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Abstract Long-term potentiation (LTP) and long-term depression (LTD) are widely used to study synaptic plasticity. However, whether proteins regulating LTP and LTD are altered in cognitive disorders and contribute to disease onset remains to be determined. Herein, we induced LTP and LTD in the hippocampal CA3-CA1 Schaffer collateral pathway, respectively, and then performed proteomic analysis of the CA1 region. We identified 20 differentially expressed proteins (DEPs) shared by the LTP and the LTD processes. Among them, we found that HtrA serine peptidase 2 (HTRA2) was mainly expressed in neurons and that HTRA2 levels were increased in both the LTP and the LTD processes in C57BL/6 mice. HTRA2 downregulation impaired synapses and reduced ATP production in cultured primary neurons. Furthermore, adeno-associated virus (AAV)-mediated HTRA2 downregulation in the hippocampus impaired synaptic plasticity and cognitive function in C57BL/6 mice. Moreover, we found that HTRA2 expression decreased in the brains of Alzheimer’s disease patients, frontotemporal lobar degeneration with ubiquitin inclusions patients, and tauopathy model mice. Finally, we showed that lentivirus-mediated HTRA2 overexpression in the hippocampus rescued PP2B reduction, alleviated tau hyperphosphorylation, and partially attenuated synaptic plasticity and cognitive deficits in the PS19 tauopathy model mice. Our study not only indicates that HTRA2 in neurons plays an important role in regulating synaptic plasticity under both physiological and pathological conditions, but also provides a novel, electrophysiology-based strategy to identify proteins regulating synaptic plasticity systematically.

Abstract Background The CD2-associated protein (CD2AP) was initially identified in peripheral immune cells and regulates cytoskeleton and protein trafficking. Single nucleotide polymorphisms (SNPs) in the CD2AP gene have been associated with Alzheimer’s disease (AD). However, the functional role of CD2AP, especially its role in microglia during AD onset, remains elusive. Methods CD2AP protein levels in cultured primary cells and in 5xFAD mice was studied. Microglial CD2AP-deficient mice were crossed with 5xFAD mice and the offspring were subjected to neuropathological assessment, behavioral tests, electrophysiology, RNA-seq, Golgi staining, and biochemistry analysis. Primary microglia were also isolated for assessing their uptake and morphology changes. Results We find that CD2AP is abundantly expressed in microglia and its levels are elevated in the brain of AD patients and the 5xFAD model mice at pathological stages. We demonstrate that CD2AP haploinsufficiency in microglia significantly attenuates cognitive and synaptic deficits, weakens the response of microglia to Aβ and the formation of disease-associated microglia (DAM), and alleviates synapse loss in 5xFAD mice. We show that CD2AP-deficient microglia exhibit compromised uptake ability. In addition, we find that CD2AP expression is positively correlated with the expression of the complement C1q that is important for synapse phagocytosis and the formation of DAM in response to Aβ deposition. Moreover, we reveal that CD2AP interacts with colony stimulating factor 1 receptor (CSF1R) and regulates CSF1R cell surface levels, which may further affect C1q expression. Conclusions Our results demonstrate that CD2AP regulates microgliosis and identify a protective function of microglial CD2AP deficiency against Aβ deposition, suggesting the importance of detailed investigation of AD-associated genes in different brain cells for thoroughly understanding their exact contribution to AD.

Abstract Background This in vitro study aimed to evaluate the effect of sodium hypochlorite (NaOCl) and ethylene diamine tetraacetic acid (EDTA) as pretreatments on the resin infiltration efficacy and acid resistance of enamel white spot lesions (WSLs). Methods Enamel blocks prepared from the buccal surfaces of sound human premolars were placed in a demineralisation solution for 3 days to establish artificial enamel WSLs. All the blocks with WSLs were randomly divided into four groups (n = 40 per group): RI (Control): resin infiltration only. N/RI: 5.25% NaOCl pretreatment + resin infiltration; E/RI: 17% EDTA pretreatment + resin infiltration; NE/RI: combined pretreatment of 5.25% NaOCl with 17% EDTA + resin infiltration; Enamel pore exposure was measured by using SEM observation and Image J software in each group after pretreatment prior to resin infiltration (n = 8 per group). Resin penetration depth and enamel surface microhardness were assessed after resin infiltration (n = 8 per group for each test) by a confocal laser scanning microscope and a Vickers’ microhardness test respectively. The remaining specimens were subjected 7 days of pH cycling after which surface enamel roughness and microhardness were assessed by an atomic force microscope and a microhardness test respectively. Results Compared to the control group, the enamel surface pore exposure (p = 0.007), resin penetration depth (p = 0.011) and enamel surface microhardness (p

Abstract Light non-aqueous phase liquids (LNAPLs) that infiltrate into the subsurface are commonly described in two distinct zones: the source zone and the plume zone. A precise differentiation between these zones is essential for constraining further migration and selecting an effective remediation method. In this study, we employ the induced polarization (IP) method to characterize the contaminants. Six time domain IP survey lines were conducted at a former chemical plant contaminated with LNAPLs. Even though the contaminated areas corresponding to BTEX concentration above 180 mg/kg are less than 5 mS/m, the source and plume zones cannot be distinguished by conductivity alone. However, a noticeable difference in phase ( $$\varphi$$ φ ) between the two zones is observed, and the threshold phase value corresponding to a critical concentration of 450 mg/kg is 20 mrad. Moreover, the normalized chargeability ( $$M_{n}$$ M n ) threshold for the source zone is 80 mS/m, and the corresponding $$M_{n}$$ M n differences between the source and plume zones are more significant than those in $$\varphi$$ φ . These results illustrate that changes in polarization characteristics associated with BTEX concentrations can aid in further distinguishing between the source and plume zones. Ultimately, it is concluded that IP imaging is a well-suited method for LNAPL investigations that permits an improved characterization of different contaminated zones, which can facilitate the optimization of drillings for further site assessment and remediation.

Spinal cord injury (SCI) results in severe neurological deficits due to disrupted neural pathways. While the spinal cord possesses limited self-repair capabilities, recent advancements in hydrogel-based therapies have shown promise. Polyphenol-based hydrogels, known for their neuroprotective properties, offer a suitable microenvironment for neural regeneration. In this study, a novel poly(lipoic acid)/poly(dopamine) adhesive hydrogel was developed as a versatile platform for delivering therapeutic agents. This hydrogel was loaded with methylcobalamin, a neurotrophic factor, and tellurium nanoenzymes, potent antioxidants. The nanoenzymes effectively mitigated oxidative stress and inflammation, while methylcobalamin promoted nerve regeneration. The combined therapeutic effects of the nanoenzymatic hydrogel demonstrated significant efficacy in repairing spinal cord injuries, highlighting its potential as a promising strategy for treating this debilitating condition.

BackgroundGiven the complexity and diversity of lichenoid vulvar disease (LVD) risk factors, it is crucial to actively explore these factors and construct personalized warning models using relevant clinical variables to assess disease risk in patients. Yet, to date, there has been insufficient research, both nationwide and internationally, on risk factors and warning models for LVD. In light of these gaps, this study represents the first systematic exploration of the risk factors associated with LVD. ObjectiveThe risk factors of LVD in women were explored and a medically evidence-based warning model was constructed to provide an early alert tool for the high-risk target population. The model can be applied in the clinic to identify high-risk patients and evaluate its accuracy and practicality in predicting LVD in women. Simultaneously, it can also enhance the diagnostic and treatment proficiency of medical personnel in primary community health service centers, which is of great significance in reducing overall health care spending and disease burden. MethodsA total of 2990 patients who attended West China Second Hospital of Sichuan University from January 2013 to December 2017 were selected as the study candidates and were divided into 1218 cases in the normal vulvovagina group (group 0) and 1772 cases in the lichenoid vulvar disease group (group 1) according to the results of the case examination. We investigated and collected routine examination data from patients for intergroup comparisons, included factors with significant differences in multifactorial analysis, and constructed logistic regression, random forests, gradient boosting machine (GBM), adaboost, eXtreme Gradient Boosting, and Categorical Boosting analysis models. The predictive efficacy of these six models was evaluated using receiver operating characteristic curve and area under the curve. ResultsUnivariate analysis revealed that vaginitis, urinary incontinence, humidity of the long-term residential environment, spicy dietary habits, regular intake of coffee or caffeinated beverages, daily sleep duration, diabetes mellitus, smoking history, presence of autoimmune diseases, menopausal status, and hypertension were all significant risk factors affecting female LVD. Furthermore, the area under the receiver operating characteristic curve, accuracy, sensitivity, and F1-score of the GBM warning model were notably higher than the other 5 predictive analysis models. The GBM analysis model indicated that menopausal status had the strongest impact on female LVD, showing a positive correlation, followed by the presence of autoimmune diseases, which also displayed a positive dependency. ConclusionsIn accordance with evidence-based medicine, the construction of a predictive warning model for female LVD can be used to identify high-risk populations at an early stage, aiding in the formulation of effective preventive measures, which is of paramount importance for reducing the incidence of LVD in women.

Circulating triglyceride (TG) and leukocytes, the main components of the vascular system, may impact each other and co-fuel atherosclerosis. While the causal relationship between plasma TG levels and leukocyte counts remains unclear. Bidirectional Mendelian randomization (MR) analysis was conducted to investigate the potential causal relationship between TG levels and the counts of leukocytes and their subtypes. A cross-lagged panel model (CLPM) using longitudinal healthy screening data (13,389 adults with a follow-up of 4 years) was fitted to examine the temporal relationship between them. Genetically predicted plasma TG levels were positively associated with total leukocyte counts (TLC) [β(se) = 0.195(0.01)], lymphocyte counts (LC) [β(se) = 0.196(0.019)], and neutrophil counts (NC) [β(se) = 0.086(0.01)], which remained significant after adjusting for several confounders. Inversely, the genetically predicted TLC [β(se) = 0.033(0.008)], LC [β(se) = 0.053(0.008)], and NC [β(se) = 0.034(0.008)] were positively associated with plasma TG levels. However, when all three of them were put into the MR model adjusted for each other, only LC was significantly associated with TG levels. There was no association between genetically predicted TG levels and monocyte counts (MC), basophil counts, and eosinophil counts. The results of CLPM showed that the temporal effect of elevated TLC, MC, LC, and NC on plasma TG levels was stronger than the inverse effect. Our findings suggest causal associations of plasma TG levels with TLC, LC, and NC. In turn, LC was positively associated with plasma TG levels. Additionally, elevated circulating LC may precede high plasma TG levels.

Abstract Objective We aimed to analyze the relationship between non-alcoholic fatty liver and progressive fibrosis and serum 25-hydroxy vitamin D (25(OH)D) in patients with type 2 diabetes mellitus. Methods A total of 184 patients with T2DM who were hospitalized in the Department of Endocrinology of the ShiDong Clinical Hospital between January 2023 and June 2023 were selected. We compared review of anthropometric, biochemical, and inflammatory parameters and non-invasive scores between groups defined by ultrasound NAFLD severity grades.We determine the correlation between 25(OH)D and FLI and FIB-4 scores, respectively. Results Statistically significant differences were seen between BMI, WC, C-peptide levels, FPG, ALT, serum 25(OH)D, TC, HDL, lumbar spine bone density, FLI, and FIB-4 in different degrees of NAFLD. Multivariate logistic regression analysis showed that 25(OH)D (OR = 1.26, p = 0.001), age (OR = 0.93, P

Spiking neural networks (SNNs) have received increasing attention due to their high biological plausibility and energy efficiency. The binary spike-based information propagation enables efficient sparse computation in event-based and static computer vision applications. However, the weight precision and especially the membrane potential precision remain as high-precision values (e.g., 32 bits) in state-of-the-art SNN algorithms. Each neuron in an SNN stores the membrane potential over time and typically updates its value in every time step. Such frequent read/write operations of high-precision membrane potential incur storage and memory access overhead in SNNs, which undermines the SNNs' compatibility with resource-constrained hardware. To resolve this inefficiency, prior works have explored the time step reduction and low-precision representation of membrane potential at a limited scale and reported significant accuracy drops. Furthermore, while recent advances in on-device AI present pruning and quantization optimization with different architectures and datasets, simultaneous pruning with quantization is highly under-explored in SNNs. In this work, we present SpQuant-SNN, a fully-quantized spiking neural network with ultra-low precision weights, membrane potential, and high spatial-channel sparsity, enabling the end-to-end low precision with significantly reduced operations on SNN. First, we propose an integer-only quantization scheme for the membrane potential with a stacked surrogate gradient function, a simple-yet-effective method that enables the smooth learning process of quantized SNN training. Second, we implement spatial-channel pruning with membrane potential prior, toward reducing the layer-wise computational complexity, and floating-point operations (FLOPs) in SNNs. Finally, to further improve the accuracy of low-precision and sparse SNN, we propose a self-adaptive learnable potential threshold for SNN training. Equipped with high biological adaptiveness, minimal computations, and memory utilization, SpQuant-SNN achieves state-of-the-art performance across multiple SNN models for both event-based and static image datasets, including both image classification and object detection tasks. The proposed SpQuant-SNN achieved up to 13× memory reduction and >4.7× FLOPs reduction with < 1.8% accuracy degradation for both classification and object detection tasks, compared to the SOTA baseline.

Abstract Diabetic retinopathy (DR) is the most frequent microvascular complication of diabetes mellitus, however, its underlying biological mechanisms remain poorly understood. We examined single nucleotide polymorphisms linked to 486 blood metabolites through extensive genome-wide association studies conducted on individuals of European ancestry. The FinnGen Biobank database served as a reference to define DR. Two-sample MR analysis was conducted to reveal the association between the levels of genetically predicted circulating metabolites and the susceptibility to DR. To validate the robustness of the obtained findings, sensitivity analyses with weighted median, weighted mode, and MR-Egger were conducted. 1-oleoylglycerophosphoethanolamine (odds ratio [OR] (OR per one standard deviation [SD] increase) = 0.414; 95% confidence interval [CI] 0.292–0.587; P = 7.613E−07, PFDR = 6.849E−06), pyroglutamine (OR per one SD increase = 0.414; 95% confidence interval [CI] 0.292–0.587; P = 8.31E−04, PFDR = 0.007), phenyllactate (PLA) (OR per one SD increase = 0.591; 95% confidence interval [CI] 0.418–0.836; P = 0.003, PFDR = 0.026), metoprolol acid metabolite (OR per one SD increase = 0.978; 95% confidence interval [CI] 0.962–0.993; P = 0.005, PFDR = 0.042), 10-undecenoate (OR per one SD increase = 0.788; 95% confidence interval [CI] 0.667–0.932; P = 0.005, PFDR = 0.049), erythritol (OR per one SD increase = 0.691; 95% confidence interval [CI] 0.513–0.932; P = 0.015, PFDR = 0.034), 1-stearoylglycerophosphoethanolamine (OR per one SD increase = 0.636; 95% confidence interval [CI] 0.431–0.937; P = 0.022, PFDR = 0.099), 1-arachidonoylglycerophosphoethanolamine (OR per one SD increase = 0.636; 95% confidence interval [CI] 0.431–0.937; P = 0.030, PFDR = 0.099) showed a significant causal relationship with DR and could have protective effects. stachydrine (OR per one SD increase = 1.146; 95% confidence interval [CI] 1.066–1.233; P = 2.270E−04, PFDR = 0.002), butyrylcarnitine (OR per one SD increase = 1.117; 95% confidence interval [CI] 1.023–1.219; P = 0.014, PFDR = 0.062), 5-oxoproline (OR per one SD increase = 1.569; 95% confidence interval [CI] 1.056–2.335; P = 0.026, PFDR = 0.082), and kynurenine (OR = 1.623; 95% CI 1.042–2.526; P = 0.041, PFDR = 0.097) were significantly associated with an increased risk of DR. This study identified metabolites have the potential to be considered prospective compounds for investigating the underlying mechanisms of DR and for selecting appropriate drug targets.

To study the effects of dazomet, which is a soil fumigant and microbial inoculant (Trichoderma harzianum) on the bacterial and fungal diversity of continuously cropped strawberry soil, this work aimed to provide a theoretical basis for the treatment of continuously cropped strawberry. The soil of a strawberry greenhouse with continuous cropping for 10 years was used as the research object, and rhizosphere soil samples from strawberry continuous cropping were collected before dazomet fumigation (M0), after dazomet fumigation (M1), after dazomet fumigation in the fruit early phase without the addition of T. harzianum (H0), and after the addition of T. harzianum (H1). The diversity of soil bacteria and fungi was detected via the Illumina HiSeq high-throughput sequencing platform. The results revealed that the richness and diversity of the soil bacterial and fungal communities decreased after dazomet fumigation and that the addition of T. harzianum after dazomet fumigation increased both the richness of the soil bacterial communities and the diversity of the fungal communities. At the genus level, the composition ratios of the soil bacterial and fungal communities in the different treatments also substantially differed. The bacterial community compositions of H0 and H1 were the most similar, while the fungal community compositions of M0 and H0 were the most similar. The analysis of beneficial and harmful dominant genera in the soil revealed that dazomet fumigation could kill pathogenic fungi such as Ilyonectria and Fusarium in the soil and reduce beneficial bacteria and fungi such as Streptomyces, Flavobacterium, Mortierella, and Talaromyces. The addition of T. harzianum to dazomet fumigation can increase the abundance of beneficial bacteria and fungi such as Bacillus, Flavobacterium, and Cladorrhinum in the soil as well as reduce the abundance of pathogenic fungi such as Monilinia, Ilyonectria, and Fusarium. In summary, the use of dazomet fumigation combined with microbial inoculation changed the microbial structure of continuously cropped soil, increased the abundance of beneficial bacteria and fungi, and reduced the abundance of the vast majority of pathogenic fungi in the soil. Therefore, dazomet fumigation combined with microbial inoculation is an effective method for overcoming obstacles to continuous cropping of the strawberry.

Background: Pelvic organ prolapse (POP) is a common condition worldwide, predominantly affecting middle-aged and elderly postmenopausal women. However, its pathogenesis, etiology, and associated risk factors remain unclear. This study aimed to analyze the distribution of POP severity stages, identify associated risk factors, and explore its underlying pathogenesis to develop strategies for early prevention and intervention. Methods: This retrospective study included all patients diagnosed with POP using the pelvic organ prolapse quantification (POP-Q) system at the outpatient clinic of West China Second Hospital, Sichuan University, between January 2015 and January 2019. A univariate Chi-square test and multivariate logistic regression analysis were performed to evaluate the relationships between the identified factors. Results: Among 9569 patients with anterior vaginal wall prolapse, the severity was distributed as follows: grade I (38.52%), grade II (60.70%), grade III (0.77%), and grade IV (0.01%). Among the 9495 patients with posterior vaginal wall prolapse, the severity was distributed as follows: grade I (90.37%), grade II (9.47%), and grade III (0.16%). Among the 932 patients with uterine prolapse, the severity was distributed as follows: grade I (85.84%), grade II (5.36%), grade III (7.62%), and grade IV (1.18%). Multivariate logistic regression analysis identified several significant risk factors associated with the progression of anterior vaginal wall prolapse, including advanced maternal age (AMA) (≥35 years), body mass index (BMI) (≥25 kg/m2), parity (≥2), and vaginal delivery (p < 0.05). For posterior vaginal wall prolapse, significant risk factors included AMA (≥35 years), BMI (≥25 kg/m2), manual labor, and vaginal delivery (p < 0.001). Additionally, AMA (≥35 years) was identified as a significant risk factor for the progression of uterine prolapse (p < 0.05). Conclusions: Grade II prolapse was most commonly observed in the anterior vaginal wall, whereas grade I prolapse predominantly occurred in the posterior vaginal wall. Key risk factors for POP include childbearing age, parity, BMI, and mode of delivery, with AMA identified as independent risk factors. Vaginal delivery specifically increases the likelihood of vaginal prolapse, while occupations involving prolonged physical labor correlate with a higher incidence of posterior vaginal wall prolapse. Based on the identified risk factors, targeted prevention and intervention measures are recommended to facilitate early identification and reduce the incidence of POP.

Abstract To evaluate the safety and efficacy of low-intensity focused ultrasound (LIFU) therapy in facilitating fundus descent and relieving postpartum breast pain compared with sham treatment. A multicentre, randomised, sham-controlled, blinded trial was conducted. A cohort of 176 eligible participants, who had normal prenatal check-ups and met the inclusion and exclusion criteria, were recruited from three medical centres and subsequently randomized into either the LIFU or sham group. All participants received three treatment sessions, wherein LIFU signal was applied to the uterus and breast sites using coupling gel, with the absence of ultrasound signal output in the sham group. Fundal height measurement and breast pain score were performed after each treatment. The primary outcome, uterine involution, was presented by measuring the fundal height of the uterus. The visual analogue scale (VAS) score, as a secondary outcome, was used to assess breast pain and determine the correlation between breast pain and fundal height as the outcome simultaneously. All participants were randomly assigned to either the LIFU group (n = 88) or sham group (n = 88), with seven individuals not completing the treatment. Overall, a statistically significant difference was noted in the rate and index of fundus descent after each treatment. The rate and index of fundus descent showed greater significance following the second treatment (rate: 1.5 (1.0, 2.0) cm/d; index: 0.15 (0.1, 0.18), P

Abstract Background Fragile X syndrome (FXS) is a leading cause of autism spectrum disorder (ASD) and resulted from a loss of the FMR1-encoded fragile X messenger ribonucleoprotein 1 (FMRP) protein due to large CGG repeat expansions in the promoter region of the FMR1 gene. The microtubule-associated protein Tau is a promising target for Tauopathic diseases and our preliminary study found that Tau protein levels were increased in the brain of Fmr1 knockout (KO) mice, a model of FXS. However, whether Tau reduction can prevent autism-like features in Fmr1 KO mice and become a novel strategy for FXS treatment remain unknown. Methods Tau was genetically reduced in Fmr1 KO mice through crossing Fmr1 ± female mice with Mapt ± male mice. The male offspring with different genotypes were subjected to various autism-related behavioral tests, RNA sequencing, and biochemical analysis. Fmr1 KO male mice were treated with Tau-targeting antisense oligonucleotide (ASO) and then subjected to behavioral tests and biochemical analysis. Results Tau expression was increased in the cortex of Fmr1 KO mice. Genetically reducing Tau prevented social defects, stereotyped and repetitive behavior, and spine abnormality in Fmr1 KO mice. Tau reduction also reversed increased periodic activity and partially rescued Per1 expression reduction in Fmr1 KO mice. Moreover, Tau reduction reversed compromised P38/MAPK signaling in Fmr1 KO mice. Finally, Tau-targeting ASO also effectively alleviated autism-like phenotypes and promoted P38/MAPK signaling in Fmr1 KO mice. Limitations Our study is limited to male mice, in agreement with the higher incidence of FXS in males than females. Whether Tau reduction also exerts protection in females deserves further scrutiny. Moreover, although Tau reduction rescues impaired P38/MAPK signaling in Fmr1 KO mice, whether this is the responsible molecular mechanism requires further determination. Conclusion Our data indicate that Tau reduction prevents autism-like phenotypes in Fmr1 KO mice. Tau may become a new target for FXS treatment.

In the context of global climate change, the frequency of sudden natural disasters is increasing. Assessing traffic road damage post-disaster is crucial for emergency decision-making and disaster management. Traditional ground observation methods for evaluating traffic road damage are limited by the timeliness and coverage of data updates. Relying solely on these methods does not adequately support rapid assessment and emergency management during extreme natural disasters. Social media, a major source of big data, can effectively address these limitations by providing more timely and comprehensive disaster information. Motivated by this, we utilized multi-source heterogeneous data to assess the damage to traffic roads under extreme conditions and established a new framework for evaluating traffic roads in cities prone to flood disasters caused by rainstorms. The approach involves several steps: First, the surface area affected by precipitation is extracted using a threshold method constrained by confidence intervals derived from microwave remote sensing images. Second, disaster information is collected from the Sina Weibo platform, where social media information is screened and cleaned. A quantification table for road traffic loss assessment was defined, and a social media disaster information classification model combining text convolutional neural networks and attention mechanisms (TextCNN-Attention disaster information classification) was proposed. Finally, traffic road information on social media is matched with basic geographic data, the classification of traffic road disaster risk levels is visualized, and the assessment of traffic road disaster levels is completed based on multi-source heterogeneous data. Using the “7.20” rainstorm event in Henan Province as an example, this research categorizes the disaster’s impact on traffic roads into five levels—particularly severe, severe, moderate, mild, and minimal—as derived from remote sensing image monitoring and social media information analysis. The evaluation framework for flood disaster traffic roads based on multi-source heterogeneous data provides important data support and methodological support for enhancing disaster management capabilities and systems.

Background: Vascular smooth muscle cell (VSMC) intimal migration, proliferation, and phenotypic transformation from a contractile to a synthetic state are hallmarks of the progression of atherosclerotic plaques. This study aims to explore the effects of exosomes derived from M2 macrophages (ExoM2) on the pathological changes of VSMCs in atherosclerosis (AS). Methods: Cell Counting Kit-8 (CCK8) and wound healing assays were used to examine the impact of ExoM2 on platelet-derived growth factor-BB (PDGF-BB)-induced VSMC proliferation and migration, respectively. Western blotting was employed to analyze changes in the expression levels of contractile markers (e.g., alpha-smooth muscle actin [α-SMA]) and synthetic ones (e.g., osteopontin [OPN]) in VSMCs with or without ExoM2 treatment. ApoE-⁣/- mice on a high fat diet were utilized to observe the effects of ExoM2 on plaque progression and stability. Serial histopathological analysis was performed to elucidate the cellular mechanisms underlying the atheroprotective effects of ExoM2. Results: Compared with controls, ExoM2 significantly inhibited PDGF-BB-induced VSMC proliferation, migration, and phenotypic transformation in vitro. In ApoE-⁣/- mice, ExoM2 treatment led to a marked reduction in plaque size, necrotic core area, the CD68/α-SMA ratio, and matrix metalloproteinase 9 (MMP9) and OPN levels, while enhancing plaque stability. Conclusions: ExoM2 inhibit AS progression by regulating VSMC proliferation, migration, and phenotypic transformation.

Instantaneous reactions of Al, Mn, Zn, Zr and Y with Ni by mixing the prepared Mg-8Al-0.4Mn, Mg-6Zn-2Y-0.5Zr and Mg-0.6Ni melts were investigated in this work to reveal the underlying mechanisms of their effects on the removal of Ni impurity. The results indicate three Ni-containing intermetallics, namely Al4NiY, Al4Ni(Y,Zr) and Al31Ni2Mn6. The former two phases present lath-like and have a relatively larger size (> 20 µm in length) than the latest one which is granular with the diameter of ∼120 nm. This illustrates that Al and Y(/Zr) can efficiently remove Ni by forming Al4NiY or Al4Ni(Y,Zr) which would precipitate to the bottom of the melt. Furthermore, adding Y into Mg-Al based alloys can simultaneously remove Fe and Ni, which contributes their excellent corrosion resistance. Finally, this paper proposes two methods helped to efficiently remove Ni for both Mg-Al based alloys and Al-free Mg alloys, and both of them are also benefit to improve alloys’ strength.

Abstract Background This study aimed to investigate the effects of different ferrule heights and crown-to-root ratios on the fracture resistance of endodontically-treated premolars restored with fiber post or cast metal post system. Methods Eighty extracted human mandibular first premolars with single root canal were treated endodontically and cut from 2.0 mm above the buccal cemento-enamel junction, to create horizontal residual roots. The roots were randomly divided into two groups. The roots in group FP were restored with a fiber post-and-core system, while the roots in group MP were restored with a cast metal post-and-core system. Each group was divided into five subgroups with different ferrule heights (0: no ferrule; 1: 1.0 mm ferrule; 2: 2.0 mm ferrule; 3: 3.0 mm ferrule; 4: 4.0 mm ferrule). All specimens were subsequently restored with metal crowns and embedded in acrylic resin blocks. The crown-to-root ratios of the specimens were controlled at approximately 0.6, 0.8, 0.9, 1.1, and 1.3 of the five subgroups, respectively. Fracture strengths and fracture patterns of the specimens were tested and recorded by a universal mechanical machine. Results Mean fracture strengths (mean ± standard deviation (kN)) of FP/0 to FP/4 and MP/0 to MP/4 were: 0.54 ± 0.09, 1.03 ± 0.11, 1.06 ± 0.17, 0.85 ± 0.11; 0.57 ± 0.10, 0.55 ± 0.09, 0.88 ± 0.13, 1.08 ± 0.17, 1.05 ± 0.18 and 0.49 ± 0.09, respectively. Two-way ANOVA revealed significant effects of different ferrule heights and crown-to-root ratios on the fracture resistance (P

BackgroundThere has existed controversy regarding the use of Ginkgo biloba (GKB) for blood metabolism among type 2 diabetes mellitus(T2DM) patients, and we tried to analyze the effects and safety of GKB on T2DM patients.MethodsWe conducted a literature search between January 2003 and December 2022 of seven online databases (PubMed, Scopus, Embase, Google Scholar, Web of Sciences, Cochrane Library, and China National Knowledge Infrastructure). A systematic literature review and meta-analysis were performed to compare the effects and safety of GKB among T2DM patients. Four groups of parameters were extracted and analyzed: hemorheology parameters, lipid profile, glycemic control markers, and adverse events.ResultsIn the end, 13 eligible articles with 11 indicators among 1573 patients were included. In the hemorheology parameters section, GKB showed significantly lower plasma viscosity (PV) (SMD=-0.91, 95%CI [-1.45, -0.36], P

BackgroundShort-term poor uterine involution manifests as uterine contraction weakness. This is one of the important causes of postpartum hemorrhage, posing a serious threat to the mother's life and safety. The study aims to investigate whether low-intensity focused ultrasound (LIFUS) can effectively shorten lochia duration, alleviate postpartum complications, and accelerate uterine involution compared with the sham treatment.MethodsA multicenter, concealed, randomized, blinded, and sham-controlled clinical trial was conducted across three medical centers involving 176 subjects, utilizing a parallel group design. Enrollment occurred between October 2019 and September 2020, with a 42-day follow-up period. Participants meeting the inclusion and exclusion criteria based on normal prenatal examinations were randomly divided into the LIFUS group or the sham operation group via computer-generated randomization. Patients in the LIFUS group received usual care with the LIFUS protocol, wherein a LIFUS signal was transmitted to the uterine site through coupling gel, or sham treatment, where no low-intensity ultrasound signal output was emitted. The primary outcome, lochia duration, was assessed via weekly telephonic follow-ups post-discharge. The involution of the uterus, measured by uterine fundus height, served as the secondary outcome.ResultsAmong the 256 subjects screened for eligibility, 176 subjects were enrolled and randomly assigned to either the LIFUS group (n = 88) or the Sham group (n = 88). Data on the height of the uterine fundus were obtained from all the patients, with 696 out of 704 measurements (99%) successfully recorded. Overall, a statistically significant difference was noted in time to lochia termination (hazard ratio: 2.65; 95% confidence interval [CI]: 1.82-3.85; P < 0.001). The decline in fundal height exhibited notable discrepancies between the two groups following the second treatment session (mean difference: -1.74; 95% CI: -1.23 to -2.25; P < 0.001) and the third treatment session (mean difference: -3.26; 95% CI: -2.74 to -3.78; P < 0.001) after delivery. None of the subjects had any adverse reactions, such as skin damage or allergies during the treatment.ConclusionsThis study found that LIFUS treatment can promote uterine involution and abbreviate the duration of postpartum lochia. Ultrasound emerges as a safe and effective intervention, poised to address further clinical inquiries in the domain of postpartum rehabilitation.

CoS2 can meet the strict requirements of high probability output capacity and high energy output capacity of thermal batteries in modern weaponry thanks to its advantages of low resistivity and high thermal decomposition temperature combined with a full Li+ conductive electrolyte. Nevertheless, CoS2 has the limitations of a low voltage platform and theorical capacity. In this case, Fe and Ni are doped into the CoS2 lattice through low-temperature solid-phase sintering to synthesize Fe0.1Co0.8Ni0.1S2 with a single-phase structure. Fe0.1Co0.8Ni0.1S2 generated by the solid phase method has higher thermal stability, which can reduce the high temperature thermal shock at the immediate start of the thermal battery and assure the safety of the thermal battery in operation. Meanwhile, the mass loss of Fe0.1Co0.8Ni0.1S2 at 615 °C is only 5 %, allowing it to discharge at the maximum effective mass at the normal operating temperature(∼500 °C). Because of the synergistic action of Fe2+, Ni2+, and Co2+ in the discharge process, the discharge voltage of CoS2 increases significantly, giving CoS2 higher specific energy. The simultaneous boost in specific energy and specific capacity indicates that doping has been highly successful in modifying CoS2, making CoS2 more appropriate for the use of high current and long-life thermal cell systems.

Natural gas pipeline projects in mountainous areas are inevitably affected by geological hazards such as landslides, which pose a serious threat to the safe operation of pipelines along the routes through landslide areas. Based on the engineering background of China-Guizhou natural gas pipeline K558 + 700 landslide, this paper studies and compares the supporting mechanism and applicability of two different support structures, namely, flower-tube micro-pile and threaded micro-pile, in pipeline landslide through indoor large-scale physical model tests. The results show that: (1) The distribution pattern of peak soil pressure along the mountain side and river side of flower tube micro-piles is basically similar along the pile depth, which is in the shape of "S" curve. The soil arching effect behind the pile is obvious, and the distribution pattern of soil pressure is generally consistent at all levels of load. In general, the distribution pattern of soil pressure on the side of the flower-pipe pile is the largest among piles, followed by the pile top, and the bottom of the pile. The soil pressure around the pile near the sliding zone is larger, so the optimization should be considered in the design of anti-slide pile. (2) The distribution diagram of the peak earth pressure along the pile depth of the threaded pile presents a double "S" curve. The distribution pattern of the peak earth pressure on the river side is significantly different from that of the mountain side, and the earth pressure at the bottom of the pile decreases greatly compared with that of the mountain side. With the increase of external load, the soil pressure around the pile increases greatly, indicating that the screw micro pile is deficient in lateral bearing capacity. (3) The bending moment of flowered pipe pile presents an "M" shape distribution along the depth direction, and the maximum positive bending moment occurs at the position 5 cm above the simulated slip surface. The pile body bending moment distribution along the depth direction is "S" shape, and the pile body positive and negative bending moment position near the simulated sliding surface roughly rotate symmetrical distribution, most of the region above the sliding surface is negative bending moment, the pile body below the sliding surface is positive bending moment. Under the same thrust load, the deformation degree of the screw micro pile is greater than that of the flower tube micro pile. (4) The load-bearing performance of the splined pipe pile is better than that of the threaded pile under thrust load, which effectively reduces the landslide thrust transferred to the pipeline; Under the large thrust load, the threaded pile can not effectively bear and offset the landslide thrust due to its insufficient flexural performance and serious deformation, and the stress transmitted to the pipe in front of the pile is large, causing more intense deformation of the pipe. Under the condition of this test, the flowered pipe micro-pile has outstanding protection benefit to the pipeline, and is more suitable for the retaining structure of the landslide area of the pipeline.

Abstract. Background:. Primary cardiac lipoma is very rare, and no consensus has been developed regarding its ideal treatment strategy. This study reviewed the surgical treatment of cardiac lipomas in 20 patients over 20 years. Methods:. Twenty patients with cardiac lipomas were treated at Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2002, to January 1, 2022. The patients’ clinical data and pathological reports were retrospectively analyzed, and the follow-up with a range of 1 year to 20 years was conducted. Results:. The cardiac lipomas were located in the right atrium (RA) or superior vena cava (SVC) in seven patients (35%) (RA in six patients and SVC in one patient), left ventricle in eight patients (40%) (left ventricular chamber in four patients and left ventricular subepicardium and myocardium in four patients), right ventricle in three patients (15%) (right ventricular chamber in one patient and right ventricular subepicardial layer and myocardium in two patients), subepicardial interventricular groove in one patient (5%), and pericardium in one patient (5%). Complete resection was achieved in 14 patients (70%), including seven patients with lipomas in the RA or SVC. Incomplete resection occurred in six patients (30%) with lipomas in the ventricles. No perioperative deaths occurred. Long-term follow-up was conducted for 19 patients (95%), including two (10%) who died. Both patients who died had lipomas incompletely resected due to ventricles involvement, and preoperative malignant arrhythmias persisted post-operatively. Conclusions:. The complete resection rate was high, and the long-term prognosis was satisfactory in patients with cardiac lipomas that did not involve the ventricle. The complete resection rate was low in patients with cardiac lipomas in ventricles; and complications, including malignant arrhythmia, were common. Failure of complete resection and post-operative ventricular arrhythmia are correlated with post-operative mortality.

This paper is concerned with the robust finite-time stability and stabilization of impulsive systems subject to hybrid disturbances that consists of external disturbances and hybrid impulses with time-varying jump maps. First, the global finite-time stability and local finite-time stability of a scalar impulsive system are ensured by the analysis of cumulative effect of hybrid impulses. Then, asymptotic stabilization and finite-time stabilization of second-order system subject to hybrid disturbances are achieved by linear sliding-mode control and non-singular terminal sliding-mode control. It shows that the stable systems under control are robust to external disturbances and hybrid impulses with non-destabilizing cumulative effect. If the hybrid impulses have destabilizing cumulative effect, the systems are also capable of absorbing the hybrid impulsive disturbances by the designed sliding-mode control strategies. Finally, the effectiveness of theoretical results is verified by numerical simulation and the tracking control of linear motor.

Fragile X syndrome (FXS) is caused by the loss of the fragile X messenger ribonucleoprotein 1 (FMRP) encoded by the FMR1 gene. Gene therapy using adeno-associated virus (AAV) to restore FMRP expression is a promising therapeutic strategy. However, so far AAV gene therapy tests for FXS only utilized rodent FMRPs driven by promoters other than the human FMR1 promoter. Restoration of human FMRP in appropriate cell types and at physiological levels, preferably driven by the human FMR1 promoter, would be more suitable for its clinical use. Herein, we generated two human FMR1 promoter subdomains that effectively drive gene expression. When AAVs expressing two different human FMRP isoforms under the control of a human FMR1 promoter subdomain were administered into bilateral ventricles of neonatal Fmr1–/y and wild-type (WT) mice, both human FMRP isoforms were expressed throughout the brain in a pattern reminiscent to that of mouse FMRP. Importantly, human FMRP expression attenuated social behavior deficits and stereotyped and repetitive behavior, and reversed dysmorphological dendritic spines in Fmr1–/y mice, without affecting WT mouse behaviors. Our results demonstrate that human FMR1 promoter can effectively drive human FMRP expression in the brain to attenuate Fmr1–/y mouse deficits, strengthening the notion of using AAV gene therapy for FXS treatment.

A comprehensive analysis and simulation of two memristor-based neuromorphic architectures for nuclear radiation detection is presented. Both scalable architectures retrofit a locally competitive algorithm to solve overcomplete sparse approximation problems by harnessing memristor crossbar execution of vector–matrix multiplications. The proposed systems demonstrate excellent accuracy and throughput while consuming minimal energy for radionuclide detection. To ensure that the simulation results of our proposed hardware are realistic, the memristor parameters are chosen from our own fabricated memristor devices. Based on these results, we conclude that memristor-based computing is the preeminent technology for a radiation detection platform.

The MgZn1.2Zr0.35 (wt%) alloys for orthopedic applications enhanced by small amount addition of zirconium and subsequent hot extrusion working based on cast MgZn1.2 system were successfully fabricated. As 0.35% zirconium (Zr) added, the mean grain sizes of as-cast MgZn1.2 alloys were found to decrease from 107 μm to 72 μm attributed to the Zr element dissolved into alloys and undissolved Zr contents providing nucleation sites which could effectively inhibit grain growth. The using of hot extrusion further significantly refined grain structure to 10 μm because there were dynamic recrystallization (DRX) behaviors. Simultaneously broken second phases particles play a role in inhibiting recrystallized grains’ growth. The yield strength (YS), ultimate tensile strength (UTS) and bending strength (BS) remarkably increase from 30 MPa to 194 MPa, 130 MPa–238 MPa and 275 MPa–496 MPa respectively without sacrificing elongation at a high level of 19%. Furthermore, MgZn1.2Zr0.35 system after hot extrusion exhibits the least degradation current density of 7.529 × 10−5 A in simulated body fluid (SBF) reduced an order of magnitude compared with 9.863 × 10−4 A of cast MgZn1.2 alloys result from that adding zirconium combined with hot extrusion effectively enhances degradation resistance attributed to the increase consistency of protective film on magnesium by means of grain refinement.

The effect of Gd content on the microstructure and tensile properties of as-cast Mg-Sm-Zn-Zr alloy has been systematically investigated. In the Mg-3Sm-0.5Zn-0.5Zr alloy, the intermetallic compounds with multiple morphologies are identified as Mg3Sm phase. In addition to Mg3RE phase, Mg5RE phase originated from Gd addition is observed in Gd-modified alloys. It should be noted that the lattice parameters of all the observed intermetallic compounds are significantly reduced by Zn segregation. The segregation behavior of Zn in Mg3Sm phase is inhibited to some extent by Gd addition due to the electronegativity difference between Sm/Gd and Zn elements. In addition, the increased Gd content effectively leads to much more accumulation of solute atoms in front of the liquid-solid interface during solidification, which can prominently promote nucleation in liquid region and then refine grains. The tensile yield stress of the present alloys is thus improved with increasing Gd addition. Finally, Gd-modified alloys exhibit significantly age-hardening effect, which can be mainly attributed to the high-volume fraction and high density nano-scale precipitates.

Since groundwater is one of the main factors that affect the stability of highway slopes in mountainous regions, a smooth drainage is of importance for the safety of cut slopes. After years of service, the cut slopes of highway are often characterized with drainage problems or even drainage failures that threaten the stability and safety. In this paper, the clogging mechanism of drainage holes in highway cut slopes is firstly clarified through on-site survey. The soil and blockage samples are collected from typical slopes for laboratory tests and analysis, and the results reveal that all the blockages are made of fine-grained particles from the slopes. Scanning electron microscope (SEM) images indicate that the blockages penetrate the drainage pipe wrappings to form the clogging. The combined effect of clayey soil, chemicals, and biological clogging exacerbate the clogging process around the drainage pipes. Laboratory tests are also performed to simulate the CaCO3 crystal clogging around the drainage holes, and the microstructure of the clogged geotechnical screens and geotextiles is observed by scanning electron microscope as well. The results confirm that the amount of CaCO3 crystal attached to the drainage pipe surface increases with the time. The single-layer structure of screens does not facilitate the three-dimensional clogging as in the case of geotextiles. After soaking in diluted hydrochloric acid at a pH of 5.0, there is no significant decrease of CaCO3 crystals attached on the screens and geotextiles. However, the CaCO3 decrease is apparent after soaking in the hydrochloric acid at a pH of 3.0. The clogging of drainage holes can be classified into two stages according to the laboratory tests and acid soaking, and the relationship and characteristics between the two stages are summarized.

Abstract The vital role of insulin resistance (IR) in the pathogenesis of isolated systolic hypertension (ISH) has been expounded at the theoretical level. However, research on the correlation between some specific IR indicators and ISH is still rare, especially at different glycemic statuses. We conducted this study to explore the association between three IR indicators and ISH among young and middle-aged adults with normal fasting plasma glucose (NFG). This large cross-sectional study included 8246 young and middle-aged men with NFG and diastolic blood pressure

Abstract Background The status of vaginal microbiota in persistent high-risk human papilloma virus (HR-HPV) infection is unclear. The present work aimed to identify the vaginal microbiota of persistent HPV infection and explore the possible underlying microbiota factors. Methods A total of 100 women were recruited in this study, of which 28 presented HR-HPV persistent infection (P group), 30 showed clearance of any subtype of HR-HPV (C group), and 42 had no history of any HR-HPV infection (NC group). The vaginal microbiota and the community structure of the three groups were compared based on the 16S rRNA sequencing of the V3–V4 region. The microbiota diversity and differential analysis were carried out to detect the potential factors associated with HR-HPV infection. Results P and C groups showed an increase of Firmicutes and Actinobacteriota but a decrease in Proteobacteria compared to the NC group. The Chao1 index indicated that the microbial richness of the NC group was greater than C group (P

Components and crystal structures of the intermetallic phases in a gravity die-cast Mg−6.0Zn−1.5Nd−0.5Zr (wt%) alloy were investigated using transmission electron microscopy. The results indicate that this alloy has multiple intermetallic phases and various inner faults. Totally, six eutectoid intermetallic phases, namely W (MgNdZn3), T (Mg39Zn55Nd6), (Mg,Zr)Zn2, Z (Mg28Zn65Nd7), H2 (Mg15Zn70Nd15), and H1 (Mg24Zn64Nd11), were simultaneously observed at grain boundaries, and six precipitates (Z, Mg7Zn3, T, Mg4Zn7, β1′-MgZn2 and β2′-MgZn2) were found in α-Mg grains. Furthermore, faults like sub-grain boundaries, orientation domains (coherent with the same matching plane but with different orientations), stacking faults and twins were observed in the eutectoid intermetallic phases. Finally, some new orientation relationships between the known intermetallic phases were revealed. This paper can provide new insight into alloy design for Mg−Zn−RE (RE: rare earth) based alloys.

Recently, ReRAM crossbar-based deep neural network (DNN) accelerator has been widely investigated. However, most prior works focus on single-task inference due to the high energy consumption of weight reprogramming and ReRAM cells’ low endurance issue. Adapting the ReRAM crossbar-based DNN accelerator for multiple tasks has not been fully explored. In this study, we propose XMA2, a novel crossbar-aware learning method with a 2-tier masking technique to efficiently adapt a DNN backbone model deployed in the ReRAM crossbar for new task learning. During the XMA2-based multi-task adaption (MTA), the tier-1 ReRAM crossbar-based processing-element- (PE-) wise mask is first learned to identify the most critical PEs to be reprogrammed for essential new features of the new task. Subsequently, the tier-2 crossbar column-wise mask is applied within the rest of the weight-frozen PEs to learn a hardware-friendly and column-wise scaling factor for new task learning without modifying the weight values. With such crossbar-aware design innovations, we could implement the required masking operation in an existing crossbar-based convolution engine with minimal hardware/memory overhead to adapt to a new task. The extensive experimental results show that compared with other state-of-the-art multiple-task adaption methods, XMA2 achieves the highest accuracy on all popular multi-task learning datasets.

Nowadays, massive photovoltaic power stations are being integrated into grid networks. However, a large number of photovoltaic facilities are located in special areas, which presents difficulties in management. Unmanned Aerial Vehicle (UAV)-assisted data collection will be a prospective solution for photovoltaic systems. In this paper, based on Deep Reinforcement Learning (DRL), we propose a UAV-assisted scheme, which could be used in scenarios without awareness of sensor nodes’ (SNs) precise locations and has better universality. The optimized data collection work was formulated as a Markov Decision Process (MDP), and the approximate optimal policy was found by Deep Q-Learning (DQN). The simulation results show efficiency and convergence and demonstrate the effectiveness of the proposed scheme compared with other benchmarks.

As an important component of new energy vehicles, the safety of lithium-ion batteries has attracted extensive attention. To reveal the mechanism and characteristics of ternary lithium-ion batteries under different trigger modes, an experimental system was established. The effects of different trigger modes on battery surface temperature, battery internal temperature, injection time, and battery voltage were analyzed. Among them, acupuncture, overheating, and overcharging are used as trigger conditions for mechanical, thermal, and electrical abuse. The results show that the injection time and surface peak temperature are positively correlated with the energy input before thermal runaway. Before the cell triggers abuse, the more input energy, the higher the cell surface temperature, the more serious the thermal runaway, and the higher the damage to the surrounding battery system. Under the same conditions, the intensity and damage degree of overcharge thermal runaway are greater than those of internal short circuit and overtemperature. The abnormal change of voltage suddenly rising and rapidly falling can be used as a condition to judge whether overcharge thermal runaway occurs. Finally, according to the temperature curves at different positions, the thermal diffusion law under different abuse conditions is summarized, which provides a basis for the safety design of the battery module.

As an essential technology for intelligent transportation management and traffic risk prevention and control, vehicle detection plays a significant role in the comprehensive evaluation of the intelligent transportation system. However, limited by the small size of vehicles in satellite remote sensing images and lack of sufficient texture features, its detection performance is far from satisfactory. In view of the unclear edge structure of small objects in the super-resolution (SR) reconstruction process, deep convolutional neural networks are no longer effective in extracting small-scale feature information. Therefore, a vehicle detection network based on remote sensing images (VDNET-RSI) is constructed in this article. The VDNET-RSI contains a two-stage convolutional neural network for vehicle detection. In the first stage, a partial convolution-based padding adopts the improved Local Implicit Image Function (LIIF) to reconstruct high-resolution remote sensing images. Then, the network associated with the results from the first stage is used in the second stage for vehicle detection. In the second stage, the super-resolution module, detection heads module and convolutional block attention module adopt the increased object detection framework to improve the performance of small object detection in large-scale remote sensing images. The publicly available DIOR dataset is selected as the experimental dataset to compare the performance of VDNET-RSI with that of the state-of-the-art models in vehicle detection based on satellite remote sensing images. The experimental results demonstrated that the overall precision of VDNET-RSI reached 62.9%, about 6.3%, 38.6%, 39.8% higher than that of YOLOv5, Faster-RCNN and FCOS, respectively. The conclusions of this paper can provide a theoretical basis and key technical support for the development of intelligent transportation.

Microstructure and tensile properties of a Mg-Sm-Zn-Zr alloy with various extrusion ratios (ERs) of 6.9, 10.4 and 17.6 were systematically investigated. It was identified that, greater ER increased dynamic recrystallization (DRX) fraction and coarsened DRX grains, which further suggests weakened basal fiber texture for the studied alloy. This is mainly due to the rising temperature from massive deformation heat when hot-extrusion. As a result, greater ER corresponds to a decreased strength but improved ductility. Finally, transmission electron microscopy (TEM) observations reveal that the dominant intermetallic phase, Mg3Sm, is metastable, and it will transform into Mg41Sm5 during extrusion with high-ER. This transformation leads to the accumulation of surplus Sm and Zn atoms, which induces the precipitation of SmZn3 phase at the surface of Mg41Sm5 matrix.

Background Hyperthermia has been reported to cause cancer stage regression, thus providing surgical opportunities in patients with unresectable tumors and improving the quality of life of patients by preserving certain organs. Methods A prospective open-label phase II trial was conducted to evaluate the efficacy of hyperthermia combined with induction chemotherapy in patients with locally advanced resectable oral squamous cell carcinoma (OSCC). Patients received hyperthermia combined with two cycles of 5-fluorouracil, cisplatin, and docetaxel (TPF) induction chemotherapy regimens or TPF induction chemotherapy alone, followed by radical surgery with postoperative radiotherapy. The primary endpoint was the clinical response rate of the induction chemotherapy. The secondary endpoints were overall survival (OS), disease-free survival (DFS), and toxicity. Results A total of 120 patients were enrolled, and 115 patients were included in the clinical response analysis. The clinical response rate was significantly higher in the experimental arm than in the control arm (65.45% vs. 40.00%, p = 0.0088). There were no unexpected toxicities, and hyperthermia and induction chemotherapy did not increase the perioperative morbidity rate. Moreover, there was a significant improvement in DFS, but no significant difference in OS between the two arms. In the subgroup analysis, increased OS and DFS rates were associated with patients with favorable clinical response after induction chemotherapy in the total population, experimental arm, and control arm. Conclusions Our study demonstrates that hyperthermia combined with induction chemotherapy is associated with a high response rate and provides a new treatment option for patients with resectable stage III or IVA OSCC.

Objective: Systemic lupus erythematosus (SLE) displays the characteristics of abnormal activity of the immune system, contributing to diverse clinical symptoms. Herein, this study was conducted for discovering novel immune cell-relevant therapeutic targets.Methods: The abundance of diverse immune cells was estimated in PBMCs of SLE and healthy controls from the GSE50772 dataset with CIBERSORT approach. Immune cell-relevant co-expression modules were screened with WGCNA and relevant characteristic genes were determined with LASSO algorithm. Inflammatory chemokines were measured in serum of twenty SLE patients and twenty controls through ELISA. Bone marrow mesenchymal stem cells (BMSCs) were isolated and TK1 expression was measured in BMSCs through RT-qPCR and western blotting. TK1-overexpressed and TK-1-silenced BMSCs of SLE were conducted and apoptosis and cell cycle were measured with flow cytometry. Apoptosis-, cell cycle- and senescence-relevant proteins were tested with western blotting.Results: We determined three co-expression modules strongly linked to immune cells. Five characteristic genes (CXCL1, CXCL2, CXCL8, CXCR1 and TK1) were screened and ROC curves proved the excellent diagnostic performance of this LASSO model. Inflammatory chemokines presented widespread up-regulations in serum of Systemic lupus erythematosus patients, demonstrating the activation of inflammatory response. TK1 expression was remarkably elevated in SLE BMSCs than controls. TK1 overexpression enhanced IL-1β expression, apoptosis, cell cycle arrest, and senescent phenotypes of SLE BMSCs and the opposite results were proved in TK1-silenced SLE BMSCs.Conclusion: Collectively, our findings demonstrate that silencing TK1 alleviates inflammation, growth arrest and senescence in BMSCs of SLE, which highlights TK1 as a promising therapeutic target against SLE.

Flood hazards resulting from short-term severe precipitation have caused serious social and economic losses and have posed extraordinary threats to the safety of lives and property. Vulnerability, which reflects the degree of the adverse impact of flooding on a city, the sensitivity of the environment, and the extent to which rescues are possible during flooding, is one of the significant factors of the disaster risk assessment. Because of this, this paper proposes an Environmental Vulnerability Analysis Model (EVAM), based on comprehensively evaluating multi-source remote sensing data. The EVAM includes a two-stage, short-term flood vulnerability assessment. In the first stage, the flood’s areal extension and land-use classification are extracted, based on the U-NET++ network, using multi-source satellite remote sensing images. The results from the first stage are used in the second stage of vulnerability assessment. In the second stage, combining multi-source data with associated feature extraction results establishes the Exposure–Sensitivity–Adaptive capacity framework. The short-term flood vulnerability index is leveraged through the analytic hierarchy process (AHP) and the entropy method is calculated for an environmental vulnerability evaluation. This novel proposed framework for short-term flood vulnerability evaluation is demonstrated for the Henan Province. The experimental results show that the proportion of vulnerable cities in the Henan Province ranging from high to low is 22.22%, 22.22%, 38.89%, and 16.67%, respectively. The relevant conclusions can provide a scientific basis for regional flood control and risk management as well as corresponding data support for post-disaster reconstruction in disaster regions.

As the use of zinc oxide nanoparticles (ZnO NPs) in everyday products grows, so does concern about health risks. However, no findings on the gastrointestinal toxicity of ZnO NPs have been published. We investigated the possible malignant transformation of ZnO NPs in the mice’s colonic tissues using the APCmin/+ mouse model with a premalignant lesion in intestinal epithelial cells. Higher doses and long-term oral exposure to ZnO NPs were found to mildly promote colonic inflammation in WT mice, while they moderately or strongly exacerbated the severity of chronic inflammation and tumorigenesis in APCmin/+ mice with intestinal adenomatous polyposis. The ZnO NPs-induced inflammation and tumorigenesis in colonic epithelial cells was linked to the activation of CXCR2/NF-κB/STAT3/ERK and AKT pathways. Analysis of the ZnO NPs-exacerbated intestinal adenomatous polyposis in APCmin/+ mice revealed that ZnO NPs could activate the APC-driven Wnt/β-catenin signaling pathway, exacerbating intestinal tumorigenesis. In fact, ZnO NPs have been shown to increase intestinal inflammation and tumorigenesis in APCmin/+ mice by releasing free Zn2+. In WT mice, a low dose of ZnO NPs (26 mg/kg/day) did not cause intestinal inflammation. In conclusion, higher doses and prolonged exposure to ZnO NPs promote the malignant transformation of precancerous epithelial cells.

Background: The vulvar lichen simplex chronicus (VLSC) is a common condition in gynecologic clinics. Though VLSC is not life-threatening, it usually causes pruritus, soreness and dispareunia, which cause general discomfort. The exact etiology of VLSC is unclear. This study was performed to explore the vaginal microbiota of VLSC and to identify the possible microbial factors in attacks. Methods: Ninety women were recruited. 45 patients with VLSC and 45 women without vulvar symptom were identified as lichen simplex chronicus (LSC) and H groups respectively. The vaginal microbiota of the two arms were compared by the V3-V4 region of 16S rRNA sequencing. Results: The LSC group had less alpha diversity than H group (p < 0.05) and the beta diversity of LSC group was also distinct from the H group. Linear discriminant analysis effect size (LEfSE) analysis indicated that genus Sneathia and family Leptotrichiaceae were discriminant taxa in LSC group. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analysis found that microbial genes related to the signal transduction, metabolism of terpenoids and polyketides, transporters, nervous system, energy metabolism and others were different in the LSC and H groups. Conclusions: VLSC was associated with dysbioss of vaginal microbiota profiles compared with healthy control cases.

Phase transformation in structural alloys is of practical significance for their security services. Understanding phase transformation of strengthening intermetallic phases and its influence on mechanical properties is therefore crucial for the alloys’ safe applications and further development. In this work, investigations using an aberration-corrected scanning transmission electron microscopy combined with density functional theory calculations reveal that the strengthening intermetallic phase, η-Al3La, of a die-casting Mg − 3.5Al − 4.2La alloy is metastable, and it will transform to α-Al11La3 via an intermediate phase, ε-Al2.12La0.88, during annealing at 250 °C. For each transformation step, two orientation relationships are obeyed due to different nucleation sites or temperatures, or because of similar interfacial energy. Furthermore, a new planar fault, namely monolayer twin (MT), was observed, and it not only offer the nucleation site for ε-Al2.12La0.88 and the fast diffusion path for Al atoms, but also provide driving force for overcoming the energy barrier of η → ε → α transformation. Finally, both intermediate and product phases will obstruct the η-Al3La phase delivering 〈c + a〉 dislocations, and the level of solute Al atoms in Mg matrix will be clearly lowered during phase transformation, which result in deterioration in plasticity and creep resistance, respectively.

Abstract Background Extranodal marginal zone B‐cell lymphoma of mucosa‐associated lymphoid tissue (MALT lymphoma) in the oromaxillofacial head and neck region is rare, with limited data available. This retrospective study explored the clinical features, stage, treatment, and prognosis of this disease. Methods Overall, 105 patients with MALT lymphomas in the oromaxillofacial head and neck region were included in this retrospective analysis. SPSS 22.0 software package was used for data analysis and a two‐tailed P value of ≤.05 was considered statistically significant. Primary endpoints of the study were the complete response (CR) rate, overall survival (OS), and progression‐free survival (PFS). Results About 52% of the patients had long‐term xerostomia, autoimmune diseases, or chronic parotitis and 81% had diseases involving the large salivary glands. Ann Arbor staging of the patients was as follows: stages I/II, 73 patients and stages III/IV, 32 patients. In the 97 patients followed up, CR rate after initial treatment was 80%. Tumor progression was observed in 12 patients and 14 patients died. There was a significant difference between the rate of CR in localized (87%) and disseminated (67%) lymphoma patients (P = .02). The 5‐ and 10‐year PFS of the localized lymphoma patients were both 91%, whereas those of the disseminated lymphoma patients were 83% and 65%, respectively (P = .03). The 5‐year PFS rates of the chemotherapy and non‐chemotherapy groups in the disseminated lymphoma patients were 85% and 73% (P = .04). Meanwhile, the 5‐year PFS rates of the rituximab and non‐rituximab groups in the disseminated lymphoma patients were 100% and 70% (P = .03). In multivariate analysis, MALT Lymphoma International Prognostic Index (MALT‐IPI) was an independent prognostic factor affecting OS, whereas Ann Arbor staging affected PFS. Conclusions This study suggests that the outcome after initial treatment of MALT lymphomas in the oromaxillofacial head and neck region is satisfactory and that this disease progresses slowly. The CR rate and PFS of localized lymphoma patients are better than those of disseminated lymphoma patients. Systemic treatment (chemotherapy or rituximab) may improve PFS in disseminated disease patients. MALT‐IPI and Ann Arbor staging are independent prognostic factors.

Ductility asymmetry in extruded Mg alloys containing dense thin long-period stacking ordered (LPSO) plates was always ignored although with yield symmetry. Here, an extruded Mg97.3Gd2.1Zn0.6 alloy of

Water plays a vital role in the weathering process of grottoes. Precipitation is a main water source in the grotto hosting mountain rock. In this study, time-lapse electrical resistivity tomography was adopted to track the movement of infiltrated water in a profile in the Yungang Grottoes. Our one-year monitoring data indicated a good resistivity response to rainfall in the shallow unconsolidated soil layers. There were only resistivity decreases in the near surface 5 m across the whole monitoring profile, and resistivity values quickly returned to a neutral state after the rain stopped. Based on the analysis of a typical rainfall event during the rainy season, we found that the infiltrated water cannot continuously move downwards to recharge local groundwater. It moves horizontally to a nearby gully due to the existence of a hydraulic conductive fine sand layer and low permeable mudstone and sandstone base rocks. An artificial infiltration experiment was carried out to further verify the fate of infiltrated water. Based on mass balance analysis, with 10 m3 of infiltrated water, it only saturated dry soil in the top 1.36 m soil layer on average and this was roughly consistent with our field borehole wetting front verifications at 1.2 and 1.3 m. There were limited horizontal expansions from the infiltrated water. Therefore, based on our monitoring data and analysis, infiltrated water was not the main source of the water involved in the weathering process of the Yungang Grottoes.