Blocking Strategies Research Articles

Electrochemical Detection and Analysis of Various Current Responses of a Single Ag Nanoparticle Collision in an Alkaline Electrolyte Solution.

A single silver (Ag) nanoparticle (NP) collision was observed and analyzed in an alkaline solution using the electrocatalytic amplification (EA) method. Previously, the observation of a single Ag NP collision was only possible through limited methods based on a self-oxidation of Ag NPs or a blocking strategy. However, it is difficult to characterize the electrocatalytic activity of Ag NPs at a single NP level using a method based on the self-oxidation of Ag NPs. When using a blocking strategy, size analysis is difficult owing to the edge effect in the current signal. The fast oxidative dissolution of Ag NPs has been a problem for observing the staircase response of a single Ag NP collision signal using the EA method. In alkaline electrolyte conditions, Ag oxides are stable, and the oxidative dissolution of Ag NPs is sluggish. Therefore, in this study, the enhanced magnitude and frequency of the current response for single Ag NP collisions were obtained using the EA method in an alkaline electrolyte solution. The peak height and frequency of single Ag NP collisions were analyzed and compared with the theoretical estimation.

Local depletion of proteoglycans mediates cartilage tissue repair in an ex vivo integration model

Successfully replacing damaged cartilage with tissue-engineered constructs requires integration with the host tissue and could benefit from leveraging the native tissue's intrinsic healing capacity; however, efforts are limited by a poor understanding of how cartilage repairs minor defects. Here, we investigated the conditions that foster natural cartilage tissue repair to identify strategies that might be exploited to enhance the integration of engineered/grafted cartilage with host tissue. We damaged porcine articular cartilage explants and using a combination of pulsed SILAC-based proteomics, ultrastructural imaging, and catabolic enzyme blocking strategies reveal that integration of damaged cartilage surfaces is not driven by neo-matrix synthesis, but rather local depletion of proteoglycans. ADAMTS4 expression and activity are upregulated in injured cartilage explants, but integration could be reduced by inhibiting metalloproteinase activity with TIMP3. These observations suggest that catabolic enzyme-mediated proteoglycan depletion likely allows existing collagen fibrils to undergo cross-linking, fibrillogenesis, or entanglement, driving integration. Catabolic enzymes are often considered pathophysiological markers of osteoarthritis. Our findings suggest that damage-induced upregulation of metalloproteinase activity may be a part of a healing response that tips towards tissue destruction under pathological conditions and in osteoarthritis, but could also be harnessed in tissue engineering strategies to mediate repair. Statement of significanceCartilage tissue engineering strategies require graft integration with the surrounding tissue; however, how the native tissue repairs minor injuries is poorly understood. We applied pulsed SILAC-based proteomics, ultrastructural imaging, and catabolic enzyme blocking strategies to a porcine cartilage explant model and found that integration of damaged cartilage surfaces is driven by catabolic enzyme-mediated local depletion of proteoglycans. Although catabolic enzymes have been implicated in cartilage destruction in osteoarthritis, our findings suggest that damage-induced upregulation of metalloproteinase activity may be a part of a healing response that tips towards tissue destruction under pathological conditions. They also suggest that this natural cartilage tissue repair process could be harnessed in tissue engineering strategies to enhance the integration of engineered cartilage with host tissue.

The Suburbanization and Revitalization of Industrial Land in Shanghai, China

Land use efficiency is one of the critical indicators of sustainable development. Increasing land use efficiency can help build a more compact urban form and reduce the urban footprint. Industrial development is often considered a major driving force of urban land use expansion and use change. Both industrial development and urban land use change are constrained and facilitated by urban planning and management, constantly shaping the spatial trajectory of urban transformation. Taking the suburbanization and revitalization of industrial land uses in Shanghai as a case study, this research uses thematical analysis and geospatial data change detection methods to investigate how the evolution of industrial spatial structure leads to urban land use growth, and how urban planning and governance reconfigure the industrial spatial structure of a city through revitalization. This study found that the unplanned suburbanization of industrial land use brought about significant residential and commercial land use expansion. The city was able to consolidate its industrial land uses by adopting the designated industrial blocks strategy to curb the sprawl of industrial land use and enhance land use efficiency. With the transformation of industry structure, the city achieved great success in transforming underutilized industrial land in the city’s central area and consolidating scattered industrial land into industrial blocks in the city’s suburban areas.

The effect of azithromycin on structural lung disease in infants with cystic fibrosis (COMBAT CF): a phase 3, randomised, double-blind, placebo-controlled clinical trial

Structural lung disease and neutrophil-dominated airway inflammation is present from 3 months of age in children diagnosed with cystic fibrosis after newborn screening. We hypothesised that azithromycin, given three times weekly to infants with cystic fibrosis from diagnosis until age 36 months, would reduce the extent of structural lung disease as captured on chest CT scans. A phase three, randomised, double-blind, placebo-controlled trial was done at eight paediatric cystic fibrosis centres in Australia and New Zealand. Infants (aged 3-6 months) diagnosed with cystic fibrosis following newborn screening were eligible. Exclusion criteria included prolonged mechanical ventilation in the first 3 months of life, clinically significant medical disease or comorbidities other than cystic fibrosis, or macrolide hypersensitivity. Participants were randomly assigned (1:1) to receive either azithromycin (10 mg/kg bodyweight orally three times per week) or matched placebo until age 36 months. Randomisation was done with a permuted block strategy and an interactive web-based response system, stratified by study site. Unblinding was done once all participants completed the trial. The two primary outcomes were the proportion of children with radiologically defined bronchiectasis, and the percentage of total lung volume affected by disease. Secondary outcomes included clinical outcomes and exploratory outcomes were inflammatory markers. Analyses were done with the intention-to-treat principle. This study is registered at ClinicalTrials.gov (NCT01270074). Between June 15, 2012, and July 10, 2017, 281 patients were screened, of whom 130 were enrolled, randomly assigned, and received first study dose. 68 participants received azithromycin and 62 received placebo. At 36 months, 88% (n=50) of the azithromycin group and 94% (n=44) of the placebo group had bronchiectasis (odds ratio 0·49, 95% CI 0·12 to 2·00; p=0·32), and total airways disease did not differ between groups (median difference -0·02%, 95% CI -0·59 to 0·56; p=0·96). Secondary outcome results included fewer days in hospital for pulmonary exacerbations (mean difference -6·3, 95% CI -10·5 to -2·1; p=0·0037) and fewer courses of inhaled or oral antibiotics (incidence rate ratio 0·88, 95% CI 0·81 to 0·97; p=0·0088) for those in the azithromycin group. For the preplanned, exploratory analysis, concentrations of airway inflammation were lower for participants receiving azithromycin, including interleukin-8 (median difference -1·2 pg/mL, 95% CI -1·9 to -0·5; p=0·0012) and neutrophil elastase activity (-0·6 μg/mL, -1·1 to -0·2; p=0·0087) at age 36 months, although no difference was noted between the groups for interleukin-8 or neutrophil elastase activity at 12 months. There was no effect of azithromycin on body-mass index at age 36 months (mean difference 0·4, 95% CI -0·1 to 0·9; p=0·12), nor any evidence of pathogen emergence with the use of azithromycin. There were few adverse outcomes with no differences between the treatment groups. Azithromycin treatment from diagnosis of cystic fibrosis did not reduce the extent of structural lung disease at 36 months of age; however, it did reduce airway inflammation, morbidity including pulmonary exacerbations in the first year of life and hospitalisations, and improved some clinical outcomes associated with cystic fibrosis lung disease. Therefore we suggest thrice-weekly azithromycin is a strategy that could be considered for the routine early management of paediatric patients with cystic fibrosis. Cystic Fibrosis Foundation.

Spherical neutralizing aptamer suppresses SARS-CoV-2 Omicron escape

Recently, the SARS-CoV-2 Omicron has spread very quickly worldwide. Several studies have indicated that the Omicron variant causes a substantial evasion of the humoral immune response and the majority of existing SARS-CoV-2 neutralizing antibodies. Here we address this challenge by applying a spherical cocktail neutralizing aptamer-gold nanoparticle (SNAP) to block the interaction of Omicron receptor binding domain (RBD) and host Angiotensin-Converting Enzyme 2 (ACE2). With the synergetic blocking strategy based on multivalent multisite aptamer binding and steric hindrance by the size-matched gold scaffold, the SNAP conjugate tightly binds to Omicron RBD with a dissociation constant of 13.6 pM, almost completely blocking the infection of Omicron pseudovirus with a half-maximal inhibitory concentration of 35.9 pM. Overall, the SNAP strategy not only fills the gap of the humoral immune evasion caused by clustered mutations on Omicron, but also provides a clue for the development of new broad neutralizing reagents against future variants.

Mixed Precision Recursive Block Diagonalization for Bivariate Functions of Matrices

Various numerical linear algebra problems can be formulated as evaluating bivariate function of matrices. The most notable examples are the Fréchet derivative along a direction, the evaluation of (univariate) functions of Kronecker-sum-structured matrices, and the solution of, Sylvester matrix equations. In this work, we propose a recursive block diagonalization algorithm for computing bivariate functions of matrices of small to medium size, for which dense linear algebra is appropriate. The algorithm combines a blocking strategy, as in the Schur--Parlett scheme, and an evaluation procedure for the diagonal blocks. We discuss two implementations of the latter. The first is a natural choice based on Taylor expansions, whereas the second is derivative-free and relies on a multiprecision perturb-and-diagonalize approach. In particular, the appropriate use of multiprecision guarantees backward stability without affecting the efficiency in the generic case. This makes the second approach more robust. The whole method has cubic complexity, and it is closely related to the well-known Bartels--Stewart algorithm for Sylvester matrix equations when applied to $f(x,y)=\frac{1}{x+y}$. We validate the performances of the proposed numerical method on several problems with different conditioning properties.

An E3 Ubiquitin Ligase Scaffolding Protein Is Proviral during Chikungunya Virus Infection in Aedes aegypti.

ABSTRACTChikungunya virus (CHIKV) is a reemerging alphavirus causing chikungunya disease (CHIKD) and is transmitted to humans by Aedes mosquitoes. The virus establishes an intricate balance of cellular interactions that ultimately helps in its replication and dodges cellular immune response. In an attempt to identify cellular host factors required during CHIKV replication in Aag2 cells, we performed global transcriptomics of CHIKV-infected Aag2 cells, and further, we compared this library with the Drosophila RNAi Screening Center (DRSC) database and identified transcripts that were regulated in Aedes aegypti during CHIKV infection. These analyses revealed specific pathways, such as ubiquitin-related pathways, proteolysis pathways, protein catabolic processes, protein modification, and cellular protein metabolic processes, involved during replication of the virus. Loss-of-function assays of selected candidates revealed their proviral or antiviral characteristics upon CHIKV infection in A. aegypti-derived Aag2 cells. Further validations identified that the ubiquitin proteasomal pathway is required for CHIKV infection in A. aegypti and that an important member of this family of proteins, namely, AeCullin-3 (Aedes ortholog of human cullin-3), is a proviral host factor of CHIKV replication in Aag2 cells.IMPORTANCE Arboviruses cause several diseases in humans and livestock. Vector control is the main strategy for controlling diseases transmitted by mosquitoes. In this context, it becomes paramount to understand how the viruses replicate in the vector for designing better transmission blocking strategies. We obtained the global transcriptome signature of A. aegypti cells during CHIKV infection, and in order to obtain the maximum information from these data sets, we further utilized the well-characterized Drosophila system and arrived upon a set of transcripts and their pathways that affect A. aegypti cells during CHIKV infection. These analyses and further validations reveal that important pathways related to protein degradation are actively involved during CHIKV infection in A. aegypti and are mainly proviral. Targeting these molecules may provide novel approaches for blocking CHIKV replication in A. aegypti.

Asymmetric Total Synthesis of (-)-Phaeocaulisin A.

The therapeutic properties of Curcuma (ginger and turmeric’s family) have long been known in traditional medicine. However, only recently have guaiane-type sesquiterpenes extracted from Curcuma phaeocaulis been submitted to biological testing, and their enhanced bioactivity was highlighted. Among these compounds, phaeocaulisin A has shown remarkable anti-inflammatory and anticancer activity, which appears to be tied to the unique bridged acetal moiety embedded in its tetracyclic framework. Prompted by the promising biological profile of phaeocaulisin A and by the absence of a synthetic route for its provision, we have implemented the first enantioselective total synthesis of phaeocaulisin A in 17 steps with 2% overall yield. Our route design builds on the identification of an enantioenriched lactone intermediate, tailored with both a ketone moiety and a conjugated alkene system. Taking advantage of the umpolung carbonyl-olefin coupling reactivity enabled by the archetypal single-electron transfer (SET) reductant samarium diiodide (SmI2), the lactone intermediate was submitted to two sequential SmI2-mediated cyclizations to stereoselectively construct the polycyclic core of the natural product. Crucially, by exploiting the innate inner-sphere nature of carbonyl reduction using SmI2, we have used a steric blocking strategy to render sites SET-unreceptive and thus achieve chemoselective reduction in a complex substrate. Our asymmetric route enabled elucidation of the naturally occurring isomer of phaeocaulisin A and provides a synthetic platform to access other guaiane-type sesquiterpenes from C. phaeocaulis—as well as their synthetic derivatives—for medicinal chemistry and drug design.

Individual Strategies of Response Organization in Multitasking Are Stable Even at Risk of High Between-Task Interference.

Recently, reliable interindividual differences were found for the way how individuals process multiple tasks (at a cognitive level) and how they organize their responses (at a response level). Previous studies have shown mixed results with respect to the flexibility of these preferences. On the one hand, individuals tend to adjust their preferred task processing mode to varying degrees of risk of crosstalk between tasks. On the other, response strategies were observed to be highly stable under varying between-resource competition. In the present study, we investigated whether the stability of response strategies also persists with increased risk of crosstalk or whether individuals adjust their choice of response strategy, similar to what has been found at the level of task processing modes. Besides, related differences in multitasking efficiency were assessed. For this purpose, 53 participants performed the Free Concurrent Dual-Tasking (FCDT) paradigm, which allows them to control their task scheduling and response organization. The participants completed the FCDT paradigm under two conditions including task pairs characterized by either low or high levels of risk of crosstalk. The free choice of task scheduling resulted in the previously found distinct response patterns, best described as blocking, switching or response grouping. Remarkably, we did not find any notable adjustments of strategies of response organization to the extent of crosstalk. However, we observed suspected performance decrements of a switching strategy in the condition of high risk of crosstalk. The results suggest that individual strategies of response organization are stable habits. Further, they illustrate disadvantages of switching vs. blocking strategies of response organization in case of high task similarity.

Hybrid Parallel Stochastic Configuration Networks for Industrial Data Analytics

As a class of randomized learner model, stochastic configuration networks (SCNs) have been successfully applied in a few data analytics tasks. Given the industrial big data modeling tasks, however, the original SCNs potentially lead to excessive training time. To this end, this article extends SCNs to a hybrid parallel version, termed hybrid parallel SCNs (HPSCNs). In the hybrid parallel learning algorithm, two SCNs are synchronously constructed. The difference between the two of them is that one employs a point-incremental algorithm, and another one adopts a block-incremental algorithm. Moreover, a data parallel method is established based on a dynamic block strategy to accelerate the establishment of candidate node pool for each SCN. Additionally, this article proposes an adaptive hyperparameter adjustment method, which allows the hyperparameters in the supervisory mechanism to be automatically adjusted along with the learning process. Comparative experiments are first conducted through four large-scale benchmark datasets, followed by the fully discussion on the algorithm parameters. Finally, a practical industrial application case is made, where a grinding particle size soft sensor is developed based on HPSCN, showing the effectiveness of the proposed algorithm.

Blocking Cancer-Nerve Crosstalk for Treatment of Metastatic Bone Cancer Pain.

The tumor microenvironment is a complex milieu where neurons constitute an important non-neoplastic cell type. From "cancer neuroscience," the crosstalk between tumors and neurons favors the rapid growth of both, making the cancer-nerve interaction a reciprocally beneficial process. Thus, cancer-nerve crosstalk may provide new targets for therapeutic intervention against cancer and cancer-related symptoms. Weproposed a nerve-cancer crosstalk blocking strategy for metastatic bone cancer pain treatment, achieved by Mg/Al layered-double-hydroxide nanoshells (Mg/Al-LDH) with AZ-23 loaded inside and alendronate decorated outside. The pain-causing H+ is rapidly eliminated by the LDH, with neurogenesis inhibited by the antagonist AZ-23. As positive feedback, the decreased pain reverses the nerve-to-cancer Ca2+ crosstalk-related cell cycle, dramatically inhibiting tumor growth. All experiments confirm the improved pain threshold and enhanced tumor inhibition. The study may inspire multidisciplinary researchers to focus on cancer-nerve crosstalk for treating cancer and accompanied neuropathic diseases.

Lignin hydrogel-based solar-driven evaporator for cost-effective and highly efficient water purification

Solar-driven interfacial evaporation is an emerging water treatment technology for fresh water generation. However, poor thermal localization performance and rapid salt accumulation of the designed evaporator are the two factors, restricting the practical application. Here, a cost-effective lignin-based hydrogel with three dimensional meso/micro-porous structures is prepared by a facile and scalable crosslinking-polymerization strategy. Benefiting from numerous hydrophilic hydroxyls in lignin as well as 3D hierarchical porous structure, the designed hydrogel exhibits sufficient water supplement, effective water activation, as well as fantastic anti-salt accumulation performance. Our lignin hydrogel-based evaporator achieves a high and stable evaporation rate of 2.25 kg·m−2·h−1 for 24 h continuous operation without salt crystallizing and blocking, and shows a good stability in a wide range of pH value from 1 to 14. In addition, heavy metal ions, including Cu2+, CrO42−, Co2+ are efficiently removed from polluted water by electrostatic interaction with excess hydroxyl groups in the lignin hydrogel. Therefore, lignin hydrogel-based evaporator offers a cost-effective and long-term anti salt blocking strategy for solar-driven water purification.

Rapid screening of monoclonal antibodies against porcine circovirus type 2 using colloidal gold-based paper test.

A proof of concept for using paper test as a suitable method in the production of monoclonal antibodies (MAbs) is reported. The paper test which detects antibodies against porcine circovirus type 2 (PCV2) using colloidal gold-labelled capsid protein as the antigen probe was applied exclusively in the screening of anti-PCV2 MAbs. It allowed the detection of 118 single cell clones within 30 min using naked eyes. MAbs with specific binding to authentic epitopes on the virus were selected using a blocking strategy in which the antibody was pre-incubated with PCV2 viral sample before applying to the test paper. Five hybridomas secreting MAbs against the capsid protein were obtained, with only three of them capable of binding to PCV2. The results were validated and confirmed using enzyme-linked immunosorbent assay and immunofluorescence assay. The paper test is simple, rapid, and independent on professional technicians and proves to be an excellent approach for the screening of MAbs against specific targets.

A Novel Solution for Distal Dilation of Chronic Dissection After Repair Involving Visceral Branches: The Road Block Strategy.

AimNotwithstanding that unprecedented endovascular progress has been achieved in recent years, it remains unclear what is the best strategy to preserve the blood perfusion of abdominal visceral arteries and promote positive aortic remodeling in patients with distal dilatation of chronic aortic dissection in abdominal visceral part (CADAV) after aortic repair. The present study developed a Road Block Strategy (RBS) to solve this conundrum.Methods and ResultsThis prospective single-center clinical study included patients suffering from symptomatic distal dilatation of CADAV after aortic repair treated with RBS from January 2015 to December 2019 and followed up regularly for at least 2 years. Stent grafts were implanted first to cover distal tears and expand the true lumen. Device embolization was performed to induce proximal and distal segmental false lumen thrombosis (FLT) apart from the level of the ostia of vital branches. Successful RBS was performed in 13 patients. Significant differences were found in maximum true lumen diameter (p < 0.05), blood flow area in false lumen (FL) (p < 0.001), and the ratio of blood lumen to FL area (p < 0.05) between the pre-procedure and the latest follow-up results. No aortic rupture, vital branches occlusion, thoracic and abdominal pain, or death occurred during hospitalization and follow-up.ConclusionsOur findings suggest that RBS is feasible in treating distal dilatation of chronic aortic dissection after prior proximal repair, inducing false lumen thrombosis, preventing deterioration of aortic dissection, and maintaining the patency of abdominal visceral arteries.

Relation between Reactive Surface Sites and Precursor Choice for Area-Selective Atomic Layer Deposition Using Small Molecule Inhibitors.

Implementation of vapor/phase dosing of small molecule inhibitors (SMIs) in advanced atomic layer deposition (ALD) cycles is currently being considered for bottom-up fabrication by area-selective ALD. When SMIs are used, it can be challenging to completely block precursor adsorption due to the inhibitor size and the relatively short vapor/phase exposures. Two strategies for precursor blocking are explored: (i) physically covering precursor adsorption sites, i.e., steric shielding, and (ii) eliminating precursor adsorption sites from the surface, i.e., chemical passivation. In this work, it is determined whether steric shielding is enough for effective precursor blocking during area-selective ALD or whether chemical passivation is required as well. At the same time, we address why some ALD precursors are more difficult to block than others. To this end, the blocking of the Al precursor molecules trimethylaluminum (TMA), dimethylaluminum isopropoxide (DMAI), and tris(dimethylamino)aluminum (TDMAA) was studied by using acetylacetone (Hacac) as inhibitor. It was found that DMAI and TDMAA are more easily blocked than TMA because they adsorb on the same surface sites as Hacac, while TMA is also reactive with other surface sites. This work shows that chemical passivation plays a crucial role for precursor blocking in concert with steric shielding. Moreover, the reactivity of the precursor with the surface groups on the non-growth area dictates the effectiveness of blocking precursor adsorption.

The Blocking and Governance Strategies in the Implementation of Green Fiscal and Tax Policies

The Blocking and Governance Strategies in the Implementation of Green Fiscal and Tax Policies

Micropore blocking strategy for mitigating adsorption and diffusion limitations in the direct epoxidation of propylene

The direct epoxidation of propylene has been a hot topic in the academic field for years. Researchers have spent extensive effort on the development of catalyst, however, only limited attention on the effect of reaction conditions, especially pressure. In this paper, we found for the first time that elevated pressure should favor the forward epoxidation reaction, it actually led to a drop of reaction rate in this system. We proposed explanation by considering the difficulty of gas molecules diffusing into and out of the micropores on the TS-1 zeolite surface. Higher pressure would inhibit the escaping of the gas molecules from the micropores and lead to carbon deposition inside the channel. To validate this hypothesis, we designed and compared catalysts with micropores blocked (BTS-1) and unblocked (TS-1) and found that the BTS-1 showed higher resistance to pressure change and significantly longer life time than the TS-1.

2'-O-(N-(Aminoethyl)carbamoyl)methyl Modification Allows for Lower Phosphorothioate Content in Splice-Switching Oligonucleotides with Retained Activity.

2′-O-(N-(Aminoethyl)carbamoyl)methyl (2′-O-AECM)-modified oligonucleotides (ONs) and their mixmers with 2′-O-methyl oligonucleotides (2′-OMe ONs) with phosphodiester linkers as well as with partial and full phosphorothioate (PS) inclusion were synthesized and functionally evaluated as splice-switching oligonucleotides in several different reporter cell lines originating from different tissues. This was enabled by first preparing the AECM-modified A, C, G and U, which required a different strategy for each building block. The AECM modification has previously been shown to provide high resistance to enzymatic degradation, even without PS linkages. It is therefore particularly interesting and unprecedented that the 2′-O-AECM ONs are shown to have efficient splice-switching activity even without inclusion of PS linkages and found to be as effective as 2′-OMe PS ONs. Importantly, the PS linkages can be partially included, without any significant reduction in splice-switching efficacy. This suggests that AECM modification has the potential to be used in balancing the PS content of ONs. Furthermore, conjugation of 2′-O-AECM ONs to an endosomal escape peptide significantly increased splice-switching suggesting that this effect could possibly be due to an increase in uptake of ON to the site of action.

Dual-chamber cardiac pacing short-term effect on left and right atria morphometric parameters and function

Abstract Funding Acknowledgements Type of funding sources: None. Background. Dual-chamber pacemaker implantation is a standard interventional treatment strategy for symptomatic sinus syndrome (SSS) or advanced atrioventricular block (AVB). It is already known that right ventricular pacing might have detrimental effects on cardiac function. However, knowledge about atrial pacing effect on left (LA) and right (RA) atria function is still lacking. Purpose. To assess the impact atrial pacing on left and right atria morphologic and functional parameters in patients after dual-chamber pacemaker implantation. Methods. We conducted a prospective study that included patients who received a dual-chamber pacemaker for an indication of AVB or SSS. A base rate of 40 bpm and no rate response in case of clear AVB indication or a base rate of 60 bpm and rate response if indication was SSS were chosen. A transthoracic echocardiography was done the next day after pacemaker implantation and after 1 and 3 months. To remove the impact of right ventricular pacing, patients with high VP percentage (&amp;gt;40%) were excluded from analysis. Patients were divided into two groups – group A with high AP (&amp;gt;50%), and group B – low AP (&amp;lt;50%). LA expansion fraction reflecting reservoir function, emptying - reflecting conduit, and active emptying reflecting "atrial kick" were analysed. To compare means the Mann Whitney U test, and for categorical variables – X² test were used. Results A total of n = 78 patients underwent dual-chamber implantation and signed informed consent. Due to significant structural heart disease or reduced ejection fraction (&amp;lt;50%) 7 patients were excluded from further analysis. Out of those, n = 21 were excluded due to a high VP percentage. Group A consisted of n = 26 and group B of – n = 24 patients. Average AP in group A was 63,5% and 68,3% at 1 and 3 months and 5,6% and 7,2% in group B respectively. The mean age (group A 74,5 SD 8,6 years vs group B 78,1 SD 8,0 years, p = 0,266), gender distribution (group A males 45,5% vs group B 48,4%, p = 0,774), and mean BMI (group A 26,4 SD 4,8 kg/m2 vs group B 29,5 SD 3,7 kg/m2, p = 0,202) did not differ significantly between the two groups. The mean left ventricular end diastolic diameter (LVEDD) and indexed LVEDD were not significantly different at baseline and did not change during the follow up period. The baseline LA and RA morphometric and functional parameters presented was not different at baseline between the two groups. The change in LA and RA functional parameters presented in figures. A tendency for a lower LA expansion fraction, active emptying fraction and LA ejection fraction were observed in group A. The trend was contant during 1 and 3 month follow-up periods. RA morphometric parameters did not change significantly between the two groups. Conclusion Impaired LA function in a higher percentage of atrial pacing is seen early after pacemaker implantation and could progress over time. Though, even longer observational period is needed. Abstract Figure. Abstract Figure.

Drug molecules bridge with small gatekeeper to co-block mesoporous silica nanoparticles for drug delivery

In this study, a filter-like blocking system based on MSN with small gatekeeper 5- mercapto-2 nitrobenzoic acid (MNBA) has developed. The MNBA grafted nanoparticle MSN-SS-MNBA shows excellent blocking performance with negligible leakage when loaded with doxorubicin (DOX), and the release profiles illustrate stimuli-responsive property when triggered by GSH. Viability experiments indicate that MSN-SS-MNBA has obvious inhibition for both Hela cells and HCT116 cells, while showing good biocompatibility for L929 cells, which suggests that the modified MNBA has a synergistic effect on cancer cells-killing. Since the small grafted molecule MNBA cannot block the channels of MSN via self-assembly, a filter-like blocking model that the loaded drug bridged with modified MNBA to fulfill the blocking process is proposed. The novel blocking strategy provides a new possible way for pore blocking, and the small nanovalve can be used as synergistic molecule for cancer therapy.