Live Birth with or without Preimplantation Genetic Testing for Aneuploidy.

BACKGROUND: Embryo selection with preimplantation genetic testing for aneuploidy (PGT-A) may improve pregnancy outcomes after initial embryo transfer. However, it remains uncertain whether PGT-A improves the cumulative live-birth rate as compared with conventional in vitro fertilization (IVF). METHODS: In this multicenter, randomized, controlled trial, we randomly assigned subfertile women with three or more good-quality blastocysts to undergo either PGT-A or conventional IVF; all the women were between 20 and 37 years of age. Three blastocysts were screened by next-generation sequencing in the PGT-A group or were chosen by morphologic criteria in the conventional-IVF group and then were successively transferred one by one. The primary outcome was the cumulative live-birth rate after up to three embryo-transfer procedures within 1 year after randomization. We hypothesized that the use of PGT-A would result in a cumulative live-birth rate that was no more than 7 percentage points higher than the rate after conventional IVF, which would constitute the noninferiority margin for conventional IVF as compared with PGT-A. RESULTS: A total of 1212 patients underwent randomization, and 606 were assigned to each trial group. Live births occurred in 468 women (77.2%) in the PGT-A group and in 496 (81.8%) in the conventional-IVF group (absolute difference, -4.6 percentage points; 95% confidence interval [CI], -9.2 to -0.0; P<0.001). The cumulative frequency of clinical pregnancy loss was 8.7% and 12.6%, respectively (absolute difference, -3.9 percentage points; 95% CI, -7.5 to -0.2). The incidences of obstetrical or neonatal complications and other adverse events were similar in the two groups. CONCLUSIONS: Among women with three or more good-quality blastocysts, conventional IVF resulted in a cumulative live-birth rate that was noninferior to the rate with PGT-A. (Funded by the National Natural Science Foundation of China and others; ClinicalTrials.gov number, NCT03118141.).

Stoichiometry and architecture of the platelet membrane complex glycoprotein Ib-IX-V.

Glycoprotein (GP) Ib-IX-V is the second most abundant platelet receptor for thrombin and other ligands crucial for hemostasis and thrombosis. Its activity is involved in platelet adhesion to vascular injury sites and thrombin-induced platelet aggregation. GPIb-IX-V is a heteromeric complex composed of four subunits, GPIbα, GPIbß, GPV and GPIX, in a stoichiometric ratio that has been wildly debated. Despite its important physiological roles, the overall structure and molecular arrangement of GPIb-IX-V are not yet fully understood. Here, we purify stable and functional human GPIb-IX-V complex from reconstituted EXPi293F cells in high homogeneity, and perform biochemical and structural characterization of this complex. Single-particle cryo-electron microscopy structure of GPIb-IX-V is determined at ∼11 Å resolution, which unveils the architecture of GPIb-IX-V and its subunit organization. Size-exclusion chromatography-multi-angle static light scattering analysis reveals that GPIb-IX-V contains GPIb-IX and GPV at a 1:1 stoichiometric ratio and surface plasmon resonance assays show that association of GPV leads to slow kinetics of thrombin binding to GPIb-IX-V. Taken together, our results provide the first three-dimensional architecture of the intact GPIb-IX-V complex, which extends our understanding of the structure and functional mechanism of this complex in hemostasis and thrombosis.

UV-enhanced photorefractive response rate in a thin-film lithium niobate microdisk.

The photorefractive (PR) effect plays a critical role in emerging photonic technologies, including dynamic volume holography and on-chip all-optical functionalities. Nevertheless, its slow response rate has posed a significant obstacle to its practical application. Here, we experimentally demonstrate the enhancement of the PR response rate in a high-Q thin-film lithium niobate (TFLN) microdisk under UV light irradiation. At an irradiation intensity of 30 mW/cm2, the PR effect achieves a high response bandwidth of approximately 256 kHz. By employing this UV-assisted PR effect, we have achieved rapid laser-cavity locking and self-stabilization, where perturbations are automatically compensated. This technique paves the way toward real-time dynamic holography, editable photonic devices on a lithium niobate platform, and high-speed all-optical information processing.

Poling-assisted hydrofluoric acid wet etching of thin-film lithium niobate.

Thin-film lithium niobate (TFLN) has been extensively investigated for a wide range of applications due to continuous advancements in its fabrication methods. The recent emergence of high-fidelity ferroelectric domain poling of TFLN provides an opportunity for achieving a precise pattern control of ferroelectric domains and a subsequent pattern transfer to the TFLN layer using hydrofluoric acid (HF). In this work, we present, to the best of our knowledge, the first demonstration of z-cut TFLN microdisks using a poling-assisted HF wet etching approach. By applying intense electric fields, we are able to induce a domain inversion in the TFLN with a designed microdisk pattern. A HF solution is subsequently utilized to transfer the inverted domain pattern to the TFLN layer with the selective etching of -z LN, ultimately revealing the microdisks.

Circuit-based neuromodulation enhances delayed recall in amnestic mild cognitive impairment.

BACKGROUND: This study aimed to investigate the efficacy of circuits-based paired associative stimulation (PAS) in adults with amnestic mild cognitive impairment (aMCI). METHODS: We conducted a parallel-group, randomised, controlled clinical trial. Initially, a cohort of healthy subjects was recruited to establish the cortical-hippocampal circuits by tracking white matter fibre connections using diffusion tensor imaging. Subsequently, patients diagnosed with aMCI, matched for age and education, were randomly allocated in a 1:1 ratio to undergo a 2-week intervention, either circuit-based PAS or sham PAS. Additionally, we explored the relationship between changes in cognitive performance and the functional connectivity (FC) of cortical-hippocampal circuits. RESULTS: FCs between hippocampus and precuneus and between hippocampus and superior frontal gyrus (orbital part) were most closely associated with the Auditory Verbal Learning Test (AVLT)_N5 score in 42 aMCI patients, thus designated as target circuits. The AVLT_N5 score improved from 2.43 (1.43) to 5.29 (1.98) in the circuit-based PAS group, compared with 2.52 (1.44) to 3.86 (2.39) in the sham PAS group (p=0.003; Cohen's d=0.97). A significant decrease was noted in FC between the left hippocampus and left precuneus in the circuit-based PAS group from baseline to postintervention (p=0.013). Using a generalised linear model, significant group×FC interaction effects for the improvements in AVLT_N5 scores were found within the circuit-based PAS group (B=3.4, p=0.017). CONCLUSIONS: Circuit-based PAS effectively enhances long-term delayed recall in adults diagnosed with aMCI, which includes individuals aged 50-80 years. This enhancement is potentially linked to the decreased functional connectivity between the left hippocampus and left precuneus. TRIAL REGISTRATION NUMBER: ChiCTR2100053315; Chinese Clinical Trial Registry.

Self-Assembled Au Nanoelectrodes: Enabling Low-Threshold-Voltage HfO2-Based Artificial Neurons.

Filamentary-type resistive switching devices, such as conductive bridge random-access memory and valence change memory, have diverse applications in memory and neuromorphic computing. However, the randomness in filament formation poses challenges to device reliability and uniformity. To overcome this issue, various defect engineering methods have been explored, including doping, metal nanoparticle embedding, and extended defect utilization. In this study, we present a simple and effective approach using self-assembled uniform Au nanoelectrodes to controll filament formation in HfO2 resistive switching devices. By concentrating the electric field near the Au nanoelectrodes within the BaTiO3 matrix, we significantly enhanced the device stability and reduced the threshold voltage by up to 45% in HfO2-based artificial neurons compared to the control devices. The threshold voltage reduction is attributed to the uniformly distributed Au nanoelectrodes in the insulating matrix, as confirmed by COMSOL simulation. Our findings highlight the potential of nanostructure design for precise control of filamentary-type resistive switching devices.

Morphological alterations of contralesional hemisphere relate to functional outcomes after stroke.

The present study aimed to investigate poststroke morphological alterations contralesionally and correlations with functional outcomes. Structural magnetic resonance images were obtained from 27 poststroke patients (24 males, 50.21 ± 10.97 years) and 20 healthy controls (13 males, 46.63 ± 12.18 years). Voxel-based and surface-based morphometry analysis were conducted to detect alterations of contralesional grey matter volume (GMV), cortical thickness (CT), gyrification index (GI), sulcus depth (SD), and fractal dimension (FD) in poststroke patients. Partial correlation analysis was used to explore the relationship between regions with significant structural differences and scores of clinical assessments, including Modified Barthel Index (MBI), Berg Balance Scale (BBS), Fugl-Meyer Assessment of Upper Extremity (FMA-UE), Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA). Correction for multiplicity was conducted within each parameter and for all tests. GMV significantly decreased in the contralesional motor-related, occipital and temporal cortex, limbic system, and cerebellum lobe (P < 0.01, family-wise error [FWE] correction). Lower CT was found in the contralesional precentral and lingual gyrus (P < 0.01, FWE correction), while lower GI found in the contralesional superior temporal gyrus and insula (P < 0.01, FWE correction). There were significant correlations between GMV of contralesional lingual gyrus and MBI (P = 0.031, r = 0.441), and BBS (P = 0.047, r = 0.409) scores, and GMV of contralesional hippocampus and FMA-UE scores (P = 0.048, r = 0.408). In conclusion, stroke patients exhibited wide grey matter loss and cortical morphological changes in the contralesional hemisphere, which correlated with sensorimotor functions and the ability of daily living.

Li2RbSO4Cl with a Short Ultraviolet Absorption Edge and an Acentric Structure through Assembling Heteroleptic [LiO3Cl] Tetrahedra.

Currently, short-wavelength nonlinear optical materials are urgently needed. Through substituting homoleptic [LiO4] in centrosymmetric LiRbSO4 with heteroleptic [LiO3Cl] tetrahedra, an acentric sulfate chloride, Li2RbSO4Cl, was designed and synthesized by the high-temperature melting method. Li2RbSO4Cl shows a relatively short ultraviolet absorption edge (<200 nm) among newly reported sulfate chlorides. Millimeter-sized crystals were grown due to the congruent melting behavior and high thermal stability of the compound.

Vanadate Crystals with an Enhanced Birefringence and a Broadened Transparency Spectrum through Controlled [VO3]∞ Chain Arrangements and Alkali Metal Cation Introduction.

The vanadate (VO) polyhedron offers a compelling avenue for exploring birefringent materials within the infrared frequency range. Among many potential building blocks, the implementation of [VO3]∞ chains demonstrated great potential as effective birefringent functional units. In this article, we successfully synthesized the Li0.8Na0.2CsV2O6·H2O compound, which exhibits a remarkable birefringence of 0.134 at 546.1 nm, as confirmed by the experiment. Notably, the introduction of alkali metals in this compound led to a significantly shorter cutoff edge at 340 nm. Through a comprehensive investigation, Li0.8Na0.2CsV2O6·H2O has the shortest UV cutoff edge among all vanadates, whose birefringences are larger than 0.1, to the best of our best knowledge. This finding underscores the application potential of this novel material as a birefringent crystal.

Prednisone vs Placebo and Live Birth in Patients With Recurrent Implantation Failure Undergoing In Vitro Fertilization: A Randomized Clinical Trial.

Importance: Implantation failure remains a critical barrier to in vitro fertilization. Prednisone, as an immune-regulatory agent, is widely used to improve the probability of implantation and pregnancy, although the evidence for efficacy is inadequate. Objective: To determine the efficacy of 10 mg of prednisone compared with placebo on live birth among women with recurrent implantation failure. Design, Setting, and Participants: A double-blind, placebo-controlled, randomized clinical trial conducted at 8 fertility centers in China. Eligible women who had a history of 2 or more unsuccessful embryo transfer cycles, were younger than 38 years when oocytes were retrieved, and were planning to undergo frozen-thawed embryo transfer with the availability of good-quality embryos were enrolled from November 2018 to August 2020 (final follow-up August 2021). Interventions: Participants were randomized (1:1) to receive oral pills containing either 10 mg of prednisone (n = 357) or matching placebo (n = 358) once daily, from the day at which they started endometrial preparation for frozen-thawed embryo transfer through early pregnancy. Main Outcomes and Measures: The primary outcome was live birth, defined as the delivery of any number of neonates born at 28 or more weeks' gestation with signs of life. Results: Among 715 women randomized (mean age, 32 years), 714 (99.9%) had data available on live birth outcomes and were included in the primary analysis. Live birth occurred among 37.8% of women (135 of 357) in the prednisone group vs 38.8% of women (139 of 358) in the placebo group (absolute difference, -1.0% [95% CI, -8.1% to 6.1%]; relative ratio [RR], 0.97 [95% CI, 0.81 to 1.17]; P = .78). The rates of biochemical pregnancy loss were 17.3% in the prednisone group and 9.9% in the placebo group (absolute difference, 7.5% [95% CI, 0.6% to 14.3%]; RR, 1.75 [95% CI, 1.03 to 2.99]; P = .04). Of those in the prednisone group, preterm delivery occurred among 11.8% and of those in the placebo group, 5.5% of pregnancies (absolute difference, 6.3% [95% CI, 0.2% to 12.4%]; RR, 2.14 [95% CI, 1.00 to 4.58]; P = .04). There were no statistically significant between-group differences in the rates of biochemical pregnancy, clinical pregnancy, implantation, neonatal complications, congenital anomalies, other adverse events, or mean birthweights. Conclusions and Relevance: Among patients with recurrent implantation failure, treatment with prednisone did not improve live birth rate compared with placebo. Data suggested that the use of prednisone may increase the risk of preterm delivery and biochemical pregnancy loss. Our results challenge the value of prednisone use in clinical practice for the treatment of recurrent implantation failure. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1800018783.

Quadratic strong coupling in AlN Kerr cavity solitons.

Photonic platforms with χ(2) nonlinearity offer new degrees of freedom for Kerr frequency comb development. Here, we demonstrate Kerr soliton generation at 1550 nm with phase-matched quadratic coupling to the 775 nm harmonic band in a single AlN microring and thus the formation of dual-band mode-locked combs. In the strong quadratic coupling regime where the χ(2) phase-matching window overlaps the pump mode, the pump-to-harmonic-comb conversion efficiency is optimized. However, the strong quadratic coupling also drastically modifies the Kerr comb generation dynamics and decreases the probability of soliton generation. By engineering the χ(2) phase-matching wavelength, we are able to achieve a balance between high conversion efficiency and high soliton formation rate under the available pump power and microring quality factors. Our numerical simulations confirm the experimental observations. These findings provide guidance on tailoring single-cavity dual-band coherent comb sources.

Shaoyao-Gancao Decoction Promoted Microglia M2 Polarization via the IL-13-Mediated JAK2/STAT6 Pathway to Alleviate Cerebral Ischemia-Reperfusion Injury.

Microglia in the penumbra shifted from M2 to M1 phenotype between 3 and 5 days after cerebral ischemia-reperfusion, which promoted local inflammation and injury. Shaoyao-Gancao Decoction (SGD) has been found to result in a significant upregulation of IL-13 in the penumbra, which has been shown to induce polarization of M2 microglia. There was thus a hypothesis that SGD could exert an anti-inflammatory and neuroprotective effect by activating IL-13 to induce microglia polarization towards M2 phenotype, and the purpose of this study was to explore the influence of SGD on microglia phenotype switching and its possible mechanism. Rats who received middle cerebral artery occlusion surgery (MCAO) were treated with SGD for 3 or 6 days, to investigate the therapeutic effect and the underlying mechanism of SGD for cerebral ischemia-reperfusion injury (CI/RP). The results indicated that SGD improved neurobehavioral scores and reduced apoptosis. Furthermore, SGD significantly decreased M1 microglia and M1-like markers, but increased M2 microglia and M2 markers. Moreover, higher levels of IL-13 and ratios of p-JAK2/JAK2 and p-STAT6/STAT6 were found in the SGD group compared to the MCAO. In conclusion, it was verified that SGD prevented injury by driving microglia phenotypic switching from M1 to M2, probably via IL-13 and its downstream JAK2-STAT6 pathway. Given that no further validation tests were included in this study, it is necessary to conduct more experiments to confirm the reliability of the above results.

ZnO-AuxCu1-x Alloy and ZnO-AuxAl1-x Alloy Vertically Aligned Nanocomposites for Low-Loss Plasmonic Metamaterials.

Hyperbolic metamaterials are a class of materials exhibiting anisotropic dielectric function owing to the morphology of the nanostructures. In these structures, one direction behaves as a metal, and the orthogonal direction behaves as a dielectric material. Applications include subdiffraction imaging and hyperlenses. However, key limiting factors include energy losses of noble metals and challenging fabrication methods. In this work, self-assembled plasmonic metamaterials consisting of anisotropic nanoalloy pillars embedded into the ZnO matrix are developed using a seed-layer approach. Alloys of AuxAl1-x or AuxCu1-x are explored due to their lower losses and higher stability. Optical and microstructural properties were explored. The ZnO-AuxCu1-x system demonstrated excellent epitaxial quality and optical properties compared with the ZnO-AuxAl1-x system. Both nanocomposite systems demonstrate plasmonic resonance, hyperbolic dispersion, low losses, and epsilon-near-zero permittivity, making them promising candidates towards direct photonic integration.

Mitigating photorefractive effect in thin-film lithium niobate microring resonators.

Thin-film lithium niobate is an attractive integrated photonics platform due to its low optical loss and favorable optical nonlinear and electro-optic properties. However, in applications such as second harmonic generation, frequency comb generation, and microwave-to-optics conversion, the device performance is strongly impeded by the photorefractive effect inherent in thin-film lithium niobate. In this paper, we show that the dielectric cladding on a lithium niobate microring resonator has a significant influence on the photorefractive effect. By removing the dielectric cladding layer, the photorefractive effect in lithium niobate ring resonators can be effectively mitigated. Our work presents a reliable approach to control the photorefractive effect on thin-film lithium niobate and will further advance the performance of integrated classical and quantum photonic devices based on thin-film lithium niobate.

Stable tuning of photorefractive microcavities using an auxiliary laser.

Cavity nonlinear optics enables intriguing physical phenomena to occur at micro- or nano-scales with modest input powers. While this enhances capabilities in applications such as comb generation, frequency conversion, and quantum optics, undesired nonlinear effects including photorefraction and thermal bistability are exacerbated. In this Letter, we propose and demonstrate a highly effective method of achieving cavity stabilization using an auxiliary laser for controlling photorefraction in a z-cut periodically poled lithium niobate (LN) microcavity system. Our numerical study accurately models the photorefractive effect under high input powers, guiding future analyses and development of LN microcavity systems.

Artesunate ameliorates cigarette smoke-induced airway remodelling via PPAR-γ/TGF-ß1/Smad2/3 signalling pathway.

BACKGROUND: Airway remodelling is the major pathological feature of chronic obstructive pulmonary disease (COPD), and leads to poorly reversible airway obstruction. Current pharmacological interventions are ineffective in controlling airway remodelling. In the present study, we investigated the potential role of artesunate in preventing and treating airway remodelling and the underlying molecular mechanisms in vitro and in vivo. METHODS: A COPD rat model was established by cigarette smoke (CS) exposure. After 12 weeks of artesunate treatment, pathological changes in the lung tissues of COPD rats were examined by ELISA and histochemical and immunohistochemical staining. A lung functional experiment was also carried out to elucidate the effects of artesunate. Human bronchial smooth muscle (HBSM) cells were used to clarify the underlying molecular mechanisms. RESULTS: Artesunate treatment inhibited CS-induced airway inflammation and oxidative stress in a dose-dependent manner and significantly reduced airway remodelling by inhibiting α-smooth muscle actin (α-SMA) and cyclin D1 expression. PPAR-γ was upregulated and TGF-ß1/Smad2/3 signalling was inactivated by artesunate treatment in vivo and in vitro. Furthermore, PPAR-γ knockdown by siRNA transfection abolished artesunate-mediated inhibition of HBSM cell proliferation by activiting the TGF-ß1/Smad2/3 signalling pathway and downregulating the expression of α-SMA and cyclin D1 in HBSM cells. CONCLUSIONS: These findings suggest that artesunate could be used to treat airway remodelling by regulating PPAR-γ/TGF-ß1/Smad signalling in the context of COPD.

Auditory and Visual Stimulation for Abdominal Postoperative Patients Experiencing Enhanced Recovery After Surgery (ERAS).

The Enhanced Recovery After Surgery program can reduce postoperative complications, hospital stay, and overall costs in patients, although the evidence for physical intervention with patients is still lacking. This study provides visual and auditory physical interventions to patients in order to explore the effects of Enhanced Recovery After Surgery following abdominal surgery. The study group consisted of patients who had undergone laparoscopic cholecystectomy, radical resection of gastric cancer, or radical resection of colon cancer; we randomly divided them into a control group and a visual and auditory intervention group. We then monitored the bowel sound frequency and time of the first anal self-exsufflation for both groups after surgery. We found that compared with the control group, patients who had undergone laparoscopic cholecystectomy and radical gastrectomy who received auditory intervention had increased bowel sound frequency and a shorter time until first anal self-exsufflation. In addition, patients with colon cancer who received both auditory and visual stimulation had increased bowel sounds and shorter time until the first anal self-exsufflation. These results suggest that visual and auditory interventions significantly improve patients' gastrointestinal function, shorten the hospitalization period, and reduce complications after operation.

Ultraviolet to mid-infrared supercontinuum generation in single-crystalline aluminum nitride waveguides.

We demonstrate ultrabroadband supercontinuum generation from ultraviolet to mid-infrared wavelengths in single-crystalline aluminum nitride waveguides. Tunable dispersive waves are observed at the mid-infrared regime by precisely controlling the waveguide widths. In addition, ultraviolet light is generated through cascaded second-harmonic generation in the modal phase-matched waveguides. Numerical simulation indicates a high degree of coherence of the generated spectrum at around the telecom pump and two dispersive waves. Our results establish a reliable path for multiple octave supercontinuum comb generation in single-crystalline aluminum nitride to enable applications including precision frequency metrology and spectroscopy.

Photonic Dissipation Control for Kerr Soliton Generation in Strongly Raman-Active Media.

Microcavity solitons enable miniaturized coherent frequency comb sources. However, the formation of microcavity solitons can be disrupted by stimulated Raman scattering, particularly in the emerging crystalline microcomb materials with high Raman gain. Here, we propose and implement dissipation control-tailoring the energy dissipation of selected cavity modes-to purposely raise or lower the threshold of Raman lasing in a strongly Raman-active lithium niobate microring resonator and realize on-demand soliton mode locking or Raman lasing. Numerical simulations are carried out to confirm our analyses and agree well with experiment results. Our work demonstrates an effective approach to address strong stimulated Raman scattering for microcavity soliton generation.

Clinical outcomes of Preimplantation genetic testing (PGT) application in couples with chromosomal inversion, a study in the Chinese Han population.

BACKGROUND: Chromosomal inversion was considered to have adverse effects on pregnancy outcomes through abnormal gametogenesis. The purpose of this retrospective study was to investigate whether preimplantation genetic testing (PGT) improves pregnancy outcomes for couples with chromosomal inversion. METHODS: A total of 188 cycles from 165 couples with one chromosomal inversion carrier were divided into two groups: PGT (136 cycles, 125 couples) and non-PGT (52 cycles, 50 couples). Biochemical pregnancy, clinical pregnancy, ongoing pregnancy, miscarriage and live birth rates of their first transfer cycles, as well as cumulative live birth rates of each cycle and euploidy rates, were analyzed. RESULTS: There were no statistically significant differences in the pregnancy outcomes between the two groups. The euploidy rate of pericentric inversion carriers was not higher than that of paracentric inversion carriers in PGT group (60.71% vs 50.54%, P = 0.073). Similarly, the euploid rate of male carriers was not higher than that of female carriers (61.2% vs 56.1%, P = 0.256). CONCLUSIONS: Due to limitation of retrospective study and small sample size, our current data showed that PGT cannot provide prominent benefits for inversion carriers in the Chinese Han population. Further prospective randomized controlled trials are needed to evaluate the effects of PGT.