High-order superlattices by rolling up van der Waals heterostructures.

Two-dimensional (2D) materials1,2 and the associated van der Waals (vdW) heterostructures3-7 have provided great flexibility for integrating distinct atomic layers beyond the traditional limits of lattice-matching requirements, through layer-by-layer mechanical restacking or sequential synthesis. However, the 2D vdW heterostructures explored so far have been usually limited to relatively simple heterostructures with a small number of blocks8-18. The preparation of high-order vdW superlattices with larger number of alternating units is exponentially more difficult, owing to the limited yield and material damage associated with each sequential restacking or synthesis step8-29. Here we report a straightforward approach to realizing high-order vdW superlattices by rolling up vdW heterostructures. We show that a capillary-force-driven rolling-up process can be used to delaminate synthetic SnS2/WSe2 vdW heterostructures from the growth substrate and produce SnS2/WSe2 roll-ups with alternating monolayers of WSe2 and SnS2, thus forming high-order SnS2/WSe2 vdW superlattices. The formation of these superlattices modulates the electronic band structure and the dimensionality, resulting in a transition of the transport characteristics from semiconducting to metallic, from 2D to one-dimensional (1D), with an angle-dependent linear magnetoresistance. This strategy can be extended to create diverse 2D/2D vdW superlattices, more complex 2D/2D/2D vdW superlattices, and beyond-2D materials, including three-dimensional (3D) thin-film materials and 1D nanowires, to generate mixed-dimensional vdW superlattices, such as 3D/2D, 3D/2D/2D, 1D/2D and 1D/3D/2D vdW superlattices. This study demonstrates a general approach to producing high-order vdW superlattices with widely variable material compositions, dimensions, chirality and topology, and defines a rich material platform for both fundamental studies and technological applications.

General synthesis of two-dimensional van der Waals heterostructure arrays.

Two-dimensional van der Waals heterostructures (vdWHs) have attracted considerable interest1-4. However, most vdWHs reported so far  are created by an arduous micromechanical exfoliation and manual restacking process5, which-although versatile for proof-of-concept demonstrations6-16 and fundamental studies17-30-is clearly not scalable for practical technologies. Here we report a general synthetic strategy for two-dimensional vdWH arrays between metallic transition-metal dichalcogenides (m-TMDs) and semiconducting TMDs (s-TMDs). By selectively patterning nucleation sites on monolayer or bilayer s-TMDs, we precisely control the nucleation and growth of diverse m-TMDs with designable periodic arrangements and tunable lateral dimensions at the predesignated spatial locations, producing a series of vdWH arrays, including VSe2/WSe2, NiTe2/WSe2, CoTe2/WSe2, NbTe2/WSe2, VS2/WSe2, VSe2/MoS2 and VSe2/WS2. Systematic scanning transmission electron microscopy studies reveal nearly ideal vdW interfaces with widely tunable moiré superlattices. With the atomically clean vdW interface, we further show that the m-TMDs function as highly reliable synthetic vdW contacts for the underlying WSe2 with excellent device performance and yield, delivering a high ON-current density of up to 900 microamperes per micrometre in bilayer WSe2 transistors. This general synthesis of diverse two-dimensional vdWH arrays provides a versatile material platform for exploring exotic physics and promises a scalable pathway to high-performance devices.

Towards the scalable synthesis of two-dimensional heterostructures and superlattices beyond exfoliation and restacking.

Two-dimensional transition metal dichalcogenides, which feature atomically thin geometry and dangling-bond-free surfaces, have attracted intense interest for diverse technology applications, including ultra-miniaturized transistors towards the subnanometre scale. A straightforward exfoliation-and-restacking approach has been widely used for nearly arbitrary assembly of diverse two-dimensional (2D) heterostructures, superlattices and moiré superlattices, providing a versatile materials platform for fundamental investigations of exotic physical phenomena and proof-of-concept device demonstrations. While this approach has contributed importantly to the recent flourishing of 2D materials research, it is clearly unsuitable for practical technologies. Capturing the full potential of 2D transition metal dichalcogenides requires robust and scalable synthesis of these atomically thin materials and their heterostructures with designable spatial modulation of chemical compositions and electronic structures. The extreme aspect ratio, lack of intrinsic substrate and highly delicate nature of the atomically thin crystals present fundamental difficulties in material synthesis. Here we summarize the key challenges, highlight current advances and outline opportunities in the scalable synthesis of transition metal dichalcogenide-based heterostructures, superlattices and moiré superlattices.

Self-Rolled-Up WSe2 One-Dimensional/Two-Dimensional Homojunctions: Enabling High-Performance Self-Powered Polarization-Sensitive Photodetectors.

Mixed-dimensional heterostructures integrate materials of diverse dimensions with unique electronic functionalities, providing a new platform for research in electron transport and optoelectronic detection. Here, we report a novel covalently bonded one-dimensional/two-dimensional (1D/2D) homojunction structure with robust junction contacts, which exhibits wide-spectrum (from the visible to near-infrared regions), self-driven photodetection, and polarization-sensitive photodetection capabilities. Benefiting from the ultralow dark current at zero bias voltage, the on/off ratio and detectivity of the device reach 1.5 × 103 and 3.24 × 109 Jones, respectively. Furthermore, the pronounced anisotropy of the WSe2 1D/2D homojunction is attributed to its low symmetry, enabling polarization-sensitive detection. In the absence of any external bias voltage, the device exhibits strong linear dichroism for wavelengths of 638 and 808 nm, with anisotropy ratios of 2.06 and 1.96, respectively. These results indicate that such mixed-dimensional structures can serve as attractive building blocks for novel optoelectronic detectors.

Highly Robust Room-Temperature Interfacial Ferromagnetism in Ultrathin Co2Si Nanoplates.

The reduced dimensionality and interfacial effects in magnetic nanostructures open the feasibility to tailor magnetic ordering. Here, we report the synthesis of ultrathin metallic Co2Si nanoplates with a total thickness that is tunable to 2.2 nm. The interfacial magnetism coupled with the highly anisotropic nanoplate geometry leads to strong perpendicular magnetic anisotropy and robust hard ferromagnetism at room temperature, with a Curie temperature (TC) exceeding 950 K and a coercive field (HC) > 4.0 T at 3 K and 8750 Oe at 300 K. Theoretical calculations suggest that ferromagnetism originates from symmetry breaking and undercoordinated Co atoms at the Co2Si and SiO2 interface. With protection by the self-limiting intrinsic oxide, the interfacial ferromagnetism of the Co2Si nanoplates exhibits excellent environmental stability. The controllable growth of ambient stable Co2Si nanoplates as 2D hard ferromagnets could open exciting opportunities for fundamental studies and applications in Si-based spintronic devices.

Highly-Efficient and Robust Zn Anodes Enabled by Sub-1-µm Zincophilic CrN Coatings.

For exploring advanced Zn-ion batteries (ZIBs) with long lifespan and high Coulombic efficiency (CE), the critically important point is to limit the undesired Zn dendrite and parasitic reactions. Among the coating for electrode is a promising strategy, relying on the trade-off between its thickness and stability to achieve the ultra-stable Zn anodes in ZIBs. Herein, a submicron-thick (≈0.4 µm) zincophilic CrN coatings are fabricated by a facile and industry-compatible magnetron sputtering approach. It is exhilarating that the ultrathin and dense CrN coatings with strong adsorption ability for Zn2+ exhibit an impressive lifespan up to 3700 h with ≈100% CE at 1 mA cm-2. Along with the experiments and theoretical calculations, it is verified that the introduced CrN coatings cannot only effectively suppress the dendrite growth and notorious parasitic reactions, but also allow the uniform Zn deposition due to the reduced nucleation energy. Moreover, the as-assembled Zn@CrN‖MnO2 full cell delivers a high specific capacity of 171.1 mAh g-1 after 1000 cycles at 1 A g-1, much better than that of Zn‖MnO2 analog (97.8 mAh g-1). This work provides a facile strategy for scalable fabrication of ultrathin zincophilic coating to push forward the practical applications of ZIBs.

Controlled growth of asymmetric chiral TeOx for broad-spectrum, high-responsivity and polarization-sensitive photodetection.

Low-dimensional nanostructures, especially one-dimensional materials, exhibit remarkable anisotropic characteristics due to their low symmetry, making them promising candidates for polarization-sensitive photodetection. Here, we present a chemical vapor deposition synthesis method for tellurium suboxide (TeOx), confirming the practicality of photodetectors constructed from TeOx nanowires (NWs) in high-responsivity, broadband, and polarization-sensitive detection. By precisely controlling the thermodynamics and kinetics of TeOx NWs growth, we achieve large-scale growth of TeOx NWs with highly controllable dimensions and propose a method to induce intrinsic built-in strain in TeOx NWs. Photodetectors based on quasi-one-dimensional TeOx NWs with ohmic contact demonstrate broadband spectral response (638-1550 nm), high responsivity (13 700 mA·W-1), and superior air stability. Particularly, owing to the inherent structural anisotropy of the photodetectors, they exhibit polarization-sensitive photodetection, with anisotropy ratios of 1.70 and 1.71 at 638 and 808 nm, respectively.

Atypical chronic myeloid leukemia found in a patient with eosinophilia for six years: a case report.

BACKGROUND: Atypical chronic myeloid leukemia (aCML) is a highly aggressive type of blood cancer that falls under the category of myelodysplastic/myeloproliferative neoplasms (MDS/MPN). In the fifth edition of the WHO classification of tumors, this category has been renamed MDS/MPN with neutrophilia. Although eosinophilia is commonly observed in blood cancers, it is rarely seen in aCML. CASE PRESENTATION: This study presents a case of aCML that was diagnosed six years after the patient developed eosinophilia. The patient had undergone tests to rule out other primary and secondary diseases, but the eosinophilia remained unexplained. Treatment with corticosteroids and hydroxyurea had proven ineffective. Six years later, the patient experienced an increase in white blood cells, primarily neutrophils. After ruling out other possible diagnoses, a combination of morphologic and molecular genetic findings led to the diagnosis of aCML. The patient responded well to treatment with azacitidine. CONCLUSIONS: This study summarizes the current state of aCML diagnosis and management and discusses the possible connection between eosinophilia and aCML.

Association between vascular aging and cognitive function in Chinese adults.

BACKGROUND: Vascular health has been associated with cognition but related evidence is limited in Chinese. The objective of this study was to examine the association of vascular aging assessed by arterial stiffness and blood pressure with cognitive function in an unselected Chinese population. METHODS: In the Tianning Cohort (N = 5158), indicators of arterial stiffness and blood pressure including carotid-femoral pulse wave velocity (cfPWV), ankle-brachial index (ABI), pulse pressure (PP), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured. Cognitive function was assessed using the Mini Mental State Examination (MMSE) questionnaire. We applied Poisson regression and logistic regression to examine the associations of vascular aging and blood pressure with cognitive function. RESULTS: 76 (1.47%) participants had impaired cognitive function diagnosed by a MMSE score of less than 24 points. Participants with a higher level of PP were more likely to have a decreased score of MMSE (ß=-0.0121, P < 0.001 for log-transformed pulse pressure) and a higher risk of having impaired cognitive function (OR = 5.95, 95%CI: 2.02-17.79, P < 0.001 for log-transformed PP). Per standard deviation increment in SBP was significantly associated with lower MMSE score (ß=-0.0020, P < 0.001) and impaired cognitive function (OR = 1.69, 95%CI: 1.38-2.06, P < 0.001). No significant associations were found regarding other parameters. CONCLUSIONS: Blood pressure and hypertension were associated with cognitive function in Chinese adults. PP may be a potential predictor for impaired cognitive function.

Modified arthroscopic tenotomy of the extensor carpi radialis brevis for refractory lateral epicondylitis: a cohort study.

BACKGROUND: Different arthroscopic techniques exist for managing the extensor carpi radials brevis (ECRB) when treating refractory lateral epicondylitis. The purpose of this study is to compare the outcomes of a standard arthroscopic débridement with ECRB tendon release to an arthroscopic ECRB tenotomy distal to its insertion without débridement using a retrospective cohort study design. METHODS: This study included patients underwent arthroscopic treatment of lateral epicondylitis during 2 different time periods: 2016-2019 (débridement) and 2019-2021 (modified tenotomy without débridement). Patients were assessed preoperatively and at the last follow-up with Mayo Elbow Performance Score (MEPS), Disabilities of the Arm, Shoulder and Hand (DASH) score, Visual Analog Scale of pain. RESULTS: A total of 69 patients completed the follow-up (38 in the débridement group and 31 in the tenotomy group). Patients in both groups showed significant improvements were found in MEPS, DASH, and Visual Analog Scale after surgery. Patients in the tenotomy group had higher MEPSs and reported less pain with a minimum 2 year follow-up after surgery. DASH scores between groups were similar at all time periods. CONCLUSION: Arthroscopic modified tenotomy of the ECRB without débridement improves function and pain significantly for patients with refractory lateral epicondylitis, which is not inferior to arthroscopic débridement technique.

Two-Tier Efficient QoE Optimization for Partitioning and Resource Allocation in UAV-Assisted MEC.

Unmanned aerial vehicles (UAVs) have increasingly become integral to multi-access edge computing (MEC) due to their flexibility and cost-effectiveness, especially in the B5G and 6G eras. This paper aims to enhance the quality of experience (QoE) in large-scale UAV-MEC networks by minimizing the shrinkage ratio through optimal decision-making in computation mode selection for each user device (UD), UAV flight trajectory, bandwidth allocation, and computing resource allocation at edge servers. However, the interdependencies among UAV trajectory, binary task offloading mode, and computing/network resource allocation across numerous IoT nodes pose significant challenges. To address these challenges, we formulate the shrinkage ratio minimization problem as a mixed-integer nonlinear programming (MINLP) problem and propose a two-tier optimization strategy. To reduce the scale of the optimization problem, we first design a low-complexity UAV partition coverage algorithm based on the Welzl method and determine the UAV flight trajectory by solving a traveling salesman problem (TSP). Subsequently, we develop a coordinate descent (CD)-based method and an alternating direction method of multipliers (ADMM)-based method for network bandwidth and computing resource allocation in the MEC system. Extensive simulations demonstrate that the CD-based method is simple to implement and highly efficient in large-scale UAV-MEC networks, reducing the time complexity by three orders of magnitude compared to convex optimization methods. Meanwhile, the ADMM-based joint optimization method achieves approximately an 8% reduction in shrinkage ratio optimization compared to baseline methods.

Multi-Agent Deep Reinforcement Learning Based Dynamic Task Offloading in a Device-to-Device Mobile-Edge Computing Network to Minimize Average Task Delay with Deadline Constraints.

Device-to-device (D2D) is a pivotal technology in the next generation of communication, allowing for direct task offloading between mobile devices (MDs) to improve the efficient utilization of idle resources. This paper proposes a novel algorithm for dynamic task offloading between the active MDs and the idle MDs in a D2D-MEC (mobile edge computing) system by deploying multi-agent deep reinforcement learning (DRL) to minimize the long-term average delay of delay-sensitive tasks under deadline constraints. Our core innovation is a dynamic partitioning scheme for idle and active devices in the D2D-MEC system, accounting for stochastic task arrivals and multi-time-slot task execution, which has been insufficiently explored in the existing literature. We adopt a queue-based system to formulate a dynamic task offloading optimization problem. To address the challenges of large action space and the coupling of actions across time slots, we model the problem as a Markov decision process (MDP) and perform multi-agent DRL through multi-agent proximal policy optimization (MAPPO). We employ a centralized training with decentralized execution (CTDE) framework to enable each MD to make offloading decisions solely based on its local system state. Extensive simulations demonstrate the efficiency and fast convergence of our algorithm. In comparison to the existing sub-optimal results deploying single-agent DRL, our algorithm reduces the average task completion delay by 11.0% and the ratio of dropped tasks by 17.0%. Our proposed algorithm is particularly pertinent to sensor networks, where mobile devices equipped with sensors generate a substantial volume of data that requires timely processing to ensure quality of experience (QoE) and meet the service-level agreements (SLAs) of delay-sensitive applications.

Multiplex CRISPR-Cas9 knockout of EIL3, EIL4, and EIN2L advances soybean flowering time and pod set.

BACKGROUND: Ethylene inhibitor treatment of soybean promotes flower bud differentiation and early flowering, suggested that there is a close relationship between ethylene signaling and soybean growth and development. The short-lived ETHYLENE INSENSITIVE2 (EIN2) and ETHYLENE INSENSITIVE3 (EIN3) proteins play central roles in plant development. The objective of this study was carried out gene editing of EIL family members in soybeans and to examine the effects on soybean yield and other markers of growth. METHODS AND RESULTS: By editing key-node genes in the ethylene signaling pathway using a multi-sgRNA-in-one strategy, we obtained a series of gene edited lines with variable edit combinations among 15 target genes. EIL3, EIL4, and EIN2L were editable genes favored by the T0 soybean lines. Pot experiments also show that the early flowering stage R1 of the EIL3, EIL4, and EIN2L triple mutant was 7.05 d earlier than that of the wild-type control. The yield of the triple mutant was also increased, being 1.65-fold higher than that of the control. Comparative RNA-seq revealed that sucrose synthase, AUX28, MADS3, type-III polyketide synthase A/B, ABC transporter G family member 26, tetraketide alpha-pyrone reductase, and fatty acyl-CoA reductase 2 may be involved in regulating early flowering and high-yield phenotypes in triple mutant soybean plants. CONCLUSION: Our results provide a scientific basis for genetic modification to promote the development of earlier-flowering and higher-yielding soybean cultivars.

Natural variation of MS2 confers male fertility and drives hybrid breeding in soybean.

A complete and genetically stable male sterile line with high outcrossing rate is a prerequisite for the development of commercial hybrid soybean. It was reported in the last century that the soybean male sterile ms2 mutant has the highest record with seed set. Here we report the cloning and characterization of the MS2 gene in soybean, which encodes a protein that is specifically expressed in the anther. MS2 functions in the tapetum and microspore by directly regulating genes involved in the biosynthesis of secondary metabolites and the lipid metabolism, which is essential for the formation of microspore cell wall. Through comparison of the field performance with the widely used male sterile mutants in the same genetic background, we demonstrated that the ms2 mutant conducts the best in outcrossing rate and makes it an ideal tool in building a cost-effective hybrid system for soybean.

The downstream network of STAT6 in promoting vascular smooth muscle cell phenotypic switch and neointimal formation.

Intimal thickening caused by the excessive multiplication of vascular smooth muscle cells (VSMCs) is the pathological process central to cardiovascular diseases, including restenosis. In response to vascular injury, VSMCs would undergo phenotypic switching from a fully differentiated, low proliferative rate phenotype to a more pro-proliferative, promigratory, and incompletely-differentiated state. The lack of a full understanding of the molecular pathways coupling the vascular injury stimuli to VSMCs phenotype switching largely limits the development of medical therapies for treating intima hyperplasia-related diseases. The role of signal transducers and activators of transcription 6 (STAT6) in modulating the proliferation and differentiation of various cell types, especially macrophage, has been well investigated, but little is known about its pathophysiological role and target genes in restenosis after vascular injury. In the present work, Stat6-/- mice were observed to exhibit less severe intimal hyperplasia compared with Stat6+/+ mice after carotid injury. The expression of STAT6 was upregulated in VSMCs located in the injured vascular walls. STAT6 deletion leads to decreased proliferation and migration of VSMCs while STAT6 overexpression enhances the proliferation and migration of VSMCs companies with reduced expression of VSMCs marker genes and organized stress fibers. The effect of STAT6 in mouse VSMCs was conserved in human aortic SMCs. RNA-deep-sequencing and experiments verification revealed LncRNA C7orf69/LOC100996318-miR-370-3p/FOXO1-ER stress signaling as the downstream network mediating the pro-dedifferentiation effect of STAT6 in VSMCs. These findings broaden our understanding of vascular pathological molecules and throw a beam of light on the therapy of a variety of proliferative vascular diseases.

Effects of glutamine on plasma protein and inflammation in postoperative patients with colorectal cancer: a meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effects of glutamine on the plasma protein and inflammatory responses in colorectal cancer (CRC) patients following radical surgery. METHODS: We thoroughly retrieved online databases (EMBASE, MEDLINE, PubMed, and others) and selected the randomized controlled trials (RCTs) with glutamine vs. conventional nutrition or blank treatment up until March 2023. The plasma protein associated markers indicators (consisting of albumin (ALB), prealbumin (PA), nitrogen balance (NB), total protein (TP)), inflammatory indicators (including TNF-α, CRP, infectious complications (ICs)), and matching 95% confidence intervals (CIs) were evaluated utilizing the pooled analysis. Subsequently, meta-regression analysis, contour-enhanced funnel plot, Egger's test, and sensitivity analysis were carried out. RESULTS: We discovered 26 RCTs, included an aggregate of 1678 patients, out of which 844 were classified into the glutamine group whereas 834 were classified into the control group. The findings recorded from pooled analysis illustrated that glutamine substantially enhanced the plasma protein markers (ALB [SMD[random-effect] = 0.79, 95% CI: 0.55 to 1.03, I2 = 79.4%], PA [SMD[random-effect] = 0.94, 95% CI: 0.69 to 1.20, I2 = 75.1%], NB [SMD[random-effect] = 1.11, 95% CI: 0.46 to 1.75, I2 = 86.9%). However, the content of TP was subjected to comparison across the 2 groups, and no statistical significance was found (SMD[random-effect] = - 0.02, 95% CI: - 0.60 to 0.57, P = 0.959, I2 = 89.7%). Meanwhile, the inflammatory indicators (including TNF-α [SMD[random-effect] = - 1.86, 95% CI: - 2.21 to - 1.59, I2 = 56.7%], CRP [SMD[random-effect] = - 1.94, 95% CI: - 2.41 to - 1.48, I2 = 79.9%], ICs [RR[fixed-effect] = 0.31, 95% CI: 0.21 to 0.46, I2 = 0.00%]) were decreased significantly followed by the treatment of glutamine. CONCLUSIONS: The current study's findings illustrated that glutamine was an effective pharmaco-nutrient agent in treating CRC patients following a radical surgical operation. PROSPERO registration number: CRD42021243327.

Improved salt-tolerance of transgenic soybean by stable over-expression of AhBADH gene from Atriplex hortensis.

KEY MESSAGE: The salt-tolerance of transgenic soybean cleared for environmental release was improved by stable over-expression of AhBADH gene from Atriplex hortensis, which was demonstrated through molecular analysis and field experiments. An effective strategy for increasing the productivity of major crops under salt stress conditions is the development of transgenics that harbor genes responsible for salinity tolerance. Betaine aldehyde dehydrogenase (BADH) is a key enzyme involved in the biosynthesis of the osmoprotectant, glycine betaine (GB), and osmotic balance in plants, and several plants transformed with BADH gene have shown significant improvements in salt tolerance. However, very few field-tested transgenic cultivars have been reported, as most of the transgenic studies are limited to laboratory or green house experiments. In this study, we demonstrated through field experiments that AhBADH from Atriplex hortensis confers salt tolerance when transformed into soybean (Glycine max L.). AhBADH was successfully introduced into soybean by Agrobacterium mediated transformation. A total of 256 transgenic plants were obtained, out of which 47 lines showed significant enhancement of salt tolerance compared to non-transgenic control plants. Molecular analyses of the transgenic line TL2 and TL7 with the highest salt tolerance exhibited stable inheritance and expression of AhBADH in progenies with a single copy insertion. TL1, TL2 and TL7 exhibited stable enhanced salt tolerance and improved agronomic traits when subjected to 300mM NaCl treatment. Currently, the transgenic line TL2 and TL7 with stable enhanced salt tolerance, which have been cleared for environmental release, are under biosafety assessment. TL 2 and TL7 stably expressing AhBADH could then be applied in commercial breeding experiments to genetically improve salt tolerance in soybean.

Hypokalemia after rituximab administration in nephrotic syndrome: two case reports.

Rituximab, a chimeric anti-CD20 monoclonal antibody, is an effective treatment for nephrotic syndrome. Hypokalemia is a rare adverse reaction among patients treated with rituximab although there have been extensive reports of acute and chronic adverse events with the administration of rituximab. We herein report two cases of symptomatic hypokalemia after intravenous rituximab administration in our center, to help health professionals consider the possibility of acute hypokalemia after rituximab administration, monitor potassium timely and develop an appropriate treatment plan.

Factors associated with disease relapse rate in the Neuromyelitis optica spectrum disorder.

BACKGROUND AND OBJECTIVES: Neuromyelitis optica spectrum disorder (NMOSD) is a group of demyelinating diseases of the nervous system with high relapse rate and high disability rate without treatment, and we aimed to explore the influencing factors related to the recurrence of NMOSD and provide basis for clinical treatment in this study. METHODS: Referring to the diagnostic criteria for NMOSD issued in 2015, 259 patients were enrolled. Clinical information, cerebrospinal fluid (CSF) and serum analysis results, brain and spinal cord magnetic resonance imaging (MRI) findings, treatment details, and prognosis were all recorded. RESULTS: 176 (68.00%) participants were found to be AQP4 Ab-positive in serum or CSF, and the relapse rate was 36.67% (95/259). These 259 individuals were separated into two groups: non-release (n = 164) and relapse (n = 95). In terms of EDSS scores at onset, EDSS score after treatment, lesion location, serum creatinine (Cr) and treatment strategy, there were statistical differences between the two groups. Multivariable logistic regression analyses revealed five predictors for recurrence of NMOSD patients within two years: EDSS scores at onset, transverse myelitis, brain/brainstem, Cr, and Rituximab/immunosuppressants. CONCLUSION: It is essential to explore the risk factors related to recurrence and prevent them to reduce the risk of disability and improve the prognosis, and the recurrence rate of NMOSD may be affected by several factors.

COX5A Alleviates Doxorubicin-Induced Cardiotoxicity by Suppressing Oxidative Stress, Mitochondrial Dysfunction and Cardiomyocyte Apoptosis.

Doxorubicin (DOX) as a chemotherapeutic agent can cause mitochondrial dysfunction and heart failure. COX5A has been described as an important regulator of mitochondrial energy metabolism. We investigate the roles of COX5A in DOX-induced cardiomyopathy and explore the underlying mechanisms. C57BL/6J mice and H9c2 cardiomyoblasts were treated with DOX, and the COX5A expression was assessed. An adeno-associated virus serum type 9 (AAV9) and lenti-virus system were used to upregulate COX5A expression. Echocardiographic parameters, morphological and histological analyses, transmission electron microscope and immunofluorescence assays were used to assess cardiac and mitochondrial function. In a human study, we found that cardiac COX5A expression was dramatically decreased in patients with end-stage dilated cardiomyopathy (DCM) compared to the control group. COX5A was significantly downregulated following DOX stimulation in the heart of mice and H9c2 cells. Reduced cardiac function, decreased myocardium glucose uptake, mitochondrial morphology disturbance, reduced activity of mitochondrial cytochrome c oxidase (COX) and lowered ATP content were detected after DOX stimulation in mice, which could be significantly improved by overexpression of COX5A. Overexpression of COX5A effectively protected against DOX-induced oxidative stress, mitochondrial dysfunction and cardiomyocyte apoptosis in vivo and in vitro. Mechanistically, the phosphorylation of Akt (Thr308) and Akt (Ser473) were also decreased following DOX treatment, which could be reserved by the upregulation of COX5A. Furthermore, PI3K inhibitors abrogated the protection effects of COX5A against DOX-induced cardiotoxicity in H9c2 cells. Thus, we identified that PI3K/Akt signaling was responsible for the COX5A-mediated protective role in DOX-induced cardiomyopathy. These results demonstrated the protective effect of COX5A in mitochondrial dysfunction, oxidative stress, and cardiomyocyte apoptosis, providing a potential therapeutic target in DOX-induced cardiomyopathy.