Biohybrid CO2 electrolysis for the direct synthesis of polyesters from CO2.

Converting anthropogenic CO2 to value-added products using renewable energy has received much attention to achieve a sustainable carbon cycle. CO2 electrolysis has been extensively investigated, but the products have been limited to some C1-3 products. Here, we report the integration of CO2 electrolysis with microbial fermentation to directly produce poly-3-hydroxybutyrate (PHB), a microbial polyester, from gaseous CO2 on a gram scale. This biohybrid system comprises electrochemical conversion of CO2 to formate on Sn catalysts deposited on a gas diffusion electrode (GDE) and subsequent conversion of formate to PHB by Cupriavidus necator cells in a fermenter. The electrolyzer and the electrolyte solution were optimized for this biohybrid system. In particular, the electrolyte solution containing formate was continuously circulated through both the CO2 electrolyzer and the fermenter, resulting in the efficient accumulation of PHB in C. necator cells, reaching a PHB content of 83% of dry cell weight and producing 1.38 g PHB using 4 cm2 Sn GDE. This biohybrid system was further modified to enable continuous PHB production operated at a steady state by adding fresh cells and removing PHB. The strategies employed for developing this biohybrid system will be useful for establishing other biohybrid systems producing chemicals and materials directly from gaseous CO2.

Enhanced Molecular Interaction of 3D Plasmonic Nanoporous Gold Alloys by Electronic Modulation for Sensitive Molecular Detection.

Three-dimensional gold and its alloyed nanoporous structures possess high surface areas and strong local electric fields, rendering them ideal substrates for plasmonic molecular detection. Despite enhancing plasmonic properties and altering molecular interactions, the effect of alloy composition on molecular detection capability has not yet been explored. Here, we report molecular interactions between nanoporous gold alloys and charged molecules by controlling the alloy composition. We demonstrate enhanced adsorption of negatively charged molecules onto the alloy surface due to positively charged gold atoms and a shifted d-band center through charge transfer between gold and other metals. Despite similar EM field intensities, nanoporous gold with silver (Au/Ag) achieves SERS enhancement factors (EF) up to 6 orders of magnitude higher than those of other alloys for negatively charged molecules. Finally, nanoporous Au/Ag detects amyloid-beta at concentrations as low as approximately 1 fM, with SERS EF up to 10 orders of magnitude higher than that of a monolayer of Au nanoparticles.

Developing Catalysts Integrated in Gas-Diffusion Electrodes for CO2 Electrolyzers.

ConspectusAs the demand for a carbon-neutral society grows rapidly, research on CO2 electrolysis has become very active. Many catalysts are reported for converting CO2 into value-added products by electrochemical reactions, which have to perform at high Faradaic and energy efficiency to become commercially viable. Various types of CO2 electrolyzers have been used in this effort, such as the H-cell, flow cell, and zero-gap membrane-electrode assembly (MEA) cell. H-cell studies are conducted with electrodes immersed in CO2-saturated electrolyte and have been used to elucidate reaction pathways and kinetic parameters of electrochemical CO2 reduction on many types of catalytic surfaces. From a transport phenomenological perspective, the low solubility and diffusion of CO2 to the electrode surface severely limit the maximum attainable current density, and this metric has been shown to have significant influence on the product spectrum. Flow and MEA cells provide a solution in the form of gas-diffusion electrodes (GDEs) that enable gaseous CO2 to closely reach the catalyst layer and yield record-high current densities. Because GDEs involve a complicated interface consisting of the catalyst surface, gaseous CO2, polymer overlayers, and liquid electrolyte, catalysts with high intrinsic activity might not show high performance in these GDE-based electrolyzers. Catalysts showing low overpotentials at low current densities may suffer from poor electron conductivity and mass transfer limitations at high current densities. Furthermore, the stability of the GDE-based catalysts is often compromised as CO2 electrolysis is pursued with high activity, most notoriously by electrolyte flooding.In this Account, we introduce recent examples where the electrocatalysts were integrated in GDEs, achieving high production rates. The performance of such systems is contingent on both GDE and cell design, and various parameters that affect the cell performance are discussed. Gaseous products, such as carbon monoxide, methane, and ethylene, and liquid products, such as formate and ethanol, have been mainly reported with high partial current density using the flow or MEA cells. Different strategies to this end are described, such as controlling microenvironments by the use of polymers mixed within the catalyst layer or the functionalization of catalyst surfaces with ligands to increase local concentrations of intermediates. Unique CO2 electrolyzer designs are also treated, including the incorporation of light-responsive plasmonic catalysts in the GDE, and combining the electrolyzer with a fermenter utilizing a microbial biocatalyst to synthesize complex multicarbon products. Basic conditions which the catalyst should satisfy to be adapted in the GDEs are listed, and our perspective is provided.

Assessment of transcranial Doppler indices after MgSO4 administration in severe preeclamptic women with neurologic symptoms.

PURPOSE: To investigate the effect of intravenous MgSO4 on maternal cerebral hemodynamics as well as the association between altered Doppler indices of the ophthalmic arteries and ocular lesions in patients with preeclampsia. METHODS: After each of the 15 included patients was diagnosed with preeclampsia, MgSO4 was infused followed by transcranial Doppler tests of the indices of the ophthalmic, anterior, middle, posterior cerebral, vertebral, and basilar arteries, followed by a second MgSO4 infusion. The peak, mean, diastolic velocity, and pulsatile and resistance indices of each artery were automatically measured during testing. Based on the emergent data, the cerebral perfusion pressure, resistance-area product, and cerebral flow index were calculated. RESULTS: The cerebral perfusion pressure of the posterior cerebral arteries significantly decreased following the infusion of MgSO4 (p < 0.05). Before the infusion of MgSO4, cerebral perfusion pressure and cerebral flow index of the ophthalmic arteries were significantly increased (p < 0.05) in the preeclamptic pregnant patients with ocular lesions compared those without ocular lesions. After the infusion of MgSO4, the cerebral perfusion pressure and cerebral flow index of both ophthalmic arteries were slightly decreased, but the difference was not significant. CONCLUSIONS: Altered Doppler indices following the infusion of MgSO4 suggest significant changes in the hemodynamics of the posterior cerebral and ophthalmic arteries that are particularly related to the neurological signs and symptoms of women with preeclampsia. These findings may improve the understanding of the mechanism of the cerebral complications of preeclampsia. Advancing comprehension of these underlying mechanisms is postulated to play a pivotal role in the mitigation of hypertensive encephalopathy associated with preeclampsia.

Retinoic Acid Treatment Mitigates PM2.5-Induced Type 2 Inflammation: Insights into Modulation of Innate Immune Responses.

Some studies have demonstrated the effects of particulate matter (PM) on chronic rhinosinusitis with nasal polyps (CRSwNP) development, as well as the therapeutic role of retinoic acid (RA) in nasal polypogenesis. However, the immunologic effect of PM in innate lymphoid cells (ILCs) and the exact mechanism of the therapeutic effect of RA remain unclear. Therefore, the present study investigated the effects of fine-dust-induced inflammation in CRSwNP and the mechanisms of the therapeutic effect of RA. PM2.5 exposure exacerbated pathological damage in the nasal mucosa of mice with nasal polyps (NP) via upregulation of type 2 inflammation. Additionally, PM2.5 exposure increased the expression of type 2 cytokines and epithelial-cell-derived cytokines (IL-33 and IL-25) significantly, as well as the ILC populations in human-NP-derived epithelial cells (HNECs). Moreover, RA supplementation significantly increased the expression of ILCreg in Lin-CD45+CD127+ cells, which in turn increased the levels of the anti-inflammatory cytokine IL-10. The findings suggest that PM2.5 exposures could aggravate the CRSwNP type 2 inflammation, and RA treatment may ameliorate fine-dust-induced inflammation by modulating the innate immune response.

Ultra-Fast Vitrification: Minimizing the Toxicity of Cryoprotective Agents and Osmotic Stress in Mouse Oocyte Cryopreservation.

Globally, women have been adopting oocyte cryopreservation (OC) for fertility preservation for various reasons, such as inevitable gonadotoxic treatment for specific pathologic states and social preferences. While conventional vitrification (C-VIT) has improved the success rate of OC, challenges of possible toxicities of high-concentration cryoprotective agents and osmotic stress persist. To overcome these challenges, we evaluated the ultra-fast vitrification (UF-VIT) method, which reduces the equilibration solution stage exposure time compared to C-VIT by observing mouse oocyte intracellular organelles and embryonic development. Consequently, compared to fresh mouse oocytes, UF-VIT presented significant differences only in endoplasmic reticulum (ER) intensity and mitochondrial (MT) distribution. Meanwhile, C-VIT showed substantial differences in the survival rate, key ER and MT parameters, and embryonic development rate. UF-VIT exhibited considerably fewer negative effects on key MT parameters and resulted in a notably higher blastocyst formation rate than C-VIT. Meiotic spindle (spindle and chromosomes) morphology showed no significant changes between the groups during vitrification/warming (VW), suggesting that VW did not negatively affect the meiotic spindle of the oocytes. In conclusion, UF-VIT seems more effective in OC owing to efficient cytoplasmic water molecule extraction, osmotic stress reduction, and minimization of cell contraction and expansion amplitude, thus compensating for the drawbacks of C-VIT.

Miniaturized MR-compatible ultrasound system for real-time monitoring of acoustic effects in mice using high-resolution MRI.

Visualization of focused ultrasound in high spatial and temporal resolution is crucial for accurately and precisely targeting brain regions noninvasively. Magnetic resonance imaging (MRI) is the most widely used noninvasive tool for whole-brain imaging. However, focused ultrasound studies employing high-resolution (> 9.4 T) MRI in small animals are limited by the small size of the radiofrequency (RF) volume coil and the noise sensitivity of the image to external systems such as bulky ultrasound transducers. This technical note reports a miniaturized ultrasound transducer system packaged directly above a mouse brain for monitoring ultrasound-induced effects using high-resolution 9.4 T MRI. Our miniaturized system integrates MR-compatible materials with electromagnetic (EM) noise reduction techniques to demonstrate echo-planar imaging (EPI) signal changes in the mouse brain at various ultrasound acoustic intensities. The proposed ultrasound-MRI system will enable extensive research in the expanding field of ultrasound therapeutics.

CD40 ligand stimulation affects the number and memory phenotypes of human peripheral CD8+ T cells.

BACKGROUND: CD40L is primarily expressed on activated CD4+ T cells and binds to CD40 which is expressed by various cells including dendritic cells, macrophages and B lymphocytes. While CD40-CD40L interaction is known to be direct between B cells and CD4+ T cells which results in proliferation and immunoglobulin isotype switching, antigen presenting cells (APCs) were thought to be involved in the delivery of CD4+ help to CD8+ T cells by cross-talk between CD4+ and CD8+ T cells and APCs. However, subsequent study demonstrated that CD40L signal can be directly delivered to CD8+ T cells by CD40 expression on CD8+ T cells. Since most studies have been carried out in murine models, we aimed to investigate the direct effect of CD40L on human peripheral CD8+ T cells. RESULTS: Human peripheral CD8+ T cells were isolated to exclude the indirect effect of B cells or dendritic cells. Upon activation, CD40 expression on CD8+ T cells was transiently induced and stimulation with artificial APCs expressing CD40L (aAPC-CD40L) increased the number of total and central memory CD8+ T cells and also pp65 specific CD8+ T cells. Stimulation with aAPC-CD40L also resulted in higher proportion of central memory CD8+ T cells. CONCLUSIONS: Our study suggests that CD40L has an effect on the increased number of CD8+ T cells through CD40 expressed on activated CD8+ T cells and has influence on memory CD8+ T cell generation. Our results may provide a new perspective of the effect of CD40L on human peripheral CD8+ T cells, which differ according to the memory differentiation status of CD8+ T cells.

Highly Durable Heterogeneous Atomic Catalysts.

ConspectusSingle-atom catalysts (SACs), in which surface metal atoms are isolated on the surface of a support, have received a tremendous amount of attention recently because this structure would utilize precious metals fully, without occluding atoms inside nanoparticles, and enable unique surface reactions which typical nanoparticle catalysts cannot induce. Various synthesis methods and characterization techniques have been reported that yield enhanced activity and selectivity. The single-atom structures were realized on various supports such as metal oxide/carbide/nitride, porous materials derived from zeolite or metal-organic frameworks, and carbon-based materials. Additionally, when the metal atoms are isolated on other metal nanoparticles, this material is denoted as a single-atom alloy (SAA). The single-atom structure, however, cannot catalyze the surface reaction that necessitates ensemble sites, where several metal atoms are located nearby. Very recently, ensemble catalysts, in which all of the metal atoms are exposed at the surface with neighboring metal atoms, have been reported, overcoming the limitation of single-atom catalysts. We call all of these materials (SACs, SAAs, and ensemble catalyst) heterogeneous atomic catalysts, indicating that the surface metal atomic structure is intentionally controlled. To use these atomic catalysts for practical applications, high durability should be guaranteed, which has received relatively less attention.In this Account, we discuss recent examples of heterogeneous atomic catalysts with high durability. Structural stability, indicating whether the surface atomic structure is thermodynamically stable, should be carefully considered. Typically, metal atoms are immobilized on a highly defective support, stabilizing both the metal atom and the support. The surface metal atoms might become destabilized upon the adsorption of chemical intermediates. This transient behavior should be carefully monitored; density functional theory (DFT) calculations are particularly useful in estimating this stability. Aside from structural stability, the catalyst performance can be degraded significantly by poisoning with impurities. If the single-atom sites are susceptible to impurities with stronger adsorption, the surface reaction would not occur efficiently, leading to a decrease in activity without structure degradation. A long-term durability test should be performed for target reactions. Heterogeneous atomic catalysts have been used for various electrochemical, photocatalytic, and thermal reactions. Although electricity, light, and heat are just different forms of energy, the specific conditions which the catalyst should satisfy are different. Whereas precious metal atoms are mostly used as surface-active sites, the properties of the support are different depending on the type of reaction. For example, the support should have high conductivity for electrochemical reactions, it should be able to absorb light for photocatalytic reactions, and it should be durable at high temperature in the presence of steam for thermal reactions. Highly durable heterogeneous atomic catalysts are certainly possible with a great potential for practical applications. These new catalysts can accelerate the current paradigm shift toward more sustainable chemical production.

Easily Scalable Shell-Structured Copper Catalyst with High Activity and Durability for Carbon Dioxide Hydrogenation.

Inducing strong metal-support interaction (SMSI) has been a useful way to control the structure of surface active sites. The SMSI often causes the encapsulation of metal particles with an oxide layer. Herein, an amorphous ceria shell was formed on Cu nanoparticles under a mild gas condition with high activity and durability for surface reaction. Cu-Ce solid solution promoted the transfer of surface oxygen species, which induced the ceria shell formation on Cu nanoparticles. This catalyst was used for CO2 hydrogenation, selectively producing CO with high low-temperature activity and good durability for operation at high temperature. CO2 activation and H2 spillover could occur at low temperatures, enhancing the activity. The shell prevented the sintering, assuring durability. This catalyst was applied to a bench-scale reactor without loss in performance, resulting in high CO productivity in all temperature ranges.

Efficient, Selective CO2 Photoreduction Enabled by Facet-Resolved Redox-Active Sites on Colloidal CdS Nanosheets.

Advances in nanotechnology have enabled precise design of catalytic sites for CO2 photoreduction, pushing product selectivity to near unity. However, activity of most nanostructured photocatalysts remains underwhelming due to fast recombination of photogenerated electron-hole pairs and sluggish hole transfer. To address these issues, we construct colloidal CdS nanosheets (NSs) with the large basal planes terminated by S2- atomic layers as intrinsic photocatalysts (CdS-S2- NSs). Experimental investigation reveals that the S2- termination endows ultrathin CdS-S2- NSs with facet-resolved redox-catalytic sites: oxidation occurs on S2--terminated large basal facets and reduction happens on side facets. Such an allocation of redox sites not only promotes spatial separation of photoinduced electrons and holes but also facilitates balanced extraction of holes and electrons by shortening the hole diffusion distance along the (001) direction of the ultrathin NSs. Consequently, the CdS-S2- NSs exhibit superb performance for photocatalytic CO2-to-CO conversion, which was verified by the isotope-labeled experiments to be a record-breaking performance: a CO selectivity of 99%, a CO formation rate of 2.13 mol g-1 h-1, and an effective apparent quantum efficiency of 42.1% under the irradiation (340 to 450 nm) of a solar simulator (AM 1.5G). The breakthrough performance achieved in this work provides novel insights into the precise design of nanostructures for selective and efficient CO2 photoreduction.

Colloidal Multiscale Assembly via Photothermally Driven Convective Flow for Sensitive In-Solution Plasmonic Detections.

The assembly of metal nanoparticles and targets to be detected in a small light probe volume is essential for achieving sensitive in-solution surface-enhanced Raman spectroscopy (SERS). Such assemblies generally require either chemical linkers or templates to overcome the random diffusion of the colloids unless the aqueous sample is dried. Here, a facile method is reported to produce 3D multiscale assemblies of various colloids ranging from molecules and nanoparticles to microparticles for sensitive in-solution SERS detection without chemical linkers and templates by exploiting photothermally driven convective flow. The simulations suggest that colloids sub 100 nm in diameter can be assembled by photothermally driven convective flow regardless of density; the assembly of larger colloids up to several micrometers by convective flow is significant only if their density is close to that of water. Consistent with the simulation results, the authors confirm that the photothermally driven convective flow is mainly responsible for the observed coassembly of plasmonic gold nanorods with either smaller molecules or larger microparticles. It is further found that the coassembly with the plasmonic nanoantennae leads to dramatic Raman enhancements of molecules, microplastics, and microbes by up to fivefold of magnitude compared to those measured in solution without the coassembly.

Multiple pathways linking early socioeconomic circumstances and depressive symptoms in late Middle age in the U.S.

Objectives: A growing number of life course studies are examining the influence of earlier life experiences on morbidity, disability, and mortality in mid-old age.Method: Drawing from the social pathway model, this study expands the life course literature by utilizing data collected over 35 years from the National Longitudinal Survey of Youth, 1979 Cohort, spanning four life course phases (childhood, young adulthood, middle adulthood, and late-middle adulthood). Through structural equation analyses with a phantom model, we estimated depressive symptoms in late middle age as a result of pathway effects starting with childhood socio-economic status (SES) which effect young adulthood and middle adulthood. The multi-pathway life course model includes three potential mediators of middle adulthood: health risk behaviors, social activity, and negative life events.Results: We found limited support for a direct effect of childhood SES disadvantage on depressive symptoms in middle age. Instead, much of the effects of childhood SES on later-year depressive symptoms appear to be mediated by SES in young adulthood. Further, the long-term pathway is mediated through the influence of health risk behaviors and negative life events in middle adulthood.Conclusion: Our findings do not propose this chain is permanent and irreversible; rather, this study highlights the possibility that interventions focused on promoting health behaviors and improving living conditions for people from socioeconomically disadvantaged backgrounds could help reduce the instance of depression in middle age and health outcomes along the life course could be improved.

Mid-term to Long-term Follow-up Results of Reconstruction for Thumb Radial Polydactyly.

BACKGROUND: Preaxial or radial polydactyly is one of the most common hand congenital anomalies in newborns. Contemporary reconstruction methods include ligament reconstruction, excision of the polydactylous thumb, osteotomy, and other surgical techniques according to the type of polydactyly. The purpose of this study was to report mid-term to long-term reconstruction results for thumb (radial) polydactyly. METHODS: We retrospectively reviewed the medical records of patients who underwent reconstruction surgery for preaxial polydactyly. Clinical outcomes, including the range of motion (ROM), pain, and complications, were evaluated. We assessed the final radiographs of the reconstructed thumb to identify the potential development of arthritis or other remaining deformities. After excluding cases without a simple radiograph and cases with a short follow-up period of fewer than 5 years, 26 thumbs were included. The surgical technique followed including excision of polydactylout thumb was tailored to the type of polydactyly. If the nail size of the thumbs was similar, the Bilhaut-Cloquet method was preferred. RESULTS: The mean age of the patients at the surgery and final follow-up was 14.9 months (range: 8 to 30 mo) and 11.9 years (range: 5.8 to 19.3 y), respectively. The mean follow-up was 128.8 months years (range: 60 to 219 mo), and the mean ROM of the thumb was 32.7 and 57.5 degrees in the distal interphalangeal joint (DIP) and metacarpophalangeal (MP) joint, respectively. Ulnar or radial side instability was prominent in 7 patients in the involved joints (26.9%). One patient underwent interphalangeal (IP) fusion for extension lag with pain. The radiologic evaluation revealed that 2 patients developed radiographic evidence of IP joint arthritis (7.7%). Radial deviation of the MP or IP joint existed in 13 cases (range: 5 to 40 degrees) (50.0%), and ulnar deviation of the MP or IP joint existed in 2 cases (range: 19 to 20 degrees) (7.7%). CONCLUSIONS: In mid-term to long-term experience, sequelae such as joint instability, joint stiffness, and remaining deformity cannot be neglected. An unstable MP joint may result if the DIP joint remains stiff or has a lower ROM. LEVEL OF EVIDENCE: Level IV-therapeutic studies.

FPCB as an Acoustic Matching Layer for 1D Linear Ultrasound Transducer Arrays.

An acoustic matching layer is an essential component of an ultrasound transducer to achieve maximum ultrasound transmission efficiency. Here, we develop a flexible printed circuit board (FPCB) with a composite structure consisting of multiple polyimide and copper layers and demonstrate it as a novel acoustic matching layer. With a flexible substrate and robust ACF bonding, the FPCB not only serves as an acoustic matching layer between piezoelectric elements and the surrounding medium but also as a ground for the electrical connection between the transducer array elements and the folded substrate. A 1D linear ultrasound transducer array with the FPCB matching layer exhibits larger output pressure, wider -3dB bandwidth, and higher ultrasound beam intensity compared to that of an ultrasound transducer array with the alumina/epoxy matching layer, which is one of the most commonly applied composite matching layers. The enhanced transmission performance verifies that the proposed FPCB is an excellent matching layer for 1D linear ultrasound transducer arrays.

Water-Wettable Open Plasmonic Nanocavities for Ultrasensitive Molecular Detections in Multiple Phases.

Plasmonic nanocavities between metal nanoparticles on metal films are either hydrophobic or fully occupied by nonmetallic spacers, preventing molecular diffusion into electromagnetic hotspots. Here we realize water-wettable open plasmonic cavities by devising gold nanoparticle with site-selectively grown ultrathin dielectric layer-on-gold film structures. We directly confirm that hydrophilic dielectric layers of SiO2 or TiO2, which are formed only at the tips of gold nanorod via precise temperature control, render sub-10 nm cavities open to the surroundings and completely water-wettable. Simulations reveal that spontaneous wetting in our cavities is driven by the presence of tip-selective hydrophilic layer and tendency of minimizing high energy air/water interface inside the cavities. Our plasmonic cavities show significant Raman enhancement of up to 4 orders of magnitude higher than those of conventional ones for molecules in various media. Our findings will offer new opportunities for sensing applications of plasmonic nanocavities and have huge impacts on cavity plasmonics.

Effect of Airborne Particulate Matter on the Immunologic Characteristics of Chronic Rhinosinusitis with Nasal Polyps.

The inflammatory mechanisms of environmental pollutants in chronic rhinosinusitis (CRS) have recently been proposed. However, the mechanisms underlying the inflammatory effects of particulate matter (PM) on nasal polyp (NP) tissues remain unknown. Here we investigated the mechanism underlying the inflammatory effects of PM10 on human nasal polyp-derived fibroblasts (NPDFs). We isolated NPDFs from human NP tissues obtained from patients with CRS with NPs (CRSwNP). The NPDFs were exposed to PM10 in vitro. Immunologic characteristics were assessed using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, Western blot, and flow cytometry. Additionally, we investigated the effect of NPDF-conditioned media (CM) on the expression of CD4+ T cell inflammatory mediators. PM10-treated NPDFs significantly upregulated interleukin (IL)-6, IL-4, and IL-33 expression and CXCL1 protein levels than PM10-treated normal tissues. MAP kinase, AP-1, and NF-kB were the primary cell signaling proteins. Immune cells in NPDF-CM had elevated IL-13, IL-17A, and IL-10 expression, but no significant difference in IFN-γ, TNF-α, and IL-4 expression. Moreover, under a Th2 inducing condition, NPDF-CM-treated CD4+ T cells had increased expression of IL-13, IL-10, and IL-17, which was reversed on ST2 inhibitor addition. Our study suggests that PM10 exposure could significantly increase the Th2 inflammatory pathway in NP tissues, specifically the IL-33/ST2 pathway-mediated immune response.

High-sensitivity C-reactive Protein and Regression of Low-grade Squamous Intraepithelial Lesion: The Role of Low-grade Inflammation in Cervical Carcinogenesis.

BACKGROUND: Inflammation is emerging as a potential mechanism of cervical carcinogenesis. However, few studies have investigated the association between host inflammatory status and the natural course of cervical precursor lesion. The aim of this study was to assess the probability of LSIL regression, associated with an inflammatory biomarker, high-sensitivity C-reactive protein (hs-CRP). METHODS: In a longitudinal cohort study, female participants were examined annually or biannually using cervical cytology between 2006 and 2015. Incident LSIL cases were included in the analysis, with regression defined as at least one consecutive normal cytologic result. A total of 520 women aged 22-64 years were followed up for LSIL regression. The multivariable-adjusted hazard ratios (HRs) for LSIL regression were estimated using a parametric proportional hazards model. RESULTS: During 827.5 person-years of follow-up, 486 out of 520 subjects (93.5%) showed LSIL regression. After adjusting several important potential confounders, a higher quartile of hs-CRP levels was significantly associated with a lower rate of regression (for quartile 4 vs quartile 1, inverse HR 1.33; 95% CI, 1.04-1.69; P for trend = 0.028). CONCLUSIONS: The low rate of spontaneous regression recorded in women with higher hs-CRP lends support to the role of the perturbated host inflammatory status in cervical carcinogenesis, and suggests that hs-CRP level could help monitor LSIL.

Thrombospondin 1 polymorphism associated with decreased expression and increased risk of pterygium.

PURPOSE: To assess the potential association of a thrombospondin 1 gene (THBS1) single-nucleotide polymorphism (rs1478604) with thrombospondin 1 (TSP-1) mRNA expression, as well as the risk of pterygium, in a pilot study. METHODS: DNA and RNA were isolated from peripheral blood samples collected from normal volunteer subjects (n = 39). In addition, DNA was isolated from conjunctival tissue samples collected during pterygium excision surgeries (n = 42). Relative expression of TSP-1 mRNA was measured by quantitative RT-PCR, and rs1478604 genotype was determined using a TaqMan SNP genotyping assay. Genotype frequencies were compared with mRNA expression and between pterygium samples and normal controls. RESULTS: Expression of TSP-1 mRNA was significantly lower in the peripheral blood of normal subjects who were homozygous for the C allele of rs1478604 (CC) compared to TT and CT genotypes (p = 0.004). When we compared rs1478604 genotypes between normal and pterygium patients, we found that the CC genotype was also associated with an increased risk of pterygium compared to TT (odds ratio (OR) = 5.39, 95% CI [1.26-22.99], p = 0.028), CT (OR = 7.86, 95% CI [1.92-32.17], p = 0.003), and combined CT and TT genotypes (OR = 6.67; 95% CI = [1.75-25.37]; p = 0.003). CONCLUSIONS: We found that the C allele of rs1478604 was associated with both lower TSP-1 expression and higher risk of pterygium, possibly implicating TSP-1 in the pathogenesis of pterygium.

IDO and CD40 May Be Key Molecules for Immunomodulatory Capacity of the Primed Tonsil-Derived Mesenchymal Stem Cells.

Background: Tonsil-derived mesenchymal stem cells (T-MSCs) were reported to have suppressive effect on T cells, yet much remains unknown about the underlying mechanisms supporting this effect. We investigated the underlying mechanism of the immunomodulatory effect of T-MSCs on immune cell proliferation and cytokine production. Methods: We isolated T-MSCs from human palatine tonsil and evaluated the immunomodulatory capacity using RT-PCR, ELISA, and flow cytometry. Additionally, we assessed the expression of various soluble factors and several costimulatory molecules to detect the priming effect on T-MSCs. Results: T-MSCs significantly inhibited the immune cell proliferation and cytokine expression (TNF-α and IFN-γ) in the direct co-culture, but there was no suppressive effect in indirect co-culture. Additionally, we detected a remarkably higher expression of indoleamine 2,3-dioxygenase (IDO) in the primed T-MSCs having co-expression CD40. Moreover, immune cells or CD4+ T cells showed lower TNF-α, IFN-γ, and IL-4 expression when the primed T-MSC were added; whereas those findings were reversed when the inhibitor for IDO (not IL-4) or CD40 were added. Furthermore, T-bet and GATA3 levels were significantly decreased in the co-cultures of the primed T-MSCs and CD4+ T cells; whereas those findings were reversed when we added the neutralizing anti-CD40 antibody. Conclusions: Primed T-MSCs expressing IDO and CD40 may have immunomodulatory capacity via Th1-mediated and Th2-mediated immune response.