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It is of great interest to overcome the problem of high-temperature oxidation of press-hardened steels (PHS) in press hardening with a cost-effective Cr alloying strategy. Therefore, since Cr is one of the expensive metals, the effect of Cr (Cr ≤ 3 wt%) content on the oxidation resistance of Cr–Si–Mn alloyed steels was investigated. It was found that Cr–Si–Mn alloyed PHS with a Cr content of about 1.5 wt% or less cannot form a continuous Cr2O3 layer during press hardening. However, when the Cr content reaches around 2.5 wt%, the PHS shows excellent oxidation resistance due to the formation of continuous Cr2O3 and amorphous SiO2 layers, as well as an Mn-rich oxide layer. However, further addition of 0.5 wt% could not significantly improve the oxidation resistance of this PHS. Moreover, the increase in Cr content simultaneously enhances the positive role of Si and Mn in high-temperature oxidation resistance. This work provides new insights into the design of the next generation of PHSs with economical and superior performance.

Abstract Aim Nutritional characteristics and additives in ultra-processed foods (UPF) are directly related to bone health. Physical activity as a modifiable lifestyle intervention also plays a possible role in bone mineral density (BMD), but effect of physical activity on association between UPF and osteoporosis is not fully understood. Herein, this study aims to explore the association of UPF with osteoporosis, and assess the potential mediating effects of some related factors on this pathway. Methods Data of adults were extracted from the National Health and Nutrition Examination Survey (NHANES) database in this cross-sectional study. Associations of unprocessed/minimally processed food (MPF), processed culinary ingredient (PCI), processed foods (PF) and UPF with femur neck BMD, total femur BMD and osteoporosis were investigated using linear regression and weighted univariate and multivariate logistic regression analyses respectively. Subgroup analyses of age, gender, physical activity, poverty income ratio (PIR), hypertension, diabetes mellitus (DM), cardiovascular disease (CVD), and dyslipidemia were performed. The potential mediating and interaction effects of physical activity and related factors on association of UPF with osteoporosis were also assessed. The evaluation indexes were β, odds ratios (ORs) and 95% confidence intervals (CIs). Results Among 10,678 eligible persons, 454 had osteoporosis. After adjusting for covariates, elevated UPF intake was associated with decreased demur neck and total femur BMD (β=-0.003). A higher UPF intake level (> 57.51%) was linked to higher odds of osteoporosis (OR = 1.789). These relationships were also significant in different subgroups. Physical activity had a potential mediating effect on the association between UPF and osteoporosis (OR = 0.47, mediating proportion = 21.54%). Conclusion UPF intake levels were associated with BMD and osteoporosis. Physical activity had an interaction effect with UPF, and had a potential mediating effect on relationship between UPF and osteoporosis.

Abstract Copy number variation (CNV) tends to occur in genetically enriched regions and is likely associated with a number of complex diseases such as skin aging. In this study, we investigated the genome-wide CNVs in 20 wrinkled skin cases (WSC) of Xiang pigs and 63 controls, and identified 7893 copy number variable regions (CNVRs). We estimated the F-statistic (Fst) at each locus and identified that 93 case-controls stratified CNVRs (Fst > = 0.15) overlapped with 87 known genes. Functional enrichment analysis showed that most of these genes were predominantly enriched in pathways and terms related to the extracellular matrix. Finally, we found that some CNVs were predicted to have high effects on genes such as VCAN, TIMP1 and FOXO1 through transcriptional amplification, transcript ablation and so on. Most of the genes overlapped with those CNVRs have been reported to be related to aging in human or animals. The copy numbers presented the positive correlations with the transcript level of the genes in skins between the cases and controls. Our results suggested that those 22 CNVRs, including 19 CNV losses and 3 CNV gains, were putatively associated with the skin wrinkle of Xiang pigs.

Abstract Background Populus spp. is a crucial fast-growing and productive tree species extensively cultivated in the mid-latitude plains of the world. However, the impact of intensive cultivation management on gene expression in plantation remains largely unexplored. Results Precision water and fertilizer-intensive management substantially increased key enzyme activities of nitrogen transport, assimilation, and photosynthesis (1.12–2.63 times than CK) in Populus × euramericana 'Neva' plantation. Meanwhile, this management approach had a significant regulatory effect on the gene expression of poplar plantations. 1554 differential expression genes (DEGs)were identified in drip irrigation (ND) compared with conventional irrigation. Relative to ND, 2761–4116 DEGs, predominantly up-regulated, were identified under three drip fertilization combinations, among which 202 DEGs were mainly regulated by fertilization. Moreover, drip irrigation reduced the expression of cell wall synthesis-related genes to reduce unnecessary water transport. Precision drip and fertilizer-intensive management promotes the synergistic regulation of carbon and nitrogen metabolism and up-regulates the expression of major genes in nitrogen transport and assimilation processes (5 DEGs), photosynthesis (15 DEGs), and plant hormone signal transduction (11 DEGs). The incorporation of trace elements further enhanced the up-regulation of secondary metabolic process genes. In addition, the co-expression network identified nine hub genes regulated by precision water and fertilizer-intensive management, suggesting a pivotal role in regulating the growth of poplar. Conclusion Precision water and fertilizer-intensive management demonstrated the ability to regulate the expression of key genes and transcription factor genes involved in carbon and nitrogen metabolism pathways, plant hormone signal transduction, and enhance the activity of key enzymes involved in related processes. This regulation facilitated nitrogen absorption and utilization, and photosynthetic abilities such as light capture, light transport, and electron transport, which faintly synergistically regulate the growth of poplar plantations. These results provide a reference for proposing highly efficient precision intensive management to optimize the expression of target genes.

Abstract Structural superlubricity (SSL) is a state of contact with no wear and ultralow friction. SSL has been characterized at contact with van der Waals (vdW) layered materials, while its stability under extreme loading conditions has not been assessed. By designing both self-mated and non-self-mated vdW contacts with materials chosen for their high strengths, we report outstanding robustness of SSL under very high pressures in experiments. The incommensurate self-mated vdW contact between graphite interfaces can maintain the state of SSL under a pressure no lower than 9.45 GPa, and the non-self-mated vdW contact between a tungsten tip and graphite substrate remains stable up to 3.74 GPa. Beyond this critical pressure, wear is activated, signaling the breakdown of vdW contacts and SSL. This unexpectedly strong pressure-resistance and wear-free feature of SSL breaks down the picture of progressive wear. Atomistic simulations show that lattice destruction at the vdW contact by pressure-assisted bonding triggers wear through shear-induced tearing of the single-atomic layers. The correlation between the breakdown pressure and material properties shows that the bulk modulus and the first ionization energy are the most relevant factors, indicating the combined structural and electronic effects. Impressively, the breakdown pressures defined by the SSL interface could even exceed the strength of materials in contact, demonstrating the robustness of SSL. These findings offer a fundamental understanding of wear at the vdW contacts and guide the design of SSL-enabled applications.

The rapid detection of grid voltage faults is crucial to achieve grid voltage fault ride-through. However, conventional grid voltage detection methods, including Fourier transform, dq axis transform, wavelet transform, and voltage peak methods, generally yield varying degrees of distortions in the detection results of short-time disturbances in grid voltage. To address this, this paper proposes an approach for quickly detecting short-time disturbances in grid voltage. Leveraging the distinctive high harmonic content present in grids, the suggested strategy involves a transformation of grid voltage calculated using the Fourier transform method, known for its robust anti-interference performance, into high-frequency signals through coordinate conversion. The integration of the rolling sliding window method addresses the extended calculation time issue associated with the Fourier transform, enabling the detection of grid voltage disturbance signals within a single high-frequency signal cycle using this method. The simulation experiment results demonstrated the wide applicability of the proposed method compared with other methods. It is not only effective for short-time grid voltage disturbances, but also suitable for long-time grid voltage disturbances. Regardless of whether high-frequency harmonics are present or absent in the grid voltage, this method allows for the rapid detection of grid voltage disturbances (within about 2 ms). Moreover, its accuracy in detecting grid voltage amplitudes aligns with requirements in engineering applications.

Forests have experienced unprecedented decline and mortality beyond their historical range in past decades, which is attributed to disturbances like drought, fire, insects and disease. Traditional disturbance detection methods that typically employ a time series perspective to identify discrete disturbance events within continuous tree growth signals and were mainly designed for gap-scale often fail to identify disturbances across populations. To more accurately identify growth suppression and release clusters based on the perspective of forest population dynamics, here we applied a novel method of detecting forest disturbances using a Gaussian mixture model with an expectation maximisation algorithm (DGE), to fit annual distributions of growth indicators, i.e., tree-ring index. We further compared our novel approach of DGE with five traditional methods based on two sets of real tree-ring data and simulated tree-ring data. The results show an improvement of accuracy (35.5 %–48.1 %), sensitivity (36.6 %–58.1 %), precision (21.2 %–51.5 %) and specificity (11.1 %–20.6 %) for the average of two real radial growth datasets and an improvement of accuracy (7.6 %–13.9 %), sensitivity (70 %), precision (100 %) and specificity (9.1 %–9.7 %) for the simulation radial growth dataset, indicating that our DGE approach performs much better than the traditional methods. This study contributes to an improved strategy and understanding for sustainable forest management in the context of climate warming, demonstrating that our DGE approach can be better applied to global forest disturbance detection under global change.

Objective: The present study aimed to explore the function of human bone marrow mesenchymal stem cells (hBMMSCs)-derived exosomal long noncoding RNA histocompatibility leukocyte antigen complex P5 (HCP5) in the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) to improve chronic periodontitis (CP). Methods: Exosomes were extracted from hBMMSCs. Alizarin red S staining was used to detect mineralised nodules. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure HCP5 and miR-24-3p expression. The mRNA and protein levels of alkaline phosphatase (ALP), osteocalcin, osterix, runt-related transcription factor 2, bone morphogenetic protein 2, osteopontin, fibronectin, collagen 1, heme oxygenase 1 (HO1), P38, and ETS transcription factor ELK1 (ELK1) were detected using RT-qPCR and Western blot. Enzyme-linked immunosorbent assay (ELISA) kits were used to determine the HO1 and carbon monoxide concentrations. Heme, biliverdin, and Fe2+ levels were determined using detection kits. Micro-computed tomography, hematoxylin and eosin staining, ALP staining, tartrate-resistant acid phosphatase staining, ELISA, and RT-qPCR were conducted to evaluate the effect of HCP5 on CP mice. Dual luciferase, RNA immunoprecipitation, and RNA pulldown experiments were performed to identify the interactions among HCP5, miR-24-3p, and HO1. Results: The osteogenic ability of hPDLSCs significantly increased when co-cultured with hBMMSCs or hBMMSCs exosomes. Overexpression of HCP5 and HO1 in hBMMSCs exosomes promoted the osteogenic differentiation of hPDLSCs, and knockdown of HCP5 repressed the osteogenic differentiation of hPDLSCs. HCP5 knockdown enhanced the inflammatory response and repressed osteogenesis in CP mice. MiR-24-3p overexpression diminished the stimulatory effect of HCP5 on the osteogenic ability of hPDLSCs. Mechanistically, HCP5 acted as a sponge for miR-24-3p and regulated HO1 expression, and HO1 activated the P38/ELK1 pathway. Conclusion: HBMMSCs-derived exosomal HCP5 promotes the osteogenic differentiation of hPDLSCs and alleviates CP by regulating the miR-24-3p/HO1/P38/ELK1 signalling pathway.

Abstract Background Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) is one of the causes of tumor immune tolerance and failure of cancer immunotherapy. Here, we found that bladder cancer (BCa)-derived exosomal circRNA_0013936 could enhance the immunosuppressive activity of PMN-MDSCs by regulating the expression of fatty acid transporter protein 2 (FATP2) and receptor-interacting protein kinase 3 (RIPK3). However, the underlying mechanism remains largely unknown. Methods BCa-derived exosomes was isolated and used for a series of experiments. RNA sequencing was used to identify the differentially expressed circRNAs. Western blotting, immunohistochemistry, immunofluorescence, qRT-PCR, ELISA and Flow cytometry were performed to reveal the potential mechanism of circRNA_0013936 promoting the immunosuppressive activity of PMN-MDSC. Results CircRNA_0013936 enriched in BCa-derived exosomes could promote the expression of FATP2 and inhibit the expression of RIPK3 in PMN-MDSCs. Mechanistically, circRNA_0013936 promoted the expression of FATP2 and inhibited the expression of RIPK3 expression via sponging miR-320a and miR-301b, which directly targeted JAK2 and CREB1 respectively. Ultimately, circRNA_0013936 significantly inhibited the functions of CD8+ T cells by up-regulating FATP2 through the circRNA_0013936/miR-320a/JAK2 pathway, and down-regulating RIPK3 through the circRNA_0013936/miR-301b/CREB1 pathway in PMN-MDSCs. Conclusions BCa-derived exosomal circRNA_0013936 promotes suppressive immunity by up-regulating FATP2 through the circRNA_0013936/miR-320a/JAK2 pathway and down-regulating RIPK3 through the circRNA_0013936/miR-301b-3p/CREB1 pathway in PMN-MDSCs. These findings help to find new targets for clinical treatment of human bladder cancer.

This paper aims to develop a distributed channel estimation (CE) algorithm for spatially non-stationary (SNS) channels in extremely large aperture array systems, addressing the issues of high communication cost and computational complexity associated with traditional centralized algorithms. However, SNS channels differ from conventional spatially stationary channels, presenting new challenges such as varying sparsity patterns for different antennas. To overcome these challenges, we propose a novel distributed CE algorithm accompanied by a simple yet effective hard thresholding scheme. The proposed algorithm is not only suitable for uniform antenna arrays but also for irregularly deployed antennas. Simulation results demonstrate the advantages of the proposed algorithm in terms of estimation accuracy, communication cost, and computational complexity.

Soil hydraulic properties are essential for understanding soil hydrological and erosion processes. The importance of roots on soil hydraulic parameters has been widely recognized, but current studies have focused mainly on the root effect of a single plant species. However, few studies have been carried out to investigate the effect of mixed plant roots on soil hydraulic parameters. Undisturbed soil samples were collected from three natural sampling sites with single plant types and four sites with mixed plant types. Both soil hydraulic parameters were measured: soil saturated hydraulic conductivity (Ks) and soil saturated water content (SW). Then the root effects on Ks and SW were subsequently evaluated. The results showed that the Ks and SW at the sites with mixed plants were higher than those at the sites with a single plant species. At all the sites, Ks and SW both exhibited a decreasing-increasing-decreasing trend with increasing root density. The critical root density for the above change was quantified. When fibrous roots were mixed with tap roots, Ks was mainly affected by tap roots, while SW was mainly affected by fibrous roots. The influence of roots on Ks and SW was mainly achieved by affecting soil organic matter, not by directly affecting Ks and SW. Based on the root density, the herbaceous coverage with optimal saturated hydraulic conductivity and water content was estimated to be 66.71%.

Abstract Background Schools are high incidence places for public health emergencies. Good health literacy helps students cope with public health emergencies. Overall, the health literacy of young students is relatively low. Health education can promote health literacy, but the health education related to public health emergencies for Chinese junior middle school students needs to be improved. To design and implement health education courses related to public health emergencies for junior middle school students and examine the impact on their health literacy, emotions, and coping styles. Methods From March to December 2022, 724 students in Grade 7 and Grade 8 of two junior middle schools in Changzhou were randomly divided into a course group (n = 359) and a control group (n = 365). The course group received an age-appropriate health education course that addressed public health emergencies; there were 12 classes, one per week. The control group received general health education. One week before and after the courses, the two groups of students were assessed with the Adolescent Health Literacy Evaluation Scale under Public Health Emergencies (AHLES-PHE), the Depression Self-Rating Scale for Children (DSRSC), the Generalized Anxiety Disorder 7-item scale (GAD-7), and the Simplified Coping Style Questionnaire (SCSQ). Results After the courses were completed, the scores of AHLES-PHE [156.0 (45.0,180.0) vs. 165.0 (54.0,180.0), P 0.05). Conclusion This suggests that the health education courses related to public health emergencies designed in this study has an effect on improving health literacy, depression and anxiety in junior middle school students.

Highlights An ingenious design achieved magnetic-dielectric-carbon coupling. Nickel and manganese oxide particles were in situ reduced and grew on the carbon aerogels. The aerogels demonstrated radar stealth, infrared stealth and thermal management capability.

Hu antigen R (HuR) plays a key role in regulating genes critical to the pathogenesis of diabetic nephropathy (DN). This study investigates the therapeutic potential of niclosamide (NCS) as an HuR inhibitor in DN. Uninephrectomized mice were assigned to four groups: normal control; untreated db/db mice terminated at 14 and 22 weeks, respectively; and db/db mice treated with NCS (20 mg/kg daily via i.p.) from weeks 18 to 22. Increased HuR expression was observed in diabetic kidneys from db/db mice, which was mitigated by NCS treatment. Untreated db/db mice exhibited obesity, progressive hyperglycemia, albuminuria, kidney hypertrophy and glomerular mesangial matrix expansion, increased renal production of fibronectin and a-smooth muscle actin, and decreased glomerular WT-1+-podocytes and nephrin expression. NCS treatment did not affect mouse body weight, but reduced blood glucose and HbA1c levels and halted the DN progression observed in untreated db/db mice. Renal production of inflammatory and oxidative stress markers (NF-κBp65, TNF-a, MCP-1) and urine MDA levels increased during disease progression in db/db mice but were halted by NCS treatment. Additionally, the Wnt1-signaling-pathway downstream factor, Wisp1, was identified as a key downstream mediator of HuR-dependent action and found to be markedly increased in db/db mouse kidneys, which was normalized by NCS treatment. These findings suggest that inhibition of HuR with NCS is therapeutic for DN by improving hyperglycemia, renal inflammation, and oxidative stress. The reduction in renal Wisp1 expression also contributes to its renoprotective effects. This study supports the potential of repurposing HuR inhibitors as a novel therapy for DN.

To achieve a rapid and stable dynamic response of the drive anti-slip system for distributed electric vehicles on low-friction surfaces, this paper proposes an adaptive acceleration slip regulation control strategy based on wheel slip rate. An attachment coefficient fusion estimation algorithm based on an improved singular value decomposition unscented Kalman filter is designed. This algorithm combines Sage–Husa with the unscented Kalman filter for adaptive improvement, allowing for the quick and accurate determination of the road friction coefficient and, subsequently, the optimal slip rate. Additionally, a slip rate control strategy based on dynamic adaptive compensation sliding mode control is designed, which introduces a dynamic weight integral function into the control rate to adaptively adjust the integral effect based on errors, with its stability proven. To verify the performance of the road estimator and slip rate controller, a model is built with vehicle simulation software, and simulations are conducted. The results show that under icy and snowy road conditions, the designed estimator can reduce estimation errors and respond rapidly to sudden changes. Compared to traditional equivalent controllers, the designed controller can effectively reduce chattering, decrease overshoot, and shorten response time. Especially during road transitions, the designed controller demonstrates better dynamic performance and stability.

The n-type semiconductor SnO2 with a wide band gap (3.6 eV) is massively used in gas-sensitive materials, but pure SnO2 still suffers from a high operating temperature, low response, and tardy responding speed. To solve these problems, we prepared small-sized pure SnO2 using hydrothermal and freeze-drying methods (SnO2-FD) and compared it with SnO2 prepared using a normal drying method (SnO2-AD). The sensor of SnO2-FD had an ultra-high sensitivity to NO2 at 100 °C with excellent selectivity and humidity stability. The outstanding gas sensing properties are attributed to the modulation of energy band structure and the increased carrier concentration, making it more accessible for electron exchange with NO2. The excellent gas sensing properties of SnO2-FD indicate its tremendous potential as a NO2 sensor.

Elucidating the characteristics and underlying mechanisms of soil organic carbon (SOC) and nitrogen mineralization in the context of sludge addition is vital for enhancing soil quality and augmenting the carbon sink capacity of soil. This study examined the chemical properties, enzyme dynamics, and organic carbon and nitrogen mineralization processes of soil from degraded grasslands on the Loess Plateau at various incubation temperatures (5, 15, 25, and 35 °C) and sludge addition rates (0%, 5.0%, 10.0%, and 20.0%) through a laboratory incubation experiment. The results showed that incubation temperature, sludge addition, and their interactive effects significantly altered the soil enzyme C:N, C:P, and N:P stoichiometries. The cumulative mineralization rates of SOC and nitrogen increased significantly with increasing incubation temperature and sludge addition rate. Principal component analysis revealed a significant linear correlation between cumulative SOC and nitrogen mineralization. Random forest analysis indicated that β-1,4-Glucosidase (BG), β-1,4-N-acetyglucosaminidase (NAG), cellobiohydrolase (CBH), ammonium nitrogen (NO3−), enzyme C:P ratio, alkaline phosphatase (ALP), and incubation temperature were crucial determinants of cumulative SOC mineralization. Structural equation modeling demonstrated that sludge addition, NO3−, NAG, ALP, and enzyme C:P positively impacted SOC mineralization, whereas dissolved organic carbon and BG had negative impacts. Conversely, incubation temperature negatively affected soil nitrogen mineralization, whereas NO3−, available phosphorus, and ALP contributed positively. Sludge addition and temperature indirectly modulated soil net nitrogen mineralization by altering soil chemical properties and enzyme activities. These findings underscore the role of SOC and nitrogen mineralization as indicators for evaluating soil nutrient retention capabilities.

Overactive bladder (OAB) is a symptom-based syndrome defined by urinary urgency, frequency, and nocturia with or without urge incontinence. The causative pathology is diverse; including bladder outlet obstruction (BOO), bladder ischemia, aging, metabolic syndrome, psychological stress, affective disorder, urinary microbiome, localized and systemic inflammatory responses, etc. Several hypotheses have been suggested as mechanisms of OAB generation; among them, neurogenic, myogenic, and urothelial mechanisms are well-known hypotheses. Also, a series of local signals called autonomous myogenic contraction, micromotion, or afferent noises, which can occur during bladder filling, may be induced by the leak of acetylcholine (ACh) or urothelial release of adenosine triphosphate (ATP). They can be transmitted to the central nervous system through afferent fibers to trigger coordinated urgency-related detrusor contractions. Antimuscarinics, commonly known to induce smooth muscle relaxation by competitive blockage of muscarinic receptors in the parasympathetic postganglionic nerve, have a minimal effect on detrusor contraction within therapeutic doses. In fact, they have a predominant role in preventing signals in the afferent nerve transmission process. β3-adrenergic receptor (AR) agonists inhibit afferent signals by predominant inhibition of mechanosensitive Aδ-fibers in the normal bladder. However, in pathologic conditions such as spinal cord injury, it seems to inhibit capsaicin-sensitive C-fibers. Particularly, mirabegron, a β3-agonist, prevents ACh release in the BOO-induced detrusor overactivity model by parasympathetic prejunctional mechanisms. A recent study also revealed that vibegron may have 2 mechanisms of action: inhibition of ACh from cholinergic efferent nerves in the detrusor and afferent inhibition via urothelial β3-AR.

Magnetic MnFe2O4 nanoparticles were successfully prepared by the rapid combustion method at 500 °C for 2 h with 30 mL absolute ethanol, and were characterized by SEM, TEM, XRD, VSM, and XPS techniques, their average particle size and the saturation magnetization were about 25.3 nm and 79.53 A·m2/kg, respectively. The magnetic MnFe2O4 nanoparticles were employed in a fixed bed experimental system to investigate the adsorption capacity of Hg0 from air. The MnFe2O4 nanoparticles exhibited the large adsorption performance on Hg0 with the adsorption capacity of 16.27 μg/g at the adsorption temperature of 50 °C with the space velocity of 4.8×104 h-1. The VSM and EDS results illustrated that the prepared MnFe2O4 nanoparticles were stable before and after adsorption and successfully adsorbed Hg0. The TG curves demonstrated that the mercury compound formed after adsorption was HgO, and both physical and chemical adsorption processes were observed. Magnetic MnFe2O4 nanoparticles revealed excellent adsorbance of Hg0 in air, which suggested that MnFe2O4 nanoparticles be promising for the removal of Hg0.

With the emergence of penicillin resistance, the development of novel antibiotics has become an urgent necessity. Semi-synthetic penicillin has emerged as a promising alternative to traditional penicillin. The demand for the crucial intermediate, 6-aminopicillanic acid (6-APA), is on the rise. Enzyme catalysis is the primary method employed for its production. However, due to certain limitations, the strategy of enzyme immobilization has also gained prominence. The magnetic Ni0.4Cu0.5Zn0.1Fe2O4 nanoparticles were successfully prepared by a rapid-combustion method. Sodium silicate was used to modify the surface of the Ni0.4Cu0.5Zn0.1Fe2O4 nanoparticles to obtain silica-coated nanoparticles (Ni0.4Cu0.5Zn0.1Fe2O4-SiO2). Subsequently, in order to better crosslink PGA, the nanoparticles were modified again with glutaraldehyde to obtain glutaraldehyde crosslinked Ni0.4Cu0.5Zn0.1Fe2O4-SiO2-GA nanoparticles which could immobilize the PGA. The structure of the PGA protein was analyzed by the PyMol program and the immobilization strategy was determined. The conditions of PGA immobilization were investigated, including immobilization time and PGA concentration. Finally, the enzymological properties of the immobilized and free PGA were compared. The optimum catalytic pH of immobilized and free PGA was 8.0, and the optimum catalytic temperature of immobilized PGA was 50°C, 5°C higher than that of free PGA. Immobilized PGA in a certain pH and temperature range showed better catalytic stability. Vmax and Km of immobilized PGA were 0.3727 μmol·min-1 and 0.0436 mol·L-1, and the corresponding free PGA were 0.7325 μmol·min-1 and 0.0227 mol·L-1. After five cycles, the immobilized enzyme activity was still higher than 25%.

Multinodular and vacuolar neuronal tumor (MVNT) is a rare and benign neuroepithelial tumor. Most reports describe tumors located in the cerebral hemisphere. A literature review found that 15 cases were located in the posterior cranial fossa, but all lacked pathological evidence. In this case, a patient sought medical attention due to insomnia and irritability. Neuroepithelial tumors were found in the imaging, and the patient underwent radiation therapy. Three years later, malignant tumors were found upon imaging examination. After surgical resection and pathological testing, MVNT occurring in the cerebellum was diagnosed. MVNT is rare in the cerebellum, and direct imaging diagnosis becomes difficult after treatment. Therefore, our report of this case helps to further accurate understanding of the imaging, pathological, and molecular genetic changes occurring before and after MVNT treatment, and will improve the accuracy of pre-treatment diagnosis and reduce the likelihood of overtreatment.

Atherosclerosis significantly contributes to the development of cardiovascular diseases (CVD) and is characterized by lipid retention and inflammation within the artery wall. Multiple immune cell types are implicated in the pathogenesis of atherosclerosis, macrophages play a central role as the primary source of inflammatory effectors in this pathogenic process. The metabolic influences of lipids on macrophage function and fatty acid β-oxidation (FAO) have similarly drawn attention due to its relevance as an immunometabolic hub. This review discusses recent findings regarding the impact of mitochondrial-dependent FAO in the phenotype and function of macrophages, as well as transcriptional regulation of FAO within macrophages. Finally, the therapeutic strategy of macrophage FAO in atherosclerosis is highlighted.

In the electronic nose (E-nose) systems, gas type recognition and accurate concentration prediction are some of the most challenging issues. This study introduced an innovative pattern recognition method of time–frequency attention convolutional neural network (TFA-CNN). A time–frequency attention block was designed in the network, aiming to excavate and effectively integrate the temporal and frequency domain information in the E-nose signals to enhance the performance of gas classification and concentration prediction tasks. Additionally, a novel data augmentation strategy was developed, manipulating the feature channels and time dimensions to reduce the interference of sensor drift and redundant information, thereby enhancing the model’s robustness and adaptability. Utilizing two types of metal-oxide-semiconductor gas sensors, this research conducted qualitative and quantitative analysis on five target gases. The evaluation results showed that the classification accuracy could reach 100%, and the coefficient of the determination (R2) score of the regression task was up to 0.99. The Pearson correlation coefficient (r) was 0.99, and the mean absolute error (MAE) was 1.54 ppm. The experimental test results were almost consistent with the system predictions, and the MAE was 1.39 ppm. This study provides a method of network learning that combines time–frequency domain information, exhibiting high performance in gas classification and concentration prediction within the E-nose system.

Aluminosilicates, such as montmorillonite, kaolinite, halloysite, and diatomite, have a uniform bidimensional structure, a high surface-to-volume ratio, inherent stiffness, a dual charge distribution, chemical inertness, biocompatibility, abundant active groups on the surface, such as silanol (Si-OH) and/or aluminol (Al-OH) groups. These compounds are on the list of U.S. Food and Drug Administration-approved active compounds and excipients and are used for various medicinal products, such as wound healing agents, antidiarrheals, and cosmetics. This review summarizes the wound healing mechanisms related to the material characteristics and the chemical components. Numerous wound dressings with different active components and multiple forms have been studied. Then, medicinal mineral resources for use in hemostatic materials can be developed.

Abstract Studies of laser-driven strong field processes subjected to a (quasi-)static field have been mainly confined to theory. Here we provide an experimental realization by introducing a bichromatic approach for high harmonic generation (HHG) in a dielectric that combines an intense 70 femtosecond duration mid-infrared driving field with a weak 2 picosecond period terahertz (THz) dressing field. We address the physics underlying the THz field induced static symmetry breaking and its consequences on the efficient production/suppression of even-/odd-order harmonics, and demonstrate the ability to probe the HHG dynamics via the modulation of the harmonic distribution. Moreover, we report a delay-dependent even-order harmonic frequency shift that is proportional to the time derivative of the THz field. This suggests a limitation of the static symmetry breaking interpretation and implies that the resultant attosecond bursts are aperiodic, thus providing a frequency domain probe of attosecond transients while opening opportunities in precise attosecond pulse shaping.

In this study, scanning electron microscopy (SEM), electron backscatter diffraction analysis (EBSD), and electron probe microanalysis (EPMA) were used to investigate the impact of rare-earth Sc on the interface microstructure and mechanical properties of Al/steel bimetallic composites fabricated by liquid–solid casting. With the addition of 0.3% Sc, the morphology of eutectic Si changed from needle-like to fibrous and granular. The addition of Sc did not change the types of intermetallic compounds in the Al/steel reaction layer, which comprised the Al5Fe2, τ1-Al2Fe3Si3, Al13Fe4, τ5-Al7Fe2Si, and τ6-Al9Fe2Si2 phases. The thickness of the first layer decreased, whereas that of the second layer increased as the Sc content increased to 0.3%. Furthermore, the Al5Fe2 and τ1 phase percentages of the reaction layer decreased, whereas the Al13Fe4, τ5, and τ6 phase percentages increased. Sc was mainly enriched in the front of the ternary compound layer (τ6) near the Al side. The addition of 0.3% Sc reduced the grain size of each phase in the interfacial reaction layer and did not change the preferred orientation of the Al5Fe2, Al13Fe4, τ5, and τ6 phases, but increased the polar density of the Al13Fe4, τ5, and τ6 phases and decreased the polar density of the Al5Fe2 phase. With the addition of 0.3% Sc, the average nanohardness of the reaction layer decreased by 5% and the bonding strength increased by 48%.

In the operating environment of power system with weak grid characteristics, the traditional current source converter control mode is prone to vibration, which increases the crossing difficulty and off-grid probability of wind turbines. Based on virtual synchronous generator (VSG) technology, a novel control strategy of voltage source converter is designed in this paper, and the voltage source converter control mode and current source converter control mode are studied. Under normal grid-connected operation conditions, voltage source converter control mode is adopted. Active power control increases active power compensation through VSG, and reactive current is injected into the front end of reactive power control. Under start-stop and high & low-voltage ride-through conditions, the current source converter control mode is adopted. The control strategy combines the advantages of voltage source converter control mode and the current source converter control mode. It has not only the frequency support characteristics, but also the fast active and reactive power response capability. The simulation and prototype experiments on the grid-connection process, active and reactive power response and high & low-voltage ride-through process of the full-power wind power converter are carried out. The results show that the proposed control scheme can achieve good control effect under each operating condition of the wind power converter, so that the wind power units have good steady-state and dynamic performance, and can well adapt to the demands of new energy grid-connection.

Abstract Background Angiogenesis plays important roles in physiological and pathologic conditions, but the mechanisms underlying this complex process often remain to be elucidated. In recent years, liquid–liquid phase separation (LLPS) has emerged as a new concept to explain many cellular functions and diseases. However, whether LLPS is involved in angiogenesis has not been studied until now. Here, we investigated the potential role of LLPS in angiogenesis and endothelial function. Results We found 1,6-hexanediol (1,6-HD), an inhibitor of LLPS, but not 2,5-hexanediol (2,5-HD) dramatically decreases neovascularization of Matrigel plug and angiogenesis response of murine corneal in vivo. Moreover, 1,6-HD but not 2,5-HD inhibits microvessel outgrowth of aortic ring and endothelial network formation. The endothelial function of migration, proliferation, and cell growth is suppressed by 1,6-HD. Global transcriptional analysis by RNA-sequencing reveals that 1,6-HD specifically blocks cell cycle and downregulates cell cycle-related genes including cyclin A1. Further experimental data show that 1,6-HD treatment greatly reduces the expression of cyclin A1 but with minimal effect on cyclin D1, cyclin E1, CDK2, and CDK4. The inhibitory effect of 1,6-HD on cyclin A1 is mainly through transcriptional regulation because proteasome inhibitors fail to rescue its expression. Furthermore, overexpression of cyclin A1 in HUVECs largely rescues the dysregulated tube formation upon 1,6-HD treatment. Conclusions Our data reveal a critical role of LLPS inhibitor 1,6-HD in angiogenesis and endothelial function, which specifically affects endothelial G1/S transition through transcriptional suppression of CCNA1, implying LLPS as a possible novel player to modulate angiogenesis, and thus, it might represent an interesting therapeutic target to be investigated in clinic angiogenesis-related diseases in future.

This study aims to investigate the anti-fatigue effect and mechanism of Syngnathus schlegeli peptides (SAP) on exercise-fatigued mice. Compared to the control group, SAP significantly reduced the accumulation of metabolites LA, BUN and MDA, increased the GSH-PX activity, inhibited oxidative stress, improved grip strength and prolonged swimming time in mice. Additionally, SAP enhanced the activity of CS, α-KGDHC, MRCC I and MRCC IV, Ca2+-Mg2+-ATPase and Na+-K+-ATPase in the gastrocnemius muscle, thereby improving mitochondrial function and increasing ATP production for energy supplementation. The anti-fatigue effect of SAP is associated with its promotion of protein expressions involved in the AMPK/PGC-1α and Keap1/NRF2 signaling pathway, as well as regulate the balance of intestinal microecology. Furthermore, DAELRMEKH was screened from the peptides identified from SAP by in silico and in vitro activity assays. The presence of hydrophobic and charged amino acids in DAELRMEKH facilitates better binding to the active pockets of AMPK and Keap1.

Homologous ventricular electrical separation is a rare electrocardiogram manifestation; it is defined as a specific subtype of ventricular separation caused by excitation that originates from the supraventricular rhythm and travels through the His-Pukenje system, resulting in severe asynchrony of biventricular depolarization and production of 2 QRS complexes. It always indicates irreversible cardiac impairment and electrical instability. (Level of Difficulty: Advanced.)

The application of transition metal hydroxides has long been plagued by its poor conductivity and stability as well as severe aggregation tendency. In this paper, a novel hierarchical core–shell architecture, using an F-doped Co(OH)2 nanorod array (Co(OH)F) as the core and Mn/Ni co-doped Co(OH)2 nanosheets (NiCoMn-LDH) as the shell, was constructed via an MOF-mediated in situ generation method. The obtained Co(OH)F@ NiCoMn-LDH composites exhibited excellent supercapacitive performance with large specific capacitance as well as improved rate capability and long-term stability. The effect of the Ni/Mn ratio on the supercapacitive performance and energy storage kinetics was systematically investigated and the related mechanism was revealed.

Montmorillonite has been refined to overcome uncertainties originating from different sources, which offers opportunities for addressing various health issues, e.g., cosmetics, wound dressings, and antidiarrheal medicines. Herein, three commercial montmorillonite samples were obtained from different sources and labeled M1, M2, and M3 for Ca-montmorillonite, magnesium-enriched Ca-montmorillonite, and silicon-enriched Na-montmorillonite, respectively. Commercial montmorillonite was refined via ultrasonic scission-differential centrifugation and labeled S, M, or L according to the particle sizes (small, medium, or large, respectively). The size distribution decreased from 2000 nm to 250 nm with increasing centrifugation rates from 3000 rpm to 12,000 rpm. Toxicological evaluations with human colon-associated cells and human skin-associated cells indicated that side effects were correlated with excess dosages and silica sand. These side effects were more obvious with human colon-associated cells. The microscopic interactions between micro/nanosized montmorillonite and human colon-associated cells or human skin-associated cells indicated that those interactions were correlated with the size distributions. The interactions of the M1 series with the human cells were attributed to size effects because montmorillonite with a broad size distribution was stored in the M1 series. The M2 series interactions with human cells did not seem to be correlated with size effects because large montmorillonite particles were retained after refining. The M3 series interactions with human cells were attributed to size effects because small montmorillonite particles were retained after refining. This illustrates that toxicological evaluations with refined montmorillonite must be performed in accordance with clinical medical practices.

Mangrove-derived actinomycetes represent a rich source of novel bioactive natural products in drug discovery. In this study, four new polyene macrolide antibiotics antifungalmycin B-E (1–4), along with seven known analogs (5–11), were isolated from the fermentation broth of the mangrove strain Streptomyces hiroshimensis GXIMD 06359. All compounds from this strain were purified using semi-preparative HPLC and Sephadex LH-20 gel filtration while following an antifungal activity-guided fractionation. Their structures were elucidated through spectroscopic techniques including UV, HR-ESI-MS, and NMR. These compounds exhibited broad-spectrum antifungal activity against Talaromyces marneffei with minimum inhibitory concentration (MIC) values being in the range of 2–128 μg/mL except compound 2. This is the first report of polyene derivatives produced by S. hiroshimensis as bioactive compounds against T. marneffei. In vitro studies showed that compound 1 exerted a significantly stronger antifungal activity against T. marneffei than other new compounds, and the antifungal mechanism of compound 1 may be related to the disrupted cell membrane, which causes mitochondrial dysfunction, resulting in leakage of intracellular biological components, and subsequently, cell death. Taken together, this study provides a basis for compound 1 preventing and controlling talaromycosis.

Surface engineering has been proved efficient and universally applicable in improving the performance of CeO2 in various fields. However, previous approaches have typically required high-temperature calcination or tedious procedures, which makes discovery of a moderate and facile modification approach for CeO2 an attractive subject. In this paper, porous CeO2 nanosheets with effective nitrogen-doping were synthesized via a low-temperature NH3/Ar plasma treatment and exhibited boosted hydrogen evolution reaction performance with low overpotential (65 mV) and long-term stability. The mechanism of the elevated performance was investigated by introducing Ar-plasma-treated CeO2 with no nitrogen-doping as the control group, which revealed the dominant role of nitrogen-doping by providing abundant active sites and improving charge transfer characteristics. This work illuminates further investigations into the surface engineering methodologies boosted by plasma and the relative mechanism of the structure–activity relationship.

BackgroundLynch syndrome (LS)-associated glioblastoma (GBM) is rare in clinical practice, and simultaneous occurrence with cutaneous porokeratosis is even rarer. In this study, we analyzed the clinicopathological and genetic characteristics of LS-associated GBMs and concurrent porokeratosis, as well as evaluated the tumor immune microenvironment (TIME) of LS-associated GBMs.MethodsImmunohistochemical staining was used to confirm the histopathological diagnosis, assess MMR and PD-1/PD-L1 status, and identify immune cell subsets. FISH was used to detect amplification of EGFR and PDGFRA, and deletion of 1p/19q and CDKN2A. Targeted NGS assay analyzed somatic variants, MSI, and TMB status, while whole-exome sequencing and Sanger sequencing were carried out to analyze the germline mutations.ResultsIn the LS family, three members (I:1, II:1 and II:4) were affected by GBM. GBMs with loss of MSH2 and MSH6 expression displayed giant and multinucleated bizarre cells, along with mutations in ARID1A, TP53, ATM, and NF1 genes. All GBMs had TMB-H but not MSI-H. CD8+ T cells and CD163+ macrophages were abundant in each GBM tissue. The primary and recurrent GBMs of II:1 showed mesenchymal characteristics with high PD-L1 expression. The family members harbored a novel heterozygous germline mutation in MSH2 and FDPS genes, confirming the diagnosis of LS and disseminated superficial actinic porokeratosis.ConclusionLS-associated GBM exhibits heterogeneity in clinicopathologic and molecular genetic features, as well as a suppressive TIME. The presence of MMR deficiency and TMB-H may serve as predictive factors for the response to immune checkpoint inhibitor therapy in GBMs. The identification of LS-associated GBM can provide significant benefits to both patients and their family members, including accurate diagnosis, genetic counseling, and appropriate screening or surveillance protocols. Our study serves as a reminder to clinicians and pathologists to consider the possibility of concurrent genetic syndromes in individuals or families.

Abstract As one kind of aggressive cancer, triple-negative breast cancer (TNBC) has become one of the major causes of women mortality worldwide. Recently, combinational chemo-PDT therapy based on nanomaterials has been adopted for the treatment of malignant tumor. However, the efficacy of PDT was partly compromised under tumor hypoxia environment due to the lack of sustainable O2 supply. In this study, CeO2-loaded nanoparticles (CeNPs) with peroxidase activity were synthesized to autonomously generate O2 by decomposing H2O2 within tumor region and reprogramming the hypoxia microenvironment as well. Meanwhile, the compound cinobufagin (CS-1) was loaded for inhibiting TNBC growth and metastasis. Moreover, the hybrid membrane camouflage was adopted to improve the biocompatibility and targeting ability of nanocomplexes. In vitro assay demonstrated that decomposition of H2O2 by CeO2 achieved sustainable O2 supply, which accordingly improved the efficacy of PDT. In turn, the generated O2 improved the cytotoxicity and anti-tumor migration effect of CS-1 by downregulating HIF-1α and MMP-9 levels. In vivo assay demonstrated that the combination of CS-1 and PDT significantly inhibited the growth and distance metastasis of tumor in MDA-MB-231 bearing mice. Thus, this chemo-PDT strategy achieved satisfactory therapeutic effects by smartly utilizing the enzyme activity of nanodrugs and special micro-environment of tumor.

Fire is a principal disturbance agent in Northeastern Asia forests with the highest fire radiative power globally. The limitation of the wide network of sites with long reconstructed fire histories restricts our understanding of factors forcing regional fire dynamics. We aggregated 30 fire scars-based fire chronologies in Northeastern Asia to create a composite region chronology from 1701 to 2010. We assessed the correlation between solar activity, drought (as represented by the Self-Calibrated Palmer Drought Severity Index, scPDSI), Arctic Oscillation (AO), and forest fire. Large fires were associated with drought, positive AO, and lower sunspot numbers, as revealed by Superposed epoch analysis. The pathways of solar activity force drought and AO, hence, driving fire activity indicated by structural equation modeling. As Solar Cycle 25 (starting in December 2019 and lasting until about 2030) is projected to be as weak as the Dalton minimum (1795–1820 AD), we expect fire activity to remain high over this period. Our findings provide insights into the extraterrestrial forcing of forest fire activity and its prediction in Northeastern Asia.

Abstract Ivermectin is a widely used antiparasitic drug and shows promising anticancer activity in various cancer types. Although multiple signaling pathways modulated by ivermectin have been identified in tumor cells, few studies have focused on the exact target of ivermectin. Herein, we report the pharmacological effects and targets of ivermectin in prostate cancer. Ivermectin caused G0/G1 cell cycle arrest, induced cell apoptosis and DNA damage, and decreased androgen receptor (AR) signaling in prostate cancer cells. Further in vivo analysis showed ivermectin could suppress 22RV1 xenograft progression. Using integrated omics profiling, including RNA-seq and thermal proteome profiling, the forkhead box protein A1 (FOXA1) and non-homologous end joining (NHEJ) repair executer Ku70/Ku80 were strongly suggested as direct targets of ivermectin in prostate cancer. The interaction of ivermectin and FOXA1 reduced the chromatin accessibility of AR signaling and the G0/G1 cell cycle regulator E2F1, leading to cell proliferation inhibition. The interaction of ivermectin and Ku70/Ku80 impaired the NHEJ repair ability. Cooperating with the downregulation of homologous recombination repair ability after AR signaling inhibition, ivermectin increased intracellular DNA double-strand breaks and finally triggered cell death. Our findings demonstrate the anticancer effect of ivermectin in prostate cancer, indicating that its use may be a new therapeutic approach for prostate cancer.

Abstract Background Drug-induced hypersensitivity syndrome (DIHS) is a rare, potentially life-threatening systemic drug reaction. Antithyroid drugs (ATDs) causing DIHS have seldom been reported before. Case presentation We present a case of propylthiouracil (PTU)-induced DIHS, which included fever, skin rash, lymphadenopathy, hepatosplenomegaly, serious liver and kidney dysfunction, peripheral blood eosinophilia, and atypical lymphocytosis. Following supportive therapy, intravenous immunoglobulin (IVIG), and systemic corticosteroid, the patient experienced a resolution of fever and rash combined with progressive normalization of hematological index and organ function. These clinical features, and the skin lesion biopsy confirmed DIHS diagnosis. Conclusions To our knowledge, this is the second reported case of PTU-induced DIHS worldwide and the first human leukocyte antigen (HLA) typing of PTU-induced DIHS. Clinicians should cautiously distinguish hyperthyroidism etiology and identify the indication of ATDs. Timely recognition and formal DIHS treatment are required in patients with ATDs.

Highlights Fabrication, characterizations and photothermal properties of MXenes are systematically described. Photothermal-derived antibacterial performances and mechanisms of MXenes-based materials are summarized and reviewed. Recent advances in the derivative applications relying on antibacterial properties of MXenes-based materials, including in vitro and in vivo sterilization, solar water evaporation and purification, and flexible antibacterial fabrics, are investigated. Abstract The pernicious bacterial proliferation and emergence of super-resistant bacteria have already posed a great threat to public health, which drives researchers to develop antibiotic-free strategies to eradicate these fierce microbes. Although enormous achievements have already been achieved, it remains an arduous challenge to realize efficient sterilization to cut off the drug resistance generation. Recently, photothermal therapy (PTT) has emerged as a promising solution to efficiently damage the integrity of pathogenic bacteria based on hyperthermia beyond their tolerance. Until now, numerous photothermal agents have been studied for antimicrobial PTT. Among them, MXenes (a type of two-dimensional transition metal carbides or nitrides) are extensively investigated as one of the most promising candidates due to their high aspect ratio, atomic-thin thickness, excellent photothermal performance, low cytotoxicity, and ultrahigh dispersibility in aqueous systems. Besides, the enormous application scenarios using their antibacterial properties can be tailored via elaborated designs of MXenes-based materials. In this review, the synthetic approaches and textural properties of MXenes have been systematically presented first, and then the photothermal properties and sterilization mechanisms using MXenes-based materials are documented. Subsequently, recent progress in diverse fields making use of the photothermal and antibacterial performances of MXenes-based materials are well summarized to reveal the potential applications of these materials for various purposes, including in vitro and in vivo sterilization, solar water evaporation and purification, and flexible antibacterial fabrics. Last but not least, the current challenges and future perspectives are discussed to provide theoretical guidance for the fabrication of efficient antimicrobial systems using MXenes.

SnO2 nanospheres with diameters of 30∼50 nm and PtxCu1-x bimetallic nanoparticles with sizes of approximately 10 nm were synthesized via hydrothermal and solvothermal methods, respectively. The PtxCu1-x bimetallic nanoparticles were impregnated on the surface of the SnO2 spheres to form PtxCu1-x-SnO2 nanocomposites. By varying the atomic ratios between platinum (Pt) and copper (Cu), we found that Pt0.75Cu0.25-SnO2, with a large specific surface area of 89.21 m2/g, enabled the selective and accurate detection of low-concentration formaldehyde compared to other metal-deposited samples and pure SnO2. The response value of Pt0.75Cu0.25-SnO2 to 500 × 10−9 formaldehyde was approximately 20 at an operating temperature of 160 ℃ with an extremely high-speed response (15 s). The porous structures with large specific surface areas, as well as the improved catalytic effects of Pt0.75Cu0.25, comprehensively contributed to the enhanced sensing performance towards formaldehyde.

Abstract Submarine methane seepage can potentially be promoted by the dissociation of the marine hydrates surrounding the continental margins due to oceanic warming since the Last Glacial Maximum. This seepage could be archived by authigenic carbonates at seeping sites, but the time lag caused by heat transmission through the sediment column leads to an inconsistency between the ages of the carbonate and the period of bottom water warming. Here we present the records of the authigenic carbonate crust from drilling site D1 in the Mid‐Okinawa Trough. Uranium–thorium dating results show that the carbonate crust mainly grew downwards during 14–6 ka. Gas hydrates hosted in the relatively thin stability zone dissociated in a rapid response to bottom water warming and intensified the methane seepage. Our study better supports the hypothesis that a considerable amount of methane can be released from marine hydrates due to global climatic changes.

N-nitrosodimethylamine (NDMA) is an environmental and food contaminant, but limited data to concern whether NDMA has adverse effects on the brain. This study first determined the concentration of NDMA in foods from aquaculture markets in Shenzhen, then analyzed the effects on C57BL/6 mice and further evaluated on the urine samples of elderly Chinese residents with normal cognition (NC, n = 144), cognitive decline (CD, n = 116) and mild cognitive impairment (MCI, n = 123). The excessive rate of NDMA in foods was 3.32% (27/813), with a exceeding range of 4.78–131.00 μg/kg. Behavioral tests showed that 60 days treatment of mice with 3 mg/kg NDMA reduced cognitive performance. Cognitive impairment in human was significantly associated with sex, educational levels, length of residence in Shenzhen, household registration, passive smoking, rice, fresh vegetables, bacon products. NDMA was detected in 55.4% (212/383) of urine samples, with a median concentration of 0.23 μg/L (1.20 × 10 –7–157.39 μg/L). The median concentration for NC, CD and MCI were 0.32, 0.27, and 0 μg/L, respectively. The urinary NDMA concentration had a strong negative correlation with cognitive impairment (Kendall’s Tau-b = −0.89, P = 0.024). The median estimated daily intake (EDI) of NDMA was determined to be 6.63 ng/kg-bw/day. Taken together, there appears to be an association between NDMA and human and murine cognition, which provides a new clue to Alzheimer’s disease (AD).

Four Si3N4 crystal structures were predicted using an ab initio evolutionary methodology. The mechanical and dynamic stabilities were confirmed by the density functional theory assuming zero-pressure conditions. Energetic stability calculations indicated that the structures are metastable phases at ambient pressure, but their formation is more favorable at high pressures. At zero pressure, the densities of the hp-Si3N4, cp-Si3N4, oc-Si3N4, and ti-Si3N4 phases were 3.21, 3.28, 3.70, and 3.24 g/cm3, respectively. The calculated band structures and densities of states indicated that they have semiconductive properties, with gaps ranging from 0.754 to 3.968 eV. Mechanical property calculations revealed that the hardness of the Si3N4 compounds ranged between 11.2 and 23.3 GPa, which were higher than the corresponding values for the synthesized Si3N4 phases. These four Si3N4 structures are potentially valuable candidates for the synthesis of Si3N4 compounds.

The montmorillonite-sodium alginate (MMT-SA) colon-targeting microcapsules have been designed as a WGX-50 encapsulation and controlled release vehicle used in oral administration. The MMT-SA microcapsule was formed from a cross-linking reaction, and the stable micropore in the microcapsule changed with a different MMT-SA mixed mass ratio. The MMT-SA microcapsule has a reinforced micropore structure and an enhanced swell–dissolution in SIF and SCF with alkaline environment, which is attributed to the incorporated MMT. The MMT-SA microcapsule exhibited a high WGX-50 encapsulation rate up to 98.81 ± 0.31% and an obvious WGX-50 controlled release in the simulated digestive fluid in vitro. The WGX-50 loaded with MMT-SA microcapsule showed a weak minimizing drug loss in SGF (Simulated Gastric Fluid) with an acidic environment, while it showed a strong maximizing drug release in SIF (Simulated Intestinal Fluid) and SCF (Simulated Colonic Fluid) with an alkaline environment. These features make the MMT-SA microcapsule a nominated vehicle for colon disease treatment used in oral administration.

Climate change is already significantly affecting the frequency of wildfires in most regions of the world, and the risk of wildfires is expected to amplify further with global warming. Accordingly, there is growing concern about the mechanisms and impacts of extreme fires. In this study, a coupling of the Weather Research and Forecasting model and the Rothermel Fire model (WRF-Fire) is employed to reproduce the spread of fire within the national boundary of inner Mongolia from 21 to 27 May 2009. Simulations were run with or without feedback from fire-to-atmosphere models, and the study focused on how the energy flux of simulated fires changes the local meteorological environment. The coupled simulation could reproduce the burned area well, and the wind speed was the dominant factor in the fire spread, with a maximum value no more than 6.4 m/s, when the terrain height changes little and the proportion of grassland is low. After the feedback, the propagation speed of the fire accelerated, accompanying the release of latent and sensible heat, and local circulation formed near the front of the fire, leading to a convergence and divergence zone in the downwind area. It is worth noting that during a period of more than 140 h of simulation, the area of the fire field increased by 17% from ignition time. Therefore, considering the fire–atmosphere interaction is necessary for accurately predicting fire behavior.

Endophytic bacteria play a crucial role in the life cycle of Spermatophyta, and exploring the beneficial interactions between seeds and endophytic bacteria is an effective strategy for sustainable agricultural development and improved crop productivity. In this study, we employed Illumina Hiseq high-throughput sequencing technology to analyze the amplified fragments of microbial 16S rRNA sequences from melon seeds of MR-1, HH and their F1 generation, which displayed varying levels of resistance to bacterial fruit blotch disease. Initially, we extracted endophytes from eight melon samples and performed sequencing, obtaining an average of 84,758 effective tags per sample. At the 97% similarity level, the number of operational taxonomic units (OTUs) derived from melon seed endophytes ranged from 447 to 492. After filtering out low-level OTUs, we obtained an average of 65,866 valid tags from the eight samples, representing approximately 160 genera and 167 species across eight phyla. It was found that the composition of the endophyte communities in the eight samples was basically similar, and their abundance showed some variability. Furthermore, we utilized the KO and COG databases to functionally predict the genes of endophytes in melon seeds. The analysis revealed a significant enrichment of genes associated with pathways related to protein synthesis, carbohydrate metabolism, substance transport, and metabolite synthesis. These findings greatly contribute to our understanding of endophytic bacteria in melon seeds and serve as a vital reference for the selection and breeding of high-quality melon seeds, as well as the prevention of seed diseases.

Abstract PandaX-4T is a ton-scale dark matter direct detection experiment using a dual-phase TPC technique at the China Jinping Underground Laboratory. Various ultra-low background technologies have been developed and applied to material screening for PandaX-4T, including HPGe gamma spectroscopy, ICP-MS, NAA, radon emanation measurement system, krypton assay station, and alpha detection system. Low background materials were selected to assemble the detector. Surface treatment procedures were investigated to further suppress radioactive background. Combining measured results and Monte Carlo simulation, the total material background rates of PandaX-4T in the energy region of 1–25 keVee are estimated to be (9.9 ± 1.9) × 10 −3 mDRU for electron recoil and (2.8 ± 0.6) × 10 −4 mDRU for nuclear recoil. In addition, natKr in the detector is estimated to be < 8 ppt.

Objective: PD-L1 and PD-L2 expression levels determine immune evasion and the therapeutic efficacy of immune checkpoint blockade. The factors that drive inducible PD-L1 expression have been extensively studied, but mechanisms that result in constitutive PD-L1 expression in cancer cells are largely unknown. Methods: DNA elements were deleted in cells by CRISPR/Cas9-mediated knockout. Protein function was inhibited by chemical inhibitors. Protein levels were examined by Western blot, mRNA levels were examined by real-time RT-PCR, and surface protein expression was determined by cellular immunofluorescence and flow cytometry. Immune evasion was examined by in vitro T cell-mediated killing. Results: We determined the core regions (chr9: 5, 496, 378–5, 499, 663) of a previously identified PD-L1L2-super-enhancer (SE). Through systematic analysis, we found that the E26 transformation-specific (ETS) variant transcription factor (ETV4) bound to this core DNA region but not to DNA surrounding PD-L1L2SE. Genetic knockout of ETV4 dramatically reduced the expressions of both PD-L1 and PD-L2. ETV4 transcription was dependent on ERK activation, and BRAF/TAK1-induced ERK activation was dependent on extracellular signaling from αvβ3 integrin, which profoundly affected ETV4 transcription and PD-L1/L2 expression. Genetic silencing or pharmacological inhibition of components of the PD-L1L2-SE-associated pathway rendered cancer cells susceptible to T cell-mediated killing. Conclusions: We identified a pathway originating from the extracellular matrix that signaled via integrin/BRAF/TAK1/ERK/ETV4 to PD-L1L2-SE to induce PD-L1-mediated immune evasion. These results provided new insights into PD-L1L2-SE activation and pathways associated with immune checkpoint regulation in cancer.

Objective: Early prostate cancer micrometastatic foci undergo a mesenchymal to epithelial reverting transition, not only aiding seeding and colonization, but also rendering the tumor cells generally chemoresistant. We previously found that upregulated E-cadherin in the epithelial micrometastases activated canonical survival pathways, including PI3K-Akt, that protected the tumor cells from death; however, the extent of protection from blocking the pathway in its entirety was modest, because different isoforms may have alternately affected cell functioning. Here, we characterized Akt isoform expressions in primary and metastatic prostate cancers, as well as their individual contributions to chemoresistance. Methods: Akt isoforms and E-cadherin were manipulated with drugs, knocked down, and over expressed. Tumor cell killing was determined in vitro and in vivo. Overall survival was calculated from patient records and specimens. Results: Pan-Akt inhibition sensitized tumor cells to chemotherapy, and specific blockade of Akt1 or/and Akt2 caused cells to be more chemoresponsive. Overexpression of Akt3 induced apoptosis. A low dose of Akt1 or Akt2 inhibitor enabled standard chemotherapies to significantly eradicate metastatic prostate tumors in a mouse model, acting as chemosensitizers. In human specimens, we found Akt1 and Akt2 positively correlated, whereas Akt3 inversely correlated, with the overall survival of prostate cancer patients. Akt1high/Akt2high/Akt3low tumors had the worst outcomes. Conclusions: E-cadherin-induced activation of Akt1/2 isoforms was the essential mechanism of chemoresistance, whereas Akt3 made cells more fragile. These findings emphasized the need to target Akt1/2, rather than pan-Akt, as a rational therapeutic approach.