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Despite the considerable progress in mesenchymal stem/stromal cells (MSCs)-based novel intervention of multiple sclerosis (MS), yet the disease-modifying effect of VCAM-1− MSCs and novel VCAM-1+ counterpart is largely obscure. In this study, we took advantage of the EAE mouse model and VCAM-1+ human umbilical cord-derived MSCs (hUC-MSCs) for the evaluation of the therapeutic effect of systematic MSCs infusion. On the one hand, we compared the protective effect of VCAM-1− and VCAM-1+ hUC-MSCs against the clinical symptoms, demyelination, active glia cells and neuroinflammation in EAE mice by conducting multifaceted detections upon spinal cord and brain tissues. On the other hand, we conducted RNA-sequencing (RNA-SEQ) and multidimensional bioinformatics analyses for the evaluation of the transcriptomic features of spinal cord tissue in EAE mice after systematic hUC-MSCs infusion. Compared to those with VCAM-1− hUC-MSCs injection, VCAM-1+ mice showed further remission in clinical manifestations, and in particular, the inflammatory infiltration and active glial cells. Mice in all groups revealed conservations in overall gene expression profiling and somatic mutation spectrum. The differentially expressed genes (DEGs) between EAE mice and those with hUC-MSCs infusion were mainly involved in neuroinflammation and inflammatory response. Our findings indicated the feasibility of VCAM-1+ hUC-MSCs for multiple sclerosis treatment, which would supply new references for the development of novel VCAM-1+ MSCs-based cytotherapy in future. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the relationship between urinary creatinine (UCr) and the risk and severity of Diabetic Kidney Disease (DKD) in patients with Type 2 Diabetes Mellitus (T2DM). The goal is to establish UCr as a potential biomarker for early DKD detection and severity assessment. Methods: A retrospective cross-sectional analysis was conducted using medical records of T2DM patients. Patients were classified into groups with and without DKD, and relevant clinical data, including demographic, blood, and urine parameters, were collected. Logistic regression and receiver operating characteristic (ROC) curve analysis evaluated the association between UCr levels and DKD. Curve fitting and threshold effect model were used to further evaluate the relationship between UCr and the incidence and severity of DKD. Results: A total of 302 T2DM patients were analyzed, with 137 diagnosed with DKD. Significant differences in clinical parameters were observed between the DKD and non-DKD groups, particularly in UCr, urine albumin levels, and eGFR. UCr levels demonstrated a strong association with DKD. Moreover, a non-linear relationship was identified, with specific inflection points indicating different correlation patterns of UCr with DKD occurrence and progression. Conclusion: The findings of this study highlight the potential of UCr as a valuable biomarker for early detection and assessment of DKD in T2DM patients. Incorporating UCr measurements into routine clinical practice could enhance early identification of patients at risk for kidney complications, leading to timely intervention and improved patient outcomes. [ABSTRACT FROM AUTHOR]

To improve the expressiveness and realism of illustration images, the experiment innovatively combines the attention mechanism with the cycle consistency adversarial network and proposes an efficient style transfer method for illustration images. The model comprehensively utilizes the image restoration and style transfer capabilities of the attention mechanism and the cycle consistency adversarial network, and introduces an improved attention module, which can adaptively highlight the key visual elements in the illustration, thereby maintaining artistic integrity during the style transfer process. Through a series of quantitative and qualitative experiments, high-quality style transfer is achieved, especially while retaining the original features of the illustration. The results show that when running on the Monet2photo dataset, when the system iterates to 72 times, the loss function value of the research method approaches the target value of 0.00. On the Horse2zebra dataset, as the sample size increases, the research method has the smallest FID value, and the value approaches 40.00 infinitely. With the change of peak signal-to-noise ratio, the accuracy of the research algorithm has been greater than 95.00%. Practical application found that the color of the image obtained by the research method is more gorgeous and the line features are more obvious. The above results all show that the research method has achieved more satisfactory results in the task of style transfer of illustration images, especially in terms of the accuracy of style transfer and the retention of image details. [ABSTRACT FROM AUTHOR]

With the increasing frequency of extreme weather events such as heavy rainstorm disasters, the stable operation of power systems is facing significant challenges. This paper proposes a two-stage restoration strategy for the distribution networks (DNs). First, a grid-based modeling approach is developed for urban DNs and transportation networks (TNs), capturing the dynamic evolution of heavy rainstorm disasters and more accurately modeling the impact on TNs and DNs. Then, a two-stage restoration strategy is designed for the DN by coordinating soft open points (SOPs) and mobile energy storage systems (MESSs). In the disaster progression stage, SOPs are utilized to enable the flexible reconfiguration and islanding of the DN, minimizing load loss. In the post-disaster recovery stage, the MESS and repair crew are optimally dispatched, taking into account the state of the TN to expedite power restoration. Finally, the experimental results demonstrate that the proposed method reduces load loss during restoration by 8.09% compared to approaches without precise TN and DN modeling. [ABSTRACT FROM AUTHOR]

Grain refinement is of very important significance for improving the microstructure and mechanical properties of Mg alloys. This work investigated how the addition of various amounts of Y element affected the microstructure and mechanical properties of Mg-9Al-1Zn alloy. It was found that the grain size of Mg-9Al-1Zn alloy decreases as Y element content increases. When 1.2 wt.% Y element content was added, the grain size of Mg-9Al-1Zn alloy could be reduced from 334.2 μm to 134.6 μm, and grain refinement efficiency of 60% was achieved. HRTEM analysis demonstrated a good orientation relationship between the Al2Y phase and the Mg interface, and therefore, it was determined that the Al2Y phase can be used as a heterogeneous nucleation site for α-Mg grains, which promotes the grain refinement of α-Mg grain. Furthermore, the addition of Y element can also significantly refine the eutectic Mg17Al12 phase of the Mg-9Al-1Zn alloy. In this way, the mechanical properties of the Mg-9Al-1Zn alloy are significantly enhanced. It was found that the YS and UTS of the Mg-9Al-1Zn alloy reached 87 MPa and 154 MPa with the addition of 0.9 wt.% of Y element—24% and 43% higher than the Mg-9Al-1Zn alloy. [ABSTRACT FROM AUTHOR]

Fujian Province is an important soil and water conservation region in hilly South China. However, there has been limited attention paid to the assessment of water production and soil conservation at the provincial level, and the distribution patterns of ecosystem services under different environmental gradients in hilly regions have not been revealed. This study evaluated the spatiotemporal characteristics of water yield and soil conservation based on the InVEST model in 2000, 2010, and 2020, and explored their differences under six environmental gradients: elevation, slope, terrain position index, geomorphy, LULC, and NDVI. The results and statistics of the InVEST model showed significant spatial differentiation and temporal change in water yield; the distribution and changes in water yield and soil conservation both exhibited obvious clustering characteristics of cold and hot spots (low and high values); and the differences in distribution and change in water yield in different cities were higher than those in soil conservation. The distribution index and Geodetector showed that there were spatiotemporal differences in distribution and change characteristics of water yield and soil retention in different environmental gradients; the distribution and change differences in water yield were generally lower than those of soil conservation and the degree of distribution and change in water yield and soil conservation were generally more sensitive to the response of terrain factors (slope, TPI, and DEM). The high-value important regions of water yield and soil conservation were 1000 to 2160 m for DEM, 25° to 70.2° for slope, 0.81 to 1.42 for TPI, medium mountain for geomorphy, forest land for LULC, and 0.9 to 0.92 for NDVI, which indicates mountainous regions with high altitude, steep slopes, significant terrain changes, and high forest vegetation coverage. This study indicates that ecosystem services exhibit spatiotemporal differences in distributions across different environmental gradients, and attention should be paid to adapting to local conditions in ecological environment development. [ABSTRACT FROM AUTHOR]

In order to study the stability of rock layers and the change in volumetric water content at different stages of mining under an environment of heavy rainfall, a self-developed large-scale open-pit-to-underground-mining similar physical model was used, and the intensity of continuous rainfall was set at 40 mm/h. The results of this study show that fissures accelerated the instability of rock strata, and when spreading to different rock strata, they were prone to form subsidence cracks and produce collapse zones. The volumetric water content is closely related to the stability of the rock formation. An 'arch-shaped collapse zone' was formed in an interval of (0.9~1.8 m), and a convex spreading zone of volumetric water content was formed in an interval of (1.2~1.6 m). The infiltration line shows different diffusion patterns in different mining stages. In the early stage of mining, the volumetric water content infiltration line is roughly parallel to the slope; in the middle stage of mining, the infiltration line diffuses parallel to the two ends of the interface with the slope and diffuses convexly in the middle; in the late stage of mining, the infiltration line shows a pattern of rapid diffusion in the lower area, rapid diffusion in the middle area, and slow diffusion in the middle area. Therefore, in the process of the mining stage, it is necessary to focus on mining area fissure changes and monitor the point water content for sudden changes and other indicators. This study has certain guiding significance for safe production. [ABSTRACT FROM AUTHOR]

The retrosplenial cortex (RSP) is a complex brain region with multiple interconnected subregions that plays crucial roles in various cognitive functions, including memory, spatial navigation, and emotion. Understanding the afferent and efferent connectivity of the RSP is essential for comprehending the underlying mechanisms of its functions. Here, via viral tracing and fluorescence micro-optical sectioning tomography (fMOST), we systematically investigated the anatomical organisation of the upstream and downstream circuits of glutamatergic and GABAergic neurons in the dorsal and ventral RSP. The cortical connections of the RSP show laminar organisation in which the input neurons are distributed more in the deeper layers of the upstream cortex. Although different types of neurons have similar upstream circuits, GABAergic neurons show bidirectional connections with the hippocampus, whereas glutamatergic neurons only show unidirectional connections. Moreover, GABAergic neurons receive more inputs from the primary sensory cortex than from the prefrontal cortex and association cortex. The dorsal and ventral subregions have preferred circuits such that the dorsal RSP exhibits spatially topological connections with the dorsal visual cortex and lateral thalamus. The systematic study on long-range connections across RSP subregions and cell types may provide useful information for future revealing of RSP working mechanisms.Dissection of long-range circuits of the mouse intermediate retrosplenial cortex reveals preferred circuits of glutamatergic and GABAergic neurons and spatially topological connections in dorsal and ventral subregions. [ABSTRACT FROM AUTHOR]

Gannan is the largest navel orange production area in China. Most studies have primarily focused on the effects of either soil or topographic factors on the quality of navel oranges. However, there has been a lack of research exploring the relationship between navel orange quality and multiple environmental factors (meteorological, topographic, and soil). This study focused on Gannan navel oranges, selecting standard orchards in the core navel orange-producing area as the research region. It employed the Partial Least Squares Regression (PLSR) method to investigate the extent of the impact of environmental factors on fruit quality. The results indicated that the effect of soil factors on fruit shape and fruit flavor was greater than that of meteorological and topographic factors in the Gannan area. And the fruit peel is more uniformly influenced by environmental factors. Based on the degree of impact of various environmental factors, multiple regression equations for fruit quality have been established to identify the optimal conditions conducive to the comprehensive development of Gannan navel oranges. These findings help determine the optimal planting areas for Gannan navel oranges, providing practical evidence for the future development of navel oranges. [ABSTRACT FROM AUTHOR]

Background Volenrelaxin is a half-life-extended recombinant human relaxin protein developed for improving kidney perfusion and cardiorenal function. This study assessed the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of volenrelaxin following single- and multiple-ascending doses (SAD and MAD) administration. Methods In this Phase 1, four-part, randomized, double-blinded, placebo-controlled SAD and MAD study in healthy participants, SAD participants (n  = 56) received an intravenous or subcutaneous dose of volenrelaxin or placebo in a dose-ascending manner. MAD participants (n  = 77) received volenrelaxin or placebo subcutaneously once weekly for 5 weeks. Effective renal plasma flow (ERPF) and measured glomerular filtration rate (mGFR) were determined by para-aminohippurate and iohexol clearance, respectively. Results Volenrelaxin demonstrated an extended half-life and increased acute and chronic placebo-adjusted ERPF change from baseline by 50% and 44%, respectively (P  < .0001). mGFR was unchanged, while filtration fraction and afferent/efferent renal arteriolar resistances were reduced. Systolic and diastolic blood pressures decreased, and pulse rate increased with increasing volenrelaxin exposures, demonstrating maximal model-derived placebo-adjusted changes (90% confidence interval) of –6.16 (–8.04, –4.28) mmHg, –6.10 (–7.61, –4.58) mmHg and +4.39 (+3.38, +5.39) bpm, respectively. Adverse events were mild, with no difference in orthostatic hypotension between volenrelaxin and placebo. Conclusion Volenrelaxin was well-tolerated, safe and suitable for weekly subcutaneous dosing. Volenrelaxin showed a sustained improvement in kidney perfusion upon repeated dosing, supporting further clinical development in chronic kidney disease and chronic heart failure. Clinical trial registration NCT04768855. [ABSTRACT FROM AUTHOR]

Sweet syndrome (SS), which is characterised by fever and erythematous tender skin lesions, has been shown to be associated with lymphoma. However, there are limited reported experiences on the wound care of SS in patients with lymphoma. This case report presents the wound care of SS in a patient with anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALK+ALCL). A 42-year-old male was referred to the The First Affiliated Hospital of Guangzhou University of Chinese Medicine Hospital with redness and pain in the left shoulder and abdomen following chemotherapy for ALK+ALCL in early 2021. Physical examination found lesions in the abdomen and shoulder. The lesions were ruptured on day 5 and found to be composed of necrotic tissues. After debridement, the wounds were successively treated with silver ion antibacterial dressing, Mepilex Border Lite (Mölnlycke Health Care, Sweden), silver sulfadiazine gauze, Shengji ointment (a traditional Chinese therapy), UrgoTül (Urgo Medical, France), and fire needling therapy (another traditional Chinese therapy). At three months later, the wound in the abdomen was healed, but the shoulder wound was still unhealed. Based on the physiological manifestations and current treatment process, the patient was diagnosed with SS after multidisciplinary consultation. Prednisone tablets were then administered and the shoulder wound completely healed after two months. [ABSTRACT FROM AUTHOR]

In this study, we provide an ~47.0‐kyr mercury (Hg) deposition record derived from a lacustrine sedimentary sequence in Dahu swamp in the eastern Nanling Mountains, China. The results indicate that organic matter (OM) input played a role in Hg accumulation, whereas the contribution of inorganic weathering detritus had a negligible impact. On the other hand, evolution of the plant community and wildfire events were also important factors affecting Hg accumulation. Compared to arboreal plants, lower (herbs and ferns) plants had stronger absorption and enrichment ability for Hg thus favoring enhanced Hg accumulation in the sediments. We therefore infer that Hg deposition in Dahu sediments was greatly controlled by changes in climatic conditions. Relatively dry and cold climatic conditions, which resulted in reduced arboreal plant communities and increased lower plants, would favor an increased Hg accumulation rate; furthermore, dry conditions may cause more wildfire events thus leading to enhanced release of Hg into the environment and increased contribution of Hg to the sediments, whereas relatively wet and warm conditions would result in the opposite situation. The record of Hg deposition demonstrates a synchronous orbital‐scale variation trend with the intensity of the East Asian summer monsoon. Period analysis reveals several millennial‐ and centennial‐scale cycles similar to solar insolation, together with several millennial events of increased Hg concentration and accumulation rate, which coincided with the corresponding Heinrich events, suggesting joint impacts of solar irradiation and the action of melting water as well as changes in zonal atmospheric circulation on Hg accumulation in Dahu sediments. [ABSTRACT FROM AUTHOR]

Mn‐based layered oxides have garnered significant attention as cathode materials for energy storage due to their environmental benignity and high theoretical specific capacity. However, practical applications remain constrained by sluggish Na+ intercalation kinetics and poor structural stability. In this study, it is engineered that the Mn‐O‐B unit through an oxygen edge‐sharing strategy to modulate Mn─O covalency in P2‐type Na0.67MnO2, thereby achieving high specific capacity and structural stability. Both experimental results and density functional theory (DFT) calculations reveal that increased TM‐O covalency facilitates Na+ diffusion in P2‐type Na0.67MnO2 while simultaneously enhancing air stability. The as‐prepared P2‐type Na0.67MnB0.05O2 exhibits a specific capacitance of 452 F g−1 at 1 A g−1, maintaining 96.75% capacity retention after 8800 cycles. This work elucidates the critical role of oxygen edge‐sharing in optimizing interactions between transition metal and oxygen atoms, establishing a relationship between Mn─O structure and functional properties. These findings advance the development of high‐performance energy storage technologies. [ABSTRACT FROM AUTHOR]

Equine infectious anemia virus (EIAV) and HIV-1 are both members of the Lentivirus genus and are similar in virological characters. EIAV is of great concern in the equine industry. Lentiviruses establish a complex interaction with the host cell to counteract the antiviral responses. There are various pattern recognition receptors in the host, for instance, the cytosolic RNA helicases interact with viral RNA to activate the mitochondrial antiviral signaling protein (MAVS) and subsequent interferon (IFN) response. However, viruses also exploit multiple strategies to resist host immunity by targeting MAVS, but the mechanism by which lentiviruses are able to target MAVS has remained unclear. In this study, we found that EIAV infection induced MAVS degradation, and that EIAV Gag protein recruited the E3 ubiquitin ligase Smurf1 to polyubiquitinate and degrade MAVS. The CARD domain of MAVS and the WW domain of Smurf1 are responsible for the interaction with Gag. EIAV Gag is a precursor polyprotein of the membrane-interacting matrix p15, the capsid p26, and the RNA-binding nucleocapsid proteins p11 and p9. Therefore, we analyzed which protein domain of Gag could interact with MAVS and Smurf1. We found that p15 and p26, but not p11 or p9, target MAVS for degradation. Moreover, we identified the key amino acid residues that support the interactions between p15 or p26 and MAVS or Smurf1. The present study describes a novel role of the EIAV structural protein Gag in targeting MAVS to counteract innate immunity, and reveals the mechanism by which the equine lentivirus can antagonize against MAVS.IMPORTANCEHost anti-RNA virus innate immunity relies mainly on the recognition by retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5), and subsequently initiates downstream signaling through interaction with mitochondrial antiviral signaling protein (MAVS). However, viruses have developed various strategies to counteract MAVS-mediated signaling, although the method of antagonism of MAVS by lentiviruses is still unknown. In this article, we demonstrate that the precursor (Pr55gag) polyprotein of EIAV and its protein domains p15 and p26 target MAVS for ubiquitin-mediated degradation through E3 ubiquitin ligase Smurf1. MAVS degradation leads to the inhibition of the downstream IFN-β pathway. This is the first time that lentiviral structural protein has been found to have antagonistic effects on MAVS pathway. Overall, our study reveals a novel mechanism by which equine lentiviruses can evade host innate immunity, and provides insight into potential therapeutic strategies for the control of lentivirus infection., Competing Interests: The authors declare no conflict of interest.

Building insights into the structure-performance relationship of catalysts has been emphasized recently. However, it remains a challenge due to catalysts' various and complex structures, especially the easily overlooked influence of the support material. Here, we reveal the crucial influences of boron introduction on synthesizing 3D carbon nanotube monoliths with embedded multistate Co metals, i.e., single atoms, clusters, and nanoparticles (Co-BNCNTs), by an interesting chemical blowing-assisted calcination method. The boron introduction can contribute to forming captivating boron-nitrogen pairs, shaping a 3D frame, and regulating electronic structure. The 3D Co-BNCNT monoliths present good catalytic performance for both the hydrogen evolution reaction (HER) at all pH values and the oxygen reduction reaction (ORR). The theoretical calculations indicate that the B incorporation in Co-NCNTs can optimize the free energy of adsorbed hydrogen and facilitate the O 2 adsorption and the protonation of the O 2 * species. Furthermore, the Co-BNCNTs-based zinc-air battery provides great battery performance with a high power density and discharge-charge durability.