Laser Patterning of Porous Support Membranes to Enhance the Effective Surface Area of Thin-Film Composite-Facilitated Transport Membranes for CO2 Separation.

Although thin-film composite membranes have achieved great success in CO2 separation, further improvements in the CO2 permeance are required to reduce the size and cost of the CO2 separation process. Herein, we report the fabrication of composite membranes with high CO2 permeability using a laser-patterned porous membrane as the support membrane. High-aspect-ratio micropatterns with well-defined micropores on their surface were carved on microporous polymer supports by a direct laser writing process using a short-pulsed laser. By using a Galvano scanner and optimizing the laser conditions and target materials, in-plane micropatterns, such as microhole arrays, microline grating, microlattices, and out-of-plane hierarchical micropatterns, were created on porous membranes. An aqueous suspension of hydrogel microparticles doped with an amine-based mobile carrier was sprayed onto the patterned surface to form a defect-free thin separation layer. The surface area of the separation layer on the patterned support is up to 80% larger than that of flat pristine membranes, resulting in a 52% higher CO2 permeance (1106 GPU) with a CO2/N2 selectivity of 172. The laser-patterned porous membranes allow the development of inexpensive and high-performance functional membranes not only for CO2 separation but also for other applications, such as water treatment, cell culture, micro-TAS, and membrane reactors.

Ultrafast sensitivity-controlled and specific detection of extracellular vesicles using optical force with antibody-modified microparticles in a microflow system.

Extracellular vesicles (EVs), including nanoscale exosomes and ectosomes, hold promise as biomarkers that provide information about the cell of origin through their cargo of nucleic acids and proteins, both on their surface and within. Here, we develop a detection method of EVs based on light-induced acceleration of specific binding between their surface and antibody-modified microparticles, using a controlled microflow with three-dimensional analysis by confocal microscopy. Our method successfully detected 103-104 nanoscale EVs in liquid samples as small as a 500 nanoliters within 5 minutes, with the ability to distinguish multiple membrane proteins. Remarkably, we achieved the specific detection of EVs secreted from living cancer cell lines with high linearity, without the need for a time-consuming ultracentrifugation process that can take several hours. Furthermore, the detection range can be controlled by adjusting the action range of optical force using a defocused laser, consistent with the theoretical calculations. These findings demonstrate an ultrafast, sensitive, and quantitative approach for measuring biological nanoparticles, enabling innovative analyses of cell-to-cell communication and early diagnosis of various diseases, including cancer.

Attogram-level light-induced antigen-antibody binding confined in microflow.

The analysis of trace amounts of proteins based on immunoassays and other methods is essential for the early diagnosis of various diseases such as cancer, dementia, and microbial infections. Here, we propose a light-induced acceleration of antigen-antibody reaction of attogram-level proteins at the solid-liquid interface by tuning the laser irradiation area comparable to the microscale confinement geometry for enhancing the collisional probability of target molecules and probe particles with optical force and fluidic pressure. This principle was applied to achieve a 102-fold higher sensitivity and ultrafast specific detection in comparison with conventional protein detection methods (a few hours) by omitting any pretreatment procedures; 47-750 ag of target proteins were detected in 300 nL of sample after 3 minutes of laser irradiation. Our findings can promote the development of proteomics and innovative platforms for high-throughput bio-analyses under the control of a variety of biochemical reactions.

Homoharringtonine is a transdermal granular permeation enhancer.

Although modulation of claudin-1-based tight junction (TJ) in stratum granulosum is an option for transdermal absorption of drugs, granular permeation enhancers have never been developed. We previously found that homoharringtonine (HHT), a natural alkanoid, weakened intestinal epithelial barrier with changing expression and cellular localization of TJ components such as claudin-1 and claudin-4. In the present study, we investigated whether HHT is an epidermal granular permeation enhancer. Treatment of normal human epidermal keratinocytes (NHEK) cells with HHT decreased claudin-1 and claudin-4 but not zonula occludens-1 and E-cadherin. HHT lowered TJ-integrity in NHEK cells, accompanied by permeation-enhancement of dextran (4 kDa) in a dose-dependent manner. Transdermal treatment of mice with HHT weakened epidermal barrier. HHT treatment enhanced transdermal absorption of dextran with a molecular mass of up to 10 kDa. Together, HHT may be a transdermal absorption enhancer.

Pregnancy Outcomes Based on Pre-Pregnancy Body Mass Index in Japanese Women.

OBJECTIVE: To verify whether body mass index (BMI) classification proposed by the Institute of Medicine (IOM) is valid in Japanese women. METHOD: A study was conducted in 97,157 women with singleton pregnancies registered in the Japan Society of Obstetrics and Gynecology (JSOG) Successive Pregnancy Birth Registry System between January 2013 and December 2013, to examine pregnancy outcomes in four groups stratified by pre-pregnancy BMI category according to the 2009 criteria recommended by the Institute of Medicine (IOM). The groups comprised 17,724 underweight women with BMI <18.5, 69,126 normal weight women with BMI 18.5-24.9, 7,502 overweight women with BMI 25-29.9, and 2,805 obese women with BMI ≥30. The pregnancy outcomes were also compared among subgroups stratified by a gestational weight gain below, within, and above the optimal weight gain. RESULTS: The higher the pre-pregnancy BMI, the higher the incidences of pregnancy-induced hypertension, gestational diabetes mellitus, macrosomia, cesarean delivery, postpartum hemorrhage, and post-term birth, but the lower the incidence of small for gestational age (SGA). In all pre-pregnancy BMI category groups, excess gestational weight gain was associated with a higher frequency of large for gestational age and macrosomia; poor weight gain correlated with a higher frequency of SGA, preterm birth, preterm premature rupture of membranes, and spontaneous preterm birth; and optimal weight gain within the recommended range was associated with a better outcome. CONCLUSION: The BMI classification by the IOM was demonstrated to be valid in Japanese women.

Warfarin-associated fetal intracranial subdural hematoma: a case report.

KEY CLINICAL MESSAGE: We present a case in which to of fetal subdural hematoma developing despite that the maternal the prothrombin time by international normalized ratio (PT/INR) during pregnancy was within the normal range.

Associations of maternal pre-pregnancy underweight with small-for-gestational-age and spontaneous preterm birth, and optimal gestational weight gain in Japanese women.

AIM: To determine associations of maternal pre-pregnancy underweight with poor outcomes and evaluate how gestational weight gain affects risks for such outcomes in pre-pregnancy underweight Japanese women. METHODS: By analyzing the January 2001-December 2012 hospital database, we retrospectively identified 6954 women with pre-pregnancy normal weights (body mass index, 18.5-24.9 kg/m²) and 1057 pre-pregnancy underweight women (body mass index, <18.5 kg/m²) who delivered at the Perinatal Maternity and Neonatal Center of Yokohama City University. These women were stratified by weekly weight gain during the second/third trimesters to investigate associations of gestational weight gain with spontaneous preterm birth and small for gestational age (SGA). Spontaneous preterm birth and SGA incidences were compared with those of women meeting Institute of Medicine (IO M) guidelines to determine optimal weight gain in Japanese women. RESULTS: Preterm birth and SGA incidences were significantly higher in pre-pregnancy underweight than in pre-pregnancy normal weight women (4.6% vs 2.4% [P=0.005] and 13.9% vs 9.7% [P = 0.003], respectively). For pre-pregnancy normal weight women, preterm birth incidence was significantly higher in those with weight gain of less than 0.2 kg/week than in those IOM guidelines. For pre-pregnancy underweight women, preterm birth and SGA incidences were significantly higher in those with weight gain of less than 0.3 kg/week than in those meeting IOM guidelines. CONCLUSION: Preterm birth and SGA incidences did not differ significantly between pre-pregnancy normal weight women with weight gain of 0.2 kg/week or more and pre-pregnancy underweight women with weight gain of 0.3 kg/week or more, as compared to women meeting IOM guidelines. These results suggest that IOM guidelines for gestational weight gain may lack external validity in Japanese women.

Selective defluorination approach to N-Cbz-3,3-difluoro-2-difluoromethylenepyrrolidine and its application to 3,3-difluoroproline dipeptide synthesis.

Mg-promoted defluorination of N-(p-methoxyphenyl)bis(trifluoromethyl)imine 1 gave perfluoroenamine 2, which was readily transformed to N-Cbz-2-trifluoromethyl-3,3-difluoropyrrolidine 10. Chemoselective defluorination from the trifluoromethyl group of 10 by LHMDS-promoted dehydrofluorination in THF provided 3,3-difluoro-2-difluoromethylenepyrrolidine 11. The product 11 was converted to 3,3-difluoroproline dipeptides 16 upon treatment with aminoesters.

A novel route to dipeptides via noncondensation of amino acids: 2-aminoperfluoropropene as a synthon for trifluoroalanine dipeptides.

2-Aminoperfluoropropene has been prepared by the Mg-promoted defluorinative N-silylation of N-p-methoxyphenyl hexafluoroacetone imine and has been employed as a synthon of trifluoroalanine for the preparation of trifluoroalanine dipeptides.