Mapping the emergence of molecular vibrations mediating bond formation.

Fundamental studies of chemical reactions often consider the molecular dynamics along a reaction coordinate using a calculated or suggested potential energy surface1-5. But fully mapping such dynamics experimentally, by following all nuclear motions in a time-resolved manner-that is, the motions of wavepackets-is challenging and has not yet been realized even for the simple stereotypical bimolecular reaction6-8: A-B + C â†’ A + B-C. Here we track the trajectories of these vibrational wavepackets during photoinduced bond formation of the gold trimer complex [Au(CN)2-]3 in an aqueous monomer solution, using femtosecond X-ray liquidography9-12 with X-ray free-electron lasers13,14. In the complex, which forms when three monomers A, B and C cluster together through non-covalent interactions15,16, the distance between A and B is shorter than that between B and C. Tracking the wavepacket in three-dimensional nuclear coordinates reveals that within the first 60 femtoseconds after photoexcitation, a covalent bond forms between A and B to give A-B + C. The second covalent bond, between B and C, subsequently forms within 360 femtoseconds to give a linear and covalently bonded trimer complex A-B-C. The trimer exhibits harmonic vibrations that we map and unambiguously assign to specific normal modes using only the experimental data. In principle, more intense X-rays could visualize the motion not only of highly scattering atoms such as gold but also of lighter atoms such as carbon and nitrogen, which will open the door to the direct tracking of the atomic motions involved in many chemical reactions.

Quadruple ultrasound, photoacoustic, optical coherence, and fluorescence fusion imaging with a transparent ultrasound transducer.

Ultrasound and optical imagers are used widely in a variety of biological and medical applications. In particular, multimodal implementations combining light and sound have been actively investigated to improve imaging quality. However, the integration of optical sensors with opaque ultrasound transducers suffers from low signal-to-noise ratios, high complexity, and bulky form factors, significantly limiting its applications. Here, we demonstrate a quadruple fusion imaging system using a spherically focused transparent ultrasound transducer that enables seamless integration of ultrasound imaging with photoacoustic imaging, optical coherence tomography, and fluorescence imaging. As a first application, we comprehensively monitored multiparametric responses to chemical and suture injuries in rats' eyes in vivo, such as corneal neovascularization, structural changes, cataracts, and inflammation. As a second application, we successfully performed multimodal imaging of tumors in vivo, visualizing melanomas without using labels and visualizing 4T1 mammary carcinomas using PEGylated gold nanorods. We strongly believe that the seamlessly integrated multimodal system can be used not only in ophthalmology and oncology but also in other healthcare applications with broad impact and interest.

Antisense Oligonucleotides against Let-7 Enhance the Therapeutic Potential of Mesenchymal Stromal Cells.

Let-7 miRNAs have pleiotropic cellular functions in cell proliferation, migration, and regenerative processes. Here, we investigate whether the inhibition of let-7 miRNAs with antisense oligonucleotides (ASOs) can be a transient and safe strategy enhancing the therapeutic potential of mesenchymal stromal cells (MSCs) to overcome their limitations in cell therapeutic trials. We first identified major subfamilies of let-7 miRNAs preferentially expressed in MSCs, and efficient ASO combinations against these selected subfamilies that mimic the effects of LIN28 activation. When let-7 miRNAs were inhibited with an ASO combination (anti-let7-ASOs), MSCs exhibited higher proliferation with delayed senescence during the passaging into a culture. They also exhibited increased migration and enhanced osteogenic differentiation potential. However, these changes in MSCs were not accompanied by cell-fate changes into pericytes or the additional acquisition of stemness, but instead occurred as functional changes accompanied by changes in proteomics. Interestingly, MSCs with let-7 inhibition exhibited metabolic reprogramming characterized by an enhanced glycolytic pathway, decreased reactive oxygen species, and lower transmembrane potential in mitochondria. Moreover, let-7-inhibited MSCs promoted the self-renewal of neighboring hematopoietic progenitor cells, and enhanced capillary formation in endothelial cells. These findings together show that our optimized ASO combination efficiently reprograms the MSC functional state, allowing for more efficient MSC cell therapy.

Development of a PCR-RFLP method for differential identification of Microcotyle sebastis and Microcotyle caudata isolated from cultured rockfish in Korea.

Microcotylid monogeneans can cause considerable health problems in cultured fish, and several Microcotyle species are reported from scorpaenid fish, an economically important aquaculture target species in Korea. We developed a PCR-RFLP assay targeting the mitochondrial cox1 gene, for discriminating Microcotyle sebastis and M. caudata from cultured Korean rockfish Sebastes schlegelii and dark-banded rockfish S. inermis. AseI enzyme treatment of the PCR products showed that M. sebastis sequence was cleaved while M. caudata was not. A total of 95.2% (118/124) of monogeneans from S. schlegelii were identified as M. sebastis, and 96.2% (126/131) of monogeneans from S. inermis were identified as M. caudata by PCR-RFLP. However, the remaining parasites from each host showed the opposite digestion pattern. Additional analyses of these specimens by targeting the ITS region by PCR-RFLP showed the same results, suggesting that cross-species infection by the parasites may have occurred. In Korea, S. inermis net cages are commonly located nearby S. schlegelii net cages, and this encaged proximity might have provided the opportunity for cross-infection to occur. Further examination of wild host populations and experimental cross-infection will be necessary to explain this phenomenon. The PCR-RFLP method in this study will help investigate the epidemiology and infection dynamics of Microcotyle species in S. inermis.

Automatic Detection and Segmentation of Thrombi in Abdominal Aortic Aneurysms Using a Mask Region-Based Convolutional Neural Network with Optimized Loss Functions.

The detection and segmentation of thrombi are essential for monitoring the disease progression of abdominal aortic aneurysms (AAAs) and for patient care and management. As they have inherent capabilities to learn complex features, deep convolutional neural networks (CNNs) have been recently introduced to improve thrombus detection and segmentation. However, investigations into the use of CNN methods is in the early stages and most of the existing methods are heavily concerned with the segmentation of thrombi, which only works after they have been detected. In this work, we propose a fully automated method for the whole process of the detection and segmentation of thrombi, which is based on a well-established mask region-based convolutional neural network (Mask R-CNN) framework that we improve with optimized loss functions. The combined use of complete intersection over union (CIoU) and smooth L1 loss was designed for accurate thrombus detection and then thrombus segmentation was improved with a modified focal loss. We evaluated our method against 60 clinically approved patient studies (i.e., computed tomography angiography (CTA) image volume data) by conducting 4-fold cross-validation. The results of comparisons to multiple other state-of-the-art methods suggested the superior performance of our method, which achieved the highest F1 score for thrombus detection (0.9197) and outperformed most metrics for thrombus segmentation.

Electric-Field-Induced Reversible Phase Transitions in a Spontaneously Ion-Intercalated 2D Metal Oxide.

Electric field driven reversible phase transitions in two-dimensional (2D) materials are appealing for their potential in switching applications. Here, we introduce potassium intercalated MnO2 as an exemplary case. We demonstrate the synthesis of large-area single-crystal layered MnO2 via chemical vapor deposition as thin as 5 nm. These crystals are spontaneously intercalated by potassium ions during the synthesis. We showed that the charge transport in 2D K-MnO2 is dominated by motion of hydrated potassium ions in the interlayer space. Under a few volts bias, separation of potassium and the structural water leads to formation of different phases at the opposite terminals, and at larger biases K-MnO2 crystals exhibit reversible layered-to-spinel phase transition. These phase transitions are accompanied by electrical and optical changes in the material. We used the electric field driven ionic motion in K-MnO2 based devices to demonstrate the memristive capabilities of two terminal devices.

Optical Kerr Effect of Liquid Acetonitrile Probed by Femtosecond Time-Resolved X-ray Liquidography.

Optical Kerr effect (OKE) spectroscopy is a method that measures the time-dependent change of the birefringence induced by an optical laser pulse using another optical laser pulse and has been used often to study the ultrafast dynamics of molecular liquids. Here we demonstrate an alternative method, femtosecond time-resolved X-ray liquidography (fs-TRXL), where the microscopic structural motions related to the OKE response can be monitored using a different type of probe, i.e., X-ray solution scattering. By applying fs-TRXL to acetonitrile and a dye solution in acetonitrile, we demonstrate that different types of molecular motions around photoaligned molecules can be resolved selectively, even without any theoretical modeling, based on the anisotropy of two-dimensional scattering patterns and extra structural information contained in the q-space scattering data. Specifically, the dynamics of reorientational (libration and orientational diffusion) and translational (interaction-induced motion) motions are captured separately by anisotropic and isotropic scattering signals, respectively. Furthermore, the two different types of reorientational motions are distinguished from each other by their own characteristic scattering patterns and time scales. The measured time-resolved scattering signals are in excellent agreement with the simulated scattering signals based on a molecular dynamics simulation for plausible molecular configurations, providing the detailed structural description of the OKE response in liquid acetonitrile.

Exciton delocalization length in chlorosomes investigated by lineshape dynamics of two-dimensional electronic spectra.

A chlorosome, a photosynthetic light-harvesting complex found in green sulfur bacteria, is an aggregate of self-assembled pigments and is optimized for efficient light harvesting and energy transfer under dim-light conditions. In this highly-disordered aggregate, the absorption and transfer of photoexcitation energy are governed by the degree of disorder. To describe the disorder, the number of molecules forming excitons, which is termed exciton delocalization length (EDL), is a relevant parameter because the EDL sensitively changes with the disorder of the constituent molecules. In this work, we determined the EDL in chlorosomes using two-dimensional electronic spectroscopy (2D-ES). Since spectral features correlated with EDL are spread out in the two-dimensional (2D) electronic spectra, we were able to determine the EDL accurately without the effects of homogeneous and inhomogeneous line broadening. In particular, by taking advantage of the multi-dimensionality and the time evolution of 2D spectra, we not only determined the excitation frequency dependence of EDL but also monitored the temporal change of EDL. We found that the EDL is ∼7 at 77 K and ∼6 at 298 K and increases with the excitation frequency, with the maximum located well above the maximum of the absorption spectrum of chlorosomes. The spectral profile of EDL changes rapidly within 100 fs and becomes flat over time due to dephasing of initial exciton coherence. From the coherent oscillations superimposed on the decay of EDL, it was learned that high-frequency phonons are more activated at 298 K than at 77 K.

Direct observation of bond formation in solution with femtosecond X-ray scattering.

The making and breaking of atomic bonds are essential processes in chemical reactions. Although the ultrafast dynamics of bond breaking have been studied intensively using time-resolved techniques, it is very difficult to study the structural dynamics of bond making, mainly because of its bimolecular nature. It is especially difficult to initiate and follow diffusion-limited bond formation in solution with ultrahigh time resolution. Here we use femtosecond time-resolved X-ray solution scattering to visualize the formation of a gold trimer complex, [Au(CN)2(-)]3 in real time without the limitation imposed by slow diffusion. This photoexcited gold trimer, which has weakly bound gold atoms in the ground state, undergoes a sequence of structural changes, and our experiments probe the dynamics of individual reaction steps, including covalent bond formation, the bent-to-linear transition, bond contraction and tetramer formation with a time resolution of ∼500 femtoseconds. We also determined the three-dimensional structures of reaction intermediates with sub-ångström spatial resolution. This work demonstrates that it is possible to track in detail and in real time the structural changes that occur during a chemical reaction in solution using X-ray free-electron lasers and advanced analysis of time-resolved solution scattering data.

Simplified Classification of Tear Film Break-Up Patterns and Their Clinicopathological Correlations in Patients With Dry Eye Disease.

PURPOSE: To analyze the pathophysiological differences between patients with dry eye disease (DED) having different tear film break-up patterns (TBUPs). METHODS: This investigative analysis involved 91 eyes of 91 patients with DED who were divided into two groups: those with "dot" break-up pattern (group I) and those with "random" break-up pattern (group II). Clinical severity was evaluated using the Ocular Surface Disease Index (OSDI), Oxford stain score system (OSS) score, and tear film break-up time (TF-BUT). Eighteen patients in group I and 17 patients in group II were selected for sampling of tears and the conjunctiva, and the concentrations of inflammatory cytokines and mucin in the tears and conjunctival tissue were measured. RESULTS: Thirty-seven patients were classified as group I and 54 patients as group II. Patients in group I had a statistically lower TF-BUT and a higher OSS score than those in group II, whereas the OSDI was not statistically different between the groups. The concentrations of interleukin (IL)-6 and IL-8 were statistically higher in group I than those in group II. Impression cytology showed that the expression of IL-1ß and IL-8 was higher in group I, whereas that of other genes was not statistically different. CONCLUSIONS: We were able to clearly classify patients with DED with different TBUPs into two groups, and each group had different clinical and pathophysiological characteristics. In patients with the dot break-up pattern, the disease was strongly associated with ocular surface inflammation, as opposed to that in patients without this pattern.

Structural Dynamics of C2F4I2 in Cyclohexane Studied via Time-Resolved X-ray Liquidography.

The halogen elimination of 1,2-diiodoethane (C2H4I2) and 1,2-diiodotetrafluoroethane (C2F4I2) serves as a model reaction for investigating the influence of fluorination on reaction dynamics and solute-solvent interactions in solution-phase reactions. While the kinetics and reaction pathways of the halogen elimination reaction of C2H4I2 were reported to vary substantially depending on the solvent, the solvent effects on the photodissociation of C2F4I2 remain to be explored, as its reaction dynamics have only been studied in methanol. Here, to investigate the solvent dependence, we conducted a time-resolved X-ray liquidography (TRXL) experiment on C2F4I2 in cyclohexane. The data revealed that (ⅰ) the solvent dependence of the photoreaction of C2F4I2 is not as strong as that observed for C2H4I2, and (ⅱ) the nongeminate recombination leading to the formation of I2 is slower in cyclohexane than in methanol. We also show that the molecular structures of the relevant species determined from the structural analysis of TRXL data provide an excellent benchmark for DFT calculations, especially for investigating the relevance of exchange-correlation functionals used for the structural optimization of haloalkanes. This study demonstrates that TRXL is a powerful technique to study solvent dependence in the solution phase.

Comparison of anesthetic effects of tiletamine-zolazepam-medetomidine or ketamine-medetomidine in captive Amur leopard cats (Prionailurus bengalensis euptailurus).

OBJECTIVE: To evaluate the effects and utility of tiletamine-zolazepam-medetomidine (TZM) and ketamine-medetomidine (KM) for anesthesia of Amur leopard cats (Prionailurus bengalensis euptailurus). STUDY DESIGN: Prospective, randomized experimental trial. ANIMALS: A total of six female (3.70 ± 0.49 kg) and six male (5.03 ± 0.44 kg; mean ± standard deviation) Amur leopard cats aged 2-6 years. METHODS: Each animal was administered four protocols separated by ≥3 weeks. Each protocol included medetomidine (0.05 mg kg-1) combined with tiletamine-zolazepam (1 mg kg-1; protocol MTZLO); tiletamine-zolazepam (2 mg kg-1; protocol MTZHI); ketamine (2 mg kg-1; protocol MKLO); or ketamine (4 mg kg-1; MKHI) administered intramuscularly. At time 0 (onset of lateral recumbency) and 30 minutes, heart rate (HR), respiratory rate (fR), rectal temperature, noninvasive mean arterial pressure (MAP) and hemoglobin oxygen saturation (SpO2) were recorded. Times to onset of lateral recumbency, duration of anesthesia and time to standing were recorded. RESULTS: Overall, animals were anesthetized with all protocols within 10 minutes, anesthesia was maintained ≥57 minutes, and recovery (time from the first head lift to standing) was completed within 5 minutes. During anesthesia with all protocols, HR, fR, rectal temperature, SpO2 and MAP were 99-125 beats minute-1, 33-44 breaths minute-1, 37.6-39.4 °C, 90-95% and 152-177 mmHg, respectively. No adverse event was observed. CONCLUSIONS AND CLINICAL RELEVANCE: TZM and KM at various dosages resulted in rapid onset of anesthesia, duration of >57 minutes and rapid recovery without administration of an antagonist. Accordingly, all these combinations are useful for anesthetizing Amur leopard cats and for performing simple procedures. However, the low doses of the anesthetic agents are recommended because there was no difference in duration of anesthesia between the dose rates studied.

FIRST REPORT OF ENTEROCYTOZOON BIENEUSI FROM AN AFRICAN LION (PANTHERA LEO) IN A ZOO IN THE REPUBLIC OF KOREA.

Enterocytozoon bieneusi is the most common species of microsporidia that infects humans and animals worldwide. However, no information is available on E. bieneusi infection among zoo animals in the Republic of Korea (ROK). Here, we investigated the prevalence of E. bieneusi among animals kept in zoos and the zoonotic potential of the E. bieneusi identified. E. bieneusi was detected only in one African lion (Panthera leo) with diarrhea, using PCR and sequencing analysis of the internal transcribed spacer (ITS) of the rRNA gene. A phylogenetic analysis based on the ITS gene showed that the lion isolate was classified into a novel genotype KPL belonging to Group 2. The KPL genotype identified in this study differed from genotype I in 6 nucleotides and from genotype I-like in 3 nucleotides, respectively, indicating that Group 2 has the capacity to infect a wide range of hosts. This is the first report of the presence of E. bieneusi in an African lion housed in a zoo in the ROK. Further investigation is necessary to study E. bieneusi infection among zoo animals in various regions and to determine the transmission route, in order to control E. bieneusi infection.

CREB coactivators CRTC2 and CRTC3 modulate bone marrow hematopoiesis.

Populations of circulating immune cells are maintained in equilibrium through signals that enhance the retention or egress of hematopoietic stem cells (HSCs) from bone marrow (BM). Prostaglandin E2 (PGE2) stimulates HSC renewal and engraftment through, for example, induction of the cAMP pathway. Triggering of PGE2 receptors increases HSC survival in part via the PKA-mediated induction of the cAMP response element-binding protein (CREB) signaling pathway. PKA stimulates cellular gene expression by phosphorylating CREB at Ser133 and by promoting the dephosphorylation of the cAMP- responsive transcriptional coactivators (CRTCs). We show here that disruption of both CRTC2 and CRTC3 causes embryonic lethality, and that a single allele of either CRTC2 or CRTC3 is sufficient for viability. CRTC2 knockout mice that express one CRTC3 allele (CRTC2/3m mice) develop neutrophilia and splenomegaly in adulthood due to the up-regulation of granulocyte-colony stimulating factor (G-CSF); these effects are reversed following administration of neutralizing anti-G-CSF antiserum. Adoptive transfer of CRTC2/3m BM conferred the splenomegaly/neutrophilia phenotype in WT recipients. Targeted disruption of both CRTC2 and CRTC3 in stromal cells with a mesenchymal Prx1-Cre transgene also promoted this phenotype. Depletion of CRTC2/3 was found to decrease the expression of Suppressor of Cytokine Signaling 3 (SOCS3), leading to increases in STAT3 phosphorylation and to the induction of CEBPß, a key regulator of the G-CSF gene. As small molecule inhibition of JAK activity disrupted CEBPß induction and reduced G-CSF expression in CRTC2/3m stromal cells, our results demonstrate how cross-coupling between the CREB/CRTC and JAK/STAT pathways contributes to BM homeostasis.

Pu-erh Tea Extract Treatment Could Be an Efficient Way to Enhance the Yield and Nutritional Value of Soybean Sprout.

Soybean sprouts are one of the most inexpensive and nutritious food items that can be easily grown year-round. Several studies have been conducted to increase their yield and nutritional values. This study was carried out to examine the effects of Pu-erh tea extracts on the production and nutrients content of soybean sprouts. Soybean seeds were soaked in 1%, 2%, or 3% (w/v) tea extracts, or tap water, before keeping for sprout cultivation; the sprout samples were named PE-1, PE-2, PE-3, and the control, respectively. The sprout yields were increased by up to 17% in PE-2 and PE-3 than in the control. The vitamin C, total free amino acid, total mineral, total isoflavone, total polyphenol, and flavonoid contents as well as the antioxidant potentials of the tea extract-treated sprouts were higher than those of the control. The results indicated that pre-soaking soybean seeds in 2% Pu-erh tea extracts could offer an easy, inexpensive, and efficient way to improve the yield and nutritional value of soybean sprouts.

De novo transcriptome sequencing and analysis of Anisakis pegreffii (Nematoda: Anisakidae) third-stage and fourth stage larvae.

Anisakis pegreffii is known as one of the causes of a fish-borne zoonosis, anisakidosis. Despite its significant public health and food hygiene impacts, little is known of the pathogenesis, genetic background of this parasite, at least partly due to the lack of genome and transcriptome information. In this study, RNA-seq and de novo assembly were conducted to obtain transcriptome profiles of the A. pegreffii third and fourth larvae. The third stage larvae (APL3) were collected from chub mackerel and the fourth stage larvae (APL4) were obtained by in vitro culture. In total, 47,243 and 43,660 unigenes were expressed in APL3 and APL4 transcriptomes. Of them, 18,753 were known and 28,490 were novel for APL3, while 18,996 were known and 24,664 were novel for APL4. The most abundantly expressed genes in APL3 were mitochondrial enzymes (COI, COII, COIII) and polyubiquitins (UBB, UBIQP_XENLA). Collagen-related genes (col-145, col-34, col-138, Bm1_54705, col-40) were the most abundantly expressed in APL4. Mitochondrial enzyme genes (COIII, COI) were also highly expressed in APL4. Among the transcripts, 614 were up-regulated in APL3, while 1,309 were up-regulated in APL4. Several protease and protein biosynthesis-related genes were highly expressed in APL3, all of which are thought to be crucial for invading host tissues. Collagen synthesis-related genes were highly expressed in APL4, reflecting active biosynthesis of collagens occurs during moulting process of APL4. Of these differentially expressed genes, several genes (SI, nas-13, EF-TSMT, SFXN2, dhs-27) were validated to highly transcribed in APL3, while other genes (col-40, F09E10.7, pept-1, col-34, VIT) in APL4. The biological roles of these genes in vivo will be deciphered when the reference genome sequences are available, together with in vitro experiments.Anisakis pegreffii is known as one of the causes of a fish-borne zoonosis, anisakidosis. Despite its significant public health and food hygiene impacts, little is known of the pathogenesis, genetic background of this parasite, at least partly due to the lack of genome and transcriptome information. In this study, RNA-seq and de novo assembly were conducted to obtain transcriptome profiles of the A. pegreffii third and fourth larvae. The third stage larvae (APL3) were collected from chub mackerel and the fourth stage larvae (APL4) were obtained by in vitro culture. In total, 47,243 and 43,660 unigenes were expressed in APL3 and APL4 transcriptomes. Of them, 18,753 were known and 28,490 were novel for APL3, while 18,996 were known and 24,664 were novel for APL4. The most abundantly expressed genes in APL3 were mitochondrial enzymes (COI, COII, COIII) and polyubiquitins (UBB, UBIQP_XENLA). Collagen-related genes (col-145, col-34, col-138, Bm1_54705, col-40) were the most abundantly expressed in APL4. Mitochondrial enzyme genes (COIII, COI) were also highly expressed in APL4. Among the transcripts, 614 were up-regulated in APL3, while 1,309 were up-regulated in APL4. Several protease and protein biosynthesis-related genes were highly expressed in APL3, all of which are thought to be crucial for invading host tissues. Collagen synthesis-related genes were highly expressed in APL4, reflecting active biosynthesis of collagens occurs during moulting process of APL4. Of these differentially expressed genes, several genes (SI, nas-13, EF-TSMT, SFXN2, dhs-27) were validated to highly transcribed in APL3, while other genes (col-40, F09E10.7, pept-1, col-34, VIT) in APL4. The biological roles of these genes in vivo will be deciphered when the reference genome sequences are available, together with in vitro experiments.

Comparison of five automated urine sediment analyzers with manual microscopy for accurate identification of urine sediment.

Background While the introduction of automated urine analyzers is expected to reduce the labor involved, turnaround time and potential assay variations, microscopic examination remains the "gold standard" for the analysis of urine sediments. In this study, we evaluated the analytical and diagnostic performance of five recently introduced automated urine sediment analyzers. Methods A total of 1016 samples were examined using five automated urine sediment analyzers and manual microscopy. Concordance of results from each automated analyzer and manual microscopy were evaluated. In addition, image and microscopic review rates of each system were investigated. Results The proportional bias for red blood cells (RBCs), white blood cells (WBCs) and squamous epithelial cells in the automated urine sediment analyzers were within ±20% of values obtained using the manual microscope, except in the cases of RBCs and WBCs analyzed using URiSCAN PlusScope and Iris iQ200SPRINT, respectively. The sensitivities of Roche Cobas® u 701 and Siemens UAS800 for pathologic casts (73.6% and 81.1%, respectively) and crystals (62.2% and 49.5%, respectively) were high, along with high image review rates (24.6% and 25.2%, respectively). The detection rates for crystals, casts and review rates can be changed for the Sysmex UF-5000 platform according to cut-off thresholds. Conclusions Each automated urine sediment analyzer has certain distinct features, in addition to the common advantages of reducing the burden of manual processing. Therefore, laboratory physicians are encouraged to understand these features, and to utilize each system in appropriate ways, considering clinical algorithms and laboratory workflow.

Fasting serum bile acids concentration is associated with insulin resistance independently of diabetes status.

Background Bile acids (BAs) have been demonstrated to exert a variety of metabolic effects and alterations in BAs have been reported in patients with obesity, insulin resistance (IR) and type 2 diabetes mellitus (T2DM). However, it is unclear which metabolic condition is the main contributor to alterations in BAs. In this study, we investigate the associations between different BA profiles with glycemia, obesity or IR status. Methods Fasting serum concentrations of 15 BA species were determined in a total of 241 individuals (71 drug-naïve patients with T2DM, 95 patients with impaired fasting glucose [IFG], and 75 healthy controls. Results A comparison of the mean values of the BAs revealed no significant differences between normoglycemic controls and patients with IFG or T2DM. However, when the entire cohort was divided according to the presence of IR as determined by a homeostasis model assessment of insulin resistance (HOMA-IR) value >2.5, the levels of total BA and most species of BAs were significantly higher in patients with IR than in patients without. In the correlation analysis, most species of BAs, as well as total BA, were significantly associated with HOMA-IR levels. Furthermore, when the subjects were divided into four groups according to IR and diabetic status, subjects with IR had significantly higher total BAs than participants without IR both in diabetic and non-diabetic groups. Ultimately, multiple linear regression analysis identified HOMA-IR as the only significant contributor to most serum BA species. Conclusions Our findings support the essential role of IR in regulating BA metabolism and that this effect is independent of diabetic status.

Fate of transient isomer of CH2I2: Mechanism and origin of ionic photoproducts formation unveiled by time-resolved x-ray liquidography.

Diiodomethane, CH2I2, in a polar solvent undergoes a unique photoinduced reaction whereby I2 - and I3 - are produced from its photodissociation, unlike for other iodine-containing haloalkanes. While previous studies proposed that homolysis, heterolysis, or solvolysis of iso-CH2I-I, which is a major intermediate of the photodissociation, can account for the formation of I2 - and I3 -, there has been no consensus on its mechanism and no clue for the reason why those negative ionic species are not observed in the photodissociation of other iodine-containing chemicals in the same polar solvent, for example, CHI3, C2H4I2, C2F4I2, I3 -, and I2. Here, using time-resolved X-ray liquidography, we revisit the photodissociation mechanism of CH2I2 in methanol and determine the structures of all transient species and photoproducts involved in its photodissociation and reveal that I2 - and I3 - are formed via heterolysis of iso-CH2I-I in the photodissociation of CH2I2 in methanol. In addition, we demonstrate that the high polarity of iso-CH2I-I is responsible for the unique photochemistry of CH2I2.