CT radiomics-based model for predicting TMB and immunotherapy response in non-small cell lung cancer.

BACKGROUND: Tumor mutational burden (TMB) is one of the most significant predictive biomarkers of immunotherapy efficacy in non-small cell lung cancer (NSCLC). Radiomics allows high-throughput extraction and analysis of advanced and quantitative medical imaging features. This study develops and validates a radiomic model for predicting TMB level and the response to immunotherapy based on CT features in NSCLC. METHOD: Pre-operative chest CT images of 127 patients with NSCLC were retrospectively studied. The 3D-Slicer software was used to outline the region of interest and extract features from the CT images. Radiomics prediction model was constructed by LASSO and multiple logistic regression in a training dataset. The model was validated by receiver operating characteristic (ROC) curves and calibration curves using external datasets. Decision curve analysis was used to assess the value of the model for clinical application. RESULTS: A total of 1037 radiomic features were extracted from the CT images of NSCLC patients from TCGA. LASSO regression selected three radiomics features (Flatness, Autocorrelation and Minimum), which were associated with TMB level in NSCLC. A TMB prediction model consisting of 3 radiomic features was constructed by multiple logistic regression. The area under the curve (AUC) value in the TCGA training dataset was 0.816 (95% CI: 0.7109-0.9203) for predicting TMB level in NSCLC. The AUC value in external validation dataset I was 0.775 (95% CI: 0.5528-0.9972) for predicting TMB level in NSCLC, and the AUC value in external validation dataset II was 0.762 (95% CI: 0.5669-0.9569) for predicting the efficacy of immunotherapy in NSCLC. CONCLUSION: The model based on CT radiomic features helps to achieve cost effective improvement in TMB classification and precise immunotherapy treatment of NSCLC patients.

Distribution, sources and ecological risks of PAHs and n-alkanes in water and sediments of typically polluted estuaries: Insights from the Xiaoqing River.

Seasonal water and sediment samples were collected from the Xiaoqing River estuary and the neighboring sea to study the spatial and temporal distributions, sources and ecological risks of polycyclic aromatic hydrocarbons (PAHs) and n-alkanes. The results showed significant spatial and temporal differences in the concentrations of PAHs and n-alkanes under the influence of precipitation, temperature, and human activities. The concentrations of PAHs in water were lower in the wet season than in the dry season, and those in sediments were higher in the wet season than in the dry season. The concentrations of n-alkanes were higher in the rainy season than in the dry season for both water and sediments. The spatial distributions of PAHs and n-alkanes were estuarine > offshore. The concentration ranges of ∑PAHs in water and sediments were 230.66-599.86 ng/L and 84.51-5548.62 ng/g, respectively, in the wet season and 192.46-8649.55 ng/L and 23.39-1208.92 ng/g, respectively, in the dry season. The proportion of three-ring PAHs in water (57.03% and 78.27% in the wet and dry seasons, respectively) was high, followed by two-ring PAHs (27.31% and 13.59% in the wet and dry seasons, respectively). The proportion of four-ring PAHs was higher in sediments (24.79% and 32.20% in the wet and dry seasons, respectively). The ecological risk of PAHs assessed using the toxicity equivalent quotient and risk quotient was at moderate to moderately high risk levels. The high concentration of n-alkane fraction C16 (611.65-75594.58 ng/L) in the water is indicative of petroleum or other fossil fuel inputs. The main peaks of n-alkanes in river sediments were C27, C29 and C31, indicating higher inputs of plant sources. The sediments in the estuary showed dominance of both short-chain C16 and long-chain C25-C31, indicating a combined input of higher plants and petroleum. The diagnostic ratios of PAHs and n-alkanes indicated that their sources were mainly oil/coal/biomass combustion and petroleum spills attributed to frequent vehicular, vessel and mariculture activities. Given the potential ecological risks of PAHs and n-alkanes in water and sediments, future studies should focus on their bioaccumulation and biotoxicity.

Assessment of spilled oil dispersion affected by dispersant: Characteristic, stability, and related mechanism.

Oil dispersion, a crucial process in oil transport, involves the detachment of oil droplets from slicks and their introduction into the water column, influencing subsequent oil migration and transformation. This study examines oil dispersion, considering characteristics, stability, and mechanisms, while evaluating the impact of dispersants and salinity. Results show the significant role of surfactant type in dispersants on oil dispersion characteristics, with anionic surfactants exhibiting higher sensitivity to salinity changes compared to nonionic surfactants. The dispersion efficiency varies with salinity, with anionic surfactants performing better in low salinity (<20‰) and nonionic surfactants showing superior performance at 30-35‰ salinities. Rheological analysis illustrates the breakup and coalescence of oil droplets within the shear rates of breaking waves. An increase in interfacial film rigidity impedes the coalescence of oil droplets, contributing to the dynamic stability of the oil-water hybrid system. The use of GM-2, a nonionic dispersant, results in the formation of a solid-like interface, characterized by increased elastic modulus, notably at 20‰ salinity. However, stable droplet size distribution (DSD) at 35‰ salinity for 60 h suggests droplets can remain dispersed in seawater. The enhancement of stability of oil dispersion is interpreted as the result of two mechanisms: stabilizing DSD and developing the strength of viscoelastic interfacial film. These findings offer insights into oil dispersion dynamics, highlighting the importance of surfactant selection and salinity in governing dispersion behavior, and elucidating mechanisms underlying dispersion stability.

Continuous Covalent Organic Frameworks Membranes: From Preparation Strategies to Applications.

Covalent organic frameworks (COFs) are porous crystalline polymeric materials formed by the covalent bonding of organic units. The abundant organic units library gives the COFs species diversity, easily tuned pore channels, and pore sizes. In addition, the periodic arrangement of organic units endows COFs regular and highly connected pore channels, which has led to the rapid development of COFs in membrane separations. Continuous defect-free and high crystallinity of COF membranes is the key to their application in separations, which is the most important issue to be addressed in the research. This review article describes the linkage types of covalent bonds, synthesis methods, and pore size regulation strategies of COFs materials. Further, the preparation strategies of continuous COFs membranes are highlighted, including layer-by-layer (LBL) stacking, in situ growth, interfacial polymerization (IP), and solvent casting. The applications in separation fields of continuous COFs membranes are also discussed, including gas separation, water treatment, organic solvent nanofiltration, ion conduction, and energy battery membranes. Finally, the research results are summarized and the future prospect for the development of COFs membranes are outlined. More attention may be paid to the large-scale preparation of COFs membranes and the development of conductive COFs membranes in future research.

microRNA-155-5p initiates childhood acute lymphoblastic leukemia by regulating the IRF4/CDK6/CBL axis.

Acute lymphoblastic leukemia (ALL) is a common malignancy in children. In this study, we aimed to explore putative mechanisms of microRNA-155-5p (miR-155-5p) involvement in childhood ALL (cALL) via interactions with casitas B-lineage lymphoma (CBL), interferon regulatory factor 4 (IRF4), and cyclin-dependent kinase 6 (CDK6). Bioinformatic analysis was performed initially to identify differentially expressed genes in cALL. The expression levels of miR-155-5p, CBL, IRF4, and CDK6 in peripheral blood lymphocytes from clinical ALL samples were determined using RT-qPCR and Western blot assays. A dual-luciferase reporter gene assay was used to ascertain a possible targeting relationship between miR-155-5p and CBL, CCK-8 assay and flow cytometry were used to measure cell activity and apoptosis of ALL cells. Co-IP was performed to investigate the interaction between CBL and IRF4 and the ubiquitination level of IRF4. Furthermore, in vivo validation was performed inducing xenograft tumor models with ALL cells in nude mice. As indicated by bioinformatic analysis, miR-155-5p and CDK6 were upregulated and CBL was downregulated in ALL. miR-155-5p was found to target CBL to inhibit CBL expression. miR-155-5p promoted the proliferation of ALL cells and inhibited their apoptosis by inhibiting the expression of CBL, which otherwise degraded IRF4 protein through ubiquitination, leading to inhibited CDK6 expression. Collectively, the results show that miR-155-5p can promote the development of cALL via the regulation on CBL-mediated IRF4/CDK6 axis.

A Cluster Sequencing Strategy To Determine the Consensus Affinity Domains in Heparin for Its Binding to Specific Proteins.

Glycosaminoglycans (GAGs) have high negative charge and are biologically and pharmaceutically important because their high charge promotes a strong interaction with many proteins. Due to the inherent heterogeneity of GAGs, multiple oligosaccharides, containing certain common domains, often can interact with clusters of basic amino acid residues on a target protein. The specificity of many GAG-protein interactions remains undiscovered since there is insufficient structural information on the interacting GAGs. Herein, we establish a cluster sequencing strategy to simultaneously deduce all major sequences of the affinity GAG oligosaccharides, leading to a definition of the consensus sequence they share that corresponds to the specific binding domain for the target protein. As a proof of concept, antithrombin III-binding oligosaccharides were examined, resulting in a heptasaccharide domain containing the well-established anticoagulant pentasaccharide sequence. Repeating this approach, a new pentasaccharide domain was discovered corresponding to the heparin motif responsible for binding interferon-γ (IFNγ). Our strategy is fundamentally important for the discovery of saccharide sequences needed in the development of novel GAG-based therapeutics.

Deep Single-Cell-Type Proteome Profiling of Mouse Brain by Nonsurgical AAV-Mediated Proximity Labeling.

Proteome profiling is a powerful tool in biological and biomedical studies, starting with samples at bulk, single-cell, or single-cell-type levels. Reliable methods for extracting specific cell-type proteomes are in need, especially for the cells (e.g., neurons) that cannot be readily isolated. Here, we present an innovative proximity labeling (PL) strategy for single-cell-type proteomics of mouse brain, in which TurboID (an engineered biotin ligase) is used to label almost all proteins in a specific cell type. This strategy bypasses the requirement of cell isolation and includes five major steps: (i) constructing recombinant adeno-associated viruses (AAVs) to express TurboID driven by cell-type-specific promoters, (ii) delivering the AAV to mouse brains by direct intravenous injection, (iii) enhancing PL labeling by biotin administration, (iv) purifying biotinylated proteins, followed by on-bead protein digestion, and (v) quantitative tandem-mass-tag (TMT) labeling. We first confirmed that TurboID can label a wide range of cellular proteins in human HEK293 cells and optimized the single-cell-type proteomic pipeline. To analyze specific brain cell types, we generated recombinant AAVs to coexpress TurboID and mCherry proteins, driven by neuron- or astrocyte-specific promoters and validated the expected cell expression by coimmunostaining of mCherry and cellular markers. Subsequent biotin purification and TMT analysis identified ∼10,000 unique proteins from a few micrograms of protein samples with excellent reproducibility. Comparative and statistical analyses indicated that these PL proteomes contain cell-type-specific cellular pathways. Although PL was originally developed for studying protein-protein interactions and subcellular proteomes, we extended it to efficiently tag the entire proteomes of specific cell types in the mouse brain using TurboID biotin ligase. This simple, effective in vivo approach should be broadly applicable to single-cell-type proteomics.

Effectiveness of cell- and colony stimulating factor-based therapy for liver cirrhosis: a network meta-analysis of randomized controlled trials.

BACKGROUND AIMS: Cirrhosis is the 11th leading cause of death worldwide. Because of the limitations of liver transplantation, cell- and granulocyte colony-stimulating factor (G-CSF)-based therapies are considered potential treatment methods. This work analyzes the effectiveness of cell- and G-CSF-based therapies by network meta-analysis. METHODS: A literature search was performed in four databases from inception to September 10, 2021. Registered randomized controlled trials (RCTs) evaluating cell-based therapies and/or G-CSF-based therapies for cirrhosis patients were included. Traditional and network meta-analyses were analyzed in terms of survival, model for end-stage liver disease (MELD) score, Child-Turcotte-Pugh (CTP) score, alanine aminotransferase levels and aspartate aminotransferase levels. RESULTS: Twenty-four studies were included in this analysis. The results showed that G-CSF-based therapies (odds ratio [OR], 2.38, 95% confidence interval [CI], 1.49-3.79, P < 0.01) and cell-based therapies (OR, 1.54, 95% CI, 1.00-2.40, P = 0.048) improved the transplantation-free survival rate compared with standard medical treatment. Network analysis results showed that G-CSF combined with erythropoietin (EPO) and growth hormone (GH) had a therapeutic advantage, and cell-based therapy with mononuclear cell (MNC) hepatic artery injection and intravenous mesenchymal stem cells (MSCs) combined with G-CSF also had a relative advantage in terms of survival outcome. For the MELD score, G-CSF plus GH and MSC portal vein injection had relative advantages. G-CSF plus GH and G-CSF plus EPO had advantages in terms of CTP scores. The included strategies demonstrated no obvious improvement in liver injury indicators. CONCLUSIONS: Cell-based therapy has potential therapeutic effects for liver cirrhosis. Among cell-based therapies, intravenous MSCs and hepatic artery injection of MNCs have advantageous therapeutic effects. The use of G-CSF was also noted in regimens that improved survival outcomes. However, more well-designed, large-scale RCTs are needed to confirm this conclusion.

Effect of fermentation pH on the structure, rheological properties, and antioxidant activities of exopolysaccharides produced by Alteromonas australica QD.

The pH value was essential for the growth and metabolism of microorganisms. Acidic pH exopolysaccharide (AC-EPS) and alkaline pH exopolysaccharide (AL-EPS) secreted by A. australica QD mediated by pH were studied in this paper. The total carbohydrate content and molecular weight of AC-EPS (79.59% ± 2.24% (w/w), 8.374 × 105 Da) and AL-EPS (82.48% ± 1.46% (w/w), 6.182 × 105 Da) were estimated and compared. In AC-EPS, mannose (3.78%) and galactose (3.24%) content was more, while the proportion of glucuronic acid was less in comparison to AL-EPS. The scanning electron microscopy revealed the structural differences among the AC-EPS and AL-EPS. Thermogravimetric analysis showed degradation temperatures of 272.8 °C and 244.9 °C for AC-EPS and AL-EPS, respectively. AC-EPS was found to exhibit better rheological properties and emulsifying capabilities, while AL-EPS had superior antioxidant activities. Overall, both AC-EPS and AL-EPS have the potential to be used as emulsifiers and biological antioxidants.

Circ_0039960 regulates growth and Warburg effect of breast cancer cells via modulating miR-1178/PRMT7 axis.

BACKGROUND: Breast cancer (BC) is a serious threat to women's life and healthy. Increasing evidence indicated that blocking Warburg effect could attenuate the development of BC. Circular RNAs (circRNAs) has been found to be dysregulated in various carcinomas, including BC. Our study aims to illustrate the role and regulatory mechanism of circ_0039960 in BC development. METHODS: RT-qPCR and western blotting were utilized to evaluate the expression of circ_0039960 in tissues recruited from 32 cases of BC patients and also BC cell lines. Circ_0039960 shRNA was transfected into cells to explore its function on cell processes. CCK-8, flow cytometry and ELISA were used to measure cell viability, cell cycle and apoptosis. Warburg effect was detected by using commercial kits. Besides, bioinformatic prediction, RIP and luciferase reporter assays were performed to validate the interactions between circ_0039960, miR-1178 and PRMT7. RESULTS: The results showed that circ_0039960 and PRMT7 were both up-regulated, while miR-1178 was down-regulated, in BC tissues and cells. Silencing circ_0039960 effectively inhibited cell viability and Warburg effect of BC cells, also, induced cell cycle arrest and apoptosis. Moreover, we validated that circ_0039960 positively mediated PRMT7 expression via directly targeting to miR-1178. The inhibition of miR-1178 and overexpression of PRMT7 reversed the effect of circ_0039960 knockdown on BC cell growth and Warburg effect. CONCLUSION: In general, our research demonstrated that circ_0039960 regulates cell growth and Warburg effect in BC cells via miR-1178/PRMT7 axis. This may provide new evidence for the exploration of BC diagnostic and therapeutic targets.

The amino acid and carnitine concentration changes in bronchoalveolar lavage fluid from lung cancer patients.

OBJECTIVE: To screen out potential biomarkers by analyzing fundamental nutrients in the bronchoalveolar lavage fluid (BALF) before confirming the lung cancer. METHODS: In this study, 44 patients were enrolled with clinical information. The concentrations of 23 amino acids and 35 carnitines in their BALF were detected with the high-performance liquid chromatography-mass spectrometry (HPLC-MS). Combined with clinicopathological diagnosis, the patients were divided into the lung cancer group (grades I & II and III & IV) and the non-cancer group for standard statistical analysis. RESULTS: The partial least squares-discriminant analysis (PLS-DA), the Shapiro-Wilk test, and the Bonferroni correction results showed that the serine concentration was higher and the butane-diacyl-carnitine (C4DC) concentration was lower in the lung cancer group, further showing the same changing trend continuously through the non-cancer stage, grades I & II stage and grades III & IV stage. Those two potential biomarkers have been identified. CONCLUSION: The HPLC-MS target detection in clinic for nutrient concentration levels is a promising technique to find the changing concentration of serine and C4DC in BALF, which provides an economical and practical way for early warning of lung cancer.

Extinction and stationary distribution of a stochastic SIQR epidemic model with demographics and non-monotone incidence rate on scale-free networks.

By taking full consideration of contact heterogeneity of individuals, quarantine measures, demographics, information transmission and random environments, we present a stochastic SIQR epidemic model with demographics and non-monotone incidence rate on scale-free networks, which introduces stochastic perturbations to death rate. The formula of the basic reproduction number of the deterministic model is obtained by utilizing the existence of the endemic equilibrium. Next, we define a stopping time, then the existence of a unique global positive solution for the stochastic model is proved by constructing appropriate Lyapunov function to demonstrate the stopping time is infinite. In addition, we also manifest sufficient conditions for diseases extinction and the existence of ergodic stationary distribution by constructing appropriate stochastic Lyapunov functions. At last, numerical simulations illustrate the analytical results.

Coupling Liquid Chromatography and Tandem Mass Spectrometry to Electrophoresis for In-Depth Analysis of Glycosaminoglycan Drugs: Heparin and the Multicomponent Sulodexide.

Glycosaminoglycans (GAGs) contribute to the treatment of many human diseases, especially in the field of thrombosis, because of their anticoagulant activity. GAGs interrupt the coagulation process by interacting with multiple coagulation factors through defined sequences within their linear and negatively charged chains, which are not fully elucidated. Numerous methods have been developed to characterize the structure of pharmaceutical GAGs, including intravenously or subcutaneously administered heparin and orally administered sulodexide. However, most currently available methods only focus on the oligosaccharide portion or analyze the whole mixture because longer-chain polysaccharides are extremely difficult to resolve by chromatographic separation. We have established two novel electrophoresis-mass spectrometry methods to provide a panoramic view of the structures of pharmaceutical GAGs. In the first method, an in-gel digestion procedure was developed to recover GAGs from the polyacrylamide gels, while in the second method, a strong anion exchange ultrafiltration procedure was developed to extract multiple GAG species from the agarose gels. Both procedures are compatible with liquid chromatography-tandem mass spectrometry, and structural information, such as disaccharide composition and chain length, can be revealed for each GAG fraction. The applications of these two methods on analysis of two different GAG drugs, heparin and sulodexide, were demonstrated. The current study offers the first robust tool to directly elucidate the structure of larger GAG chains with more biological importance rather than obtaining a vague picture of all chains as a mixture, which is fundamental for better understanding the structure-activity relationship and quality control of the GAG drugs.

Brain and lesion segmentation in multiple sclerosis using fully convolutional neural networks: A large-scale study.

OBJECTIVE: To investigate the performance of deep learning (DL) based on fully convolutional neural network (FCNN) in segmenting brain tissues in a large cohort of multiple sclerosis (MS) patients. METHODS: We developed a FCNN model to segment brain tissues, including T2-hyperintense MS lesions. The training, validation, and testing of FCNN were based on ~1000 magnetic resonance imaging (MRI) datasets acquired on relapsing-remitting MS patients, as a part of a phase 3 randomized clinical trial. Multimodal MRI data (dual-echo, FLAIR, and T1-weighted images) served as input to the network. Expert validated segmentation was used as the target for training the FCNN. We cross-validated our results using the leave-one-center-out approach. RESULTS: We observed a high average (95% confidence limits) Dice similarity coefficient for all the segmented tissues: 0.95 (0.92-0.98) for white matter, 0.96 (0.93-0.98) for gray matter, 0.99 (0.98-0.99) for cerebrospinal fluid, and 0.82 (0.63-1.0) for T2 lesions. High correlations between the DL segmented tissue volumes and ground truth were observed (R2 > 0.92 for all tissues). The cross validation showed consistent results across the centers for all tissues. CONCLUSION: The results from this large-scale study suggest that deep FCNN can automatically segment MS brain tissues, including lesions, with high accuracy.

Continuous and Rapid Synthesis of UiO-67 by Electrochemical Methods for the Electrochemical Detection of Hydroquinone.

Continuous and rapid synthesis of UiO-67 under mild conditions has been achieved by electrochemical methods for the first time. In the reaction system, a zirconium sheet was utilized as electrodes and a metal source for the assembly of UiO-67. High-crystalline UiO-67 with a regular tetrahedral morphology of around 1 µm was obtained within 1.5 h under the optimized solvent composition, voltage, and temperature conditions. This electrochemical synthetic method of UiO-67 in our work overcomes the shortcomings of high temperature and pressure of a traditional solvothermal method, which proposes new ideas for the large-scale and rapid synthesis of UiO-67. The UiO-67 synthesized by an electrochemical method was prepared as a UiO-67-carbon paste electrode (CPE), which exhibited a linear response to hydroquinone (HQ) in the range of 5-300 µM with a detection limit of 3.6 × 10-9 M (S/N = 3), for the electrochemical detection of HQ. It was confirmed that UiO-67-CPE possessed excellent reusability and antiinterference ability for the detection of HQ, and its detection ability even did not change after standing for 3 months. We further tried to apply UiO-67-CPE to the practical determination of HQ in tap water and river water samples, and the results proved that the recovery rate is 97.9-104.7% in real samples.

Non-O1/non-O139 Vibrio cholerae bacteraemia in mainland China from 2005 to 2019: clinical, epidemiological and genetic characteristics.

In mainland China, the clinical, epidemiological and genetic features of non-O1/non-O139 Vibrio cholerae (NOVC) bacteraemia have been scarcely investigated. Herein, we describe a patient with NOVC bacteraemia diagnosed in our hospital and present a retrospective analysis of literature reports of 32 other cases in China, detailing the clinical epidemiology, antibiotic resistance and molecular characteristics of isolates. Most patients were male (84.8%; median age, 53 years) and had predisposing factors, such as cirrhosis, malignant tumours, blood diseases and diabetes. In addition to fever, gastroenteritis was the most frequent presenting symptom. The mortality rate during hospitalisation was 12.1%. NOVC bacteraemia cases were more common in June-August, with the majority in coastal provinces and the Yangtze River basin. Only 42.4% of cases were attributed to consumption of marine (aquatic) products. Tetracycline, third-generation cephalosporins, and fluoroquinolones were the most effective antimicrobial agents, and the highest frequencies of resistance were recorded for ampicillin/sulbactam (37.5%), amoxicillin/clavulanic acid (33.3%), ampicillin (29.2%) and sulfamethoxazole (20%). Multi-drug resistant isolates were not detected. Limited data indicate that ctxAB and tcpA genes were absent in all NOVC isolates but other putative virulence genes (hlyA, toxR, hap and rtxA) were common. Ten multilocus sequence types were identified with marked genetic heterogeneity between different isolates. As clinical manifestations of NOVC bacteraemia may vary widely, and isolates exhibit genetic diversity, clinicians and public health experts should be alerted to the possibility of infection with this pathogen because of the high prevalence of liver disease in China.

Efficacy of Nucleotide/Nucleoside Analogues and Hepatitis B Immunoglobulin Therapy in Blocking Mother-to-Child Transmission of Hepatitis B in an Eastern Chinese Group.

The objective of this study was to investigate the efficacy and potential side-effects of nucleotide/nucleoside analogues and hepatitis B immunoglobulin injection of newborns in blocking mother-to-child transmission of hepatitis B virus in the middle and late pregnancy period. 238 cases of enrolled pregnant women were divided into the Telbivudine group, the Tenofovir group, the Lamivudine group, and the hepatitis B immunoglobulin (HBIG) group. Enrolled patients received corresponding therapies. Clinical and laboratory data were collected. Results showed that the levels of HBV DNA of the enrolled pregnant women in the Telbivudine, Tenofovir, and Lamivudine groups decreased rapidly after 12 weeks of drug intervention compared with those in the control. HBsAg positive rate in newborns and in children 24 weeks after birth was 0/60, 0/60, 0/60, 3/30, and 11/28 in the Telbivudine, Tenofovir, Lamivudine, HBIG, and control groups, respectively. No significant side-effects were identified after following up to 12 months after birth. Our results show that routine HBV vaccine plus HBIG injections is insufficient in blocking mother-to-child HBV transmission. Administration of nucleotide/nucleoside analogues or HBIG at pregnancy is suggested to maximize the blocking of vertical HBV transmission.

Rapid and Low-Cost Electrochemical Synthesis of UiO-66-NH2 with Enhanced Fluorescence Detection Performance.

Rapid and low-cost synthesis of metal-organic frameworks (MOFs) are very meaningful for their future practical application. In the present study, a Zr-based ultrastable MOF, UiO-66-NH2, was successfully synthesized by electrochemical method using metal Zr as the metal source at room temperature and atmospheric pressure. The effects of the reaction conditions, including the ratio of solvent (electrolyte), the applied voltage and different reaction time, on the crystallinity, morphology, and synthesis rate of the product were fully investigated. The results confirm that electrochemically synthesized UiO-66-NH2 under the optimized condition possesses apparent merits such as high crystallinity, uniform morphology and high porosity. Moreover, the electrochemical synthesis method of UiO-66-NH2 is promising for the large-scale and economical synthesis of nanoscale product to gramme degree. Interestingly, the resulting UiO-66-NH2 synthesized by this electrochemical method exhibits more excellent performance for the fluorescence detection of Fe3+ ions in water (detection limit of 10-8 mol/L) than that of the material prepared by solvothermal method.

Enriching Silver Nanocrystals with a Second Noble Metal.

Noble-metal nanocrystals have received considerable interests owing to their fascinating properties and promising applications in areas including plasmonics, catalysis, sensing, imaging, and medicine. As demonstrated by ample examples, the performance of nanocrystals in these and related applications can be augmented by switching from monometallic to bimetallic systems. The inclusion of a second metal can enhance the properties and greatly expand the application landscape by bringing in new capabilities. Seeded growth offers a powerful route to bimetallic nanocrystals. This approach is built upon the concept that preformed nanocrystals with uniform, well-controlled size, shape, and structure can serve as seeds to template and direct the deposition of metal atoms. Seeded growth is, however, limited by galvanic replacement when the deposited metal is less reactive than the seed. The involvement of galvanic replacement not only makes it difficult to control the outcome of seeded growth but also causes degradation to some properties. We have successfully addressed this issue by reducing the salt precursor(s) into atoms with essentially no galvanic replacement. In the absence of self-nucleation, the atoms are preferentially deposited onto the seeds to generate bimetallic nanocrystals with controlled structures. In this Account, we use Ag nanocubes as an example to demonstrate the fabrication of Ag@M and Ag@Ag-M (M = Au, Pd, or Pt) nanocubes with a core-frame or core-shell structure by controlling the deposition of M atoms. A typical synthesis involves the titration of Mn+ (a precursor to M) ions into an aqueous suspension containing Ag nanocubes, ascorbic acid, and poly(vinylpyrrolidone) under ambient conditions. In one approach, aqueous sodium hydroxide is introduced to increase the initial pH of the reaction system. At pH = 11.9, ascorbic acid is dominated by ascorbate monoanion, a much stronger reductant, to suppress the galvanic replacement between Mn+ and Ag. In this case, the M atoms derived from the reduction by ascorbate monoanion are sequentially deposited on the edges, corners, and side faces to generate Ag@M core-frame and then core-shell nanocubes. The other approach involves the use of ascorbic acid as a relatively weak reductant while Mn+ is cotitrated with Ag+ ions in the absence of sodium hydroxide. At pH = 3.2, when the molar ratio of Ag+ to Mn+ is sufficiently high, the added Ag+ ions can effectively push the galvanic reaction backward and thus inhibit it. As a result, coreduction of the two precursors by ascorbic acid produces Ag and M atoms for the generation of Ag@Ag-M core-frame nanocubes with increasingly thicker ridges. The Ag@Ag-Pd core-frame nanocubes can serve as a dual catalyst to promote the stepwise reduction of nitroaromatics to aminoaromatics and then oxidation to azo compounds. The consecutive reactions can be monitored using surface-enhanced Raman scattering (SERS). The Ag@Au core-shell nanocubes with Au shells of three or six atomic layers exhibit plasmonic peaks almost identical to those of the Ag nanocubes while the chemical stability and SERS activity are substantially augmented. For both types of bimetallic nanocubes, the Ag cores can be selectively removed to generate nanoframes and nanoboxes.

Folic Acid Functionalized Zirconium-Based Metal-Organic Frameworks as Drug Carriers for Active Tumor-Targeted Drug Delivery.

Nanoscale metal-organic frameworks (NMOFs) have proven to be a class of promising drug carriers as a result of their high porosity, crystalline nature with definite structure information, and potential for further functionality. However, MOF-based drug carriers with active tumor-targeting function have not been extensively researched until now. Here we show a strategy for constructing active tumor-targeted NMOF drug carriers by anchoring functional folic acid (FA) molecules onto the metal clusters of NMOFs. Two zirconium-based MOFs, MOF-808 and NH2 -UiO-66, were chosen as models to reduce to the nanoscale for application as drug carriers, and then the terminal carboxylates of FA molecules were coordinated to Zr6 clusters on the surfaces of the nanoparticles by substitution of the original formate or terminal -OH ligands. The successful modification with FA was confirmed by solid-state 13 C MAS NMR and UV/Vis spectroscopy and other characterization methods. Drug loading and controlled release behavior at different pH were determined by utilizing the anticancer drug 5-fluorouracil (5-FU) as the model drug. Confocal laser scanning microscopy measurements further demonstrated that 5-FU-loaded FA-NMOFs have excellent targeting ability through the efficient cellular uptake of FA-NMOFs. This work opens up a new avenue to the construction of active tumor-targeted NMOF-based drug carriers with potential for cancer therapies.