Compact bone mesenchymal stem cells-derived paracrine mediators for cell-free therapy in sepsis.

Sepsis, a life-threatening condition resulting in multiple organ dysfunction, is characterized by a dysregulated immune response to infection. Current treatment options are limited, leading to unsatisfactory outcomes for septic patients. Here, we present a series of studies utilizing compact bone mesenchymal stem cells (CB-MSCs) and their derived paracrine mediators, especially exosome (CB-MSCs-Exo), to treat mice with cecal ligation and puncture-induced sepsis. Our results demonstrate that CB-MSCs treatment significantly improves the survival rate of septic mice by mitigating excessive inflammatory response and attenuating sepsis-induced organ injuries. Furthermore, CB-MSCs-conditioned medium, CB-MSCs secretome (CB-MSCs-Sec), and CB-MSCs-Exo exhibit potent anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated murine macrophage (RAW264.7). Intriguingly, intravenous administration of CB-MSCs-Exo confers superior protection against inflammation and organ damage in septic mice compared to CB-MSCs in certain aspects. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS) shotgun proteomic analysis, we identify a range of characterized proteins derived from the paracrine activity of CB-MSCs, involved in critical biological processes such as immunomodulation and apoptosis. Our findings highlight that the paracrine products of CB-MSCs could serve as a promising cell-free therapeutic agent for sepsis.

Colossal Orbital Current Induced by Gradient Oxidation for High-Efficiency Magnetization Switching.

Orbital angular momentum flow can be used to develop a low-dissipation electronic information device by manipulating the orbital current. However, efficiently generating and fully harnessing orbital currents is a formidable challenge. In this study, an approach is presented that induces a colossal orbital current by gradient oxidation in Pt/Ta to enhance spin-orbit torque (SOT) and achieve high-efficiency magnetization switching. The maximum efficiency of the SOT before and after the gradient oxidation of Ta is improved relative to that of Pt by ≈600 and 1200%, respectively. The large SOT originates from the colossal orbital current because of the orbital Rashba-Edelstein effect induced by the gradient oxidation of Ta. In addition, a large spin-to-charge conversion efficiency is observed in yttrium iron garnet/Pt/TaOx because of the inverse orbital Rashba-Edelstein effect. Harnessing the orbital current can help effectively minimize the critical current density of the current-induced magnetization switching to 2.26-1.08 × 106 A cm-2, marking a 12-fold reduction compared to that using Pt. This findings provide a new path for research on low-dissipation spin-orbit devices and improve the tunability of orbital current generation.

IL-1ß, the first piece to the puzzle of sepsis-related cognitive impairment?

Sepsis is a leading cause of death resulting from an uncontrolled inflammatory response to an infectious agent. Multiple organ injuries, including brain injuries, are common in sepsis. The underlying mechanism of sepsis-associated encephalopathy (SAE), which is associated with neuroinflammation, is not yet fully understood. Recent studies suggest that the release of interleukin-1ß (IL-1ß) following activation of microglial cells plays a crucial role in the development of long-lasting neuroinflammation after the initial sepsis episode. This review provides a comprehensive analysis of the recent literature on the molecular signaling pathways involved in microglial cell activation and interleukin-1ß release. It also explores the physiological and pathophysiological role of IL-1ß in cognitive function, with a particular focus on its contribution to long-lasting neuroinflammation after sepsis. The findings from this review may assist healthcare providers in developing novel interventions against SAE.

Room-temperature sub-100 nm Néel-type skyrmions in non-stoichiometric van der Waals ferromagnet Fe3-xGaTe2 with ultrafast laser writability.

Realizing room-temperature magnetic skyrmions in two-dimensional van der Waals ferromagnets offers unparalleled prospects for future spintronic applications. However, due to the intrinsic spin fluctuations that suppress atomic long-range magnetic order and the inherent inversion crystal symmetry that excludes the presence of the Dzyaloshinskii-Moriya interaction, achieving room-temperature skyrmions in 2D magnets remains a formidable challenge. In this study, we target room-temperature 2D magnet Fe3GaTe2 and unveil that the introduction of iron-deficient into this compound enables spatial inversion symmetry breaking, thus inducing a significant Dzyaloshinskii-Moriya interaction that brings about room-temperature Néel-type skyrmions with unprecedentedly small size. To further enhance the practical applications of this finding, we employ a homemade in-situ optical Lorentz transmission electron microscopy to demonstrate ultrafast writing of skyrmions in Fe3-xGaTe2 using a single femtosecond laser pulse. Our results manifest the Fe3-xGaTe2 as a promising building block for realizing skyrmion-based magneto-optical functionalities.

Semantic Consistency Reasoning for 3-D Object Detection in Point Clouds.

Point cloud-based 3-D object detection is a significant and critical issue in numerous applications. While most existing methods attempt to capitalize on the geometric characteristics of point clouds, they neglect the internal semantic properties of point and the consistency between the semantic and geometric clues. We introduce a semantic consistency (SC) mechanism for 3-D object detection in this article, by reasoning about the semantic relations between 3-D object boxes and its internal points. This mechanism is based on a natural principle: the semantic category of a 3-D bounding box should be consistent with the categories of all points within the box. Driven by the SC mechanism, we propose a novel SC network (SCNet) to detect 3-D objects from point clouds. Specifically, the SCNet is composed of a feature extraction module, a detection decision module, and a semantic segmentation module. In inference, the feature extraction and the detection decision modules are used to detect 3-D objects. In training, the semantic segmentation module is jointly trained with the other two modules to produce more robust and applicable model parameters. The performance is greatly boosted through reasoning about the relations between the output 3-D object boxes and segmented points. The proposed SC mechanism is model-agnostic and can be integrated into other base 3-D object detection models. We test the proposed model on three challenging indoor and outdoor benchmark datasets: ScanNetV2, SUN RGB-D, and KITTI. Furthermore, to validate the universality of the SC mechanism, we implement it in three different 3-D object detectors. The experiments show that the performance is impressively improved and the extensive ablation studies also demonstrate the effectiveness of the proposed model.

Gate-Tunable Berry Curvature Dipole Polarizability in Dirac Semimetal Cd_{3}As_{2}.

We reveal the gate-tunable Berry curvature dipole polarizability in Dirac semimetal Cd_{3}As_{2} nanoplates through measurements of the third-order nonlinear Hall effect. Under an applied electric field, the Berry curvature exhibits an asymmetric distribution, forming a field-induced Berry curvature dipole, resulting in a measurable third-order Hall voltage with a cubic relationship to the longitudinal electric field. Notably, the magnitude and polarity of this third-order nonlinear Hall effect can be effectively modulated by gate voltages. Furthermore, our scaling relation analysis demonstrates that the sign of the Berry curvature dipole polarizability changes when tuning the Fermi level across the Dirac point, in agreement with theoretical calculations. The results highlight the gate control of nonlinear quantum transport in Dirac semimetals, paving the way for promising advancements in topological electronics.

Intestinal Barrier Function and Neurodegenerative Disease.

Neurodegenerative diseases are caused by the loss of neurons and/or their myelin sheaths, which deteriorate over time and become dysfunctional. Alzheimer's disease, Parkinson's disease, and multiple sclerosis are among the most prominent neurodegenerative diseases that affect millions of older adults worldwide. Despite extensive research over several decades, controversies still surround the etiology of neurodegenerative diseases, and many of them remain incurable. Meanwhile, an increasing number of new mechanistic studies related to the microbiota-gut-brain axis have emerged, among which the relationship between the function of the intestinal barrier and neurodegenerative diseases has received widespread attention. As one of the first lines of defense between the body and the external environment, the impaired function of the intestinal barrier is closely related to the development of neurodegenerative pathologies. Among them, the microbiota-gut-brain axis disorder characterized by intestinal barrier disruption mainly includes impaired function of the intestinal microbial barrier, chemical barrier, mechanical barrier, and immune barrier. This review focuses on the structure and molecular mechanisms of the various layers of the intestinal barrier as well as their relationship with neurodegenerative lesions. In recent years, intestinal barrier repair therapies have provided new ideas for the studied disease treatment modalities. We believe that a better understanding of the role of the intestinal barrier in neurodegenerative diseases would provide new insights for the development of viable therapeutic strategies for patients.

A case misdiagnosed as hyperthyroid heart disease: Surgical repair of unroofed coronary sinus syndrome with severe tricuspid regurgitation.

Unroofed coronary sinus syndrome (URCS), also known as coronary sinus septal defect, is a rare congenital heart disease. Because of its special anatomy and the lack of typical clinical symptoms, the disease is easily missed and misdiagnosed. This case report particularly describes a middle-aged male patient with URCS misdiagnosed for more than 19 years, covered by hyperthyroid heart disease, who subsequently developed uncontrollable symptoms such as chest tightness and shortness of breath and came to our hospital. After a clear diagnosis in our hospital, the patient was successfully cured after treatment with coronary sinus repair and tricuspid valvuloplasty under extracorporeal circulation.

Broad and colossal edge supercurrent in Dirac semimetal Cd3As2 Josephson junctions.

Edge supercurrent has attracted great interest recently due to its crucial role in achieving and manipulating topological superconducting states. Proximity-induced superconductivity has been realized in quantum Hall and quantum spin Hall edge states, as well as in higher-order topological hinge states. Non-Hermitian skin effect, the aggregation of non-Bloch eigenstates at open boundaries, promises an abnormal edge channel. Here we report the observation of broad edge supercurrent in Dirac semimetal Cd3As2-based Josephson junctions. The as-grown Cd3As2 nanoplates are electron-doped by intrinsic defects, which enhance the non-Hermitian perturbations. The superconducting quantum interference indicates edge supercurrent with a width of ~1.6 µm and a magnitude of ~1 µA at 10 mK. The wide and large edge supercurrent is inaccessible for a conventional edge system and suggests the presence of non-Hermitian skin effect. A supercurrent nonlocality is also observed. The interplay between band topology and non-Hermiticity is beneficial for exploiting exotic topological matter.

Room-temperature orbit-transfer torque enabling van der Waals magnetoresistive memories.

The non-volatile magnetoresistive random access memory (MRAM) is believed to facilitate emerging applications, such as in-memory computing, neuromorphic computing and stochastic computing. Two-dimensional (2D) materials and their van der Waals heterostructures promote the development of MRAM technology, due to their atomically smooth interfaces and tunable physical properties. Here we report the all-2D magnetoresistive memories featuring all-electrical data reading and writing at room temperature based on WTe2/Fe3GaTe2/BN/Fe3GaTe2 heterostructures. The data reading process relies on the tunnel magnetoresistance of Fe3GaTe2/BN/Fe3GaTe2. The data writing is achieved through current induced polarization of orbital magnetic moments in WTe2, which exert torques on Fe3GaTe2, known as the orbit-transfer torque (OTT) effect. In contrast to the conventional reliance on spin moments in spin-transfer torque and spin-orbit torque, the OTT effect leverages the natural out-of-plane orbital moments, facilitating field-free perpendicular magnetization switching through interface currents. Our results indicate that the emerging OTT-MRAM is promising for low-power, high-performance memory applications.

Involvement of IL-1ß-Mediated Necroptosis in Neurodevelopment Impairment after Neonatal Sepsis in Rats.

The mechanism of long-term cognitive impairment after neonatal sepsis remains poorly understood, although long-lasting neuroinflammation has been considered the primary contributor. Necroptosis is actively involved in the inflammatory process, and in this study, we aimed to determine whether neonatal sepsis-induced long-term cognitive impairment was associated with activation of necroptosis. Rat pups on postnatal day 3 (P3) received intraperitoneal injections of lipopolysaccharide (LPS, 1 mg/kg) to induce neonatal sepsis. Intracerebroventricular injection of IL-1ß-siRNA and necrostatin-1 (NEC1) were performed to block the production of IL-1ß and activation of necroptosis in the brain, respectively. The Morris water maze task and fear conditioning test were performed on P28-P32 and P34-P35, respectively. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time PCR (RT-PCR), and Western blotting were used to examine the expression levels of proinflammatory cytokines and necroptosis-associated proteins, such as receptor-interacting protein 1 (RIP1) and receptor-interacting protein 3 (RIP3). Sustained elevation of IL-1ß level was observed in the brain after initial neonatal sepsis, which would last for at least 32 days. Sustained necroptosis activation was also observed in the brain. Knockdown of IL-1ß expression in the brain alleviated necroptosis and improved long-term cognitive function. Direct inhibition of necroptosis also improved neurodevelopment and cognitive performance. This research indicated that sustained activation of necroptosis via IL-1ß contributed to long-term cognitive dysfunction after neonatal sepsis.

Biodegradability enhancement of waste lubricating oil regeneration wastewater using electrocoagulation pretreatment.

As a sustainable management of fossil fuel resources and ecological environment protection, recycling used lubricating oil has received widespread attention. However, large amounts of waste lubricating-oil regeneration wastewater (WLORW) are inevitably produced in the recycling process, and challenges are faced by traditional biological treatment of WLORW. Thus, this study investigated the effectiveness of electrocoagulation (EC) as pretreatment and its removal mechanism. The electrolysis parameters (current density, initial pH, and inter-electrode distance) were considered, and maximal 60.06% of oil removal was achieved at a current density of 15 mA/cm2, initial pH of 7, and an inter-electrode distance of 2 cm. The dispersed oil of WLORW was relatively easily removed, and most of the oil removal was contributed by emulsified oil within 5-10 µm. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that effective removal of the biorefractory organic compounds could contribute to the improvement of biodegradability of WLORW. Thus, the 5-day biochemical oxygen demand/chemical oxygen demand ratio (BOD5/COD) was significantly enhanced by 4.31 times, which highly benefits future biological treatment. The routes of WLORW removal could be concluded as charge neutralization, adsorption bridging, sweep flocculation, and air flotation. The results demonstrate that EC has potential as an effective pretreatment technology for WLORW biological treatment.

Single-crystalline van der Waals layered dielectric with high dielectric constant.

The scaling of silicon-based transistors at sub-ten-nanometre technology nodes faces challenges such as interface imperfection and gate current leakage for an ultrathin silicon channel1,2. For next-generation nanoelectronics, high-mobility two-dimensional (2D) layered semiconductors with an atomic thickness and dangling-bond-free surfaces are expected as channel materials to achieve smaller channel sizes, less interfacial scattering and more efficient gate-field penetration1,2. However, further progress towards 2D electronics is hindered by factors such as the lack of a high dielectric constant (κ) dielectric with an atomically flat and dangling-bond-free surface3,4. Here, we report a facile synthesis of a single-crystalline high-κ (κ of roughly 16.5) van der Waals layered dielectric Bi2SeO5. The centimetre-scale single crystal of Bi2SeO5 can be efficiently exfoliated to an atomically flat nanosheet as large as 250 × 200 µm2 and as thin as monolayer. With these Bi2SeO5 nanosheets as dielectric and encapsulation layers, 2D materials such as Bi2O2Se, MoS2 and graphene show improved electronic performances. For example, in 2D Bi2O2Se, the quantum Hall effect is observed and the carrier mobility reaches 470,000 cm2 V-1 s-1 at 1.8 K. Our finding expands the realm of dielectric and opens up a new possibility for lowering the gate voltage and power consumption in 2D electronics and integrated circuits.

Control over Berry Curvature Dipole with Electric Field in WTe_{2}.

Berry curvature dipole plays an important role in various nonlinear quantum phenomena. However, the maximum symmetry allowed for nonzero Berry curvature dipole in the transport plane is a single mirror line, which strongly limits its effects in materials. Here, via probing the nonlinear Hall effect, we demonstrate the generation of Berry curvature dipole by applied dc electric field in WTe_{2}, which is used to break the symmetry constraint. A linear dependence between the dipole moment of Berry curvature and the dc electric field is observed. The polarization direction of the Berry curvature is controlled by the relative orientation of the electric field and crystal axis, which can be further reversed by changing the polarity of the dc field. Our Letter provides a route to generate and control Berry curvature dipole in broad material systems and to facilitate the development of nonlinear quantum devices.

Xenon attenuated neonatal lipopolysaccharide exposure induced neuronal necroptosis and subsequently improved cognition in juvenile rats.

Background: Neonatal sepsis is known to cause neurodevelopment impairment and has been reported to increase risks for neurological/psychiatric disorders. In this study, we investigated the effect of xenon, a well-known potent neuroprotective gas, on neonatal sepsis-induced neurodevelopment impairment in rats together with underlying mechanism by focusing on receptor-interacting protein kinase (RIP) mediated neuronal necroptosis. Methods: 3-day-old Sprague-Dawley rat pups were exposed to either 70% xenon or N2 balanced with O2 for 6 h, during which lipopolysaccharide (LPS) was injected intraperitoneally for 3 times (500 µg/kg for the 1st and 250 µg/kg for the second and third dose; n = 6-10/group). In another cohort of 3-day-old rat pups, intracerebroventricular injection of necrostatin-1 (4 µg in 4 µl saline, a RIP-1-targeted inhibitor of necroptosis) was performed 20 min after the third dose of LPS. The learning ability and memory were assessed 25 days after LPS injection. Then, their hippocampus was collected for neuronal necroptosis with RIP and MIKL assessments using western blot and in situ immunostaining. Systemic and neuro-inflammation was also assessed. Results: LPS insult resulted in elevation of pro-inflammatory cytokine TNF-𝝰 and IL-6, caused neuronal necroptosis and damaged synaptic integrity at the brain developing stage, which finally led to the long-term cognitive impairment. Xenon inhibited necroptosis associated mediator RIP-1, RIP-3, and MLKL activation, protected neurons and attenuated cognitive dysfunction induced by LPS. Like xenon, the similar pattern changes induced by a RIP-1 inhibitor Necrostatin-1 were also found. Conclusion: This study indicates that necroptosis is involved in neonatal sepsis-induced neurofunctional impairments and xenon may be a novel therapeutic strategy to prevent/treat cognitive impairment in neonatal septic patients.

Topological nature of higher-order hinge states revealed by spin transport.

One-dimensional (1D) gapless hinge states are predicated in the three-dimensional (3D) higher-order topological insulators and topological semimetals, because of the higher-order bulk-boundary correspondence. Nevertheless, the topologically protected property of the hinge states is still not demonstrated so far, because it is not accessible by conventional methods, such as spectroscopy experiments and quantum oscillations. Here, we reveal the topological nature of hinge states in the higher-order topological semimetal Cd3As2 nanoplate through spin potentiometric measurements. The results of current induced spin polarization indicate that the spin-momentum locking of the higher-order hinge state is similar to that of the quantum spin Hall state, showing the helical characteristics. The spin-polarized hinge states are robust up to room temperature and can nonlocally diffuse a long distance larger than 5µm, further indicating their immunity protected by topology. Our work deepens the understanding of transport properties of the higher-order topological materials and should be valuable for future electronic and spintronic applications.

Comparison of Febuxostat and Allopurinol in the Treatment of Patients with Chronic Kidney Disease Stage 3∼5 with Hyperuricemia.

Objective: To compare the efficacy of febuxostat and allopurinol in the treatment of chronic kidney disease (CKD) at stages 3∼5 with hyperuricemia. Methods: A total of 100 patients with stage 3 to 5 CKD with hyperuricemia in our hospital from July 2018 to December 2019 were selected and divided into the control group (n = 50) and the experimental group (n = 50) according to the random number expression method, the control group on the basis of conventional treatment with allopurinol treatment, the experimental group based on conventional treatment using the febuxostat be treatment. The clinical efficacy, incidence of adverse reactions, and renal function indexes, blood urea nitrogen (BUN), serum creatinine (Scr), serum sodium (Na), serum potassium (K), and serum uric acid (UA) before and after treatment were compared between the two groups. Results: The total effective rate of the experimental group and the control group was 82.00% and 78.00%, respectively, with little difference (P > 0.05); compared with before treatment, BUN, Scr, and UA of the two groups were decreased (P < 0.05); and the degree of decline in the experimental group was significantly greater than that in the control group (P < 0.05); the incidence of adverse reactions in the control group was 22.00%, which was significantly higher than that in the experimental group (10.00%) (P < 0.05). Conclusion: Compared with allopurinol, febuxostat can improve renal function, reduce UA levels, and reduce the occurrence of complications, with high safety, which is worthy of further clinical promotion.

Metasurface Enabled Photothermoelectric Photoresponse of Semimetal Cd3As2 for Broadband Photodetection.

The artificial engineering of photoresponse is crucial for optoelectronic applications, especially for photodetectors. Here, we designed and fabricated a metasurface on a semimetallic Cd3As2 nanoplate to improve its thermoelectric photoresponse. The metasurface can enhance light absorption, resulting in a temperature gradient. This temperature gradient can contribute to thermoelectric photoresponse through the photothermoelectric effect. Furthermore, power-dependent measurements showed a linearly dependent photoresponse of the Cd3As2 metasurface device, indicating a second-order photocurrent response. Wavelength-dependent measurements showed that the metasurface can efficiently separate photoexcited carriers in the broadband range of 488 nm to 4 µm. The photoresponse near the metasurface boundaries exhibits a responsivity of ∼1 mA/W, which is higher than that near the electrode junctions. Moreover, the designed metasurface device provided an anisotropic polarization-dependent photoresponse rather than the isotropic photoresponse of the original Cd3As2 device. This study demonstrates that metasurfaces have excellent potential for artificial controllable photothermoelectric photoresponse of various semimetallic materials.

Superconducting Proximity in Intrinsic Magnetic Topological Insulator MnBi2Te4-NbN Hybrid Device Modulated by Coulomb Blockade Effect.

The combination of nontrivial topology, magnetism, and superconductivity could offer the potential to realize exotic excitations of quasiparticles. MnBi2Te4, as an intrinsic magnetic topological insulator, may be a good platform to create Majorana fermions if coupled to an s-wave superconductor. Here, we report the transport properties of a MnBi2Te4-NbN hybrid device. This device exhibits clear Coulomb blockade oscillations. We observe a large zero-bias conductance peak that exists over considerable changes in gate voltage, magnetic field, and temperature, which is interpreted as a not fully developed supercurrent. The zero-bias peak shows a nonmonotonic evolution with a magnetic field and an abrupt π phase shift with changing temperature. Zero-energy bound states and a topological phase transition may exist in this hybrid system. Our results provide the first experimental investigation into the properties of the intrinsic magnetic topological insulator/superconductor hybrid structures modulated by the Coulomb blockade effect.

The Effect of Long-Term or Repeated Use of Antibiotics in Children and Adolescents on Cognitive Impairment in Middle-Aged and Older Person(s) Adults: A Cohort Study.

Objectives: We evaluated the effects of long-term/recurrent use of antibiotics in childhood on developing cognitive impairment in middle and old age from UK Biobank Database. Methods: UK Biobank recruited participants aged 37-73 years. Cognitive impairment was ascertained by fluid intelligence questionnaire. Primary outcome was the occurrence of cognitive impairment in middle and old age. Multivariate logistic regression models were used to explore the relationship between long-term/recurrent use of antibiotics and cognitive impairment. Results: Over 3.8-10.8 years' follow-up, 4,781 of the 35,921 participants developed cognitive impairment. The odds of cognitive impairment in middle and old age among long-term/recurrent use of antibiotics in childhood were increased by 18% compared with their counterparts (adjusted odd ratio 1.18, 95% confidence interval 1.08-1.29, p < 0.01). The effect of long-term/recurrent use of antibiotics in childhood on cognitive impairment was homogeneous across different categories of various subgroup variables such as sex, age, APOE4, ethnic groups, income before tax, smoking status, alcohol status, BMI, hypertension and diabetes but the effect of long-term/recurrent use of antibiotics in childhood was modified by the educational qualification (p-value for interaction <0.05). Conclusion: Long-term/recurrent use of antibiotics in childhood may increase the risk of cognitive impairment in middle and old age.