, OAS3) are identified and validated in vitro and in vivo. Furthermore, we apply this TDDC approach to various types of vaccines, providing novel insights into their early immune response signatures and their heterogeneity in vaccine recipients. Our findings suggest that a standardizable TDDC model is a promising predictive approach to assessing early immunity in DCs. Further research into vaccine efficacy assessment approaches on various types of immune cells could lead to a systemic regimen for vaccine development in the future.

Detection of Glucose Based on Noble Metal Nanozymes: Mechanism, Activity Regulation, and Enantioselective Recognition.

Glucose monitoring is essential to evaluate the degree of glucose metabolism disorders. The enzymatic determination has been the most widely used method in glucose detection because of its high efficiency, accuracy, and sensitivity. Noble metal nanomaterials (NMs, i.e., Au, Ag, Pt, and Pd), inheriting their excellent electronic, optical, and enzyme-like properties, are classified as noble metal nanozymes (NMNZs). As the NMNZs are often involved in two series of reactions, the oxidation of glucose and the chromogenic reaction of peroxide, here the chemical mechanism by employing NMNZs with glucose oxidase (GOx) and peroxidase (POD) mimicking activities is briefly summarized first. Subsequently, the regulation strategies of the GOx-like, POD-like and tandem enzyme-like activities of NMNZs are presented in detail, including the materials, size, morphology, composition, and the reaction condition of the representative NMs. In addition, in order to further mimic the enantioselectivity of enzyme, the design of NMNZs with enantioselective recognition of d-glucose and l-glucose by using different chiral compounds (DNA, amino acids, and cyclodextrins) and molecular imprinting is further described in this review. Finally, the feasible solutions to the existing challenges and a vision for future development possibilities are discussed.

Transforms of Cell Surface Glycoproteins Charge Influences Tumor Cell Metastasis via Atypically Inhibiting Epithelial-Mesenchymal Transition Including Matrix Metalloproteinases and Cell Junctions.

Cell communication and signal transduction rely heavily on the charge on the cell surface. The cell surface is negatively charged, with glycoproteins on the cell membrane providing a large percentage of the charge. Sialic acid is found on the outermost side of glycan chains and contributes to glycoprotein's negative charge. Sialic acid is highly expressed in tumor cells and plays an important role in tumor metastasis and immune escape by interacting with extracellular ligands. However, the specific effect of negative charge changes on glycoproteins is still poorly understood. In this study, we used 9-azido sialic acid (9Az-Sia) to create artificial epitopes on glycoproteins via metabolic glycan labeling, and we attached charged groups such as amino and carboxyl to 9Az-Sia via a click reaction with dibenzocyclooctyne (DBCO). The charge of glycoproteins was changed by metabolic glycan labeling and click modification. The results showed that the migration and invasion ability of the MDA-MB-231 cell labeled with 9Az-Sia was significantly reduced after the modification with amino groups rather than carboxyl groups. Epithelial-mesenchymal transition (EMT) is the biological process of metastatic tumor cells, with an increasing ability of tumor cells to migrate and invade. In particular, the expression of adhesion molecules increased in the amine-linked group, whereas the expression of matrix metalloproteinases (MMPs) increased significantly, which is not identical to EMT characteristics. In vivo experiments have demonstrated that the loss of negative charge on glycoproteins has an inhibitory effect on tumors. In conclusion, modifying the positive charge on the surface of glycoproteins can inhibit tumor cell metastasis and has great potential for tumor therapy.

The metabolic score for insulin resistance as a predictor of clinical outcome in stroke patients treated by intravenous thrombolysis.

BACKGROUND AND PURPOSE: Insulin resistance is associated with clinical outcomes among patients with ischemic stroke. We aimed to investigate the association between metabolic score for insulin resistance (METS-IR) and clinical outcomes in stroke patients treated by intravenous thrombolysis (IVT). METHODS: We recruited participants treated with IVT from a prospective registry including 3 stroke centers. Poor outcome was defined as a modified Rankin scale score ≥ 3 points at 90 days after the index stroke. We performed logistic regression models to investigate the association between METS-IR and the risk of poor outcome. We used the receiver operative characteristic to assess the discriminative ability and the restricted cubic spline to explore the relationship between METS-IR and the poor outcome. RESULTS: This study enrolled a total of 1074 patients (median age, 68; 63.8% male). Three hundred sixty (33.5%) patients had poor outcome after IVT. METS-IR was associated with the risk of the poor outcome with the increase of confounding factors in models (odds ratio [OR], 1.078; 95% confidence interval [CI], 1.058-1.099; P < 0.001). The area under the curve for METS-IR for predicting the poor outcome was 0.790 (95% CI, 0.761-0.819). The restricted cubic spline revealed an increasing and non-linear association between METS-IR and the poor outcome (P for non-linearity < 0.001). CONCLUSION: Our study found that METS-IR was associated with an increased risk of poor outcome after IVT. Further studies are warranted to investigate the efficacy of anti-diabetic agents regarding IR on clinical outcomes after IVT.

Does local government competition affect the dependence on polluting industries? Evidence from China's land market.

Many countries have formulated strict environmental regulation policies, but unfortunately, environmental pollution is still severe. We believe that this phenomenon may result from institutional factors. We study whether local government competition affects the dependence on polluting industries and test it with the transaction data of China's land market. We find that the decline in the economic ranking of cities increases the scale of land transferred to polluting industries, and the more the ranking decline, the larger the scale of land in polluting industries. Besides, we analyze the impact of the first decline in the urban economic ranking, finding that the land transfer scale of polluting industries exhibits a trend of slowing down after a rapid rise in the short term. Heterogeneity analysis shows that officials with lower education levels and before-retirement age will dependent more on polluting industries to a greater extent when they face local government competition, and cities with economic growth lower than the national average will increase their dependence on polluting industries to a greater extent. This paper provides new insights into the causes of the environmental governance dilemma, which also highlights the need to weaken economic indicators and strengthen environmental indicators in government performance assessment.

Nanoparticle Ligand Exchange and Its Effects at the Nanoparticle-Cell Membrane Interface.

The nanoparticle (nano)-cell membrane interface is one of the most important interactions determining the fate of nanoparticles (NPs), which can stimulate a series of biological events, allowing theranostic and other biomedical applications. So far, there remains a lack of knowledge about the mechanisms governing the nanoparticle-cell membrane interface, especially the impact of ligand exchange, in which molecules on the nanosurface become replaced with components of the cell membrane, resulting in unique interfacial phenomena. Herein, we describe a family of gold nanoparticles (AuNPs) of the same core size (∼13 nm core), modified with 12 different kinds of surface ligands, and the effects of their exchangeable ligands on both nanoparticle-supported lipid bilayers (SLBs) and nanoparticle-natural cell membrane interfaces. The ligands are categorized according to their molecular weight, charge, and bonding modes (physisorption or chemisorption). Importantly, we found that, depending on the adsorption affinity and size of ligand molecules, physisorbed ligands on the surface of NPs can be exchanged with lipid molecules. At a ligand exchange-dominated interface, the AuNPs typically aggregated into an ordered monolayer in the lipid bilayers, subsequently affecting cell membrane integrity, NP uptake efficiency, and the NP endocytosis pathways. These findings advance our understanding of the underlying mechanisms of the biological effects of nanoparticles from a new point of view and will aid in the design of novel, safe, and effective nanomaterials for biomedicine.

Probing Adsorption Behaviors of BSA onto Chiral Surfaces of Nanoparticles.

Chiral properties of nanoscale materials are of importance as they dominate interactions with proteins in physiological environments; however, they have rarely been investigated. In this study, a systematic investigation is conducted for the adsorption behaviors of bovine serum albumin (BSA) onto the chiral surfaces of gold nanoparticles (AuNPs), involving multiple techniques and molecular dynamic (MD) simulation. The adsorption of BSA onto both L- and D-chiral surfaces of AuNPs shows discernible differences involving thermodynamics, adsorption orientation, exposed charges, and affinity. As a powerful supplement, MD simulation provides a molecular-level understanding of protein adsorption onto nanochiral surfaces. Salt bridge interaction is proposed as a major driving force at protein-nanochiral interface interaction. The spatial distribution features of functional groups (COO- , NH3+ , and CH3 ) of chiral molecules on the nanosurface play a key role in the formation and location of salt bridges, which determine the BSA adsorption orientation and binding strength to chiral surfaces. Sequentially, BSA corona coated on nanochiral surfaces affects their uptake by cells. The results enhance the understanding of protein corona, which are important for biological effects of nanochirality in living organisms.

Thermal Unfolding Process of Lysozyme on PEGylated Gold Nanoparticles Reveals Length-Dependent Effects of PEG Layer.

Characterization of bio-nano interface is crucial for developing safer and more efficient nanoparticles in nanomedical application. PEGylation is commonly used in nanocarrier for drug delivery, as it confers nanoparticles good stability, stealth effect and better targeting specificity compared with those without PEGylation. However, the protein binding state on PEGylated AuNP is still limited known. In present work, we prepared 13 nm AuNPs and then PEGylated them with thiol PEG methoxy. Lysozyme is selected as a model protein and to investigate the interactions on protein-PEGylated/AuNP interface. The thermal unfolding processes of lysozyme in absence and presence of PEGylated AuNP were measured by synchrotron radiation based circular dichroism (SRCD), dynamic light scattering (DLS) and infrared spectroscopy (IR). The results suggest that in terms of secondary structural changes, α helix content is decreased, while ß sheet content is increased, and thus the adsorbed lysozyme may be present in PEG layer.

Transferrin Adsorbed on PEGylated Gold Nanoparticles and Its Relevance to Targeting Specificity.

Polyethylene glycol (PEG) has been frequently used for surface modification of nanoparticles (NPs) to reduce non-specific binding of proteins on NPs. The investigation of protein absorption on PEGylated nanoparticles is necessary. In the work, the conjugation of transferrin (Tf) to PEGylated AuNPs via adsorption or bonding was studied. The 13 nm AuNPs were coated with various molecular weight (300, 2000, 5000) carboxyl and methoxy PEG thiol. The presence of Tf on PEGylated AuNP was characterized by dynamic light scattering (DLS) and infrared spectroscopy (IR). The data of IR confirmed the presence of Tf on PEGylated AuNPs. The diameter decrease of PEGylated AuNPs after Tf adsorption was observed by DLS measurement, which is attributed to competitive adsorption between Tf and PEG molecules. These phenomena may be important to the preservation of Tf targeting specificity on PEGylated AuNPs.

Warning Function of Frank's Sign in Pre-Existing Cardiac Disease Patients: A Case Report.

Frank's sign (FS) refers to a diagonal skin fold between the tragus and the outer edge of the earlobe. FS has been identified as an independent variable in coronary artery disease (CAD). Young patients with FS and previous myocardial infarction are still rarely reported in clinical studies. We report the case of a 49-year-old male smoker and diabetic, with a history of myocardial infarction, who presented to the emergency department due to 2 h typical cardiac chest pain. His urgent electrocardiography (ECG) showed ST elevation, and cardiac biomarkers were elevated after admission. A diagonal earlobe crease (DELC) was observed in physical tests. The preliminary diagnosis considered acute coronary syndrome (ACS). Subsequently, acute coronary artery angiography demonstrated a slit-like contrast defect in the proximal right coronary artery (RCA), with stenosis and occlusion in the distal segment. The percutaneous coronary intervention (PCI) was performed immediately. The patient's chest pain symptoms were relieved significantly after intervention. Our case indicates that FS should be highly regarded as a routine cardiovascular clinical examination, which can be effortlessly applied and be easily interpreted for screening to suspect the presence of ischemic heart disease. This may set strategies for primary screening in a younger population and prompt early diagnosis and treatment.

The moderating effect of participation in online learning activities and perceived importance of online learning on EFL teachers' teaching ability.

With the sudden outbreak of COVID-19, many educational contexts shifted from traditional face-to-face instruction to online and remote modes of delivery. This inspired a surge of scholarly attention in various countries to disclose the status and perceptions of stakeholders regarding online education. However, most of the existing studies in second/foreign language contexts are limited to students' and teachers' perceived emotions and experiences in e-instruction. Moreover, the extent to which online participation and the perceived importance of e-education influence teachers' teaching ability has been widely overlooked. To fill this gap, this study explored the moderating influence of EFL teachers' participation in online learning activities and the perceived importance of online learning on their teaching ability. In doing so, a questionnaire was spread and filled in by 453 Chinese EFL teachers with different backgrounds. The results of Structural Equation Modeling (SEM) obtained by Amos (v. 24) indicated that individual/demographic factors do not affect teachers' perceived importance of online learning. It was also demonstrated that the perceived importance of online learning and learning time does not predict EFL teachers' teaching ability. Furthermore, the results reveal that EFL teachers' teaching ability does not predict their perceived importance of online learning. However, teachers' participation in online learning activities predicted and explained 66% of the variance in their perceived importance of online learning. The study has implications for EFL teachers and teacher trainers in that it improves their awareness of the value of technologies in L2 education and practice.

Understanding teachers' online professional learning: A "community of inquiry" perspective on the role of Chinese middle school teachers' sense of self-efficacy, and online learning achievement.

Teachers' online professional development (PD) has been valued as a crucial and effective way to promote teaching competencies. Forming a professional learning community has been recognized as a means to promote effective PD. Within this realm of research, the Community of Inquiry (CoI) framework was deemed as a collaborative-constructivist process model that describes successful online learning experiences. The CoI has been associated with many psychological and educational variables, such as learning achievement and self-efficacy. This study leveraged on the CoI framework to assess teachers' online professional learning quality and explored its relationship with their self-efficacy and online professional learning achievement. A total of 456 teacher participants from Chinese middle schools participated in our study. A suite of questionnaires (the Community of Inquiry Questionnaire, the Teacher Efficacy Scale, and the Perceived Online Learning Achievement Scale) was distributed. Linear regression, PROCESS Macro mediation, and moderation analyses were run on the data to answer the research questions. Results revealed a significant relationship between teachers' online learning quality and their self-efficacy and learning achievement. The mediating roles of self-efficacy and learning achievement were confirmed. The moderating role of time spent on receiving online professional learning was also recognized. Implications and future directions were discussed.

Developing the Metacognitive Awareness of Grit Scale for a better understanding of learners of English as a foreign language.

The prominent impact of metacognition on learners' academic achievement is widely discussed. Learners armed with appropriate metacognitive strategies should witness enhancement in learning performance. Similarly, the concept of grit is also valued as a crucial factor contributing to the improvement of academic achievement. Nevertheless, discussion of the relationship between metacognition and grit or their collective influence on other educational and psychological variables is limited, not to mention that an instrument measuring learners' metacognitive awareness of grit is a desideratum. Hence, by incorporating the constructs of metacognition and grit, the present research developed a measurement scale to address this need, named the Metacognitive Awareness of Grit Scale (MCAGS). The MCAGS consists of four components and initially included 48 items. It was later distributed to 859 participants for the purpose of scale validation. Confirmatory factor analysis was applied to evaluate the scale's validity and explore the factor-item relationship. A final model containing 17 items was retained. Implications and future directions were discussed.

Directional methanolysis of kitchen waste for the co-production of methyl levulinate and fatty acid methyl esters: Catalytic strategy and machine learning modeling.

To add value to ordinary kitchen waste, heterogeneous acid-base catalytic methanolysis was conducted to produce high-value liquid biofuels, methyl levulinate (ML) and fatty acid methyl esters (FAMEs). Yields of 53.3 % ML and 98.5 % FAME were achieved by methanolysis of kitchen waste under the co-catalysis of carbon-silica composite (C/Si-SO3H) and zirconium modified ultrastable Y zeolite (Zr/USY). These target products can be easily recovered from the methanolic phase and can be purified at the end of the reaction. The collaborative combination of C/Si-SO3H and Zr/USY exhibited higher activity than their commercial counterpart. This strategy can be applied to differently composed kitchen waste and kitchen waste with different water content. Product yields were predicted using an artificial neural network method, and the relative importance of the influencing factors was investigated by the random forest method. The systematic insight gained from this work supports the value-added utilization of kitchen waste.

Dendrobium officinale Xianhu 2 polysaccharide helps forming a healthy gut microbiota and improving host immune system: An in vitro and in vivo study.

Dendrobium officinale is widely consumed owing to its numerous beneficial effects. We aimed to characterize polysaccharides of Dendrobium officinale (DOP) from the stems of Dendrobium officinale Xianhu 2 and clarify whether it benefit the intestinal microbiota and the immune system. The DOP weighed 291 kDa and comprised mannose, glucose, galactose, and rhamnose at 59.31:33.31:1.00:0.51 M ratio. In in vitro/vivo studies, DOP significantly increased benign intestinal microbe proportion (Lactobacillus, etc.), but reduced harmful bacteria (Escherichia_Shigella) (P < 0.05), and significantly increased butyric acid production (P < 0.05). Concentrations of 2 g/L DOP for in vitro fermentation and 100 mg/kg body weight for the mouse model were effective. In mice, DOP significantly reduced CRP, CD3, CD4, and TNF-α levels and increased C4 levels (P < 0.05). DOP might influence the immune system indirectly through regulation of the gut microbiota. Its possible regulation mechanism was that DOP reduced CD4+ Th cells proliferation so that reduced the secretion of TNF-α.

Impact of ecological reserves on the local residents' health: Evidence from a natural experiment in China.

The potential influence of natural ecosystems on human health has been widely acknowledged globally. Nevertheless, the causality of such a correlation among the middle-aged and older populations in developing countries awaits further investigations. This study aims to understand how a specific natural ecosystem change, namely the establishment of ecological reserves, improves the physical and mental health of middle-aged and older residents in China. Two batches of national key eco-function zones (NKEFZs) in 2011 and 2016 are selected as a quasi-experiment; and a total of 128,755 middle-aged and older residents from a combined data set from the China Family Panel Studies (CFPS) and China Health and Retirement Longitudinal Studies (CHARLS) from 2010 to 2020. A difference-in-differences method was used to identify the causal effects of the natural ecosystem improvement on human health outcomes. The results indicate significant and sustained improvements in the physical health of local middle-aged and elderly residents following the implementation of the NKEFZs policy. Notably, ecological reserves with a water conservation function and those in Karst area have the most salient effects on physical health. Furthermore, this study shows that the creation of ecological reserves improves the mental health of middle-aged and older residents, with the effect varying based on changes in physical health. This study provides new insights into the positive impact of natural ecosystem improvement on human health outcomes, in particular physical and mental health.

An exopolysaccharide from Lactobacillus pentosus YY-112: structure and effect on the human intestinal microbiota.

The development of novel prebiotics, which could regulate the intestinal microbiota, may help prevent and treat intestinal diseases. Here, we studied a homogeneous polysaccharide, LPE-2, produced by Lactobacillus pentosus YY-112 during fermentation. Methylation and gas chromatography-mass spectrometry analysis, combined with nuclear magnetic resonance results, suggested that the structural unit of LPE-2 comprises a branched mannan moiety and a linear glucan moiety. In vitro simulated intestinal fermentation showed that LPE-2 reduced harmful intestinal gas production and promoted short-chain fatty acid production (especially propionic acid). Moreover, it reduced the relative abundance of Escherichia-Shigella, increased that of Bifidobacterium and Lactobacillus, and had a stronger regulatory effect on intestinal flora in women than in men. The potential sex-specific prebiotic effects of LPE-2 on human intestinal health, were possibly related to its mannan branch with (1→2) and (1→3) linkages and backbones with flexible α configurations, which are sheared and degraded/utilized easier by Bifidobacterium and Lactobacillus.

A Questionnaire Survey on Extrapulmonary Tuberculosis Control and Prevention - China, 2021.

What is already known about this topic?: Tuberculosis (TB) is a multisystem disease that might affect any organ. Currently, the National TB Program (NTP) issued by the State Council of China, only covers pulmonary tuberculosis (PTB), and the status of extrapulmonary tuberculosis (EPTB) remains unclear nationwide. What is added by this report?: The survey conducted by China CDC reported that there were no specific health facilities responsible for diagnosis, treatment and management of EPTB in China, while more than half of counties thought it should be included into NTP. What are the implications for public health practice?: China should include EPTB into NTP to achieve the target of End-TB strategy, a world free of TB. Zero deaths, disease and suffering due to TB.

Biomimetic, self-coacervating adhesive with tough underwater adhesion for ultrafast hemostasis and infected wound healing.

Massive bleeding and wound infection due to severe traumas pose a huge threat to the life and health of sufferers; therefore, it is of clinical importance to fabricate adhesives with rapid hemostatic and superior antibacterial capabilities. However, the weak wet adhesion and insufficient function of existing bioadhesives limits their practical application. In this study, a sandcastle worm protein inspired polyelectrolyte self-coacervate adhesive of poly-γ-glutamic acid (PGA) and lysozyme (LZM) was developed. The adhesive exhibited strong underwater adhesion to various surfaces (>250 kPa for solid plates and >50 kPa for soft tissues) and maintained a 80 kPa even when soaked in water for 7 days. Rat liver and tail defect bleeding models revealed that the hemostatic efficiency was superior to that of commercial samples. The in vitro antimicrobial tests showed that the bacterial inhibition to Staphylococcus aureus and Escherichia coli reached almost 100%. Additionally, the infected wound regeneration model demonstrated that the healing rate of the adhesive group was about 100% within 15 days, which was greater than that of the control group. In vitro and in vivo experiments proved that this facilely prepared adhesive will be a promising material to fulfil the integration functions for rapid wound closure and facilitating wound healing.

Induction of Metabolic Reprogramming in Kidney by Singlet Diradical Nanoparticles.

Polycyclic aromatic compounds with an open-shell singlet diradical ground state, namely singlet diradicals, have recently gained attention in the fields of organic electronics, photovoltaics, and spintronics owing to their unique electronic structures and properties. Notably, singlet diradicals exhibit tunable redox amphoterism, which makes them excellent redox-active materials for biomedical applications. However, the safety and therapeutic efficacy of singlet diradicals in biological systems have not yet been explored. Herein, the study presents a newly designed singlet diradical nanomaterial, diphenyl-substituted biolympicenylidene (BO-Ph), exhibiting low cytotoxicity in vitro, non-significant acute nephrotoxicity in vivo, and the ability to induce metabolic reprogramming in kidney organoids. Integrated transcriptome and metabolome analyses reveal that the metabolism of BO-Ph stimulates glutathione (GSH) synthesis and fatty acid degradation, increases the levels of intermediates in the tricarboxylic acid (TCA) and carnitine cycles, and eventually boosts oxidative phosphorylation (OXPHOS) under redox homeostasis. Benefits of BO-Ph-induce metabolic reprogramming in kidney organoids include enhancing cellular antioxidant capacity and promoting mitochondrial function. The results of this study can facilitate the application of singlet diradical materials in the treatment of clinical conditions induced by mitochondrial abnormalities in kidney.