Effects of Citrobacter freundii on sturgeon: Insights from skin mucosal immunology and microbiota.

Skin mucus analysis has recently been used as a non-invasive method to evaluate for fish welfare. The present research study was conducted to examine the skin mucosal immunity and skin microbiota profiles of sturgeons infected with Citrobacter freundii. Our histology results showed that the thickness of the epidermal layer of skin remained thinner, and the number of mucous cells was significantly decreased in sturgeons after infection (p < 0.05). Total protein, alanine aminotransferase, aspartate aminotransferase, superoxide dismutase, and creatine kinase levels in the mucus showed biphasic pattern (decrease and then increase). Lactate dehydrogenase, lysozyme, and acid phosphatase activities in the mucus showed an increasing trend after infection. Furthermore, 16S rRNA sequencing also revealed that C. freundii infection also affected the diversity and community structure of the skin mucus microbiota. An increase in microbial diversity (p > 0.05) and a decrease in microbial abundance (p < 0.05) after infection were noted. The predominant bacterial phyla in the skin mucus were Proteobacteria, Fusobacteria, Bacteroidetes, Firmicutes, and Actinobacteria. Specifically, the relative abundance of Fusobacteria increased after infection. The predominant bacterial genera in the skin mucus were Cetobacterium, Pelomonas, Bradyrhizobium, Flavobacterium, and Pseudomonas. The relative abundance of Cetobacterium, Pseudomonas, and Flavobacterium increased after infection. Our current research findings will provide new insights into the theoretical basis for future research studies exploring the mechanism of sturgeon infection with C. freundii.

Relationship between serum uric acid and sarcopenia in geriatric heart failure patients with preserved ejection fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) presents a serious risk to human health. The increased prevalence of sarcopenia in the HFpEF population has a negative impact on patient prognosis. Uric acid (UA) is the byproduct of purine metabolism and is harmful to the cardiovascular system. This study aims to establish the potential relationship between sarcopenia and serum UA in HFpEF patients. METHODS: Data were obtained from 180 individuals (aged ≥60 years) with HFpEF admitted to the Geriatric Department of Jiangsu Province Hospital between January 2021 and December 2022. The UA values were grouped into 4 quartiles (Q1-Q4). Logistic generalized linear models and restricted cubic spline (RCS) regression were used to analyze the relationship between sarcopenia and UA. Subgroups based on gender were utilised for further analysis. RESULTS: After adjusting for covariates, odds ratios (ORs) and 95 % confidence intervals (CIs) for sarcopenia prevalence in the 2nd, 3rd, and 4th quartiles were 2.56 (0.57-12.65), 4.94 (1.10-24.49), and 6.95 (1.30-44.25), respectively, unlike the 1st quartile (P for trend = 0.022). The RCS plot demonstrated a positive linear relationship between serum UA levels and sarcopenia (P for non-linearity = 0.190). A sex-based subgroup analysis revealed a statistically significant relationship between UA and sarcopenia in males (P < 0.05). CONCLUSIONS: In summary, the prevalence of sarcopenia is positively related to serum UA levels among the elderly diagnosed with HFpEF. Due to the cross-sectional nature of the study design, additional investigations are necessary to validate our findings and identify the optimal range for UA reduction.

Perfluorooctanoate and nano titanium dioxide impair the byssus performance of the mussel Mytilus coruscus.

Perfluorooctanoate (PFOA) is widely used as a surfactant and has metabolic, immunologic, developmental, and genetic toxicity on marine organisms. However, the effects of PFOA on individual defense functions in mussels in the presence of titanium dioxide nanoparticles (nano-TiO2) are poorly understood. To investigate the defense strategies and regulatory mechanisms of mussels under combined stressors, the thick-shell mussels Mytilus coruscus were exposed to different PFOA concentrations (0, 2 and 200 µg/L) and nano-TiO2 (0 and 0.1 mg /L, size: 25 nm) for 14 days. The results showed that, compared to the control group, PFOA and nano-TiO2 significantly reduced the number of byssal threads (NBT), byssal threads length (BTL), diameter of proximal threads (DPB), diameter of middle threads (DMB), diameter of distal byssal threads (DDB), adhesive plaque area (BPA), and breaking force of byssal threads (N). Under the influence of PFOA and nano-TiO2, the morphological surface smoothness of the fractured byssal threads surface increased, concurrently inducing an increased surface roughness in the adhesive plaques. Additionally, under the presence of PFOA and nano-TiO2, the foot displayed dispersed tissue organization and damaged villi, accompanied by an increased incidence of cellular apoptosis and an upregulation of the apoptosis gene caspase-8. Expression of the adhesion gene mfp-3 and byssal threads strength genes (preCOL-D, preCOL-NG) was upregulated. An interactive effect on the performance of byssal threads is observed under the combined influence of PFOA and nano-TiO2. Under co-exposure to PFOA and nano-TiO2, the performance of the byssal threads deteriorates, the foot structure is impaired, and the genes mRNA expression of byssal thread secretory proteins have compensated for the adhesion and byssal threads strength by up-regulation. Within marine ecosystems, organic and particulate contaminants exert a pronounced effect on the essential life processes of individual organisms, thereby jeopardizing their ecological niche within community assemblages and perturbing the dynamic equilibrium of the overarching ecosystem. ENVIRONMENTAL IMPLICATION: Perfluorooctanoic acid (PFOA) is prone to accumulate in marine organisms. TiO2 nanoparticles (nano-TiO2) are emerging environmental pollutants frequently found in marine environment. The effects of PFOA and nano-TiO2 on marine mussels are not well understood, and their toxic mechanisms remain largely unknown. We investigated the impacts of PFOA and nano-TiO2 on mussel byssus defense mechanisms. By assessing byssus performance indicators, morphological structures of the byssus, subcellular localization, and changes in byssal secretion-related genes, we revealed the combined effects and mechanisms through which these two types of pollutants may affect the functional capabilities and survival of mussels in the complex marine ecosystem.

Association of urinary thallium with hypertension in children and adolescents aged 8-17 years: NHANES 2005-2018.

Hypertension is a key risk factor for cardiovascular disease (CVD). Thallium is a highly toxic metal that exists in all aspects of our lives and can cause damage to human health. The aim of this study was to identify the potential correlation between urinary thallium (U-Tl) and hypertension in American youth aged 8-17 years. The National Health and Nutritional Examination Survey (NHANES) database was mined for cross-sectional information on 2295 American children and adolescents aged 8-17 years. Inductively coupled plasma mass spectrometry (ICP-MS) was utilized to measure U-Tl levels, and the results were categorized into four quartiles (Q1-Q4). Logistic generalized linear models and unweighted restricted cubic spline (RCS) regression were used to investigate the relationship between U-Tl and hypertension. After adjusting for covariates, the odds ratios (ORs) at 95% confidence intervals (CIs) for hypertension prevalence in the 2nd, 3rd, and 4th quartiles were 0.43 (0.22-0.81), 0.54 (0.29-0.99), and 0.43 (0.22-0.81), when compared to the lowest quartile (P for trend = 0.024). RCS plot showed a negative linear correlation between log2-transformed U-Tl levels and hypertension (P for non-linearity = 0.869). Subgroup analysis based on sex indicated a statistically significant link between U-Tl and hypertension in male (P < 0.05). There is a negative linear relationship between U-Tl and hypertension in American children and adolescents aged 8-17 years with low thallium exposure. Due to the nature of cross-sectional studies, further studies are necessary to validate our conclusions and elucidate possible mechanisms.

Response of moulting genes and gut microbiome to nano-plastics and copper in juvenile horseshoe crab Tachypleus tridentatus.

Nanoplastics (NPs) and heavy metals are typical marine pollutants, affecting the gut microbiota composition and molting rate of marine organisms. Currently, there is a lack of research on the toxicological effects of combined exposure to horseshoe crabs. In this study, we investigated the effects of NPs and copper on the expression of molt-related genes and gut microbiome in juvenile tri-spine horseshoe crabs Tachypleus tridentatus by exposing them to NPs (100 nm, 104 particles L-1) and/or Cu2+ (10 µgL-1) in seawater for 21 days. Compared with the control group, the relative mRNA expression of ecdysone receptor (EcR), retinoid x receptor (RXR), calmodulin-A-like isoform X1 (CaM X1), and heat shock 70 kDa protein (Hsp70) were significantly increased under the combined stress of NPs and Cu2+. There were no significant differences in the diversity and abundance indices of the gut microbial population of horseshoe crabs between the NPs and/or Cu2+ groups and the control group. According to linear discriminant analysis, Oleobacillus was the most abundant microorganism in the NPs and Cu2+ stress groups. These results indicate that exposure to either NPs stress alone or combined NPs and Cu2+ stress can promote the expression levels of juvenile molting genes. NPs exposure has a greater impact on the gut microbial community structure of juvenile horseshoe crabs compared to Cu2+ exposure. This study is helpful for predicting the growth and development of horseshoe crabs under complex environmental pollution.

Practice of pharmaceutical services and prescription analysis in internet-based psychiatric hospitals during COVID-19 pandemic in Wuxi, China.

Objective: To study the practice of pharmaceutical services in internet-based psychiatric hospitals, and to analyze the prescriptions to ensure the safety and efficacy of internet-based medication in Wuxi, China. Methods: All 1,259 internet-based prescriptions from our hospital in 2022 were collected, and data on patients' age, gender, diagnosis, medications used, medication types, dosage forms, rationality of medication use, and reasons for irrationality were analyzed through descriptive statistics. Results: In the electronic prescriptions of internet-based psychiatric hospitals, females accounted for the majority (64.50%), with a female-to-male ratio of 1.82:1. Middle-aged and young adults accounted for the majority of patients (57.50%). There were 47 diagnosed diseases involved, with 89 types of medications used and 1,938prescriptions issued. Among them, there were 78 types of western medicine with 1,876 prescriptions (96.80%), and 11 types of traditional Chinese medicine with 62 prescriptions (3.20%). The main medications used were anti-anxiety and antidepressant medications (44.94%) and psychiatric medications (42.21%). The dosage forms were all oral, with tablets (78.53%), capsules (17.54%), and solution preparations (2.17%) being the top three in frequency. According to the prescription review results, the initial pass rate of internet-based system review was 64.26%. After intervention by the internet-based system and manual review by pharmacist reviewers, the final pass rate of internet-based prescriptions reached 99.76%. Conclusion: The practice of pharmaceutical services and prescription analysis in internet-based psychiatric hospitals could significantly improve medication rationality, which fills the research gap in this field. In addition, it promotes the transformation of pharmaceutical service models.

Improving drug-target affinity prediction via feature fusion and knowledge distillation.

Rapid and accurate prediction of drug-target affinity can accelerate and improve the drug discovery process. Recent studies show that deep learning models may have the potential to provide fast and accurate drug-target affinity prediction. However, the existing deep learning models still have their own disadvantages that make it difficult to complete the task satisfactorily. Complex-based models rely heavily on the time-consuming docking process, and complex-free models lacks interpretability. In this study, we introduced a novel knowledge-distillation insights drug-target affinity prediction model with feature fusion inputs to make fast, accurate and explainable predictions. We benchmarked the model on public affinity prediction and virtual screening dataset. The results show that it outperformed previous state-of-the-art models and achieved comparable performance to previous complex-based models. Finally, we study the interpretability of this model through visualization and find it can provide meaningful explanations for pairwise interaction. We believe this model can further improve the drug-target affinity prediction for its higher accuracy and reliable interpretability.

Theoretical Studies on Selectivity of HPK1/JAK1 Inhibitors by Molecular Dynamics Simulations and Free Energy Calculations.

Hematopoietic progenitor kinase 1 (HPK1) is a negative regulator of T cell receptor, which has been regarded as a potential target for immunotherapy. Yu et al. observed the off-target effect of the high-throughput screening HPK1 kinase inhibitor hits on JAK1 kinase. The off-target effect is usually due to the lack of specificity of the drug, resulting in toxic side effects. Therefore, exploring the mechanisms to selectively inhibit HPK1 is critical for developing effective and safe inhibitors. In this study, two indazole compounds as HPK1 inhibitors with different selectivity towards JAK1 were used to investigate the selectivity mechanism using multiple computational methods, including conventional molecular dynamics simulations, binding free energy calculations and umbrella sampling simulations. The results indicate that the salt bridge between the inhibitor and residue Asp101 of HPK1 favors their selectivity towards HPK1 over JAK1. Information obtained from this study can be used to discover and design more potent and selective HPK1 inhibitors for immunotherapy.

Evaluation of clinical relevance and underlying pathology for hemodynamic compromise in acute small subcortical infarction using MRI-based neuroimaging markers.

BACKGROUND: Hemodynamic compromise has been observed in patients with acute small subcortical infarction (SSI), and it may play a critical role in the development of early neurological deterioration (END). This study aimed to evaluate the clinical relevance and underlying pathology of hemodynamic compromise in SSI using MRI-based neuroimaging markers. METHODS: We retrospectively analyzed data and imaging of previous prospective studies. Patients with acute SSI in penetrating artery territories were recruited, all of whom underwent perfusion MRI within 24 h of stroke onset. We examined the relationships among perfusion defects and neuroimaging markers of small vessel disease, including white matter hyperintensities, cerebral microbleeds, enlarged perivascular spaces (EPVSs) and lacunes. RESULTS: One hundred and seven patients were recruited, of whom 21 (19.6%) had END and 55 (51.4%) had visible perfusion defects. Patients with perfusion defects were associated with a higher rate of END (34.5% vs. 3.8%; p < 0.001), higher initial National Institutes of Health Stroke Scale scores (5.4 vs. 3.4, p < 0.001), higher rate of branch atheromatous disease (61.8% vs. 34.6%, p = 0.005) and higher rate of poor outcome at 3 months (40.0% vs. 5.4%; p = 0.005). In multiple logistic regression, perfusion defects were significantly associated with basal ganglia EPVS scores (adjusted odds ratio [aOR]: 3.93; 95% confidence interval [CI]: 1.76-8.77; p = 0.001) and branch atheromatous disease (aOR: 2.64; 95% CI: 1.06-6.60; p = 0.037). CONCLUSION: Hemodynamic compromise in acute SSI was highly related to the development of END, basal ganglia EPVS and branch atheromatous disease, suggesting the correlation with underlying pathologies of hypertensive arteriopathy and atherosclerosis.

Early Neurocognitive Function With Propofol or Desflurane Anesthesia After Laser Laryngeal Surgery With Low Inspired Oxygen.

PURPOSE: The effects of general anesthetics on cognitive impairment are unclear and complicated. Laser laryngeal surgery (LLS) requires the administration of low levels of oxygen, which may increase the risk of desaturation and brain function impairment. This prospective randomized trial aimed to compare the effects of desflurane and propofol-based general anesthesia on the occurrence of early postoperative cognitive decline in elderly patients undergoing LLS. METHODS: Seventy-three patients classified as American Society of Anesthesiologists grade I or II and at least 65 years of age were randomly allocated to receive either desflurane-based (Group D) or propofol-based (Group P) anesthesia during LLS. The standard anesthesia protocol was performed, with a bispectral index between 40 and 60 and a mean arterial pressure within 20% of baseline values. Intraoperative regional oxygen saturation values were recorded. Each patient was assessed using the mini-mental state examination (MMSE) test during the preoperative period (baseline), 30 min after extubation in the postanesthesia care unit, and 1, 3, and 24 h after surgery. RESULTS: MMSE scores improved slightly in both groups compared to baseline during the early postoperative period, but these increases were not statistically significant. No significant differences were identified in MMSE scores between groups. Only three patients (9.6%) in group D and one patient (3.1%) in group P developed cognitive impairment (p = 0.583). CONCLUSION: Low intraoperative inspired oxygen concentration during short-duration LLS did not reduce early postoperative cognitive function in elderly patients. Desflurane or propofol-based anesthesia had similar effects on early neurocognition after LLS. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:640-646, 2023.

Study on the Collection Efficiency of Bioaerosol Nanoparticles by Andersen-Type Impactors.

Airborne transmission is much more common than previously thought. Based on our knowledge about SARS-COV-2 (COVID-19) infection, the aerosol transmission routes for all respiratory infections must be reassessed. Thus far, the COVID-19 outbreak has caused catastrophic public health and economic crises, posing a serious threat to the lives and health of people around the world and directing public attention toward the airborne transmission of pathogens. The novel coronavirus transmission in the form of nanoaerosols in a wider range hinders prevention and early warning efforts. As a classical bioaerosol sampler, the Andersen six-stage sampler is widely used in the collection and research of aerosol particles. In this study, the physical and biological collection efficiency of the six-stage sampler was explored by qPCR and colony counting method. Results showed that the physical collection efficiency reached more than 50% when the particle size was larger than 0.75 µm. However, the overall biological collection efficiency was only 0.25%. In addition, fluorescence microscopy and flow cytometry were used to detect the microbial state after sampling, and the results showed that the proportion of the collected live bacteria was less than 15% of the total. This result is of great significance not only for the application of the Andersen six-stage sampler in collecting nanosized bioaerosols, but also provides reference for the selection of subsequent detection technologies for effective collection.

Polymorphism analysis and expression profile of the estrogen receptor 2 gene in Leizhou black duck.

Our previous study on the ovarian transcriptomic analysis in Leizhou black duck revealed that the ESR2 gene was involved in hormone regulation in reproduction and the estrogen signaling pathway related to reproductive performance was enriched. This suggested that ESR2 may have a functional role in the reproductive performance of the Leizhou black duck. Thus, this study aimed at evaluating the polymorphism of the ESR2 gene and its association with egg-laying traits and the distribution pattern of ESR2 mRNA in laying and non-laying Leizhou black ducks. In this study, genomic DNA was extracted from blood samples of 101 Leizhou black ducks to identify single nucleotide polymorphisms (SNPs) of the ESR2 gene to elucidate molecular markers highly associated with egg-laying traits. Four each of laying and non-laying Leizhou black ducks were selected to collect different tissues to analyze the ESR2 gene expression. A total of 23 SNPs were identified and association analysis of the single SNP sites showed that SNPs g.56805646 T>C and exon 3-20G>A were significantly (P < 0.05) associated with egg weight. Ducks with CT and AG genotypes had significantly higher (P < 0.05) egg weights than their respective other genotypes. Haplotype association analysis of g.56805646 T>C and exon 3-20G>A showed that the haplotypes were significantly associated with egg weight. Higher egg weight was seen in individuals with H3H4 haplotypes. In the hypothalamus-pituitary-gonadal (HPG) axis, the results of qRT/PCR showed that ESR2 mRNA was significantly (P < 0.05) expressed in the ovaries of both duck groups than in the hypothalamus and pituitary. In the oviduct, ESR2 was significantly (P < 0.05) higher in the infundibulum and magnum of laying and non-laying ducks respectively. This study provides a molecular marker for selecting Leizhou black ducks for egg production. In addition, it offers theoretical knowledge for studying the related biological functions of the ESR2 gene at the cellular level.

Perfusion Defects and Collateral Flow Patterns in Acute Small Subcortical Infarction: a 4D Dynamic MRI Study.

The hemodynamic changes of acute small subcortical infarction (SSI) are not well understood. We evaluate the hemodynamic changes and collaterals in acute SSI using perfusion magnetic resonance imaging (MRI). A total of 103 patients with acute SSI in penetrating artery territories were recruited and underwent MRI within 24 h of stroke onset. Using 4D dynamic perfusion MRI, they were divided into three patterns: 25 (24%) with normal perfusion, 31 (30%) with compensated perfusion, and 47 (46%) with hypoperfusion. The development of anterograde or retrograde collaterals was also evaluated. Patients with hypoperfusion pattern had the highest rate of early neurological deterioration (32%, p = 0.007), the largest initial and final infarction volumes (p < 0.001 and p = 0.029), the lowest relative cerebral blood flow (0.63, p < 0.001), and the lowest rate of anterograde and retrograde collaterals (19%, p < 0.001; 66%, p = 0.002). The anterograde collaterals were associated with higher relative cerebral blood volume (0.91 vs. 0.77; p = 0.024) and a higher rate of deep cerebral microbleeds (48 vs. 21%; p = 0.028), whereas retrograde collaterals were associated with higher systolic and diastolic blood pressure (p = 0.031 and 0.020), smaller initial infarction volume (0.81 vs. 1.34 ml, p = 0.031), and a higher rate of lobar cerebral microbleeds (30 vs. 0%; p = 0.013). Both anterograde and retrograde collaterals may play a critical role in maintaining cerebral perfusion and can have an impact on patient clinical outcomes. Further studies are warranted to verify these findings and to investigate effective treatments.

Decorin regulates myostatin and enhances proliferation and differentiation of embryonic myoblasts in Leizhou black duck.

Skeletal muscle is one of the most important economic traits in the poultry industry whose development goes through several processes influenced by several candidate genes. This study explored the regulatory role of DCN on MSTN and the influence of these genes on the proliferation and differentiation of embryonic myoblasts in Leizhou black ducks. Embryonic myoblasts were transfected with over-expressing DCN, Si-DCN, and empty vector and cultured for 24 h, 48 h, and 72 h of proliferation and the comparative expression of DCN and MSTN were measured. The results showed that cells transfected with the over-expression DCN had a significantly (P < 0.05) higher expression of DCN mRNA than the normal group and the expression of MSTN mRNA showed a downward trend during the proliferation of myoblasts. DCN mRNA expression was lower in cells transfected with Si-DCN than the normal group in all stages of proliferation. While the expression of MSTN in the Si-DCN transfected group was higher than the normal group with a significant (P < 0.05) difference at the 72 h stage. DCN mRNA increased at the early stage of differentiation but decreased (P > 0.05) from the 6th day to the 8th day of differentiation. The level of MSTN increased gradually during the differentiation process of myoblasts until it decreased significantly on the 8th day. These results show that DCN enhances the proliferation and differentiation of Leizhou black duck myoblasts and suppresses MSTN activity.

Ovarian transcriptomic analysis and follicular development of Leizhou black duck.

This study investigated the factors that caused the differences in egg production during the development of ovarian follicles in Leizhou black ducks. Leizhou black ducks population was divided into 2 groups as high-yield group (HG) and low-yield group (LG). The number of eggs (NE), age at first egg (AFE), weight at first egg, and egg weight (EW) of both groups were recorded, and differences were analyzed using the t test. The logistic model was used to simulate the egg production curves to analyze the production rules. The ovarian follicles of both duck groups were collected to count the number of different grades sized follicles, weigh the ovaries, and observe follicular sections to analyze the developmental differences. Ovarian transcriptomic sequencing was performed to investigate differentially expressed genes and signal pathways in both duck groups. The results revealed a significant difference (P < 0.01) in the NE laid, AFE, and EW between both groups. Comparatively, HG had significantly more (P < 0.01) large yellow follicles (LYF) than LG. The density of medullary layer cells of the follicle section was greater in HG than LG ducks. Transcriptome sequencing revealed a total of 1,027 differentially expressed genes between the HG and LG ducks of which 495 genes were upregulated, and 532 genes were downregulated. Fifty genes were related to reproduction and reproductive processes. Kyoto Encyclopedia of Genes and Genomes-enriched signaling pathways revealed 274 signal pathways enriched in these differentially expressed genes of which the steroid biosynthesis pathway was significantly enriched. Analysis (Q < 0.05) showed that HSD3ß â†’ gonadotropin-releasing hormone (GnRH) and estrogen receptor (ESR) → LHß/ERK1/2 were enriched in the steroid biosynthesis signal pathway. Follicle-stimulating hormone signal pathway mediated by HSD3ß â†’ GnRH and ESR → LHß/ERK1/2 may be involved in ovarian follicle development to regulate LYF reserve process and affect its ovulation cycle, which in turn influence the egg production of Leizhou black ducks.

Cancer cell specific fluorescent methionine protected gold nanoclusters for in-vitro cell imaging studies.

Benefiting from the excellent photostability and biocompatibility, fluorescent nanoclusters have recently emerged as a highly attractive bio-sensing and imaging material, especially in early diagnosis of cancer. However, their clinic applications were limited by the unsatisfactory specificity and the complex synthesis. In this study, novel methionine coated gold nanoclusters (Met-AuNCs) have been prepared via an easily-achievable one-pot synthetic method. The prepared Met-AuNCs showed high imaging-specificity: after incubating with Met-AuNCs for 1 h, cancer cells (including A549, Hela, MCF-7, HepG2) were fluorescent, while the normal cells (WI-38 and CHO) showed no fluorescence. According to a series of controlled experiments, the reason for the high imaging-selectivity was proposed to originate from the specific recognition of L-type amino acid transporter overexpressed in cancer cells.

A Novel Neuroimaging Model to Predict Early Neurological Deterioration After Acute Ischemic Stroke.

OBJECTIVE: In acute ischemic stroke, early neurological deterioration (END) may occur in up to one-third of patients. However, there is still no satisfying or comprehensive predictive model for all the stroke subtypes. We propose a practical model to predict END using magnetic resonance imaging (MRI). METHOD: Patients with anterior circulation infarct were recruited and they underwent an MRI within 24 hours of stroke onset. END was defined as an elevation of ≥2 points on the National Institute of Health Stroke Scale (NIHSS) within 72 hours of stroke onset. We examined the relationships of END to individual END models, including: A, infarct swelling; B, small subcortical infarct; C, mismatch; and D, recurrence. RESULTS: There were 163 patients recruited and 43 (26.4%) of them had END. The END models A, B and C significantly predicted END respectively after adjusting for confounding factors (p=0.022, p=0.007 and p<0.001 respectively). In END model D, we examined all imaging predictors of Recurrence Risk Estimator (RRE) individually and only the "multiple acute infarcts" pattern was significantly associated with END (p=0.032). When applying END models A, B, C and D, they successfully predicted END (p<0.001; odds ratio: 17.5[95% confidence interval: 5.1- 60.8]), with 93.0% sensitivity, 60.0% specificity, 45.5% positive predictive value and 96.0% negative predictive value. CONCLUSION: The results demonstrate that the proposed model could predict END in all stroke subtypes of anterior circulation infarction. It provides a practical model for clinical physicians to select high-risk patients for more aggressive treatment to prevent END.

Development a hydrazide-functionalized thermosensitive polymer based homogeneous system for highly efficient N-glycoprotein/glycopeptide enrichment from human plasma exosome.

As one of the most common post-translational modifications, protein N-glycosylation precipitates in many important biological processes and has closely correlations with the occurrence and progression of multiple diseases. Plasma exosomes secreted by cells contain various bioactive N-glycoproteins which may serve as potential biomarkers for early disease diagnosis and treatment. However, the protein N-glycosylation profile in human plasma exosome is largely unknown, due to the technical challenges in glycoprotein identification. Signals of the rare N-glycoproteins/N-glycopeptides are severely suppressed by the abundant coexisting non-glycosylated counterparts in mass spectrometry analysis. Therefore, specific enrichment of N-glycoprotein/glycopeptide is a prerequisite for large scale N-glycosylation profiling. In this work, we developed a hydrazide functionalized thermosensitive polymer for efficient enrichment and in-depth identification of protein N-glycosylation in human plasma exosome by mass spectrometry. The polymer chains completely dissolve in the enrichment system to form a homogeneous solution. Therefore, efficient covalent coupling between the N-glycoprotein/glycopeptide and the polymer chain is achieved, due to the reduced interfacial mass transfer resistance and the densely packed accessible functional groups on the polymer chains. Furthermore, the thermosensitive polymer can be easily precipitated and recovered by simply rising the system temperature to above 34 °C. As a result, 329 N-glycosylation sites corresponding to 180 N-glycoproteins were enriched and identified from plasma exosomes of glioma patients and healthy subjects using the thermosensitive polymer. By quantitative comparison, we found 26 N-glycoproteins significantly changed between the glioma patients and the healthy subjects, demonstrating the potential of this new strategy for N-glycoproteome research of plasma exosome and biomarker discovery.

Design and mechanistic study of a novel gold nanocluster-based drug delivery system.

Chemically-triggered drug delivery systems (DDSs) have been extensively studied as they do not require specialized equipment to deliver the drug and can deeply penetrate human tissue. However, their syntheses are complicated and they tend to be cytotoxic, which restricts their clinical utility. In this work, the self-regulated drug loading and release capabilities of peptide-protected gold nanoclusters (Pep-Au NCs) are investigated using vancomycin (Van) as the model drug. Gold nanoclusters (Au NCs) coated with a custom-designed pentapeptide are synthesized as drug delivery nanocarriers and loaded with Van - a spontaneous process reliant on the specific binding between Van and the custom-designed peptide. The Van-loaded Au NCs show comparable antimicrobial activity with Van on its own, and the number of Van released by the Pep-Au NCs is found to be proportional to the amount of bacteria present. The controlled nature of the Van release is very encouraging, and predominantly due to the stronger binding affinity of Van with bacteria than that with Au NCs. In addition, these fluorescent Au NCs could also be used to construct temperature sensors, which enable the in vitro and in vivo bioimaging.

X-ray crystal structure and doping mechanism of bimetallic nanocluster Au36-xCux(m-MBT)24 (x = 1-3).

A novel Au36-xCux(m-MBT)24 (x = 1-3, m-MBT = 3-methylbenzenethiolate) nanocluster has been prepared. According to the X-ray single crystal diffractometer, the structure of Au36-xCux(m-MBT)24 is similar to that of Au36(SPhtBu)24. The Au36-xCux(m-MBT)24 nanocluster contains a face-centered cubic (FCC) M28 core, which is protected by 4 M2S3 (M = Au/Cu) staple motifs and 12 bridging SR ligands. The Cu dopants could possibly occupy 14 sites (six in the sub-surface and eight in the staple motifs). Spectral monitoring indicates that the number of Cu dopants sequentially increased on increasing the amount of Cu precursors (relative to a Au control). Meanwhile, DFT calculations imply that the maximum doping number of Cu is 3, and doping occurs preferentially at the staple sites and sub-surface sites (instead of the centre of the core). Because the atomic orbital of the peripheral locations hardly contributes to the frontier molecular orbitals, the UV-vis of the AuCu alloy is almost the same as that of its homometallic Au counterpart.