Nonlinear optical diode effect in a magnetic Weyl semimetal.

Diode effects are of great interest for both fundamental physics and modern technologies. Electrical diode effects (nonreciprocal transport) have been observed in Weyl systems. Optical diode effects arising from the Weyl fermions have been theoretically considered but not probed experimentally. Here, we report the observation of a nonlinear optical diode effect (NODE) in the magnetic Weyl semimetal CeAlSi, where the magnetization introduces a pronounced directionality in the nonlinear optical second-harmonic generation (SHG). We demonstrate a six-fold change of the measured SHG intensity between opposite propagation directions over a bandwidth exceeding 250 meV. Supported by density-functional theory, we establish the linearly dispersive bands emerging from Weyl nodes as the origin of this broadband effect. We further demonstrate current-induced magnetization switching and thus electrical control of the NODE. Our results advance ongoing research to identify novel nonlinear optical/transport phenomena in magnetic topological materials and further opens new pathways for the unidirectional manipulation of light.

Gate-Defined Topological Josephson Junctions in Bernal Bilayer Graphene.

Recent experiments on Bernal bilayer graphene (BLG) deposited on monolayer WSe_{2} revealed robust, ultraclean superconductivity coexisting with sizable induced spin-orbit coupling. Here, we propose BLG/WSe_{2} as a platform to engineer gate-defined planar topological Josephson junctions, where the normal and superconducting regions descend from a common material. More precisely, we show that if superconductivity in BLG/WSe_{2} is gapped and emerges from a parent state with intervalley coherence, then Majorana zero-energy modes can form in the barrier region upon applying weak in-plane magnetic fields. Our results spotlight a potential pathway for "internally engineered" topological superconductivity that minimizes detrimental disorder and orbital-magnetic-field effects.

Josephson Diode Effect Induced by Valley Polarization in Twisted Bilayer Graphene.

Recently, the Josephson diode effect (JDE), in which the superconducting critical current magnitudes differ when the currents flow in opposite directions, has attracted great interest. In particular, it was demonstrated that gate-defined Josephson junctions based on magic-angle twisted bilayer graphene showed a strong nonreciprocal effect when the weak-link region is gated to a correlated insulating state at half filling (two holes per moiré cell). However, the mechanism behind such a phenomenon is not yet understood. In this Letter, we show that the interaction-driven valley polarization, together with the trigonal warping of the Fermi surface, induce the JDE. The valley polarization, which lifts the degeneracy of the states in the two valleys, induces a relative phase difference between the first and the second harmonics of the supercurrent and results in the JDE. We further show that the nontrivial current phase relation, which is responsible for the JDE, also generates the asymmetric Shapiro steps.

Orbital Fulde-Ferrell Pairing State in Moiré Ising Superconductors.

In this Letter, we study superconducting moiré homobilayer transition metal dichalcogenides where the Ising spin-orbit coupling (SOC) is much larger than the moiré bandwidth. We call such noncentrosymmetric superconductors, moiré Ising superconductors. Because of the large Ising SOC, the depairing effect caused by the Zeeman field is negligible and the in-plane upper critical field (B_{c2}) is determined by the orbital effects. This allows us to study the effect of large orbital fields. Interestingly, when the applied in-plane field is larger than the conventional orbital B_{c2}, a finite-momentum pairing phase would appear which we call the orbital Fulde-Ferrell (FF) state. In this state, the Cooper pairs acquire a net momentum of 2q_{B}, where 2q_{B}=eBd is the momentum shift caused by the magnetic field B and d denotes the layer separation. This orbital field-driven FF state is different from the conventional FF state driven by Zeeman effects in Rashba superconductors. Remarkably, we predict that the FF pairing would result in a giant superconducting diode effect under electric gating when layer asymmetry is induced. An upturn of the B_{c2} as the temperature is lowered, coupled with the giant superconducting diode effect, would allow the detection of the orbital FF state.

Human leukocyte antigens: the unique expression in trophoblasts and their crosstalk with local immune cells.

Trophoblasts differentiate and form the placenta during pregnancy in a complex and finely orchestrated process, which is dependent on the establishment of maternal-fetal immune tolerance and the proper function of trophoblasts. Trophoblasts express HLA-C and non-classical HLA-Ib molecules (HLA-E, HLA-F, and HLA-G). Numerous studies have shown that the unique expression pattern of the HLA molecules is closely linked to the successful acceptance of allogeneic fetus by the mother during pregnancy. However, some controversies still exist concerning the exact expression and recognition patterns of HLA molecules in different trophoblast subpopulations and cell lines. Thus, we summarize three types of trophoblast subpopulations as well as the common trophoblast lineages. Then, the classification and structural characteristics of HLA molecules were elucidated. Finally, the presence of HLA-C and non-classical HLA-Ib molecules (HLA-E, HLA-F, and HLA-G) in various trophoblasts and cell lines, as well as their potential role in establishing and maintaining normal pregnancy were also discussed. Together, this review will help people comprehensively understand the complex immune interactions between maternal and fetal crosstalk during pregnancy and ultimately better understand the physiological and pathological etiologies of pregnancy.

Phosphoglycerate mutase 5 promotes necroptosis in trophoblast cells through activation of dynamin-related protein 1 in early-onset preeclampsia.

OBJECTIVES: Placentae from patients with preeclampsia have increased susceptibility to necroptosis and phosphoglycerate mutase 5 (PGAM5) plays a role in many necrosis pathways. We determined whether PGAM5 promotes necroptosis of trophoblast cells and the underlying mechanisms in this study. METHODS: The injury model was established by treating JEG3 cells with hypoxia for 24 h. The functional measurements were assessed by the cell counting kit-8, propidium iodide (PI)/Annexin V staining, JC-1 staining and firefly luciferase ATP assay. The expression of proteins in human placentae and JEG3 cells was measured Western blot. PGAM5 was knocked down to study its role in hypoxia-induced necroptosis. RESULTS: The placentae from patients with preeclampsia showed up-regulation of PGAM5 and decreased levels of p-Drp1-S637, accompanied by increased necroptosis-relevant proteins expression. The expression of PGAM5 in JEG3 cells was up-regulated under hypoxia, which promoted dephosphorylation of Drp1 at Serine 637 residue, mitochondrial dysfunction (elevated ROS level and reduced mitochondrial membrane potential and ATP content) and cellular necroptosis (increased PI+ /Annexin V+ cells and decreased cell viability), accompanied by increased expression of necroptosis-relevant proteins; knockdown of PGAM5 attenuated these phenomena. CONCLUSIONS: Our results indicate that PGAM5 can promote necroptosis in trophoblast cells through, at least in part, activation of Drp1. It may be used as a new therapeutic target to prevent trophoblast dysfunction in preeclampsia.

Valley-Polarized Quantum Anomalous Hall State in Moiré MoTe_{2}/WSe_{2} Heterobilayers.

Moiré heterobilayer transition metal dichalcogenides (TMDs) emerge as an ideal system for simulating the single-band Hubbard model and interesting correlated phases have been observed in these systems. Nevertheless, the moiré bands in heterobilayer TMDs were believed to be topologically trivial. Recently, it was reported that both a quantum valley Hall insulating state at filling ν=2 (two holes per moiré unit cell) and a valley-polarized quantum anomalous Hall state at filling ν=1 were observed in AB stacked moiré MoTe_{2}/WSe_{2} heterobilayers. However, how the topologically nontrivial states emerge is not known. In this Letter, we propose that the pseudomagnetic fields induced by lattice relaxation in moiré MoTe_{2}/WSe_{2} heterobilayers could naturally give rise to moiré bands with finite Chern numbers. We show that a time-reversal invariant quantum valley Hall insulator is formed at full filling ν=2, when two moiré bands with opposite Chern numbers are filled. At half filling ν=1, the Coulomb interaction lifts the valley degeneracy and results in a valley-polarized quantum anomalous Hall state, as observed in the experiment. Our theory identifies a new way to achieve topologically nontrivial states in heterobilayer TMD materials.

Exosomes derived from PC-3 cells suppress osteoclast differentiation by downregulating miR-148a and blocking the PI3K/AKT/mTOR pathway.

Prostate cancer is a leading malignancy in men that can also disrupt the bone tissue balance. Among all urological cancers, prostate cancer is associated with the highest rate of bone metastases, which can greatly reduce a patient's quality of life. In recent years, cell-derived exosomes, which can contain a wide range of biologically active molecules, have been reported as a novel method of communication among individual cells. However, the specific role that exosomes serve in this disease has not been fully elucidated. The prostate cancer cell line PC-3 were applied in the present study, where its exosomes were isolated to explore their potential effects on osteoclast differentiation. Exosomes are extracellular vesicles secreted by cells. The size of exosomes is 30-150 nm. They have double membrane structure and saucer-like morphology. They contain rich contents (including nucleic acid, protein and lipid) and participate in molecular transmission between cells. The combined results of tartrate-resistant acid phosphatase staining (to identify osteoclasts obtained from human peripheral blood mononuclear cells), reverse transcription-quantitative PCR and western blotting showed that PC-3-derived exosomes attenuated osteoclast differentiation by downregulating marker genes associated with osteoclastic maturation, including V-maf musculoaponeurotic fibrosarcoma oncogene homolog B, matrix metalloproteinase 9 and integrin ß3. microRNA (miR)-148a expression was also found to be downregulated in osteoclasts by PC-3-derived exosomes. In addition, the mTOR and AKT signaling pathways were blocked after exposure to these PC-3 cell-derived exosomes. Therefore, results from the present study suggest that miR-148a mimics may be a new therapeutic approach for the prevention of prostate cancer bone metastases.

Kramers nodal line metals.

Recently, it was pointed out that all chiral crystals with spin-orbit coupling (SOC) can be Kramers Weyl semimetals (KWSs) which possess Weyl points pinned at time-reversal invariant momenta. In this work, we show that all achiral non-centrosymmetric materials with SOC can be a new class of topological materials, which we term Kramers nodal line metals (KNLMs). In KNLMs, there are doubly degenerate lines, which we call Kramers nodal lines (KNLs), connecting time-reversal invariant momenta. The KNLs create two types of Fermi surfaces, namely, the spindle torus type and the octdong type. Interestingly, all the electrons on octdong Fermi surfaces are described by two-dimensional massless Dirac Hamiltonians. These materials support quantized optical conductance in thin films. We further show that KNLMs can be regarded as parent states of KWSs. Therefore, we conclude that all non-centrosymmetric metals with SOC are topological, as they can be either KWSs or KNLMs.

Hypertensive disorders of pregnancy and risks of adverse pregnancy outcomes: a retrospective cohort study of 2368 patients.

Hypertensive disorders of pregnancy (HDP) comprise a group of hypertension-related diseases and represent the most common medical disorders in pregnancy. The aim of this study was to investigate the risks of adverse pregnancy outcomes in patients with different types of HDP, including gestational hypertension, chronic hypertension, preeclampsia (PE, early or late onset), PE superimposed on chronic hypertension (superimposed PE), eclampsia, and HELLP syndrome. Data from a multicenter retrospective patient cohort in China were analyzed. Seventeen adverse maternal or perinatal outcomes were evaluated. Logistic regression was used to estimate the risk of adverse outcomes for each HDP subgroups, using the gestational hypertension group as the reference. The final analysis included 2368 patients with HDP. Of these, 39.9% of patients reported at least one adverse pregnancy outcome. Patients with early onset PE had the highest risk for having both adverse maternal and perinatal outcomes (OR = 7.28, 95% CI: 2.68, 19.79). The risk of perinatal death significantly increased in HELLP syndrome, superimposed PE, and early onset PE, (OR = 13.81, 6.32, and 4.84, respectively, p < 0.05) groups. This study highlights that among patients with HDP, those with early onset PE had the highest risk for having both adverse maternal and perinatal outcomes, and patients with HELLP syndrome had the highest risk for perinatal death.

Single-cell RNA sequencing reveals heterogeneity and differential expression of decidual tissues during the peripartum period.

OBJECTIVES: The decidua is a tissue that contacts both maternal and foetal components and is pivotal to labour onset due to its location. Due to the heterogeneity of decidual tissue, it is challenging to study its role in the peripartum period. Herein, we analysed the transcriptomes of peripartum decidua at single-cell resolution. MATERIALS AND METHODS: Single-cell RNA sequencing was performed for 29 231 decidual cells before and after delivery to characterize the transcriptomes. RESULTS: Eight major cell types (including endothelial cells, fibroblasts) and subtypes of decidual stromal cells, extravillous trophoblasts and T cells were identified and found to have various functions. Compared with before delivery, the activation of decidual stromal cell, extravillous trophoblast and T-cell subtypes to different degrees was observed after delivery. Furthermore, the activation involved multiple functions, such as cell proliferation, and several pathways, such as the activator protein 1 pathway. The results of pseudotemporal ordering showed differentiation of decidual stromal cell and extravillous trophoblast subtypes, suggesting inhomogeneity of these subgroups in decidualization (decidual stromal cell) and invasion (extravillous trophoblast). CONCLUSIONS: The peripartum decidual tissue is heterogeneous. This study revealed changes in the decidua and its components at single-cell resolution; these findings provide a new perspective for the study of peripartum decidua.

Single-cell transcriptomics analysis showing functional heterogeneity in decidual stromal cells during labor.

To investigate the heterogeneity of decidual stromal cells (DSCs) and their functional alterations during delivery, we conducted single-cell RNA sequencing analysis to characterize the transcriptomic profiles of DSCs before and after labor onset. According to their transcriptomic profiles, DSCs (6382 cells) were clustered into five subgroups with different functions. Similar to stromal cells, cells in cluster 1 were involved in cell substrate adhesion. On the other hand, cells in clusters 2 and 3 were enriched in signal transduction-related genes. Labor onset led to significant alterations in many pathways, including the activator protein 1 pathway (all clusters), as well as in the response to lipopolysaccharide (clusters 1-3). The downregulated genes were involved in coagulation, ATP synthesis, and oxygen homeostasis, possibly reflecting the oxygen and energy balance during delivery. Our findings highlight that peripartum DSCs are heterogeneous and play multiple roles in labor.

Spin-Orbit-Parity-Coupled Superconductivity in Topological Monolayer WTe_{2}.

Recent experiments reported gate-induced superconductivity in the monolayer 1T^{'}-WTe_{2} which is a two-dimensional topological insulator in its normal state. The in-plane upper critical field B_{c2} is found to exceed the conventional Pauli paramagnetic limit B_{p} by one to three times. The enhancement cannot be explained by conventional spin-orbit coupling which vanishes due to inversion symmetry. In this Letter, we unveil some distinctive superconducting properties of centrosymmetric 1T^{'}-WTe_{2} which arise from the coupling of spin, momentum and band parity degrees of freedom. As a result of this spin-orbit-parity coupling (SOPC): (i) there is a first-order superconductor-metal transition at B_{c2} that is much higher than the Pauli paramagnetic limit B_{p}, (ii) spin-susceptibility is anisotropic with respect to in-plane directions and can result in possible anisotropic B_{c2}, and (iii) the B_{c2} exhibits a strong gate dependence as the spin-orbit-parity coupling is significant only near the topological band crossing points. The importance of SOPC on the topologically nontrivial inter-orbital pairing phase is also discussed. Our theory generally applies to centrosymmetric materials with topological band inversions.

Author Correction: Evidence of higher-order topology in multilayer WTe2 from Josephson coupling through anisotropic hinge states.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Evidence of higher-order topology in multilayer WTe2 from Josephson coupling through anisotropic hinge states.

Td-WTe2 (non-centrosymmetric and orthorhombic), a type-II Weyl semimetal, is expected to have higher-order topological phases with topologically protected, helical one-dimensional hinge states when its Weyl points are annihilated. However, the detection of these hinge states is difficult due to the semimetallic behaviour of the bulk. In this study, we have spatially resolved the hinge states by analysing the magnetic field interference of the supercurrent in Nb-WTe2-Nb proximity Josephson junctions. The Josephson current along the a axis of the WTe2 crystal, but not along the b axis, showed a sharp enhancement at the edges of the junction, and the amount of enhanced Josephson current was comparable to the upper limits of a single one-dimensional helical channel. Our experimental observations suggest a higher-order topological phase in WTe2 and its corresponding anisotropic topological hinge states, in agreement with theoretical calculations. Our work paves the way for the study of hinge states in topological transition-metal dichalcogenides and analogous phases.

Signature of a pair of Majorana zero modes in superconducting gold surface states.

Under certain conditions, a fermion in a superconductor can separate in space into two parts known as Majorana zero modes, which are immune to decoherence from local noise sources and are attractive building blocks for quantum computers. Promising experimental progress has been made to demonstrate Majorana zero modes in materials with strong spin-orbit coupling proximity coupled to superconductors. Here we report signatures of Majorana zero modes in a material platform utilizing the surface states of gold. Using scanning tunneling microscope to probe EuS islands grown on top of gold nanowires, we observe two well-separated zero-bias tunneling conductance peaks aligned along the direction of the applied magnetic field, as expected for a pair of Majorana zero modes. This platform has the advantage of having a robust energy scale and the possibility of realizing complex designs using lithographic methods.

KIF21B Expression in Osteosarcoma and Its Regulatory Effect on Osteosarcoma Cell Proliferation and Apoptosis Through the PI3K/AKT Pathway.

Osteosarcoma (OS) is the most common malignancy that occurs mainly during childhood and adolescence; however, no clear molecular or biological mechanism has been identified. In this study, we aimed to explore new biomarkers for the early diagnosis, targeted treatment, and prognostic determination of osteosarcoma. We first used bioinformatics analysis to show that KIF21B can be used as a biomarker for the diagnosis and prognosis of osteosarcoma. We then examined the expression of KIF21B in human osteosarcoma tissues and cell lines using immunohistochemistry, western blotting, and qRT-PCR. It was found that KIF21B expression was significantly upregulated in osteosarcoma tissues and cell lines. After knocking down the expression of KIF21B in the osteosarcoma cell lines 143B and U2-OS, we used cell fluorescence counting, CCK-8 assays, flow cytometry, and TUNEL staining to examine the effects of KIF21B on osteosarcoma cell proliferation and apoptosis. The results demonstrated that knocking down KIF21B in 143B and U2-OS cells could increase cell apoptosis, inhibit cell proliferation, and reduce tumor formation in nude mice. Subsequently, we used gene chips and bioinformatics to analyze the differential gene expression caused by knocking down KIF21B. The results showed that KIF21B may regulate OS cell proliferation and apoptosis by targeting the PI3K/AKT pathway. We then examined the expression of PI3K/AKT- and apoptosis-related proteins using western blotting. KIF21B knockdown inhibited the PI3K pathway, downregulated Bcl-2, and upregulated Bax. Moreover, the use of PI3K/AKT pathway agonists reversed the regulatory effect of KIF21B on the apoptosis and proliferation of 143B and U2-OS cells. In conclusion, our results indicated that KIF21B plays a key role in osteosarcoma. Low KIF21B expression might indirectly increase the apoptosis and inhibit the proliferation of osteosarcoma cells through the PI3K/AKT pathway.

Spectroscopic fingerprint of chiral Majorana modes at the edge of a quantum anomalous Hall insulator/superconductor heterostructure.

With the recent discovery of the quantum anomalous Hall insulator (QAHI), which exhibits the conductive quantum Hall edge states without external magnetic field, it becomes possible to create a topological superconductor (SC) by introducing superconductivity into these edge states. In this case, 2 distinct topological superconducting phases with 1 or 2 chiral Majorana edge modes were theoretically predicted, characterized by Chern numbers (N) of 1 and 2, respectively. We present spectroscopic evidence from Andreev reflection experiments for the presence of chiral Majorana modes in an Nb/(Cr0.12Bi0.26Sb0.62)2Te3 heterostructure with distinct signatures attributed to 2 different topological superconducting phases. The results are in qualitatively good agreement with the theoretical predictions.

Detection of HER2-positive Circulating Tumor Cells Using the LiquidBiopsy System in Breast Cancer.

BACKGROUND: Most previous studies of circulating tumor cells (CTCs) are based on the CellSearch platform, but CellSearch has a number of limitations. This study aimed to use the LiquidBiopsy system and immunofluorescence to test the human epidermal growth factor receptor 2 (HER2) status of CTCs in patients with breast cancer. MATERIALS AND METHODS: The LiquidBiopsy system was used to detect HER2-positive (HER2+) cells in whole blood by microfluidic immunomagnetic bead screening and immunofluorescence assay, according to the manufacturer;s instructions. HER2 expression on CTCs was assessed using the Ariol system, calibrated through spiking experiments of 100 cells (BT474, SKBR3, A431, and MDA-MB-231) and 2.5 × 107 white blood cells/mL from healthy donors. Seventy-one patients with breast cancer and 107 non-cancer donors consented to provide blood. RESULTS: Based on breast cancer cell lines experiments, HER2+ CTCs were defined as CTCs with HER2 immunofluorescence intensity ≥ 3.5 times higher than the CD45 immunofluorescence intensity (100% sensitivity and 99.9% specificity). Among the 71 patients with breast cancer, 31 (43.7%) had HER2+ tumor. Among the HER2+ patients, 41.9% (13/31) were found to be HER2+ based on CTC ≥ 1, and 25.8% (8/31) were positive based on CTC ≥ 3. In HER2-negative patients by pathologic examination, 1 (2.5%) patient was found to have ≥ 3 HER2+ CTCs, whereas 15 (37.5%) patients had ≥ 1 HER2+ CTC. HER2+ CTCs were detected at all stages, even in early breast cancer, but the detection rate was higher in metastatic breast cancer. CONCLUSION: This proof-of-concept study strongly suggests that HER2+ CTCs can be detected using the LiquidBiopsy system.

Preterm birth, low birthweight, and small for gestational age among women with preeclampsia: Does maternal age matter?

OBJECTIVES: To better understand the effects of maternal age on birth outcomes among preeclampsia (PE) patients, we examined the rates of preterm birth, low birthweight, and small for gestational age (SGA) among different age groups and explored whether maternal age was associated with those adverse outcomes. STUDY DESIGN: This is a multicenter retrospective study. Data from 1128 PE patients, including 580 with early onset PE and 548 with late onset PE, were analyzed. MAIN OUTCOME MEASURES: Maternal age was categorized into three groups: <25, 25-34, and ≥35 years. The outcome variables were preterm birth (<37 weeks; subgroups: <28 weeks, 28-33 weeks, and 34-36 weeks), low birthweight (<2500 g; subgroups: <1500 g and <1000 g), and SGA. Logistic regression was used to analyze the associations between maternal age groups and outcomes. RESULTS: In early onset PE, compared with maternal age 25-34 years, maternal age ≥35 years was associated with elevated risk for preterm delivery before 28 weeks, and maternal age <25 years was associated with elevated risk for low birthweight and SGA. When the analysis was restricted to women who underwent cesarean section, elevated risks for preterm birth and/or low birthweight were observed for women younger than 25 years in both early and late onset PE. CONCLUSIONS: Among women with PE, maternal age <25 years could add risk to preterm birth and/or low birthweight. For women with early onset PE, maternal age ≥35 years is a risk factor for preterm delivery before 28 weeks.