Determination of Critical Dimensions of Microchannels to Ensure the Electrokinetic Biomolecule Preconcentration: Analytical and Numerical Studies.

Preconcentration of biomolecules based on ion concentration polarization (ICP) has been splendidly applied to various biomedical and chemical processes. However, in many circumstances, biomolecule preconcentration could not occur due to the lack of full studies on the preconcentration mechanism, especially on the effect of microchannel dimensions. In this work, we provide analytical studies on the critical dimensions (minimum and maximum) of microchannels for the preconcentration of biomolecules. These formulas are verified with the numerical results by fully solving the coupled governing equations: Poisson-Nernst-Planck and Navier-Stokes experiments with appropriate boundary conditions and assumptions. In addition, we examine the impact of operational parameters, such as electric potentials and critical external pressures, on the formation of the preconcentration. Moreover, two important results are provided for the first time, including the position of the preconcentrated biomolecule region and the concentration enhancement factor of the biomolecules. These analytical and numerical results are consistent with experimental observations and, therefore, could provide sharp insight into the mechanism of biomolecule preconcentration and give useful guidelines to better design and optimize ICP-based microfluidic preconcentration devices.

Multiphysics analytical and numerical studies of biomolecule preconcentration utilizing ion concentration polarization: a case study of convergent microchannels.

A convergent sector in microfluidic devices utilizing ion concentration polarization (ICP) can help increase the preconcentration rate and the concentration enhancement factor (CEF) of biomolecules. In this work, we present a detailed study of the nozzle-like-squeeze effect of a convergent channel on the preconcentration of biomolecules. By numerically solving coupled Nernst-Planck-Poisson-Navier-Stokes governing equations for the 2D channel model, we report the first study on the critical width of a convergent region in the channel to retain the advantage of the nozzle-like-squeeze effect in speeding up preconcentration and augmenting CEF. In addition, we investigated the impact of the location and the dimensions of a convergent sector on the mechanism of biomolecule preconcentration. The location of an ion-selective membrane was also determined to ensure that biomolecules are focused on the convergent region of the channel. Moreover, we introduce analytical studies to compare and verify simulation findings. Specifically, the formulas for the critical dimensions of a convergent channel, location of a preconcentrated biomolecule plug, and position of an ion-selective membrane are presented. Furthermore, important working parameters, including electric potentials and hydrostatic pressures, were examined to scrutinize their effect on convergent concentrators. These detailed analytical solutions and numerical simulation results are consistent with experimental observations, providing deep insights into the ICP phenomenon and the preconcentration mechanism of biomolecules in convergent microfluidic concentration devices.

Prediction of Changes in Functional Outcomes During the First Year After Inpatient Stroke Rehabilitation: A Longitudinal Study.

OBJECTIVE: To identify meaningful changes in patients in 3 functional domains (basic mobility [BM], daily activity [DA], and applied cognition [AC]) after discharge from inpatient stroke rehabilitation and to identify the predictors of 1-year functional improvement. DESIGN: A longitudinal, multicenter, prospective cohort study. SETTING: The acute care wards of 3 hospitals in the Greater Taipei area of Taiwan. PARTICIPANTS: Five hundred patients with stroke in acute care wards (mean age=60±12.2 years, 62% men, N=500). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): The Mandarin version of the Activity Measure for Post-Acute Care (AM-PAC) short forms were assessed at discharge and 3-, 6-, and 12-month follow-up. The minimal detectable change (MDC) was used to categorize changes in the scores as improved and unimproved at the 4 time points. RESULTS: The mean scores of the AM-PAC BM and DA subscales substantially increased over the first 3 months after discharge (86% of participants exhibited improvement) and slightly increased during the subsequent 9 months (5∼26% of participants exhibited improvement). However, the mean score of the AC subscale decreased within the first 3 months and increased over the subsequent 9 months (22-23% of participants exhibited improvement). The BM, AC scores at discharge were the dominant predictors of subsequent functional improvement (P<.05). Patients with a higher functional stage at discharge were more likely to experience significant improvement. CONCLUSION: This study established the capacity of the AM-PAC to predict functional improvement in 3 domains during the early, middle, and late stages of recovery. The findings can assist clinicians in identifying patients at risk of unfavorable long-term functional recovery and providing such patients with tailored interventions during the early stage of rehabilitation.

Photodegradable antimicrobial agents: towards structure optimization.

Antibiotic resistance continues to be an ominous threat facing human health globally and urgent action is required to limit the loss of human life. The pollution of antibiotics into the environment is one of the drivers behind the crisis. With this in mind, we have developed novel photodecomposable antimicrobial agents based on an ethanolamine scaffold, which upon photoirradiation decomposes into two major inactive fragments. Herein we describe our further work on the synthesis of novel ethanolamines with a particular focus on structure activity relationship, resulting in four new active compounds which photodecomposed into inactive fragments.

Identify Primary Air Pollution Sources of BTEX by Using Positive Matrix Factorization (PMF): A Case Study of Ho Chi Minh City, Vietnam.

Ho Chi Minh City (HCMC) is one of the main socioeconomic and financial centers of Vietnam. The city also faces serious air pollution. However, the city polluted with benzene, toluene, ethylbenzene, and xylene (BTEX) has rarely been studied. We used positive matrix factorization (PMF) to analyze BTEX concentrations measured at two sampling locations to identify the main sources of BTEX in HCMC. The locations represented residential area (i.e., To Hien Thanh) and industrial area (i.e., Tan Binh Industrial Park). At the To Hien Thanh location, the average concentrations of benzene, ethylbenzene, toluene, and xylene were 6.9, 14.4, 4.9, and 12.7 µg/m3, respectively. At the Tan Binh location, the average concentrations of benzene, ethylbenzene, toluene, and xylene were 9.8, 22.6, 2.4, and 9.2 µg/m3, respectively. The results showed that PMF was a reliable model for source apportionment in HCMC. Traffic activities were the main sources of BTEX. Besides, industrial activities also contributed to BTEX emissions, especially the location near the industrial park. The majority of BTEXs at the To Hien Thanh sampling site come from traffic sources accounting for 56.2%. Activities from traffic and photochemical reactions (42.7%) and industrial sources (40.5%) were the main sources affecting BTEX emissions at the sampling site of Tan Binh Industrial Park. This study can be used as a reference for mitigation solutions to reduce the BTEX emission in HCMC.

Essential Oils from the Leaves, Stem, and Roots of Blumea lanceolaria (Roxb.) Druce in Vietnam: Determination of Chemical Composition, and In Vitro, In Vivo, and In Silico Studies on Anti-Inflammatory Activity.

Blumea lanceolaria (Roxb.) Druce, a flowering plant, is used for treating cancer and inflammatory diseases. In this study, we determined the chemical composition of the EOs extracted from the leaves (LBEO), stem (SBEO), and roots (RBEO) of B. lanceolaria and analyzed their anti-inflammation potential. Overall, 30 compounds representing 99.12%, 98.44%, and 96.89% of total EO constituents of the leaves, stem, and roots, respectively, were identified using GC-MS. ELISA, Western blotting, and qRT-PCR studies showed that LBEO, SBEO, and RBEO inhibited multiple steps in the inflammatory responses in the RAW 264.7 cell model, including NO production; TNF-α, IL-6, iNOS, and COX-2 transcription and translation; and phosphorylation of IκBα and p65 of the NF-κB pathway. In the carrageenan-induced paw edema model, all three EOs inhibited paw edema at both early and delayed phases. Molecular docking studies indicated that the main components of B. lanceolaria EOs (BEOs) targeted and inhibited major components of inflammation-related pathways, including the arachidonic acid metabolic pathway, NF-κB pathway, and MAPK pathway. We present the first study to characterize the chemical composition of BEOs and confirm their potent anti-inflammatory effects in in vitro, in vivo, and in silico analysis. These results can facilitate the development of effective anti-inflammatory drugs with limited side effects in the future.

Graphene Nanoparticles for Ultralow Friction at Extremely High Pressures and Temperatures.

This study uses the molecular dynamics approach to design graphene nanoparticles from the graphene sheets seeded randomly and investigates their lubricity. These nanoparticles are found to provide stable lubrication at extremely high pressure and temperature of up to 15 GPa and 2000 K, respectively. From the influences of both nanoparticle and graphene, the friction between the diamond slab and the nanoparticles shows ultralow values of the friction coefficient of 0.0034-0.0162 under 1-15 GPa and 300 K and 0.0065-0.0338 under 300-2000 K and 1 or 10 GPa. Providing stable lubrication and ultralow friction under these conditions is the large advantage of graphene nanoparticles.

The Impact of High Ambient Temperature on Human Sperm Parameters: A Meta-Analysis.

Background: Global warming, lifestyle, or working in a high temperature environment leads to have increased health risk factors. This meta-analysis was conducted to determine the impact of high ambient temperature on male reproductive function. Methods: Scientific articles were screened in the database including MEDLINE, EMBASE, National center for biotechnology information (NCBI) or Web of Science with relating keywords. Impact data of high ambient temperature on semen parameters were extracted and analyzed by STATA software according to the Random Effects Model. The high ambient temperature exposure group and Non-exposure group were compared using the standard mean difference (SMD). Publications were evaluated for publication bias by Egger test. Results: Nine articles were finally selected from databases examining the effect of high ambient temperature on male reproductive health of 356 men from Iran, Italy, Thailand, China, Egypt. High ambient temperature showed a significant decrease in the seminal parameters, semen volume during each ejaculation (SMD = -0.74; 95% CI -1.11, -0.36), sperm concentration (SMD = -1.07; 95% CI -1.42, -0.72), total sperm count (SMD = -1.52; 95% CI -2.96, -0.08), sperm motility (SMD = -1.93; 95% CI -2.83, -1.04), sperm progressive motility (SMD = -1.65; 95% CI -2.39, -0.91) and normal morphology (SMD = -2.41; 95% CI -3.30, -1.52). Conclusion: High ambient temperature negatively affects sperm quality, including decreased semen volume, sperm count, sperm concentration, motility and normal morphology. This might lead to protective strategies to avoid the adverse effects of high ambient temperature on male fertility.

Left ventricular diverticulum: A case report and review of the literature.

Left ventricular diverticulum is a rare congenital left ventricular outpouchings. The disease is often diagnosed during childhood because it is frequently associated with midline thoracoabdominal defects and other congenital cardiac anomalies. Most cases are asymptomatic, often discovered incidentally. Some complications have been reported including infarction, arrhythmia, heart failure. The most severe complication is rupture of the diverticulum, which can cause a patient's death. Therefore, this congenital defect should be detected early to assess potential risks for appropriate treatment. In this article, we report a case of a 3-month-old boy with left ventricular diverticulum diagnosed with Doppler ultrasound and cardiac MSCT. Complete resection was undertaken. The patient remained asymptomatic with good heart function 2 months after surgery.

A Bayesian belief data mining approach applied to rice and shrimp aquaculture.

In many parts of the world, conditions for small scale agriculture are worsening, creating challenges in achieving consistent yields. The use of automated decision support tools, such as Bayesian Belief Networks (BBNs), can assist producers to respond to these factors. This paper describes a decision support system developed to assist farmers on the Mekong Delta, Vietnam, who grow both rice and shrimp crops in the same pond, based on an existing BBN. The BBN was previously developed in collaboration with local farmers and extension officers to represent their collective perceptions and understanding of their farming system and the risks to production that they face. This BBN can be used to provide insight into the probable consequences of farming decisions, given prevailing environmental conditions, however, it does not provide direct guidance on the optimal decision given those decisions. In this paper, the BBN is analysed using a novel, temporally-inspired data mining approach to systematically determine the agricultural decisions that farmers perceive as optimal at distinct periods in the growing and harvesting cycle, given the prevailing agricultural conditions. Using a novel form of data mining that combines with visual analytics, the results of this analysis allow the farmer to input the environmental conditions in a given growing period. They then receive recommendations that represent the collective view of the expert knowledge encoded in the BBN allowing them to maximise the probability of successful crops. Encoding the results of the data mining/inspection approach into the mobile Decision Support System helps farmers access explicit recommendations from the collective local farming community as to the optimal farming decisions, given the prevailing environmental conditions.

Structural order of water molecules around polyrotaxane including PEG, α-cyclodextrin, and α-lipoic acid linker on gold surface by molecular dynamics simulations.

In materials science, water plays an important part, especially at the molecular level. It shows various properties when sorbed onto surfaces of polymers. The structure of the molecular water ensemble in the vicinity of the polymers is under discussion. In this study, we used molecular dynamics methods to analyze the structure of water in the vicinity of the polymer polyrotaxane (PR), composed of α-cyclodextrins (α-CDs), a poly(ethylene glycol) (PEG) axial chain, and α-lipoic acid linkers, at various temperatures. The distribution of water around the functional groups, hydrogen bond network, and tetrahedral order were analyzed to classify the various types of water around the polymer. We found that the tetrahedral order of water had a strained relationship from the XES experiment. Four water regions were separated from each other in the vicinity of 1 to 5 Å around PR. The intermediate and non-freezing water were formed due to the interaction between water molecules and the functional groups, such as hydroxyl, ether, and ester.

Effects of common full-sib families on accuracy of genomic prediction for tagging weight in striped catfish Pangasianodon hypophthalmus.

Common full-sib families (c 2 ) make up a substantial proportion of total phenotypic variation in traits of commercial importance in aquaculture species and omission or inclusion of the c 2 resulted in possible changes in genetic parameter estimates and re-ranking of estimated breeding values. However, the impacts of common full-sib families on accuracy of genomic prediction for commercial traits of economic importance are not well known in many species, including aquatic animals. This research explored the impacts of common full-sib families on accuracy of genomic prediction for tagging weight in a population of striped catfish comprising 11,918 fish traced back to the base population (four generations), in which 560 individuals had genotype records of 14,154 SNPs. Our single step genomic best linear unbiased prediction (ssGLBUP) showed that the accuracy of genomic prediction for tagging weight was reduced by 96.5%-130.3% when the common full-sib families were included in statistical models. The reduction in the prediction accuracy was to a smaller extent in multivariate analysis than in univariate models. Imputation of missing genotypes somewhat reduced the upward biases in the prediction accuracy for tagging weight. It is therefore suggested that genomic evaluation models for traits recorded during the early phase of growth development should account for the common full-sib families to minimise possible biases in the accuracy of genomic prediction and hence, selection response.

Cultivation of Caenorhabditis elegans on new cheap monoxenic media without peptone.

The study of species biodiversity within the Caenorhabditis genus of nematodes would be facilitated by the isolation of as many species as possible. So far, over 50 species have been found, usually associated with decaying vegetation or soil samples, with many from Africa, South America and Southeast Asia. Scientists based in these regions can contribute to Caenorhabditis sampling and their proximity would allow intensive sampling, which would be useful for understanding the natural history of these species. However, severely limited research budgets are often a constraint for these local scientists. In this study, we aimed to find a more economical, alternative growth media to rear Caenorhabditis and related species. We tested 25 media permutations using cheaper substitutes for the reagents found in the standard nematode growth media (NGM) and found three media combinations that performed comparably to NGM with respect to the reproduction and longevity of C. elegans. These new media should facilitate the isolation and characterization of Caenorhabditis and other free-living nematodes for the researchers in the poorer regions such as Africa, South America, and Southeast Asia where nematode diversity appears high.

The Direct and Indirect Costs of Colorectal Cancer in Vietnam: An Economic Analysis from a Social Perspective.

The incidence and mortality of colorectal cancer (CRC) has increased rapidly in Vietnam, but the economic burden of this disease has never been estimated. We estimate the direct and indirect cost of CRC patients in Vietnam in 2018 using a prevalence-based approach and human capital method. The total economic cost of CRC was VND 3041.88 billion (~$132.9 million), representing 0.055% of the 2018 gross domestic product. Notably, indirect costs comprised 83.58 % of the total cost, 82.61% of which is future income loss, because CRC occurs during productive years. The economic burden of CRC in Vietnam is substantial. The medical cost for CRC diagnosis and treatment is higher for younger patients and for those in advanced stages. Strategies to decrease the economic burden of CRC at the patient and national level, such as screening programs, should be developed and implemented in Vietnam.

Measurement of Health-Related Quality of Life Among Colorectal Cancer Patients Using the Vietnamese Value Set of the EQ-5D-5L.

PURPOSE: Health-related quality of life (HRQoL) is an important construct in clinical settings, and it is crucial that it should be properly measured. As the EuroQol-5-dimensions-5 levels (EQ-5D-5L) is more effective for such measurement than the 3-level model, data on economic models, clinical studies, and public health evaluations previously collected through the EQ-5D-3L need to be revaluated using the EQ-5D-5L. This study evaluated colorectal cancer (CRC) patients' HRQoL scores using the Vietnamese EQ-5D-5L value set. PATIENTS AND METHODS: The cross-sectional study included CRC patients treated at a tertiary public hospital. HRQoL was assessed using the EQ-5D-5L, and HRQoL utility scores were calculated using the Vietnamese value set. Tobit regression examined factors associated with HRQoL. RESULTS: The analysis included 197 CRC patients. Ages ranged from 20 to 87 years (M = 57.64, SD = 13.5); 42.2% and 57.8% were diagnosed with cancer of the colon or rectum/anus, respectively. Mean EQ-5D-5L was 0.561 (range, -0.5115 to 1). Most participants experienced anxiety/depression (88%), followed by pain/discomfort (87%), mobility (71%), usual activity (69%), and self-care (67%). Advanced CRC stage (stage II: ß -0.303, se 0.08; stage III: ß -0.305, se 0.07; stage IV: ß -0.456, se 0.07) and surgery (ß -0.113, se 0.05) were negatively associated with EQ-5D-5L scores. Advanced education (high school: ß 0.273, se 0.07); college/vocational: ß 0.134se 0.05; university/higher: Coef 0.213, se 0.08;) and older age (age group 35-44: ß 0.253, se 0.10; 45-54: ß 0.327, se 0.09; 55-64: ß 0.355 se 0.09; 65+ ß 0.204, se 0.09) were positively associated with EQ-5D-5L scores. CONCLUSION: Patients in advanced CRC stages or undergoing surgery experienced lower HRQoL and higher prevalence of anxiety/depression and pain/discomfort. Older age and high educational attainment predicted high HRQoL. This study provides information on CRC patients' health utility based on various patient characteristics, which can be used in future economic evaluations.

Molecular typing of conjunctivitis-causing adenoviruses in Hanoi, Vietnam from 2017 to 2019 and complete genome analysis of the most prevalent type (HAdV-8).

Adenoviral conjunctivitis is a common epidemic worldwide. In Vietnam, up to 80,000 patients are infected with adenoviral conjunctivitis annually. However, there are few investigations on the pathogenic adenoviruses that cause conjunctivitis. In total, 120 eye-swab samples were collected from patients with viral conjunctivitis symptoms in Hanoi, Vietnam from 2017 to 2019. Human adenoviruse (HAdV) was detected in 67 samples (55.83%) using polymerase chain reaction amplification of at least one of three HAdV-specific marker genes (hexon, penton, and fiber). Of the 67 HAdV samples, 46 samples could be analyzed by all three marker genes. DNA sequence analysis and phylogenetic tree building based on the three marker genes from the 46 HAdV samples revealed five different HAdV types associated with conjunctivitis in Hanoi, including HAdV-3 (4.3%), HAdV-4 (2.2%), HAdV-8 (89.1%), HAdV-37 (2.2%), and a potential recombinant type between types HAdV-8 and HAdV-3 (2.2%). This showed that HAdV-8 was the most common type identified in Hanoi. Complete genome analysis of HAdV-8 isolated from a Vietnamese patient (VN2017) using Sanger sequencing revealed 34 unique nucleotide changes, indicating that the adenovirus continuously accumulates new mutations. Hence, continuous surveillance of HAdV-8 changes in Vietnam is necessary in the future.

Improved genomic resources for the black tiger prawn (Penaeus monodon).

World production of farmed crustaceans was 7.8 million tons in 2016. While only making up approximately 10% of world aquaculture production, crustaceans are generally high-value species and can earn significant export income for producing countries. Viet Nam is a major seafood producing country earning USD 7.3 billion in 2016 in export income with shrimp as a major commodity. However, there is a general lack of genomic resources available for shrimp species, which is challenging to obtain due to the need to deal with large repetitive genomes, which characterize many decapod crustaceans. The first tiger prawn (P. monodon) genome assembly was assembled in 2016 using the standard Illumina PCR-based pair-end reads and a computationally-efficient but relatively suboptimal assembler, SOAPdenovo v2. As a result, the current P. monodon draft genome is highly fragmented (> 2 million scaffolds with N50 length of <1000 bp), exhibiting only moderate genome completeness (< 35% BUSCO complete single-copy genes). We sought to improve upon the recently published P. monodon genome assembly and completeness by generating Illumina PCR-free pair-end sequencing reads to eliminate genomic gaps associated with PCR-bias and performing de novo assembly using the updated MaSurCA de novo assembler. Furthermore, we scaffolded the assembly with low coverage Nanopore long reads and several recently published deep Illumina transcriptome paired-end sequencing data, producing a final genome assembly of 1.6 Gbp (1,211,364 scaffolds; N50 length of 1982 bp) with an Arthropod BUSCO completeness of 96.8%. Compared to the previously published P. monodon genome assembly from China (NCBI Accession Code: NIUS01), this represents an almost 20% increase in the overall BUSCO genome completeness that now consists of more than 90% of Arthropod BUSCO single-copy genes. The revised P. monodon genome assembly (NCBI Accession Code: VIGR01) will be a valuable resource to support ongoing functional genomics and molecular-based breeding studies in Vietnam.

Anionic Conjugated Polyelectrolytes for FRET-based Imaging of Cellular Membrane Potential.

We report a Förster resonance energy transfer (FRET)-based imaging ensemble for the visualization of membrane potential in living cells. A water-soluble poly(fluorene-cophenylene) conjugated polyelectrolyte (FsPFc10) serves as a FRET donor to a voltage-sensitive dye acceptor (FluoVolt™ ). We observe FRET between FsPFc10 and FluoVolt™ , where the enhancement in FRET-sensitized emission from FluoVolt™ is measured at various donor/acceptor ratios. At a donor/acceptor ratio of 1, the excitation of FluoVolt™ in a FRET configuration results in a three-fold enhancement in its fluorescence emission (compared to when it is excited directly). FsPFc10 efficiently labels the plasma membrane of HEK 293T/17 cells and remains resident with minimal cellular internalization for ~ 1.5 h. The successful plasma membrane-associated colabeling of the cells with the FsPFc10-FluoVolt™ donor-acceptor pair is confirmed by dual-channel confocal imaging. Importantly, cells labeled with FsPFc10 show excellent cellular viability with no adverse effect on cell membrane depolarization. During depolarization of membrane potential, HEK 293T/17 cells labeled with the donor-acceptor FRET pair exhibit a greater fluorescence response in FluoVolt™ emission relative to when FluoVolt™ is used as the sole imaging probe. These results demonstrate the conjugated polyelectrolyte to be a new class of membrane labeling fluorophore for use in voltage sensing schemes.

Return flow ion concentration polarization desalination: A new way to enhance electromembrane desalination.

In electromembrane desalination processes such as electrodialysis (ED) and ion concentration polarization (ICP) desalination, ion-depleted boundary layers constitute the desalted, product stream, yet also cause high resistivity and voltage drop. Directly manipulating fluid flow streams is a new method to break this fundamental trade-off for electromembrane desalination. In this work, we are introducing a novel electromembrane desalination architecture that allows a feed stream to return to the feed inlet side of the membrane (hereby named as return-flow (RF) architecture) to improve the energy efficiency by re-distributing and controlling the depleted boundary layer, even at high current values. The technical feasibility of this idea was examined in ICP desalination process (RF-ICP) with a wide range of feed salinity from 10 to 70 g/L. For a partial desalination, RF-ICP (∼75 cm2 of membrane area) has achieved similar power consumption compared to batch-ED with 3 times bigger membrane area (200 cm2) with a higher area efficiency for salt removal, which translates into lower optimal desalination cost. The techno-economic analysis of RF-ICP have been performed for the treatment of 70 g/L brine waste. For partial desalination of 70 g/L brine down to 35 g/L, RF-ICP desalination achieved overall water cost as low as $2.57/m3 ($0.41/barrel). This could translate into reduction in total water cost up to 31% for zero brine release scenarios, depending on the concentrated brine treatment cost. These results show that return-flow architecture can improve the performance of electromembrane desalination, enabling more flexible water treatment for many real-world applications.

Homologous Lympho-Epithelial Kazal-type Inhibitor Domains Delay Blood Coagulation by Inhibiting Factor X and XI with Differential Specificity.

Despite being initially identified in the blood filtrate, LEKTI is a 15-domain Kazal-type inhibitor mostly known in the regulation of skin desquamation. In the current study, screening of serine proteases in blood coagulation cascade showed that LEKTI domain 4 has inhibitory activity toward only FXIa, whereas LEKTI domain 6 inhibits both FXIa and FXaB (bovine FXa). Nuclear magnetic resonance structural and dynamic experiments plus molecular dynamics simulation revealed that LEKTI domain 4 has enhanced backbone flexibility at the reactive-site loop. A model of the LEKTI-protease complex revealed that FXaB has a narrower S4 pocket compared with FXIa and hence prefers only small side-chain residues at the P4 position, such as Ala in LEKTI domain 6. Mutational studies combined with a molecular complex model suggest that both a more flexible reactive-site loop and a bulky residue at the P4 position make LEKTI domain 4 a weaker but highly selective inhibitor of FXIa.