Measurement of 19F(p, γ)20Ne reaction suggests CNO breakout in first stars.

Proposed mechanisms for the production of calcium in the first stars (population III stars)-primordial stars that formed out of the matter of the Big Bang-are at odds with observations1. Advanced nuclear burning and supernovae were thought to be the dominant source of the calcium production seen in all stars2. Here we suggest a qualitatively different path to calcium production through breakout from the 'warm' carbon-nitrogen-oxygen (CNO) cycle through a direct experimental measurement of the 19F(p, γ)20Ne breakout reaction down to a very low energy point of 186 kiloelectronvolts, reporting a key resonance at 225 kiloelectronvolts. In the domain of astrophysical interest2, at around 0.1 gigakelvin, this thermonuclear 19F(p, γ)20Ne rate is up to a factor of 7.4 larger than the previous recommended rate3. Our stellar models show a stronger breakout during stellar hydrogen burning than previously thought1,4,5, and may reveal the nature of calcium production in population III stars imprinted on the oldest known ultra-iron-poor star, SMSS0313-67086. Our experimental result was obtained in the China JinPing Underground Laboratory7, which offers an environment with an extremely low cosmic-ray-induced background8. Our rate showcases the effect that faint population III star supernovae can have on the nucleosynthesis observed in the oldest known stars and first galaxies, which are key mission targets of the James Webb Space Telescope9.

HIPK2 mediates M1 polarization of microglial cells via STAT3: A new mechanism of depression-related neuroinflammation.

This study aimed to investigate the role of protein kinase HIPK2 in depression and its associated mechanism. The chronic unpredictable mild stress (CUSM) model was constructed to simulate mice with depression to detect the mouse behaviors. Moreover, by using mouse microglial cells BV2 as the model. After conditional knockdown of HIPK2, the depressive behavior disorder of mice was improved, meanwhile, neuroinflammation was alleviated, and the M1 cell proportion was reduced. Similar results were obtained after applying the HIPK2 inhibitor tBID or ASO-HIPK2 treatment. HIPK2 was overexpressed in BV2 cells, which promoted M1 polarization of cells, while tBID suppressed the effect of HIPK2 and reduced the M1 polarized level in BV2 cells. Pull-down assay results indicated that HIPK2 bound to STAT3 and promoted STAT3 phosphorylation. We found that HIPK2 can bind to STAT3 to promote its phosphorylation, which accelerates M1 polarization of microglial cells, aggravates the depressive neuroinflammation, and leads to abnormal behaviors. HIPK2 is promising as the new therapeutic target of depression.

Regional disparities and risk factors of mortality among patients at high risk of sudden cardiac death in emerging countries: a nonrandomized controlled trial.

BACKGROUND: Comprehensive data on patients at high risk of sudden cardiac death (SCD) in emerging countries are lacking. The aim was to deepen our understanding of the SCD phenotype and identify risk factors for death among patients at high risk of SCD in emerging countries. METHODS: Patients who met the class I indication for implantable cardioverter-defibrillator (ICD) implantation according to guideline recommendations in 17 countries and regions underrepresented in previous trials were enrolled. Countries were stratified by the WHO regional classification. Patients were or were not implanted with an ICD at their discretion. The outcomes were all-cause mortality and SCD. RESULTS: We enrolled 4222 patients, and 3889 patients were included in the analysis. The mean follow-up period was 21.6 ± 10.2 months. There were 433 (11.1%) instances of all-cause mortality and 117 (3.0%) cases of SCD. All-cause mortality was highest in primary prevention (PP) patients from Southeast Asia and secondary prevention (SP) patients from the Middle East and Africa. The SCD rates among PP and SP patients were both highest in South Asia. Multivariate Cox regression modelling demonstrated that in addition to the independent predictors identified in previous studies, both geographic region and ICD use were associated with all-cause mortality in patients with high SCD risk. Primary prophylactic ICD implantation was associated with a 36% (HR = 0.64, 95% CI 0.531-0.802, p < 0.0001) lower all-cause mortality risk and an 80% (HR = 0.20, 95% CI = 0.116-0.343, p < 0.0001) lower SCD risk. CONCLUSIONS: There was significant heterogeneity among patients with high SCD risk in emerging countries. The influences of geographic regions on patient characteristics and outcomes were significant. Improvement in increasing ICD utilization and uptake of guideline-directed medical therapy in emerging countries is urgent. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02099721.

Fast 3D fMRI acquisition with high spatial resolutions over a reduced FOV.

PURPOSE: To develop and demonstrate a fast 3D fMRI acquisition technique with high spatial resolution over a reduced FOV, named k-t 3D reduced FOV imaging (3D-rFOVI). METHODS: Based on 3D gradient-echo EPI, k-t 3D-rFOVI used a 2D RF pulse to reduce the FOV in the in-plane phase-encoding direction, boosting spatial resolution without increasing echo train length. For image acceleration, full sampling was applied in the central k-space region along the through-slab direction (kz) for all time frames, while randomized undersampling was used in outer kz regions at different time frames. Images were acquired at 3T and reconstructed using a method based on partial separability. fMRI detection sensitivity of k-t 3D-rFOVI was quantitively analyzed with simulation data. Human visual fMRI experiments were performed to evaluate k-t 3D-rFOVI and compare it with a commercial multiband EPI sequence. RESULTS: The simulation data showed that k-t 3D-rFOVI can detect 100% of fMRI activations with an acceleration factor (R) of 2 and ˜80% with R = 6. In the human fMRI data acquired with 1.5-mm spatial resolution and 800-ms volume TR (TRvol), k-t 3D-rFOVI with R = 4 detected 46% more activated voxels in the visual cortex than the multiband EPI. Additional fMRI experiments showed that k-t 3D-rFOVI can achieve TRvol of 480 ms with R = 6, while reliably detecting visual activation. CONCLUSIONS: k-t 3D-rFOVI can simultaneously achieve a high spatial resolution (1.5-mm isotropically) and short TRvol (480-ms) at 3T. It offers a robust acquisition technique for fast fMRI studies over a focused brain volume.

Simultaneous perfusion, diffusion, T2 *, and T1 mapping with MR fingerprinting.

PURPOSE: Quantitative mapping of brain perfusion, diffusion, T2 *, and T1 has important applications in cerebrovascular diseases. At present, these sequences are performed separately. This study aims to develop a novel MRI technique to simultaneously estimate these parameters. METHODS: This sequence to measure perfusion, diffusion, T2 *, and T1 mapping with magnetic resonance fingerprinting (MRF) was based on a previously reported MRF-arterial spin labeling (ASL) sequence, but the acquisition module was modified to include different TEs and presence/absence of bipolar diffusion-weighting gradients. We compared parameters derived from the proposed method to those derived from reference methods (i.e., separate sequences of MRF-ASL, conventional spin-echo DWI, and T2 * mapping). Test-retest repeatability and initial clinical application in two patients with stroke were evaluated. RESULTS: The scan time of our proposed method was 24% shorter than the sum of the reference methods. Parametric maps obtained from the proposed method revealed excellent image quality. Their quantitative values were strongly correlated with those from reference methods and were generally in agreement with values reported in the literature. Repeatability assessment revealed that ADC, T2 *, T1 , and B1 + estimation was highly reliable, with voxelwise coefficient of variation (CoV) <5%. The CoV for arterial transit time and cerebral blood flow was 16% ± 3% and 25% ± 9%, respectively. The results from the two patients with stroke demonstrated that parametric maps derived from the proposed method can detect both ischemic and hemorrhagic stroke. CONCLUSION: The proposed method is a promising technique for multi-parametric mapping and has potential use in patients with stroke.

A ratiometric fluorescence assay for the detection of DNA methylation based on an alkaline phosphatase triggered in situ fluorogenic reaction.

The accurate and sensitive quantification of DNA methylation is significant for the early diagnosis of cancer. In this work, an alkaline phosphatase (ALP) triggered in situ fluorogenic reaction between ascorbic acid (AA) and 2,3-DAN was employed as a ratiometric fluorescent probe for the accurate and sensitive detection of DNA methylation with the assistance of ALP encapsulated liposomes. The quinoxaline derivative with a yellow fluorescence emission (I525) was generated from the reaction between AA and 2,3-DAN. Meanwhile, the consumption of 2,3-DAN declined its fluorescence intensity (I386). A ratiometric fluorescent probe (I525/I386) constructed by the above in situ fluorogenic reaction was applied for the accurate detection of DNA methylation. The methylated DNA was first captured by its complementary DNA in 96-well plates. Then, 5mC antibody (Ab) linked liposomes that were encapsulated with ALP recognized and combined with the methylation sites of the target DNA. After the liposomes were lysed by Triton X-100, the released ALP triggered the hydrolysis of ascorbic acid diphosphate (AAP) to form AA, participating in the fluorogenic reaction with 2,3-DAN to produce a quinoxaline derivative. Thus, the ratiometric fluorescence detection of DNA methylation was achieved using I525/I386 values. Using the ALP-enzyme catalyzed reaction and liposomes as signal amplifiers, a low detection limit of 82 fM was obtained for DNA methylation detection. Moreover, the accuracy of the assay could be improved using ratiometric fluorescent probes. We hope that the proposed assay will pave a new way for the accurate determination of low-abundance biomarkers.

The dynamics of deltamethrin resistance evolution in Aedes albopictus has an impact on fitness and dengue virus type-2 vectorial capacity.

BACKGROUND: Worldwide invasion and expansion of Aedes albopictus, an important vector of dengue, chikungunya, and Zika viruses, has become a serious concern in global public health. Chemical insecticides are the primary means currently available to control the mosquito populations. However, long-term and large-scale use of insecticides has selected for resistance in the mosquito that is accompanied by a genetic load that impacts fitness. RESULTS: A number of laboratory strains representing different resistance mechanisms were isolated and identified from laboratory-derived, deltamethrin-resistant Ae. albopictus recovered in previous work. Resistance levels and fitness costs of the strains were evaluated and compared to characterize the evolution of the resistance genotypes and phenotypes. The heterozygous F1534S mutation (1534F/S) in the voltage gated sodium channel (vgsc) gene product (VGSC), first detected in early stages of resistance evolution, not only confers high-level resistance, but also produces no significant fitness costs, leading to the rapid spread of resistance in the population. This is followed by the increase in frequency of homozygous F1534S (1534S/S) mosquitoes that have significant fitness disadvantages, prompting the emergence of an unlinked I1532T mutation with fewer side effects and a mating advantage better adapted to the selection and reproductive pressures imposed in the experiments. Metabolic resistance with no significant fitness cost and mediating a high-tolerance resistance phenotype may play a dominant role in the subsequent evolution of resistance. The different resistant strains had similar vector competence for dengue virus type-2 (DENV-2). Furthermore, a comparative analysis of vectorial capacity revealed that increased survival due to deltamethrin resistance balanced the negative fitness cost effects and contributed to the risk of dengue virus (DENV) transmission by resistant populations. The progressive evolution of resistance results in mosquitoes with both target-site insensitivity and metabolic resistance with lower fitness costs, which further leads to resistant populations with both high resistance levels and vectorial capacity. CONCLUSIONS: This study reveals a possible mechanism for the evolution of deltamethrin resistance in Aedes albopictus. These findings will help guide practical strategies for insecticide use, resistance management and the prevention and control of mosquito-borne disease.

Genome-wide identification and expression analysis of the NRT genes in Ginkgo biloba under nitrate treatment reveal the potential roles during calluses browning.

Nitrate is a primary nitrogen source for plant growth, and previous studies have indicated a correlation between nitrogen and browning. Nitrate transporters (NRTs) are crucial in nitrate allocation. Here, we utilized a genome-wide approach to identify and analyze the expression pattern of 74 potential GbNRTs under nitrate treatments during calluses browning in Ginkgo, including 68 NITRATE TRANSPORTER 1 (NRT1)/PEPTIDE TRANSPORTER (PTR) (NPF), 4 NRT2 and 2 NRT3. Conserved domains, motifs, phylogeny, and cis-acting elements (CREs) were analyzed to demonstrate the evolutionary conservation and functional diversity of GbNRTs. Our analysis showed that the NPF family was divided into eight branches, with the GbNPF2 and GbNPF6 subfamilies split into three groups. Each GbNRT contained 108-214 CREs of 19-36 types, especially with binding sites of auxin and transcription factors v-myb avian myeloblastosis viral oncogene homolog (MYB) and basic helix-loop-helix (bHLH). The E1X1X2E2R motif had significant variations in GbNPFs, indicating changes in the potential dynamic proton transporting ability. The expression profiles of GbNRTs indicated that they may function in regulating nitrate uptake and modulating the signaling of auxin and polyphenols biosynthesis, thereby affecting browning in Ginkgo callus induction. These findings provide a better understanding of the role of NRTs during NO3- uptake and utilization in vitro culture, which is crucial to prevent browning and develop an efficient regeneration and suspension production system in Ginkgo.

Genomic Shifts, Phenotypic Clines, and Fitness Costs Associated With Cold Tolerance in the Asian Tiger Mosquito.

Climatic variation is a key driver of genetic differentiation and phenotypic traits evolution, and local adaptation to temperature is expected in widespread species. We investigated phenotypic and genomic changes in the native range of the Asian tiger mosquito, Aedes albopictus. We first refine the phylogeographic structure based on genome-wide regions (1,901 double-digest restriction-site associated DNA single nucleotide polymophisms [ddRAD SNPs]) from 41 populations. We then explore the patterns of cold adaptation using phenotypic traits measured in common garden (wing size and cold tolerance) and genotype-temperature associations at targeted candidate regions (51,706 exon-capture SNPs) from nine populations. We confirm the existence of three evolutionary lineages including clades A (Malaysia, Thailand, Cambodia, and Laos), B (China and Okinawa), and C (South Korea and Japan). We identified temperature-associated differentiation in 15 out of 221 candidate regions but none in ddRAD regions, supporting the role of directional selection in detected genes. These include genes involved in lipid metabolism and a circadian clock gene. Most outlier SNPs are differently fixed between clades A and C, whereas clade B has an intermediate pattern. Females are larger at higher latitude yet produce no more eggs, which might favor the storage of energetic reserves in colder climate. Nondiapausing eggs from temperate populations survive better to cold exposure than those from tropical populations, suggesting they are protected from freezing damages but this cold tolerance has a fitness cost in terms of egg viability. Altogether, our results provide strong evidence for the thermal adaptation of A. albopictus across its wide temperature range.

Detection of Retinoic Acid-Active Chemicals in Diverse Sample Matrices Via a Quantum Dots-Based Nuclear Receptor Fluorescence Probe-Mediated Biosensor.

Developing a sensitive and reliable method for the screening of various endocrine-disrupting chemicals (EDCs) is in high demand and yet remains a significant challenge. Herein, we developed a CdSe/ZnS QDs-based nuclear receptor fluorescence probe (QDs-NRFP)-mediated biosensor for the screening of retinoic acid (RA)-active chemicals (a class of EDCs). The QDs-NRFP can be prepared on the spot via an antigen-antibody immunobinding interaction between the GST tag of the human retinoic acid receptor ß ligand-binding domain (GST-hRARß-LBD) and the CdSe/ZnS QDs-labeled anti-GST tag antibody. It can not only maintain the high binding activity of GST-hRARß-LBD but also improve the sensitivity due to the high quantum yield of CdSe/ZnS QDs. Based on the indirect competition bioassay, the developed biosensor showed a detection limit of 1.8 ng/L all-trans-retinoic acid binding activity equivalent (atRA-BAE) with a linear range of 7.5-1183.6 ng/L. Compared with many cell-dependent in vitro assays, the QDs-NRFP-mediated biosensor is cell-free and unaffected by the cytotoxic substances in matrices and exhibited obvious superiority in detection time (within 40 min) and accuracy. As a case study, the biosensor was applied to detect RA binding activities in various sample matrices obtained from a wastewater treatment plant (WWTP) and physiological samples and showed satisfactory accuracy and reliability. The developed QDs-NRFP-mediated biosensor is expected to be capable of screening various EDCs with universality based on different nuclear receptor signaling pathways, which will substantially accelerate the assessment of global EDCs.

Ultrasensitive Screening of Endocrine-Disrupting Chemicals Using a Surface Plasmon Resonance Biosensor with Polarization-Compensated Laser Heterodyne Feedback.

Developing an ultrasensitive and reliable device for continuous monitoring of various endocrine-disrupting chemicals (EDCs) is in high demand, yet it remains a significant challenge. Traditional label-free surface plasmon resonance (SPR) sensing relies on the interaction of the surface plasmon wave and the sensing liquid via intensity modulation, endowed with simple structure and easy-to-miniaturization, however suffering from inferior sensitivity and stability. Here, we propose a novel optical structure in which the frequency-shifted light of different polarization returned to the laser cavity to stimulate laser heterodyne feedback interferometry (LHFI), hence amplifying the reflectivity change caused by the refractive index (RI) variations on the gold-coated SPR chip surface, and the s-polarized light could be further used as a reference to compensate for the noise of the LHFI-amplified SPR system, resulting in nearly three orders of magnitude enhancement of the RI sensing resolution (5.9 × 10-8 RIU) compared to the original SPR system (2.0 × 10-5 RIU). To further boost intense signal enhancement, custom-designed gold nanorods (AuNRs), which were optimized by the finite-difference time-domain (FDTD) simulation, were used to generate localized surface plasmon resonance (LSPR). By exploiting the estrogen receptor as the recognition material, estrogenic active chemicals were detected with a 17ß-estradiol/L detection limit of 0.004 ng, which is nearly 180-fold lower than that of the system without introducing AuNRs. The developed SPR biosensor is expected to be capable of screening various EDCs with universality by using several nuclear receptors, such as the androgen receptor and thyroid receptor, and will substantially accelerate the assessment of global EDCs.

Multi-readout DWI with a reduced FOV for studying the coupling between diffusion and T 2 * relaxation in the prostate.

PURPOSE: To develop a DWI sequence with multiple readout echo-trains in a single shot (multi-readout DWI) over a reduced FOV, and to demonstrate its ability to achieve high data acquisition efficiency in the study of coupling between diffusion and relaxation in the human prostate. METHODS: The proposed multi-readout DWI sequence plays out multiple EPI readout echo-trains after a Stejskal-Tanner diffusion preparation module. Each EPI readout echo-train corresponded to a distinct effective TE. To maintain a high spatial resolution with a relatively short echo-train for each readout, a 2D RF pulse was used to limit the FOV. Experiments were performed on the prostate of six healthy subjects to acquire a set of images with three b values (0, 500, and 1000 s/mm2 ) and three TEs (63.0, 78.8, and 94.6 ms), producing three ADC maps at different TEs and three T 2 * $$ {T}_2^{\ast } $$ maps at different b values. RESULTS: Multi-readout DWI enabled a threefold acceleration without compromising the spatial resolution when compared with a conventional single-readout sequence. Images with three b values and three TEs were obtained in 3 min 40 s with an adequate SNR (≥ 26.9). The ADC values (1.45 ± 0.13, 1.52 ± 0.14, and 1.58 ± 0.15  µm 2 / ms $$ {\upmu \mathrm{m}}^2/\mathrm{ms} $$ ; P < 0.01) exhibited an increasing trend as TEs increased (63.0 ms, 78.8 ms, and 94.6 ms), whereas T 2 * $$ {T}_2^{\ast } $$ values (74.78 ± 13.21, 63.21 ± 7.84, and 56.61 ± 5.05 ms; P < 0.01) decreases as the b values increased (0, 500, and 1000 s/mm2 ). CONCLUSION: The multi-readout DWI sequence over a reduced FOV provides a time-efficient technique to study the coupling between diffusion and relaxation times.

Time-dependent diffusion MRI using multiple stimulated echoes.

PURPOSE: To develop a time-efficient pulse sequence that acquires multiple diffusion-weighted images with distinct diffusion times in a single shot by using multiple stimulated echoes (mSTE) with variable flip angles (VFA). METHODS: The proposed diffusion-weighted mSTE with VFA (DW-mSTE-VFA) sequence begins with two 90° RF pulses that straddle a diffusion gradient lobe (GD ) to excite and restore one half of the magnetization into the longitudinal axis. The restored longitudinal magnetization was successively re-excited by a series of RF pulses with VFA, each followed by another GD , to generate a set of stimulated echoes. Each of the multiple stimulated echoes was acquired with an EPI echo train. As such, the train of multiple stimulated echoes produced a set of diffusion-weighted images with varying diffusion times in a single shot. This technique was experimentally demonstrated on a diffusion phantom, a fruit, and healthy human brain and prostate at 3 T. RESULTS: In the phantom experiment, the mean ADC measured at different diffusion times using DW-mSTE-VFA were highly consistent (r = 0.999) with those from a commercial spin-echo diffusion-weighted EPI sequence. In the fruit and brain experiments, DW-mSTE-VFA exhibited similar diffusion-time dependence to a standard diffusion-weighted stimulated echo sequence. The ADC showed significant time dependence in the human brain (p = 0.003 in both white matter and gray matter) and prostate tissues (p = 0.003 in both peripheral zone and central gland). CONCLUSION: DW-mSTE-VFA offers a time-efficient tool for investigating the diffusion-time dependency in diffusion MRI studies.

Comparison of uniform-density, variable-density, and dual-density spiral samplings for multi-shot DWI.

PURPOSE: To compare the performances of uniform-density spiral (UDS), variable-density spiral (VDS), and dual-density spiral (DDS) samplings in multi-shot diffusion imaging, and determine a sampling strategy that balances reliability of shot navigator and overall DWI image quality. THEORY AND METHODS: UDS, VDS, and DDS trajectories were implemented to achieve four-shot diffusion-weighted spiral imaging. First, the static B0 off-resonance effects in UDS, VDS, and DDS acquisitions were analyzed based on a signal model. Then, in vivo experiments were performed to verify the theoretical analyses, and fractional anisotropy (FA) fitting residuals were used to quantitatively assess the quality of spiral diffusion data for tensor estimation. Finally, the SNR performances and g-factor behavior of the three spiral samplings were evaluated using a Monte Carlo-based pseudo multiple replica method. RESULTS: Among the three spiral trajectories with the same readout duration, UDS sampling exhibited the least off-resonance artifacts. This was most evident when the static B0 off-resonance effect was severe. The UDS diffusion images had higher anatomical fidelity and lower FA fitting residuals than the other two counterparts. Furthermore, the four-shot UDS acquisition achieved the best SNR performance in diffusion imaging with 12.11% and 40.85% improvements over the VDS and DDS acquisitions with the same readout duration, respectively. CONCLUSION: UDS sampling is an efficient spiral acquisition scheme for high-resolution diffusion imaging with reliable navigator information. It provides superior off-resonance performance and SNR efficiency over the VDS and DDS samplings for the tested scenarios.

Three-dimensional echo-shifted EPI with simultaneous blip-up and blip-down acquisitions for correcting geometric distortion.

PURPOSE: EPI with blip-up/down acquisition (BUDA) can provide high-quality images with minimal distortions by using two readout trains with opposing phase-encoding gradients. Because of the need for two separate acquisitions, BUDA doubles the scan time and degrades the temporal resolution when compared to single-shot EPI, presenting a major challenge for many applications, particularly fMRI. This study aims at overcoming this challenge by developing an echo-shifted EPI BUDA (esEPI-BUDA) technique to acquire both blip-up and blip-down datasets in a single shot. METHODS: A 3D esEPI-BUDA pulse sequence was designed by using an echo-shifting strategy to produce two EPI readout trains. These readout trains produced a pair of k-space datasets whose k-space trajectories were interleaved with opposite phase-encoding gradient directions. The two k-space datasets were separately reconstructed using a 3D SENSE algorithm, from which time-resolved B0 -field maps were derived using TOPUP in FSL and then input into a forward model of joint parallel imaging reconstruction to correct for geometric distortion. In addition, Hankel structured low-rank constraint was incorporated into the reconstruction framework to improve image quality by mitigating the phase errors between the two interleaved k-space datasets. RESULTS: The 3D esEPI-BUDA technique was demonstrated in a phantom and an fMRI study on healthy human subjects. Geometric distortions were effectively corrected in both phantom and human brain images. In the fMRI study, the visual activation volumes and their BOLD responses were comparable to those from conventional 3D echo-planar images. CONCLUSION: The improved imaging efficiency and dynamic distortion correction capability afforded by 3D esEPI-BUDA are expected to benefit many EPI applications.

Clinical use conditions of lead deployment and simulated lead fracture rate in left bundle branch area pacing.

INTRODUCTION: Left bundle branch area pacing (LBBAP) is achieved by advancing the lead tip deep in the septum. Most LBBAP implants are performed using the Medtronic SelectSecure™ MRI SecureScan™ Model 3830 featuring a unique 4 Fr fixed helix lumenless design. Details of lead use conditions and long-term reliability have not been reported. This study was designed to quantify the mechanical use conditions for the 3830 lead during and after LBBAP implant, and to evaluate reliability using bench testing and simulation. METHODS: Fifty bradycardia patients with implantation of the 3830 lead for LBBAP were enrolled. Use conditions of lead deployment at implantation were collected and computed tomography (CT) scans were performed at 3-month follow-up. Curvature amplitude along the pacing lead was determined with CT images. Fatigue bending was performed using accelerated testing in a more severe environment than routine clinical use conditions. Conductor fracture rate in a simulated patient population was estimated based on clinical use conditions and fatigue test results. RESULTS: The number of attempts to place the 3830 lead for LBBAP was 2.1 ± 1.3 (range: 1-7) with 13 ± 6 lead rotations at the final attempt. Extreme implant conditions were simulated in bench testing with 5 applications of 20 turns followed by up to 400 million bending cycles. Reliability modeling predicted a 10-year fracture rate of 0.02%. CONCLUSIONS: LBBAP implants require more lead rotations than standard pacing implants and result in unique lead bending. Application of simulated LBBAP use conditions to the 3830 lead in an accelerated in-vitro model does not produce excess conductor fractures. IMAGE-LBBP Study ID of ClinicalTrial.GOV: NCT04119323.

A novel approach for developing left bundle branch pacing and left bundle branch block in a canine model.

BACKGROUND AND OBJECTIVE: Left bundle branch pacing (LBBP) has shown the benefits in the treatment of dyssynchronous heart failure (HF). The purpose of this study was to develop a novel approach for LBBP and left bundle branch block (LBBB) in a canine model. METHODS: A "triangle-center" method by tricuspid valve annulus angiography for LBBP implantation was performed in 6 canines. A catheter was then applied for retrograde His potential recording and left bundle branch (LBB) ablation simultaneously. The conduction system was stained to verify the "triangle-center" method for LBBP and assess the locations of the LBB ablation site in relation to the left septal fascicle (LSF). RESULTS: The mean LBB potential to ventricular interval and stimulus-peak left ventricular activation time were 11.8 ± 1.2 and 35.7 ± 3.1 ms, respectively. The average intrinsic QRS duration was 44.7 ± 4.7 ms. LBB ablation significantly prolonged the QRS duration (106.3 ± 8.3 ms, p < .001) while LBBP significantly shortened the LBBB-QRS duration to 62.5 ± 5.3 ms (p < .001). After 6 weeks of follow-up, both paced QRS duration (63.0 ± 5.4 ms; p = .203) and LBBB-QRS duration (107.3 ± 7.4 ms; p = .144) were unchanged when comparing to the acute phase, respectively. Anatomical analysis of 6 canine hearts showed that the LBBP lead-tip was all placed in LSF area. CONCLUSION: The new approach for LBBP and LBBB canine model was stable and feasible to simulate the clinical dyssynchrony and resynchronization. It provided a useful tool to investigate the basic mechanisms of underlying physiological pacing benefits.

Large aperture and defect-free liquid crystal planar optics enabled by high-throughput pulsed polarization patterning.

The liquid crystal (LC) geometrical phase optics, which is realized by the high-resolution control of the optical axis orientation in transparent micrometer-thin polymer films, is emerging as a next generation of planar optics. It features pronounced optical properties and stimuli-responsive behaviors, which could introduce appealing and new possibilities for photonic purposes. The development of fabrication techniques producing elements with large aperture sizes and arbitrarily varying molecular orientation is of significance in terms of practical utility. Here, we propose the pulsed polarization patterning technique to create large-aperture and defect-free LC geometrical phase elements. We investigated the capability of the azo photo-alignment material responding to nanosecond laser pulses and the corresponding anchoring behaviors to LCs. The threshold was reduced to one fourth of that under the continuous wave recording. The patterning resolution was found to be enhanced to around 0.71 µm, due to the ultra-fast interaction nature of the photo-alignment material with the polarized light field. We proposed the flying exposure mode to deliver high frequency modulated polarized laser pulses (8 kHz), with the precision stage moving in a uniform velocity for light-field stitching and the servo auto-focusing in the sample normal, enabling the stable and reliable polarization patterning for large aperture sizes. We further report on representative fabrication of LC polarization gratings with an aperture of 4 inch and 99.2% average diffraction efficiency.

Double-negative T cells regulate the progression of liver fibrosis through Th9 cells differentiation.

Our previous study found that double negative T cells (DNTs) could promote the NLRP3 activation through high expression of TNF-α, thereby leading to hepatic fibrosis progression. We focused on investigating the role and mechanism of DNTs in regulating the Th9 cells differentiation in liver fibrosis. In our results, among patients with liver fibrosis, the proportions of peripheral blood DNTs and Th9 cells were up-regulated and positively correlated. While promoting the progression of liver fibrosis in mice, DNTs could elevate the proportion of Th9 cells and activate the TNFR2-STAT5-NF-κB pathway. The use of IL-9 and TNF-α monoclonal antibodies (mAbs) inhibited the effect of DNTs and lowered the proportion of Th9 cells in tissues. In vitro experiments showed that DNTs could promote the Th9 cells differentiation of Naive T cells, while TNF-α mAbs could inhibit such effect of DNTs to lower the proportion of Th9 cells. We found that DNTs can activate TNFR2-STAT5-NF-κB pathway by secreting TNF-α, thereby promoting the Th9 Cells differentiation to facilitate the progression of liver fibrosis. There is interaction between DNTs and Th9 cells.

An Ultrasensitive and Universal Surface Plasmonic Biosensor for Detection of Micropollutants in Aquatic Environments.

Simple yet ultrasensitive and accurate quantification of a variety of analytical targets by virtue of a universal sensing device holds promise to revolutionize environmental monitoring, medical diagnostics, and food safety. Here, we propose a novel optical surface plasmon resonance (SPR) system in which the frequency-shifted light of different polarizations returned the laser cavity to stimulate laser heterodyne feedback interferometry (LHFI), hence amplifying the reflectivity change caused by the refractive index (RI) variations on the gold-coated SPR chip surface. In addition, the s-polarized light was further used as the reference to compensate the noise of the LHFI-amplified SPR system, resulting in nearly 3 orders of magnitude enhancement of RI resolution (5.9 × 10-8 RIU) over the original SPR system (2.0 × 10-5 RIU). By exploiting nucleic acids, antibodies, and receptors as recognition materials, a variety of micropollutants were detected with ultralow detection limits, ranging from a toxic metal ion (Hg2+, 70 ng/L) to a group of commonly occurring biotoxin (microcystins, 3.9 ng microcystin-LR/L) and a class of environmental endocrine disruptors (estrogens, 0.7 ng 17ß-estradiol/L). This sensing platform exhibits several distinct characteristics, including dual improvement of sensitivity and stability and common-path optical construction without needing optical alignment, demonstrating a promising avenue toward environmental monitoring.