JUST-Net: Jointly unrolled cross-domain optimization based spatio-temporal reconstruction network for accelerated 3D myelin water imaging.

PURPOSE: We introduced a novel reconstruction network, jointly unrolled cross-domain optimization-based spatio-temporal reconstruction network (JUST-Net), aimed at accelerating 3D multi-echo gradient-echo (mGRE) data acquisition and improving the quality of resulting myelin water imaging (MWI) maps. METHOD: An unrolled cross-domain spatio-temporal reconstruction network was designed. The main idea is to combine frequency and spatio-temporal image feature representations and to sequentially implement convolution layers in both domains. The k-space subnetwork utilizes shared information from adjacent frames, whereas the image subnetwork applies separate convolutions in both spatial and temporal dimensions. The proposed reconstruction network was evaluated for both retrospectively and prospectively accelerated acquisition. Furthermore, it was assessed in simulation studies and real-world cases with k-space corruptions to evaluate its potential for motion artifact reduction. RESULTS: The proposed JUST-Net enabled highly reproducible and accelerated 3D mGRE acquisition for whole-brain MWI, reducing the acquisition time from fully sampled 15:23 to 2:22 min within a 3-min reconstruction time. The normalized root mean squared error of the reconstructed mGRE images increased by less than 4.0%, and the correlation coefficients for MWI showed a value of over 0.68 when compared to the fully sampled reference. Additionally, the proposed method demonstrated a mitigating effect on both simulated and clinical motion-corrupted cases. CONCLUSION: The proposed JUST-Net has demonstrated the capability to achieve high acceleration factors for 3D mGRE-based MWI, which is expected to facilitate widespread clinical applications of MWI.

A pGpG-specific phosphodiesterase regulates cyclic di-GMP signaling in Vibrio cholerae.

The bacterial second messenger bis-(3'-5')-cyclic diguanylate monophosphate (c-di-GMP) controls various cellular processes, including motility, toxin production, and biofilm formation. c-di-GMP is enzymatically synthesized by GGDEF domain-containing diguanylate cyclases and degraded by HD-GYP domain-containing phosphodiesterases (PDEs) to 2 GMP or by EAL domain-containing PDE-As to 5'-phosphoguanylyl-(3',5')-guanosine (pGpG). Since excess pGpG feedback inhibits PDE-A activity and thereby can lead to the uncontrolled accumulation of c-di-GMP, a PDE that degrades pGpG to 2 GMP (PDE-B) has been presumed to exist. To date, the only enzyme known to hydrolyze pGpG is oligoribonuclease Orn, which degrades all kinds of oligoribonucleotides. Here, we identified a pGpG-specific PDE, which we named PggH, using biochemical approaches in the gram-negative bacteria Vibrio cholerae. Biochemical experiments revealed that PggH exhibited specific PDE activity only toward pGpG, thus differing from the previously reported Orn. Furthermore, the high-resolution structure of PggH revealed the basis for its PDE activity and narrow substrate specificity. Finally, we propose that PggH could modulate the activities of PDE-As and the intracellular concentration of c-di-GMP, resulting in phenotypic changes including in biofilm formation.

Exploring the JAK/STAT Signaling Pathway in Hepatocellular Carcinoma: Unraveling Signaling Complexity and Therapeutic Implications.

Hepatocellular Carcinoma (HCC) continues to pose a substantial global health challenge due to its high incidence and limited therapeutic options. In recent years, the Janus Kinase (JAK) and Signal Transducer and Activator of Transcription (STAT) pathway has emerged as a critical signaling cascade in HCC pathogenesis. The review commences with an overview of the JAK/STAT pathway, delving into the dynamic interplay between the JAK/STAT pathway and its numerous upstream activators, such as cytokines and growth factors enriched in pathogenic livers afflicted with chronic inflammation and cirrhosis. This paper also elucidates how the persistent activation of JAK/STAT signaling leads to diverse oncogenic processes during hepatocarcinogenesis, including uncontrolled cell proliferation, evasion of apoptosis, and immune escape. In the context of therapeutic implications, this review summarizes recent advancements in targeting the JAK/STAT pathway for HCC treatment. Preclinical and clinical studies investigating inhibitors and modulators of JAK/STAT signaling are discussed, highlighting their potential in suppressing the deadly disease. The insights presented herein underscore the necessity for continued research into targeting the JAK/STAT signaling pathway as a promising avenue for HCC therapy.

Active role of glia-like supporting cells in the organ of Corti: Membrane proteins and their roles in hearing.

The organ of Corti, located in the cochlea in the inner ear, is one of the major sensory organs involved in hearing. The organ of Corti consists of hair cells, glia-like supporting cells, and the cochlear nerve, which work in harmony to receive sound from the outer ear and transmit auditory signals to the cochlear nucleus in the auditory ascending pathway. In this process, maintenance of the endocochlear potential, with a high potassium gradient and clearance of electrolytes and biochemicals in the inner ear, is critical for normal sound transduction. There is an emerging need for a thorough understanding of each cell type involved in this process to understand the sophisticated mechanisms of the organ of Corti. Hair cells have long been thought to be active, playing a primary role in the cochlea in actively detecting and transmitting signals. In contrast, supporting cells are thought to be silent and function to support hair cells. However, growing lines of evidence regarding the membrane proteins that mediate ionic movement in supporting cells have demonstrated that supporting cells are not silent, but actively play important roles in normal signal transduction. In this review, we summarize studies that characterize diverse membrane proteins according to the supporting cell subtypes involved in cochlear physiology and hearing. This review contributes to a better understanding of supporting cell functions and facilitates the development of potential therapeutic tools for hearing loss.

Catalytically inactive T7 DNA polymerase imposes a lethal replication roadblock.

Bacteriophage T7 encodes its own DNA polymerase, the product of gene 5 (gp5). In isolation, gp5 is a DNA polymerase of low processivity. However, gp5 becomes highly processive upon formation of a complex with Escherichia coli thioredoxin, the product of the trxA gene. Expression of a gp5 variant in which aspartate residues in the metal-binding site of the polymerase domain were replaced by alanine is highly toxic to E. coli cells. This toxicity depends on the presence of a functional E. coli trxA allele and T7 RNA polymerase-driven expression but is independent of the exonuclease activity of gp5. In vitro, the purified gp5 variant is devoid of any detectable polymerase activity and inhibited DNA synthesis by the replisomes of E. coli and T7 in the presence of thioredoxin by forming a stable complex with DNA that prevents replication. On the other hand, the highly homologous Klenow fragment of DNA polymerase I containing an engineered gp5 thioredoxin-binding domain did not exhibit toxicity. We conclude that gp5 alleles encoding inactive polymerases, in combination with thioredoxin, could be useful as a shutoff mechanism in the design of a bacterial cell-growth system.

Hand-Held Raman Spectrometer-Based Dual Detection of Creatinine and Cortisol in Human Sweat Using Silver Nanoflakes.

The conventional tissue biopsy method yields isolated snapshots of a narrow region. Therefore, it cannot facilitate comprehensive disease characterization and monitoring. Recently, the detection of tumor-derived components in body fluids─a practice known as liquid biopsy─has attracted increased attention from the biochemical research and clinical application viewpoints. In this vein, surface-enhanced Raman scattering (SERS) has been identified as one of the most powerful liquid-biopsy analysis techniques, owing to its high sensitivity and specificity. Moreover, it affords high-capacity spectral multiplexing for simultaneous target detection and a unique ability to obtain intrinsic biomolecule-fingerprint spectra. This paper presents the fabrication of silver nanosnowflakes (SNSFs) using the polyol method and their subsequent dropping onto a hydrophobic filter paper. The SERS substrate, which comprises the SNSFs and hydrophobic filter paper, facilitates the simultaneous detection of creatinine and cortisol in human sweat using a hand-held Raman spectrometer. The proposed SERS system affords Raman spectrometry to be performed on small sample volumes (2 µL) to identify the normal and at-risk creatinine and cortisol groups.

High Blood Glucose Levels Affect Auditory Brainstem Responses after Acoustic Overexposure in Rats.

INTRODUCTION: Diabetes mellitus (DM) is a systemic disease characterized by hyperglycemia and several pathological changes. DM-related hearing dysfunctions are associated with histological changes. Here, we explore hearing function and synaptic changes in the inner hair cells (IHCs) of rats with streptozotocin (STZ)-induced diabetes. METHODS: STZ was injected to trigger diabetes. Rats with DM were exposed to narrow-band noise (105 dB SPL) for 2 h, and hearing function was analyzed 1, 3, 7, and 14 days later. Both the hearing threshold and the peak 1 amplitude of the tone auditory brainstem response were assessed. After the last functional test, animals were sacrificed for histological evaluation. RESULTS: We found no changes in the baseline hearing threshold; however, the peak 1 amplitude at the low frequency (4 kHz) was significantly higher in both DM groups than in the control groups. The hearing threshold had not fully recovered at 14 days after diabetic rats were exposed to noise. The peak 1 amplitude at the higher frequencies (16 and 32 kHz) was significantly larger in both DM groups than in the control groups. The histological analysis revealed that the long-term DM group had significantly more synapses in the 16 kHz region than the other groups. CONCLUSIONS: We found that high blood glucose levels increased peak 1 amplitudes without changing the hearing threshold. Diabetic rats were less resilient in threshold changes and were less vulnerable to peak 1 amplitude and synaptic damage than control animals.

Exposure to long-term evolution radiofrequency electromagnetic fields decreases neuroblastoma cell proliferation via Akt/mTOR-mediated cellular senescence.

The aim of this study was to examine the potential effects of long-term evolution (LTE) radiofrequency electromagnetic fields (RF-EMF) on cell proliferation using SH-SY5Y neuronal cells. The growth rate and proliferation of SH-SY5Y cells were significantly decreased upon exposure to 1760 MHz RF-EMF at 4 W/kg specific absorption rate (SAR) for 4 hr/day for 4 days. Cell cycle analysis indicated that the cell cycle was delayed in the G0/G1 phase after RF-EMF exposure. However, DNA damage or apoptosis was not involved in the reduced cellular proliferation following RF-EMF exposure because the expression levels of histone H2A.X at Ser139 (γH2AX) were not markedly altered and the apoptotic pathway was not activated. However, SH-SY5Y cells exposed to RF-EMF exhibited a significant elevation in Akt and mTOR phosphorylation levels. In addition, the total amount of p53 and phosphorylated-p53 was significantly increased. Data suggested that Akt/mTOR-mediated cellular senescence led to p53 activation via stimulation of the mTOR pathway in SH-SY5Y cells. The transcriptional activation of p53 led to a rise in expression of cyclin-dependent kinase (CDK) inhibitors p21 and p27. Further, subsequent inhibition of CDK2 and CDK4 produced a fall in phosphorylated retinoblastoma (pRb at Ser807/811), which decreased cell proliferation. Taken together, these data suggest that exposure to RF-EMF might induce Akt/mTOR-mediated cellular senescence, which may delay the cell cycle without triggering DNA damage in SH-SY5Y neuroblastoma cells.

Relationship between blood pressure stability and mortality in cardiac surgery patients: retrospective cohort study.

Performance measurement variables can be applied in clinical practice to evaluate hemodynamic instability. This study aimed to evaluate the relationship between the performance measurement of mean arterial pressure during cardiac surgery using cardiopulmonary bypass and postoperative mortality. A retrospective cohort study of patients who underwent cardiac surgery requiring cardiopulmonary bypass between 2013 and 2016 was conducted. The median performance error (MDPE) and median absolute performance error (MDAPE) were calculated using the preoperative mean arterial pressure as a reference, and intraoperative mean arterial pressures as measured values. Multivariable logistic regression analyses were performed using performance measurement variables to predict 30-day mortality. Overall survival according to performance measurement variables was evaluated using Cox proportional hazard models and Kaplan-Meier survival curves were generated to compare survival probability. Among 1203 patients, 110 (9.1%) died after surgery, and the 30-day mortality rate was 2.3% (28/1203). After adjusting for confounders, MDPE and MDAPE were significant mean arterial pressure derived predictors of 30-day mortality and overall survival. Intraoperative hypotension measured by performance measurement variables was independently associated with 30-day and overall mortality after cardiac surgery requiring cardiopulmonary bypass. Kaplan-Meier survival curves showed lower survival probability in patients with higher MDAPE during the pre- and post- cardiopulmonary bypass periods (P < 0.001 by log-rank test). Intraoperative hypotension measured by performance measurement variables was independently associated with 30-day and overall mortality after cardiac surgery requiring CPB. We propose that performance measurement variables are useful for quantifying the degree of intraoperative hypotension and predicting survival following cardiac surgery.Trial registration: ClinicalTrials.gov, identifier: NCT03785132.

Parametric Investigations of Magnetic Nanoparticles Hyperthermia in Ferrofluid using Finite Element Analysis.

Recently, magnetic nanoparticles (MNPs) based hyperthermia therapy has gained much attention due to its therapeutic potential in biomedical applications. This necessitates the development of numerical models that can reliably predict the temporal and spatial changes of temperature during the therapy. The objective of this study is to develop a comprehensive numerical model for quantitatively estimating temperature distribution in the ferrofluid system. The reliability of the numerical model was validated by comparative analysis of temperature distribution between experimental measurements and numerical analysis based on finite element method. Our analysis showed that appropriate incorporation of the heat effects of electromagnetic energy dissipation as well as thermal radiation from the ferrofluid system to the surrounding in the modeling resulted in the estimation of temperature distribution that is in close agreement with the experimental results. In summary, our developed numerical model is useful to evaluate the thermal behavior of the ferrofluid system during the process of magnetic fluid hyperthermia.

Impact of Mitral Valve Repair Case Volume on Postoperative Mortality　- A Nationwide Korean Cohort Study.

BACKGROUND: Although mitral valve repair is recommended over replacement due to better outcomes, repair rates vary significantly among centers. This study examined the effect of institutional mitral valve repair volume on postoperative mortality.Methods and Results:All cases of adult mitral valve repair performed in Korea between 2009 and 2016 were analyzed. The association between case volume and 1-year mortality was analyzed after categorizing centers according to the number of mitral valve repairs performed as low-, medium-, or high-volume centers (<20, 20-40, and >40 cases/year, respectively). The effect of case volume on cumulative all-cause mortality was also assessed. In all, 6,041 mitral valve repairs were performed in 86 centers. The 1-year mortality in low-, medium-, and high-volume centers was 10.1%, 8.7%, and 4.7%, respectively. Low- and medium-volume centers had increased risk of 1-year mortality compared with high-volume centers, with odds ratios of 2.80 (95% confidence interval [CI] 2.15-3.64; P<0.001) and 2.66 (95% CI 1.94-3.64; P<0.001), respectively. The risk of cumulative all-cause mortality was also worse in low- and medium-volume centers, with hazard ratios of 1.96 (95% CI 1.68-2.29; P<0.001) and 1.77 (95% CI 1.47-2.12; P<0.001), respectively. CONCLUSIONS: Lower institutional case volume was associated with higher mortality after mitral valve repair. A minimum volume standard may be required for hospitals performing mitral valve repair to guarantee adequate outcome.

Quantitative analysis of the coupling between proton and electron transport in peptide/manganese oxide hybrid films.

Understanding how electrons and protons move in a coupled manner and affect one another is important to the design of proton-electron conductors and achieving biological transport in synthetic materials. In this study, a new methodology is proposed that allows for the quantification of the degree of coupling between electrons and protons in tyrosine-rich peptides and metal oxide hybrid films at room temperature under a voltage bias. This approach is developed according to the Onsager principle, which has been thoroughly established for the investigation of mixed ion-electron conductors with electron and oxide ion vacancies as carriers at high temperatures. Herein, a new device platform using electron-blocking electrodes provides a new strategy to investigate the coupling of protons and electrons in bulk materials beyond the molecular level investigation of coupled proton and electron transfer. Two Onsager transport parameters, αi* and σe', are obtained from the device, and the results of these transport parameters demonstrate that the coupled transport of electrons and protons inside the hybrid film plays an important role in the macroscopic-scale conduction. The results suggest that an average of one electron is dragged by one proton in the absence of a direct driving force for electron movement ∇ηe.

A review on numerical modeling for magnetic nanoparticle hyperthermia: Progress and challenges.

Recent progress in nanotechnology has advanced the development of magnetic nanoparticle (MNP) hyperthermia as a potential therapeutic platform for treating diseases. Due to the challenges in reliably predicting the spatiotemporal distribution of temperature in the living tissue during the therapy of MNP hyperthermia, critical for ensuring the safety as well as efficacy of the therapy, the development of effective and reliable numerical models is warranted. This article provides a comprehensive review on the various mathematical methods for determining specific loss power (SLP), a parameter used to quantify the heat generation capability of MNPs, as well as bio-heat models for predicting heat transfer phenomena and temperature distribution in living tissue upon the application of MNP hyperthermia. This article also discusses potential applications of the bio-heat models of MNP hyperthermia for therapeutic purposes, particularly for cancer treatment, along with their limitations that could be overcome.

DNA translocation through a nanopore in an ultrathin self-assembled peptide membrane.

Here, we explore the possibility of using peptide-based materials as a membrane in solid-state nanopore devices in an effort to develop a sequence-specific, programmable biological membrane platform. We use a recently developed tyrosine-mediated self-assembly peptide sheet. At the air/water interface, the 5mer peptide YFCFY self-assembles into a uniform and robust two-dimensional (2D) structure, and the peptide sheet is easily transferred to a low-noise glass substrate. The thickness of the peptide membrane can be adjusted to approximately 5 nm (or even to 2 nm) by an etching process, and the diameters of the peptide nanopores can be precisely controlled using a focused electron beam with an attuned spot size. The ionic current noise of the peptide nanopore is comparable to those of typical silicon nitride nanopores or multilayer 2D materials. Using this membrane, we successfully observe translocation of 1000 bp double-stranded DNA with a sufficient signal-to-noise ratio of ∼30 and an elongated translocation speed of ∼1 bp µs-1. Our results suggest that the self-assembled peptide film can be used as a sensitive nanopore membrane and employed as a platform for applying biological functionalities to solid-state substrates.

Clinical Implications of Poloxamer 407 as Packing Material in an Animal Model.

BACKGROUND: Endoscopic ear surgery has recently increased, but it is still inconvenient and time-consuming to place packing material in the middle ear with one hand. Poloxamer 407 (P407) is a thermo-reversible gel that can be easily administered with one hand into the middle ear cavity in liquid form. Upon warming to body temperature, the gel form of P407 can support the graft in the target position and is known to prevent postsurgical tissue adhesion. OBJECTIVES: We aim to investigate the feasibility of P407 as packing material in an animal model. Male Hartley guinea pigs (350 and 400 g) were utilized in this study. METHOD: The animals were randomly divided into 3 groups according to the packing material: the control group, the P407 group, and the gelatin group. To assess the role of packing material on bacterial colonization, left ears were inoculated with Streptococcus pneumoniae through the tympanic membrane using a 0° endoscope. Five days after inoculation, the middle ear cavity was packed through a transbullar approach using 18% P407 or gelatin in both ears. In the control group, no ear pack was inserted. The tympanic membrane was examined every week using a 0° 1.9-mm endoscope until 6 weeks. Half of the animals in each group were sacrificed 6 weeks after placement of the packing materials. RESULTS: Compared with the absorbable gelatin sponge, the P407 group showed little inflammation or fibrosis in the tympanic membrane and middle ear mucosa regardless of bacterial inoculation. The gelatin group showed severe otorrhea or perforation until 2 weeks in the right ear (2 of 4) and the left ear (1 of 4). Even though the endoscopic findings were similar between both packing groups at 6 weeks, histological analysis showed persistent packing material, inflammatory cells, and fibrosis in the gelatin group compared to the P407 group. CONCLUSIONS: This study suggested that P407 is feasible as a packing material to handle with one hand and to prevent adhesion, especially in infected middle ear mucosa. Although there is a lack of data on how well P407 supports grafts, we suggest that P407 could be a candidate for packing material in endoscopic ear surgery.

Milk Fat Globule-EGF Factor 8, Secreted by Mesenchymal Stem Cells, Protects Against Liver Fibrosis in Mice.

BACKGROUND & AIMS: Mesenchymal stem cells (MSCs) mediate tissue repair and might be used to prevent or reduce liver fibrosis. However, little is known about the anti-fibrotic factors secreted from MSCs or their mechanisms. METHODS: Umbilical cord-derived MSCs (UCMSCs) were differentiated into hepatocyte-like cells (hpUCMSCs), medium was collected, and secretome proteins were identified and quantified using nanochip-liquid chromatography/quadrupole time-of-flight mass spectrometry. Liver fibrosis was induced in mice by intraperitoneal injection of thioacetamide or CCl4; some mice were then given injections of secretomes or proteins. Liver tissues were collected and analyzed by histology or polymerase chain reaction array to analyze changes in gene expression patterns. We analyzed the effects of MSC secretomes and potential anti-fibrotic proteins on transforming growth factor ß 1 (TGFß1)-mediated activation of human hepatic stellate cell (HSC) lines (hTert-HSC and LX2) and human primary HSCs. Liver tissues were collected from 16 patients with liver cirrhosis and 16 individuals without cirrhosis (controls) in Korea and analyzed by immunohistochemistry and immunoblots. RESULTS: In mice with fibrosis, accumulation of extracellular matrix proteins was significantly reduced 3 days after injecting secretomes from UCMSCs, and to a greater extent from hpUCMSCs; numbers of activated HSCs that expressed the myogenic marker α-smooth muscle actin (α-SMA, encoded by ACTA2 [actin, alpha 2, smooth muscle]) were also reduced. Secretomes from UCMSCs, and to a greater extent from hpUCMSCs, reduced liver expression of multiple fibrotic factors, collagens, metalloproteinases, TGFß, and Smad proteins in the TGFß signaling pathways. In HSC cell lines and primary HSCs, TGFß1-stimulated upregulation of α-SMA was significantly inhibited (and SMAD2 phosphorylation reduced) by secretomes from UCMSCs, and to a greater extent from hpUCMSCs. We identified 32 proteins in secretomes of UCMSCs that were more highly concentrated in secretomes from hpUCMSCs and inhibited TGFß-mediated activation of HSCs. One of these, milk fat globule-EGF factor 8 (MFGE8), was a strong inhibitor of activation of human primary HSCs. We found MFGE8 to down-regulate expression of TGFß type I receptor by binding to αvß3 integrin on HSCs and to be secreted by MSCs from umbilical cord, teeth, and bone marrow. In mice, injection of recombinant human MFGE8 had anti-fibrotic effects comparable to those of the hpUCMSC secretome, reducing extracellular matrix deposition and HSC activation. Co-injection of an antibody against MFGE8 reduced the anti-fibrotic effects of the hpUCMSC secretome in mice. Levels of MFGE8 were reduced in cirrhotic liver tissue from patients compared with controls. CONCLUSIONS: MFGE8 is an anti-fibrotic protein in MSC secretomes that strongly inhibits TGFß signaling and reduces extracellular matrix deposition and liver fibrosis in mice.

Prediction of hepatotoxicity for drugs using human pluripotent stem cell-derived hepatocytes.

Drug-induced liver toxicity is a main reason for withdrawals of new drugs in late clinical phases and post-launch of the drugs. Thus, hepatotoxicity screening of drug candidates in pre-clinical stage is important for reducing drug attrition rates during the clinical development process. Here, we show commercially available hepatocytes that could be used for early toxicity evaluation of drug candidates. From our hepatic differentiation technology, we obtained highly pure (≥98%) hepatocytes from human embryonic stem cells (hESCs) having mature phenotypes and similar gene expression profiles with those of primary human tissues. Furthermore, we optimized 96-well culture condition of hESC-derived hepatocytes suitable for toxicity tests in vitro. To this end, we demonstrated the efficacy of our optimized hepatocyte model for predicting hepatotoxicity against the Chinese herbal medicines and showed that toxicity patterns from our hepatocyte model was similar to those of human primary cultured hepatocytes. We conclude that toxicity test using our hepatocyte model could be a good alternative cell source for pre-clinical study to predict potential hepatotoxicity in drug discovery industries.

Effect of insemination timing on pregnancy outcome in association with female age, sperm motility, sperm morphology and sperm concentration in intrauterine insemination.

AIM: We investigated the effect of insemination timing on pregnancy outcomes in intrauterine insemination (IUI) cycles. METHODS: This is a retrospective study of 411 IUI cycles performed with a diagnosis of unexplained infertility and male factor infertility. The cycles were divided according to the interval between insemination and ovulation: ≤36 h, 36-37 h, 37-38 h and >38 h. The overall pregnancy rate, chemical pregnancy rate and clinical pregnancy rate were compared. We also analyzed the association between pregnancy outcomes and clinical characteristics, including age, duration of infertility, sperm concentration, body mass index (BMI), anti-Müllerian hormone (AMH) and number of mature follicles at ovulation. RESULTS: There were no differences regarding age, duration of infertility, BMI, AMH, sperm concentration and number of mature follicles between different IUI timing groups. Sperm morphology was significantly lower in ≤36 h group (5.3 ± 1.4) compared to 36-37 h, 37-38 h and >38 h (6.3 ± 2.5 vs 6.5 ± 2.7 vs 6.5 ± 3.5, P = 0.004) groups. The ≤36 h group showed lowest total pregnancy rate (5.0%) compared to other IUI timings (21.8% vs 24.8% vs 20.0%, P = 0.05). Multivariate analysis showed that sperm morphology was associated with pregnancy in 36-37 h (odd ratio 1.42, 95% confidence interval 1.03-1.95, P = 0.02). CONCLUSION: Insemination at least 36 h after ovulation is associated with increased pregnancy rate compared to IUIs performed ≤36 h following ovulation.

A 1.15 µW 200 kS/s 10-b Monotonic SAR ADC Using Dual On-Chip Calibrations and Accuracy Enhancement Techniques.

Herein, we present an energy efficient successive-approximation-register (SAR) analog-to-digital converter (ADC) featuring on-chip dual calibration and various accuracy-enhancement techniques. The dual calibration technique is realized in an energy and area-efficient manner for comparator offset calibration (COC) and digital-to-analog converter (DAC) capacitor mismatch calibration. The calibration of common-mode (CM) dependent comparator offset is performed without using separate circuit blocks by reusing the DAC for generating calibration signals. The calibration of the DAC mismatch is efficiently performed by reusing the comparator for delay-based mismatch detection. For accuracy enhancement, we propose new circuit techniques for a comparator, a sampling switch, and a DAC capacitor. An improved dynamic latched comparator is proposed with kick-back suppression and CM dependent offset calibration. An accuracy-enhanced bootstrap sampling switch suppresses the leakage-induced error <180 µV and the sampling error <150 µV. The energy-efficient monotonic switching technique is effectively combined with thermometer coding, which reduces the settling error in the DAC. The ADC is realized using a 0.18 µm complementary metal⁻oxide⁻semiconductor (CMOS) process in an area of 0.28 mm². At the sampling rate fS = 9 kS/s, the proposed ADC achieves a signal-to-noise and distortion ratio (SNDR) of 55.5 dB and a spurious-free dynamic range (SFDR) of 70.6 dB. The proposed dual calibration technique improves the SFDR by 12.7 dB. Consuming 1.15 µW at fS = 200 kS/s, the ADC achieves an SNDR of 55.9 dB and an SFDR of 60.3 dB with a figure-of-merit of 11.4 fJ/conversion-step.

Arginine-Presenting Peptide Hydrogels Decorated with Hydroxyapatite as Biomimetic Scaffolds for Bone Regeneration.

Hydrogels are promising candidates for biomimetic scaffolds of the extracellular matrix in tissue engineering applications. However, their use in bone tissue engineering is limited due to their low mechanical properties. In this study, we designed and synthesized multicomponent peptide-based hydrogels composed of fluorenyl-9-methoxycarbonyl diphenylalanine (FmocFF), which contributed to the rigidity and stability of the hydrogel, and Fmoc-arginine (FmocR), which mediated high affinity to hydroxyapatite (HAP) due to the arginine moiety. The new hydrogels composed of nanometric fibril networks were decorated with HAP and demonstrated high mechanical strength with a storage modulus of up to 29 kPa. In addition, the hydrogels supported cell adhesion and in vitro cell viability. These properties suggest using these multicomponent organic-inorganic hydrogels as functional biomaterials for improved bone regeneration.