The Effect of Relative Humidity in Conductive Atomic Force Microscopy.

Conductive atomic force microscopy (CAFM) analyzes electronic phenomena in materials and devices with nanoscale lateral resolution, and it is widely used by companies, research institutions, and universities. Most data published in the field of CAFM is collected in air at a relative humidity (RH) of 30-60%. However, the effect of RH in CAFM remains unclear because previous studies often made contradictory claims, plus the number of samples and locations tested is scarce. Moreover, previous studies on this topic did not apply current limitations, which can degrade the CAFM tips and generate false data. This article systematically analyzes the effect of RH in CAFM by applying ramped voltage stresses at over 17,000 locations on ten different samples (insulating, semiconducting, and conducting) under seven different RH. An ultra-reliable setup with a 110-pA current limitation during electrical stresses is employed, and excellent CAFM tip integrity after thousands of tests is demonstrated. It is found that higher RH results in increased currents due to the presence of a conductive water meniscus at the tip/sample junction, which increases the effective area for electron flow. This trend is observed in insulators and ultra-thin semiconductors; however, in thicker semiconductors the electron mean free path is high enough to mask this effect. Metallic samples show no dependence on RH. This study clarifies the effect of relative humidity in CAFM, enhances understanding of the technique, and teaches researchers how to improve the reliability of their studies in this field.

A dual-recognition strategy based on pH-responsive molecularly imprinted membrane for highly selective capture of catecholamines: From construction to practical application.

BACKGROUND: Catecholamines (CAs) are involved in a wide range of physiological and pathological processes in the body and are progressively being used as important biomarkers for a variety of diseases. It is of great significance for accurate quantification of CAs to the diagnosis and treatment of diseases. However, the separation of CAs from complex biological matrices is still a great challenge due to the trace levels of CAs and the limited selectivity of existing pretreatment methods. RESULTS: In this work, a dual-recognition imprinted membrane (BA-MIM) was developed to utilize the synergistic action of pH-responsive boron affinity and molecular imprinted cavities for highly selective capture and release of CAs. The prepared BA-MIM possessed remarkable adsorption capacity (maximum capacity, 43.3 mg g-1), desirable surface hydrophilicity (46.2°), superior selectivity (IF = 6.2, α = 14.3), as well as favorable reusability (number of cycles, 6 times). On this basis, an integrated analytical method based on BA-MIM extraction combined with ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was innovatively developed to highly selective separation, enrichment, and detection of CAs in rat brain tissue. Under the optimum conditions, a low quantitation limits (0.05-0.10 ng mL-1), wide linear range (10-1000 ng mL-1), good linearity (r2 > 0.99), and satisfactory recoveries (88.5%-98.5 %) were obtained for CAs. The proven method was further applied to kidney-yang-deficiency-syndrome (KYDS) group rat model, revealed the intrinsic connection between kidney disease and catecholamine metabolism. SIGNIFICANCE: This work provides an excellent reference paradigm for the effective construction of dual-recognition functional membrane material to the high-selective analysis of trace targets in complex matrices. Additionally, this integrated analytical strategy demonstrates its efficiency, sustainability, versatility, and convenience, showing remarkable prospect in a variety of applications for biological sample analysis.

Toxicity and decomposition activity inhibition of VO2 micro/nanoparticles to white rot fungus Phanerochaete chrysosporium.

Vanadium dioxide (VO2) is an excellent phase transition material widely used in various applications, and thus inevitably enters the environment via different routes and encounters various organisms. Nonetheless, limited information is available on the environmental hazards of VO2. In this study, we investigated the impact of two commercial VO2 particles, nanosized S-VO2 and micro-sized M-VO2 on the white rot fungus Phanerochaete chrysosporium. The growth of P. chrysosporium is significantly affected by VO2 particles, with S-VO2 displaying a higher inhibitory effect on weight gain. In addition, VO2 at high concentrations inhibits the formation of fungal fibrous hyphae and disrupts the integrity of fungus cells as evidenced by the cell membrane damage and the loss of cytoplasm. Notably, at 200 µg/mL, S-VO2 completely alters the morphology of P. chrysosporium, while the M-VO2 treatment does not affect the mycelium formation of P. chrysosporium. Additionally, VO2 particles inhibit the laccase activity secreted by P. chrysosporium, and thus prevent the dye decoloration and sawdust decomposition by P. chrysosporium. The mechanism underlying this toxicity is related to the dissolution of VO2 and the oxidative stress induced by VO2. Overall, our findings suggest that VO2 nanoparticles pose significant environmental hazards and risks to white rot fungi.

Nonlinear analysis of neuronal firing modulated by sinusoidal stimulation at axons in rat hippocampus.

Introduction: Electrical stimulation of the brain has shown promising prospects in treating various brain diseases. Although biphasic pulse stimulation remains the predominant clinical approach, there has been increasing interest in exploring alternative stimulation waveforms, such as sinusoidal stimulation, to improve the effectiveness of brain stimulation and to expand its application to a wider range of brain disorders. Despite this growing attention, the effects of sinusoidal stimulation on neurons, especially on their nonlinear firing characteristics, remains unclear. Methods: To address the question, 50 Hz sinusoidal stimulation was applied on Schaffer collaterals of the rat hippocampal CA1 region in vivo. Single unit activity of both pyramidal cells and interneurons in the downstream CA1 region was recorded and analyzed. Two fractal indexes, namely the Fano factor and Hurst exponent, were used to evaluate changes in the long-range correlations, a manifestation of nonlinear dynamics, in spike sequences of neuronal firing. Results: The results demonstrate that sinusoidal electrical stimulation increased the firing rates of both pyramidal cells and interneurons, as well as altered their firing to stimulation-related patterns. Importantly, the sinusoidal stimulation increased, rather than decreased the scaling exponents of both Fano factor and Hurst exponent, indicating an increase in the long-range correlations of both pyramidal cells and interneurons. Discussion: The results firstly reported that periodic sinusoidal stimulation without long-range correlations can increase the long-range correlations of neurons in the downstream post-synaptic area. These results provide new nonlinear mechanisms of brain sinusoidal stimulation and facilitate the development of new stimulation modes.

Effect of HDAC9-induced deacetylation of glycolysis-related GAPDH lysine 219 on rotavirus replication in rotavirus-infected Caco-2 cells.

Post-translational modifications (PTMs), as epigenetic modifications, are significant in the interaction between virus and its host. However, it is unclear whether rotavirus (RV) causes changes in both the host cell epigenetic protein modification and the regulatory mechanism of viral replication. Here, we analyzed the proteome of Caco-2 cells to determine if acetylation modification occurred within the cells after RV infection. We found that glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a protein involved in glycolysis, was deacetylated at lysine 219 via histone deacetylase 9 (HDAC9) in 50 h after the RV infection. Remarkably, the deacetylation of GAPDH promoted RV replication. Finally, we found that glycolysis was alterable in Caco-2 cells by RV or the deacetylation of GAPDH lysine 219, using the Seahorse XF Glycolysis Stress Test. In conclusion, our results demonstrate for the first time that RV infection promoted deacetylation of GAPDH at lysine 219 in order to increase its own viral replication in Caco-2 cells.

Meta-analysis of the efficacy and safety of radiofrequency catheter ablation for pediatric paroxysmal supraventricular tachycardia.

INTRODUCTION: This meta-analysis was to evaluate the efficacy and safety of radiofrequency catheter ablation (RFCA) in treating children with paroxysmal supraventricular tachycardia (PSVT). METHODS: From inception to December 16, 2023, PubMed, Embase, Cochrane Library, Web of Science, CNKI (China National Knowledge Infrastructure), VIP (Chinese Science and Technology Periodical Database), and WanFang were searched for this meta-analysis. Children under the age of 18, diagnosed with atrioventricular reentrant tachycardia (AVRT) and atrioventricular nodal reentrant tachycardia (AVNRT) were enrolled. The outcomes included the success rate of RFCA, the recurrence rate of PSVT following RFCA treatment, and any complications associated with the procedure. Newcastle-Ottawa Scale (NOS) was used to assess the quality of studies. The outcome data were represented as rates (RATE), and corresponding 95% confidence intervals (CIs). Subgroup analyses were conducted based on regions and follow-ups. RESULTS: Fourteen articles encompassing 6,032 children were included in the study. RFCA demonstrated remarkable efficacy in children patients, achieving success rates of 98% (RATE: 0.98, 95% CI: 0.96 to 0.99) for AVRT and 99% (RATE: 0.99, 95% CI: 0.98 to 1.00) for AVNRT. The analysis also reveals that post-RFCA, the recurrence rates for AVRT were 5% (RATE: 0.05, 95% CI: 0.03 to 0.07), while for AVNRT, they were slightly lower at 4% (RATE: 0.04, 95% CI: 0.02 to 0.08). In the subset of Asian children patients, these recurrence rates were observed to be 5% for AVRT and 3% for AVNRT. Monitoring for a duration of up to 12 months post-RFCA indicated recurrence rates of 4% for AVRT and 3% for AVNRT. However, for follow-up periods extending beyond one year, there was a slight increase in these rates to 4% for AVRT and 6% for AVNRT. Additionally, the complication rates associated with RFCA in the children population were relatively minimal, recorded at 2% (RATE: 0.02, 95% CI: -0.01 to 0.06) for AVRT and 1% (RATE: 0.01, 95% CI: 0.00 to 0.02) for AVNRT. CONCLUSION: RFCA appears to be a highly effective and safe treatment option for AVRT and AVNRT in children, with high success rates and relatively low recurrence and complication rates. However, long-term follow-up may be necessary to monitor for potential recurrences. These findings are valuable for clinicians and patients in making informed decisions about the treatment of these cardiac arrhythmias in pediatric patients.

Efficacy, immunogenicity and safety of CoronaVac® in children and adolescents aged 6 months to 17 years: a multicenter, randomized, double-blind, placebo-controlled phase III clinical trial.

Safe and effective vaccines against COVID-19 for children and adolescents are needed. This international multicenter, randomized, double-blind, placebo-controlled, phase III clinical trial assessed the efficacy, immunogenicity, and safety of CoronaVac® in children and adolescents (NCT04992260). The study was carried out in Chile, South Africa, Malaysia, and the Philippines. The enrollment ran from September 10, 2021 to March 25, 2022. For efficacy assessment, the median follow-up duration from 14 days after the second dose was 169 days. A total of 11,349 subjects were enrolled. Two 3-µg injections of CoronaVac® or placebo were given 28 days apart. The primary endpoint was the efficacy of the CoronaVac®. The secondary endpoints were the immunogenicity and safety. The vaccine efficacy was 21.02% (95% CI: 1.65, 36.67). The level of neutralizing antibody in the vaccine group was significantly higher than that in the placebo group (GMT: 390.80 vs. 62.20, P <0.0001). Most adverse reactions were mild or moderate. All the severe adverse events were determined to be unrelated to the investigational products. In conclusion, in the Omicron-dominate period, a two-dose schedule of 3 µg CoronaVac® was found to be safe and immunogenic, and showed potential against symptomatic COVID-19 in healthy children and adolescents.

The role of coffee and potential mediators in subclinical atherosclerosis: insights from Mendelian randomization study.

Background and aims: Coffee contains many bioactive compounds, and its inconsistent association with subclinical atherosclerosis has been reported in observational studies. In this Mendelian randomization study, we investigated whether genetically predicted coffee consumption is associated with subclinical atherosclerosis, as well as the role of potential mediators. Methods: We first conducted a two-sample Mendelian randomization analysis to examine the causal effect of coffee and its subtypes on subclinical atherosclerosis inferred from coronary artery calcification (CAC). Next, the significant results were validated using another independent dataset. Two-step Mendelian randomization analyses were utilized to evaluate the causal pathway from coffee to subclinical atherosclerosis through potential mediators, including blood pressure, blood lipids, body mass index, and glycated hemoglobin. Mendelian randomization analyses were performed using the multiplicative random effects inverse-variance weighted method as the main approach, followed by a series of complementary methods and sensitivity analyses. Results: Coffee, filtered coffee, and instant coffee were associated with the risk of CAC (ß = 0.79, 95% CI: 0.12 to 1.47, p = 0.022; ß = 0.66, 95% CI: 0.17 to 1.15, p = 0.008; ß = 0.66, 95% CI: 0.20 to 1.13, p = 0.005; respectively). While no significant causal relationship was found between decaffeinated coffee and CAC (ß = -1.32, 95% CI: -2.67 to 0.04, p = 0.056). The association between coffee and CAC was validated in the replication analysis (ß = 0.27, 95% CI: 0.07 to 0.48, p = 0.009). Body mass index mediated 39.98% of the effect of coffee on CAC (95% CI: 9.78 to 70.19%, p = 0.009), and 5.79% of the effect of instant coffee on CAC (95% CI: 0.54 to 11.04%, p = 0.030). Conclusion: Our study suggests that coffee other than decaffeinated coffee increases the risk of subclinical atherosclerosis inferred from CAC. Body mass index mediated 39.98 and 5.79% of the causal effects of coffee and instant coffee on CAC, respectively. Coffee should be consumed with caution, especially in individuals with established cardiovascular risk factors, and decaffeinated coffee appears to be a safer choice.

The use of bimetallic metal-organic frameworks as restoration materials for pollutants removal from water environment.

Bimetallic metal-organic frameworks (BMOFs) are a class of functional porous materials constructed by coordination between nodes containing two different metal ions and organic ligands. Studies have shown that the catalytic activity of BMOFs is greatly improved owing to the adjustment of charge distribution and the increase of active sites as well as the synergistic effect between the bimetals, and the advantages of their large specific surface area, high porosity, unique structure and dispersed active centres make them available as important organic materials applied in the field of wastewater treatment. In this review, the preparation and construction methods for BMOFs in recent years are summarized, and we focus on their removal of different types of pollutants in the aqueous environment, including ions, dyes, pharmaceuticals or personal care products, phenolic compounds and microorganisms, as well as their corresponding removal mechanisms. In addition, we provide an outlook on their future opportunities and challenges in wastewater treatment.

Giant viruses as reservoirs of antibiotic resistance genes.

Nucleocytoplasmic large DNA viruses (NCLDVs; also called giant viruses), constituting the phylum Nucleocytoviricota, can infect a wide range of eukaryotes and exchange genetic material with not only their hosts but also prokaryotes and phages. A few NCLDVs were reported to encode genes conferring resistance to beta­lactam, trimethoprim, or pyrimethamine, suggesting that they are potential vehicles for the transmission of antibiotic resistance genes (ARGs) in the biome. However, the incidence of ARGs across the phylum Nucleocytoviricota, their evolutionary characteristics, their dissemination potential, and their association with virulence factors remain unexplored. Here, we systematically investigated ARGs of 1416 NCLDV genomes including those of almost all currently available cultured isolates and high-quality metagenome-assembled genomes from diverse habitats across the globe. We reveal that 39.5% of them carry ARGs, which is approximately 37 times higher than that for phage genomes. A total of 12 ARG types are encoded by NCLDVs. Phylogenies of the three most abundant NCLDV-encoded ARGs hint that NCLDVs acquire ARGs from not only eukaryotes but also prokaryotes and phages. Two NCLDV-encoded trimethoprim resistance genes are demonstrated to confer trimethoprim resistance in Escherichia coli. The presence of ARGs in NCLDV genomes is significantly correlated with mobile genetic elements and virulence factors.

Wafer-Scale Transfer of MXene Films with Enhanced Device Performance via 2D Liquid Intercalation.

Wafer-scale transfer processes of 2D materials significantly expand their application space in scalable microelectronic devices with excellent and tunable properties through van der Waals (vdW) stacking. Unlike many 2D materials, wafer-scale transfer of MXene films for vdW contact engineering has not yet been reported. With their rich surface chemistry and tunable properties, the transfer of MXenes can enable enormous possibilities in electronic devices using interface engineering. Taking advantage of the MXene hydrophilic surface, a straightforward, green, and fast process for the transfer of MXene films at the wafer scale (4-inch) is developed. Uniform vdW stacking of several types of large-area heterojunctions including MXene/MXene (Ti3C2Tx, Nb2CTx, and V2CTx), MXene/MoS2, and MXene/Au is further demonstrated. Multilayer support is applied to minimize damage or deformation in the transfer process of patterned Ti3C2Tx film. It allows us to fabricate thin film transistors and manipulate the MXene/MoS2 interface through the intercalation of various 2D liquids. Particularly noteworthy is the significant enhancement of the interfacial carrier transfer efficiency by ≈2 orders of magnitude using hydrogen iodide (HI) intercalation. This finding indicates a wide range of possibilities for interface engineering by transferring MXene films and employing liquid-assisted interfacial intercalation.

A Simple Binary Supramolecular Co-Assembly Platform for Enhanced Tumor Imaging and Therapy.

The primary challenges in tumor imaging and therapy revolve around improving targeting efficiency, enhancing probe/drug delivery efficacy, and minimizing off-target signals and toxicity. Although various carriers have been developed, many are difficult to synthesize, costly, and not universally applicable. Furthermore, numerous carriers exhibit limited delivery rates in solid tumors, particularly larger nanocarriers. To address these challenges, a simple binary co-assembly drug delivery platform has been designed using the readily synthesized small molecule Cys(SEt)-Lys-CBT (CKCBT) as the self-assembly building block. CKCBT can effectively penetrate tumor cells due to its positively charged Lys side chain and small size. Upon glutathione reduction, CKCBT co-assembles with Nile red or Chlorin e6 to form nanofibers inside tumor cells. This enables their specific accumulation in tumor cells rather than normal cells and extends their exposure time, resulting in precise and enhanced tumor imaging and treatment. Hence, this uncomplicated and highly efficient binary co-assembly drug delivery platform can be easily adapted to a broad spectrum of probes and drugs, presenting a novel approach for advancing clinical diagnosis and therapy.

Chromium Affects Mitochondrial Function, Leading to Apoptosis and Autophagy in Turtle Primary Hepatocytes.

Hexavalent chromium (Cr(VI)), a pervasive industrial contaminant, is highly toxic to both humans and animals. However, its effects on turtles are largely unexplored. Our study aimed to investigate the toxic effects of Cr(VI) on the Reeves' turtles (Mauremys reevesii) primary hepatocytes. We exposed hepatocytes to two concentrations (25 µM and 50 µM) of Cr(VI) for 24 h. The results showed that compared to controls, Cr(VI)-treated cells showed elevated antioxidant enzyme activity (catalase (CAT) and superoxide dismutase (SOD)) and increased reactive oxygen species (ROS) levels. Adenosine triphosphatae (ATP) levels decreased, indicating mitochondrial dysfunction. Additionally, we found significant changes in mitochondrial dynamics related genes, with downregulation of mitofusin 2 (Mfn2) and silent information regulator 1 (SIRT1) and a decrease in sirtuin 3 (SIRT3) and tumor protein 53 (p53) mRNA levels. Annexin V-FITC fluorescence staining-positive cells increased with higher Cr(VI) concentrations, marked by elevated bcl-2-associated X protein (Bax) and cysteinyl aspartate specific proteinase (Caspase3) mRNA levels and reduced B-cell lymphoma-2 (Bcl2) expression. Autophagy-related genes were also affected, with increased microtubule-associated protein 1 light chain 3 (LC3-I), microtubule-associated protein light chain 3II (LC3-II), unc-51-like autophagy-activating kinase 1 (ULK1), and sequestosome 1 (p62/SQSTM1) mRNA levels and decreased mammalian target of rapamycin (mTOR) and Beclin1 expression. Taken together, Cr(VI) promotes cell apoptosis and autophagy in turtle hepatocytes by inducing oxidative stress and disrupting mitochondrial function. These findings highlight the serious health risks posed by Cr(VI) pollution and emphasize the need for protecting wild turtle populations.

[One-pot synthesis of itaconic acid by engineered Halomonas bluephagenesis TDZI-08].

Itaconic acid (IA) is one of the twelve high value-added platform compounds applied in various fields including coatings, adhesives, plastics, resins, and biofuels. In this study, we established a one-pot catalytic synthesis system for IA from citric acid based on the engineered salt-tolerant bacterial strain Halomonas bluephagenesis TDZI-08 after investigating factors that hindered the process and optimizing the carbon source, nitrogen source, inducer addition time, and surfactant dosage. The open, non-sterile, one-pot synthesis with TDZI-08 in a 5 L fermenter achieved the highest IA titer of 40.50 g/L, with a catalytic yield of 0.68 g IA/g citric acid during the catalytic stage and a total yield of 0.42 g IA/g (citric acid+gluconic acid). The one-pot synthesis system established in this study is simple and does not need sterilization or aseptic operations. The findings indicate the potential of H. bluephagenesis for industrial production of IA.

Fasting hypertriglyceridemia in relation to mortality in an elderly male Chinese population.

We investigated fasting hypertriglyceridemia as predictors of all-cause, cardiovascular, and non-cardiovascular mortality in an elderly male Chinese population, while accounting for various conventional cardiovascular risk factors. Our participants were elderly men recruited from residents living in a suburban town of Shanghai (≥60 years of age, n = 1583). Hypertriglyceridemia was defined as a fasting serum triglycerides concentration ≥1.70 mmol/L. Subgroup analyses were performed according to current smoking (yes vs. no), alcohol intake (yes vs. no), and the presence and absence of hypertension and hyperglycemia. During a median of 7.9 years follow-up, all-cause, cardiovascular, and non-cardiovascular deaths occurred in 279, 112, and 167 participants, respectively. After adjustment for confounding factors, fasting hypertriglyceridemia was not significantly (p ≥ .33) associated with the risk of all-cause, cardiovascular, and non-cardiovascular mortality. However, there was significant (p = .03) interaction between hypertriglyceridemia and the presence and absence of hypertension in relation to all-cause mortality. In normotensive, but not hypertensive individuals, hypertriglyceridemia was significantly associated with a higher risk of all-cause mortality (hazard ratio 1.57, 95% confidence interval 1.06-2.31). In further non-parametric analyses in normotensive individuals, the age-standardized rate for all-cause mortality increased from 18.9 in quartile 1 to 20.0, to 24.7, and to 39.9 per 1000 person-years in quartiles 2, 3, and 4 of serum triglycerides concentration, respectively (ptrend = .0004). Similar results were observed for cardiovascular mortality. Our study in elderly male Chinese showed that fasting hypertriglyceridemia was associated with a higher risk of all-cause and cardiovascular mortality in patients with normotension but not those with hypertension.

Single-cell multi-modal chromatin profiles revealing epigenetic regulations of cells in hepatocellular carcinoma.

BACKGROUND: Various epigenetic regulations systematically govern gene expression in cells involving various biological processes. Dysregulation of the epigenome leads to aberrant transcriptional programs and subsequently results in diseases, such as cancer. Therefore, comprehensive profiling epigenomics is essential for exploring the mechanisms underlying gene expression regulation during development and disease. METHODS: In this study, we developed single-cell chromatin proteins and accessibility tagmentation (scCPA-Tag), a multi-modal single-cell epigenetic profile capturing technique based on barcoded Tn5 transposases and a droplet microfluidics platform. scCPA-Tag enables the simultaneous capture of DNA profiles of histone modification and chromatin accessibility in the same cell. RESULTS: By applying scCPA-Tag to K562 cells and a hepatocellular carcinoma (HCC) sample, we found that the silence of several chromatin-accessible genes can be attributed to lysine-27-trimethylation of the histone H3 tail (H3K27me3) modification. We characterized the epigenetic features of the tumour cells and different immune cell types in the HCC tumour tissue by scCPA-Tag. Besides, a tumour cell subtype (C2) with more aggressive features was identified and characterized by high chromatin accessibility and a lower abundance of H3K27me3 on tumour-promoting genes. CONCLUSIONS: Our multi-modal scCPA-Tag provides a comprehensive approach for exploring the epigenetic landscapes of heterogeneous cell types and revealing the mechanisms of gene expression regulation during developmental and pathological processes at the single-cell level. HIGHLIGHTS: scCPA-Tag offers a highly efficient and high throughput technique to simultaneously profile histone modification and chromatin accessibility within a single cell. scCPA-Tag enables to uncover multiple epigenetic modification features of cellular compositions within tumor tissues. scCPA-Tag facilitates the exploration of the epigenetic landscapes of heterogeneous cell types and provides the mechanisms governing gene expression regulation.

Luciferase-Loaded Calcium Phosphate Nanoparticles for Persistent Bioluminescence Imaging of Orthotopic Breast Tumors.

Bioluminescence imaging (BLI) is an important noninvasive optical imaging technique that has been widely used to monitor many biological processes due to its high sensitivity, resolution, and signal-to-noise ratio. However, the BLI technique based on the firefly luciferin-luciferase system is limited by the expression of exogenous luciferase and the short half-life of firefly luciferin, which pose challenges for long-term tracking in vivo. To solve the problems, here we rationally designed an intelligent strategy for persistent BLI in tumors by combining luciferase-loaded calcium phosphate nanoparticles (Luc@CaP NPs) to provide luciferase and the probe Cys(SEt)-Lys-CBT (CKCBT) to slowly produce the luciferase substrate amino luciferin (Am-luciferin). Luc@CaP NPs constructed with CaP as a carrier could enable luciferase activity to be maintained in vivo for at least 12 h. And compared to the conventional substrate luciferin, CKCBT apparently prolonged the BL time by up to 2 h through GSH-induced intracellular self-assembly and subsequent protease degradation-induced release of Am-luciferin. We anticipate that this strategy could be applied for clinical translation in more disease diagnosis and treatment in the near future.

Vaccination with a trivalent Klebsiella pneumoniae vaccine confers protection in a murine model of pneumonia.

Klebsiella pneumoniae (K. pneumoniae) is an opportunistic pathogen and the major cause of healthcare-associated infections, which are increasingly complicated by the prevalence of highly invasive and hyper-virulent K. pneumoniae strains, necessitating the development of alternative strategies for combatting infections caused by this bacterium. In this study, we successfully constructed a fusion antigen called KP-Ag1, comprising three antigens (GlnH, FimA, and KPN_00466) that were previously identified through reverse vaccinology. Immunization with KP-Ag1 formulated with Al(OH)3 adjuvant elicited robust humoral and cellular immune response in mice, and conferred protective immunity in a murine model of K. pneumoniae lung infection. Further analysis of serum IgG subtypes from mice immunized with KP-Ag1 revealed a predominant IgG1 response, indicating that KP-Ag1 predominantly induces a Th2-biased immune response. Additionally, opsonophagocytic killing assay suggested that humoral immune responses play a pivotal role in mediating protection conferred by KP-Ag1. Moreover, KP-Ag1 was found to promote the activation and maturation of BMDCs in vitro, which is essential for subsequent efficient antigen presentation. More importantly, vaccination with KP-Ag1 demonstrated cross-protective efficacy against clinical isolates of K. pneumoniae varying in serotypes, antibiotic resistance, and virulence profiles. Therefore, KP-Ag1 holds promise as a candidate for K. pneumoniae vaccine development.

Ubiquity and ecological risks of conjugated steroids cannot be overlooked: First evidence from estuarine sediments.

Steroids, renowned for endocrine-disrupting capabilities, have garnered significant research interest, predominantly centered on their parent forms. This study was the first to explore the composition, spatiotemporal characteristics, sources, mass inventories, and ecological risks of steroids in free and conjugated forms in estuarine sediments. Seventeen steroids were identified in sediments with the total levels of 1.3-4.3 ng/g. Most natural steroids and metabolites existed in free forms, while synthetic ones predominantly stored in conjugates. Environmental factors exerted limited impacts on steroid distribution. Raw domestic wastewater, drug consumption, and mariculture may be leading steroid sources in estuarine sediments, with total mean mass inventories of 177-219 µg/m2. The predominant contributors to the ecological risk were cortisol, prednisolone, 20α-dihydroprogesterone, 20ß-dihydroprogesterone, and progesterone. This research gives the first insight into the understanding of conjugated steroids in the marine environment, and advocates for more studies on the fate and ecotoxicology of conjugated steroids.

Research progress in stroke risk perception assessment tool.

BACKGROUND: One of the main illnesses in the globe that causes impairment and death in people is stroke. In the globe today, it ranks as the second leading cause of death and the leading cause of death in China. OBJECTIVE: This paper analyses into the critical role of risk perception in developing individual awareness of stroke risk and encouraging proactive preventive health behaviors, essential for effective primary stroke prevention strategies and reduced stroke incidence. It discusses the concept of risk perception, the content and dimensions of global stroke assessment tools, and their application status, aiming to provide insights for their development and intervention research. METHODS: Risk perception encompasses subjective assessments of stroke likelihood and severity, influenced by personal experiences, knowledge of risk factors, beliefs about prevention effectiveness, and emotional responses. Global stroke assessment tools, like the Framingham Stroke Risk Score and CHA2DS2-VASc Score, evaluate stroke risk based on factors such as age, gender, blood pressure, and cholesterol levels. In order to improve risk perception and proactive health management and lower the burden of strokes, the paper assesses the advantages and disadvantages of these tools and makes recommendations for improving accessibility, customizing interventions, running educational campaigns, promoting multidisciplinary collaboration, and integrating technology. RESULTS: By combining the research tools of stroke risk perception, it is found that the evaluation tools are mostly single-dimensional evaluation tools centered on the two dimensions of onset possibility and susceptibility. CONCLUSION: Some scholars have developed multi-dimensional evaluation tools, but the evaluation population is relatively limited, and the evaluation system lacks comprehensiveness and systematization.