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Purpose: To explore the mediating role of trait anxious personality in the association between quality of life (QoL) and death anxiety (DA), as well as to test the moderating effect of social support in the mediation model. Methods: The Death Anxiety Scale, Quality of Life Scale, State-Trait Anxiety Scale, and Social Support Rating Scale were used to measure 588 family caregivers of advanced cancer patients. We then constructed a moderated mediation model. Results: The presence of QoL was negatively associated with DA (β = − 0.67, p < 0.01). Trait anxious personality partially mediated the relationship between QoL and DA (indirect effect β = − 0.08, p < 0.01). Social support moderated both the antecedent and subsequent segments of the mediating paths of “QoL → trait anxious personality → DA” and the direct relationship between QoL and DA. Among caregivers with a low level of social support, the mediating effect coefficient of trait anxious personality was higher at 0.25 (95% confidence interval (CI): 0.059–0.182), in contrast to caregivers with a high level of social support, where the mediating effect coefficient of trait anxious personality was 0.11 (95% CI: 0.029–0.072). Conclusion: QoL is directly associated with an increased risk of DA and indirectly related to DA by increasing the risk of trait anxious personality among caregivers. Social support can moderate the mediating effect of trait anxious personality and the relationship between QoL and DA. The intervention strategy for preventing DA among caregivers who have encountered QoL reduction should focus on reducing trait anxious personality and social support. [ABSTRACT FROM AUTHOR]

Oxidative stress is a frequently occurring pathophysiological feature of spinal cord injury (SCI) and can result in secondary injury to the spinal cord and skeletal muscle atrophy. Studies have reported that glycine and N-acetylcysteine (GlyNAC) have anti-aging and anti-oxidative stress properties; however, to date, no study has assessed the effect of GlyNAC in the treatment of SCI. In the present work, we established a rat model of SCI and then administered GlyNAC to the animals by gavage at a dose of 200 mg/kg for four consecutive weeks. The BBB scores of the rats were significantly elevated from the first to the eighth week after GlyNAC intervention, suggesting that GlyNAC promoted the recovery of motor function; it also promoted the significant recovery of body weight of the rats. Meanwhile, the 4-week heat pain results also suggested that GlyNAC intervention could promote the recovery of sensory function in rats to some extent. Additionally, after 4 weeks, the levels of glutathione and superoxide dismutase in spinal cord tissues were significantly elevated, whereas that of malondialdehyde was significantly decreased in GlyNAC-treated animals. The gastrocnemius wet weight ratio and total antioxidant capacity were also significantly increased. After 8 weeks, the malondialdehyde level had decreased significantly in spinal cord tissue, while reactive oxygen species accumulation in skeletal muscle had decreased. These findings suggested that GlyNAC can protect spinal cord tissue, delay skeletal muscle atrophy, and promote functional recovery in rats after SCI. [ABSTRACT FROM AUTHOR]

Organic heterostructures (OHTs) with the desired geometry organization on micro/nanoscale have undergone rapid progress in nanoscience and nanotechnology. However, it is a significant challenge to elucidate the epitaxial-growth process for various OHTs composed of organic units with a lattice mismatching ratio of > 3%, which is unimaginable for inorganic heterostructures. Herein, we have demonstrated a vivid visualization of the morphology evolution of epitaxial-growth based on a doped interfacial-layer, which facilitates the comprehensive understanding of the hierarchical self-assembly of core-shell OHT with precise spatial configuration. Significantly, the barcoded OHT with periodic shells obviously illustrate the shell epitaxial-growth from tips to center parts along the seeded rods for forming the core-shell OHT. Furthermore, the diameter, length, and number of periodic shells were modulated by finely tuning the stoichiometric ratio, crystalline time, and temperature, respectively. This epitaxial-growth process could be generalized to organic systems with facile chemical/structural compatibility for forming the desired OHTs.Organic heterostructures with controlled geometry on the micro and nanoscale are important in nanotechnology, but epitaxial growth processes with high lattice mismatching are challenging to achieve. Here, the authors report a visualisation process for morphology evolution on epitaxial growth. [ABSTRACT FROM AUTHOR]

Electromagnetic stirring is one of the widely applied techniques to modify the quality of casting billets. Different from conventional rotate stirring, the helical stirring is more professional in assisting multi-dimensional flow of molten metal and eliminating solidification defects. In this study, the single-winding helical stirring (SWHS) was introduced, offering advantages such as smaller volume and lower electromagnetic shielding compared to traditional helical stirring methods. Following a comprehensive numerical simulation, the stirring parameters of SWHS were adjusted to yoke inclination angle of 43° and frequency of 12 Hz. The higher electromagnetic force and flow velocity in drawing direction, as well as the lower temperature gradient induced by the SWHS, are positive factors for homogeneous solidification of billet. The experimental results on Al-8%Si alloy and 0.4%C-1.1%Mn steel demonstrate that compared to rotate stirring, the SWHS process can induce better billet quality and is more effective in accelerating the equiaxed expansion and reducing element segregation. The SWHS process can enhance the equiaxed ratio of the billet by 58.3% and reduce segregation degree of carbon element by 10.97%. Consequently, SWHS holds great promise as a potential approach for improving the quality of continuous casting billets. [ABSTRACT FROM AUTHOR]

Introduction: Psoriasis, an incurable chronic inflammatory disease, affects over 6 million people in China. Ixekizumab, a monoclonal antibody against interleukin-17A, has demonstrated efficacy and safety for the treatment of moderate-to-severe plaque psoriasis, although limited data are available regarding its use in routine clinical practice in China. We investigated the real-world application of ixekizumab in China. Methods: Adults (≥ 18 years) with moderate-to-severe plaque psoriasis prescribed ixekizumab in routine clinical practice were enrolled in this prospective, observational, single-arm, multicenter, post-marketing surveillance study. The primary endpoint was the safety of ixekizumab at week 12. The effectiveness of ixekizumab, based on the Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI), was assessed as a secondary endpoint. Results: In total, 666 patients were enrolled; 663 were included in the safety analysis, and 612 in the effectiveness analysis. At least one adverse event (AE) was reported by 42.7% (283/663) of patients, most of which were mild (242/283, 85.5%), and 32.7% (217/663) of patients reported AEs related to study treatment. The most frequently reported AEs were injection site reactions. AEs led to discontinuation in five patients (0.8%). Only three patients had a serious AE. Mean ± standard deviation (SD) change from baseline in PASI score was reduction in 10.79 ± 9.55 at week 2 and 16.80 ± 12.15 at week 12. At week 2, 63.7% of patients achieved PASI 50. At week 12, 93.2%, 77.4%, and 45.1% of patients achieved PASI 75, PASI 90, and PASI 100, respectively. Mean ± SD change from baseline in DLQI was reduction in 5.91 ± 6.27 at week 2 and 9.76 ± 7.16 at week 12. DLQI 0/1 was achieved by 19.8% and 59.9% of patients at week 2 and 12, respectively. Conclusion: Ixekizumab was well tolerated and effective in real-world clinical practice in Chinese adults with moderate-to-severe plaque psoriasis. [ABSTRACT FROM AUTHOR]

With the rapidly growing body of medical knowledge, physicians must engage in lifelong learning. Physicians' orientation toward lifelong learning is of crucial importance. This study aimed to explore the effects of job characteristics on physicians' lifelong learning. A multicenter study collecting data from physicians from three medical centers in Taiwan was performed. A total of 321 physicians were surveyed with the Chinese version of the Job Content Questionnaire (C-JCQ) and the revised Jefferson Scale of Physician Lifelong Learning (JeffSPLL) to assess their job characteristics (i.e., job demands, job control, social support) and orientation toward lifelong learning. Exploratory factor analysis was employed to validate both questionnaires. Hierarchical regression was utilized to explore the relationship of job characteristics and predictors with physicians' lifelong learning. The results revealed that job demands (β = 0.10), job control (β = 0.19), social support from supervisors (β = 0.16), the interaction of job demands × job control (β = − 0.11) and the interaction of job demands × social support from colleagues (β = 0.13) were significantly (p <.05, p <.001) related to lifelong learning. Moreover, physicians in the active group (high demand, high control) possessed a stronger orientation toward lifelong learning (mean = 3.57) than those in the low-strain group (mean = 3.42), high-strain group (mean = 3.39) and passive group (mean = 3.20). In conclusion, examining physicians' job demands, job control and social support helps us to understand their orientation toward lifelong learning and may provide insight to improve educational strategies. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune disease of unexplained causes. Its pathological features include synovial tissue hyperplasia, inflammatory cell infiltration in joint cavity fluid, cartilage bone destruction, and joint deformation. C–C motif chemokine ligand 3 (CCL3) belongs to inflammatory cell chemokine. It is highly expressed in inflammatory immune cells. Increasingly, studies have shown that CCL3 can promote the migration of inflammatory factors to synovial tissue, the destruction of bone and joint, angiogenesis, and participate in the pathogenesis of RA. These symptoms indicate that the expression of CCL3 is highly correlated with RA disease. Therefore, this paper reviews the possible mechanism of CCL3 in the pathogenesis of RA, which may provide some new insights for the diagnosis and treatment of RA. [ABSTRACT FROM AUTHOR]

Chaperone-mediated autophagy (CMA) plays multiple roles in cell metabolism. We found that lysosome-associated membrane protein type 2A (LAMP2A), a crucial protein of CMA, plays a key role in the control of mesenchymal stem cell (MSC) adipo-osteogenesis. We identified a differentially expressed CMA gene (LAMP2) in GEO datasets (GSE4911 and GSE494). Further, we performed co-expression analyses to define the relationships between CMA components genes and other relevant genes including Col1a1, Runx2, Wnt3 and Gsk3β. Mouse BMSCs (mMSCs) exhibiting Lamp2a gene knockdown (LA-KD) and overexpression (LA-OE) were created using an adenovirus system; then we investigated LAMP2A function in vitro by Western blot, Oil Red staining, ALP staining, ARS staining and Immunofluorescence analysis. Next, we used a modified mouse model of tibial fracture to investigate LAMP2A function in vivo. LAMP2A knockdown in mMSCs decreased the levels of osteogenic-specific proteins (COL1A1 and RUNX2) and increased those of the adipogenesis markers PPARγ and C/EBPα; LAMP2A overexpression had the opposite effects. The active-β-catenin and phospho-GSK3β (Ser9) levels were upregulated by LAMP2A overexpression and downregulated by LAMP2A knockdown. In the mouse model of tibial fracture, mMSC-overexpressing LAMP2A improved bone healing, as demonstrated by microcomputed tomography and histological analyses. In summary, LAMP2A positively regulates mMSC osteogenesis and suppresses adipo-osteogenesis, probably via Wnt/β-catenin/GSK3β signaling. LAMP2A promoted fracture-healing in the mouse model of tibial fracture. Key messages: • LAMP2 positively regulates the mBMSCs osteogenic differentiation. • LAMP2 negatively regulates the mBMSCs adipogenic differentiation. • LAMP2 regulates mBMSCs osteogenesis via Wnt/β-catenin/GSK3β signaling pathway. • LAMP2 overexpression mBMSCs promote the fracture healing. [ABSTRACT FROM AUTHOR]

As a candidate bound for the Binary Black Hole (BBH) merger events detected by LIGO/Virgo, Primordial Black Holes (PBHs) provide a useful tool to investigate the primordial curvature perturbations on small scales. Using the GWTC-1 to GWTC-3 catalogs, under the scenario that PBHs originate from large primordial curvature perturbations on small scales during inflationary epoch, we for the first time reconstruct the power spectrum of primordial curvature perturbations on small scales. It is found that the value of the amplitude of the primordial power spectrum is enhanced to O ( 10 − 2 ) on scales O (1) pc . This may imply the validity of PBH as a possible BBH merger candidate. [ABSTRACT FROM AUTHOR]

Various deterministic and uncertain factors are widely present in mechanical equipment and their working conditions. Attenuation of the contact stiffness of bolted joints caused by bolt loosening will directly affect the dynamic characteristics of the joint surface and the working state of the equipment. This paper proposes a contact stiffness attenuation model that considers time-varying uncertainty of the bolt pre-tightening force as a theoretical basis for designing the initial bolt pre-tightening force and secondary tightening strategies. First, the microscopic contact mechanism of the bolted joint surface was revealed, and then a joint contact load and contact stiffness model based on Hertz contact theory and fractal theory was established. A nonlinear mechanical model of the bolted contact surface was obtained. Considering the decrease in bolt pre-tightening force during service, a contact stiffness attenuation law for bolted joints is explored, and a model of the connection reliability of group bolt joints with time-varying uncertainty is established. The bolt pre-tightening force of a railway locomotive was taken as an example and the connection reliability of group bolt structures was predicted, and it is defined that the bolted structure fails when the contact stiffness drops to 80% of the initial value, and the reliability of the group bolts will drop sharply on the 15th day after service, and will almost completely fail on the 22nd day. The proposed theory improves the accuracy of contact modeling and provides a new direction for bolt tightening strategies. [ABSTRACT FROM AUTHOR]

Purpose: Hepatitis B virus (HBV) infection is such a global health problem that hundreds of millions of people are HBV carriers. Current anti-viral agents can inhibit HBV replication, but can hardly eradicate HBV. Cytosine-phosphate-guanosine (CpG) oligodeoxynucleotides (ODNs) are an adjuvant that can activate plasmacytoid dendritic cells (pDCs) and conventional dendritic cells (cDCs) to induce therapeutic immunity for HBV eradication. However, efficient delivery of CpG ODNs into pDCs and cDCs remains a challenge. In this study, we constructed a series of cationic lipid-assisted nanoparticles (CLANs) using different cationic lipids to screen an optimal nanoparticle for delivering CpG ODNs into pDCs and cDCs. Methods: We constructed different CLANCpG using six cationic lipids and analyzed the cellular uptake of different CLANCpG by pDCs and cDCs in vitro and in vivo, and further analyzed the efficiency of different CLANCpG for activating pDCs and cDCs in both wild type mice and HBV-carrier mice. Results: We found that CLAN fabricated with 1,2-Dioleoyl-3-trimethylammonium propane (DOTAP) showed the highest efficiency for delivering CpG ODNs into pDCs and cDCs, resulting in strong therapeutic immunity in HBV-carrier mice. By using CLANCpG as an immune adjuvant in combination with the injection of recombinant hepatitis B surface antigen (rHBsAg), HBV was successfully eradicated and the chronic liver inflammation in HBV-carrier mice was reduced. Conclusion: We screened an optimized CLAN fabricated with DOTAP for efficient delivery of CpG ODNs to pDCs and cDCs, which can act as a therapeutic vaccine adjuvant for treating HBV infection. [ABSTRACT FROM AUTHOR]

Despite the environmental challenges and nutrient scarcity, the geographically isolated Challenger Deep in Mariana trench, is considered a dynamic hotspot of microbial activity. Hadal viruses are the least explored microorganisms in Challenger Deep, while their taxonomic and functional diversity and ecological impact on deep-sea biogeochemistry are poorly described. Here, we collect 13 sediment cores from slope and bottom-axis sites across the Challenger Deep (down to ~11 kilometers depth), and identify 1,628 previously undescribed viral operational taxonomic units at species level. Community-wide analyses reveals 1,299 viral genera and distinct viral diversity across the trench, which is significantly higher at the bottom-axis vs. slope sites of the trench. 77% of these viral genera have not been previously identified in soils, deep-sea sediments and other oceanic settings. Key prokaryotes involved in hadal carbon and nitrogen cycling are predicted to be potential hosts infected by these viruses. The detected putative auxiliary metabolic genes suggest that viruses at Challenger Deep could modulate the carbohydrate and sulfur metabolisms of their potential hosts, and stabilize host's cell membranes under extreme hydrostatic pressures. Our results shed light on hadal viral metabolic capabilities, contribute to understanding deep sea ecology and on functional adaptions of hadal viruses for future research. Analysis of 13 sediment cores from the Challenger Deep of Marian Trench (down to 11 kilometers depth) identified distinct operational taxonomic units and relevant auxiliary metabolic genes, providing further insight into deep-sea viral metabolic capabilities and ecology. [ABSTRACT FROM AUTHOR]

The Heisenberg product is an associative product defined on symmetric functions which interpolates between the usual product and the Kronecker product. In 1938, Murnaghan discovered that the Kronecker product of two Schur functions stabilizes. We prove an analogous result for the Heisenberg product of Schur functions. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) were analyzed in a variety of coastal marine seafood from the Wentai fishing area, which is in proximity to highly urbanized areas and provides a significant portion of the marine aquatic products in Eastern China. Specifically, total PAHs ranged from 320 to 2500 ng/g d.w., whereas carcinogenic PAHs ranged from 21 to 92 ng/g d.w. According to the source diagnosis, the PAHs in the seafood were generally from sources highly related to fossil fuel. Thus, it is necessary to control the unintentional use of fossil fuels and optimize the energy structure in the terrestrial area nearby. Moreover, the food chain structure and the environmental behavior of PAHs through the food chain, which are relevant to dietary risk, were assessed. The δ15N values fell in a narrow range, which indicates a relatively short food chain, which is due to overfishing in this area. Furthermore, in this shortened food chain, the trophic magnification factors (TMFs) ranged from 0.23 to 6.6, which were generally higher than those in more complex food chains. The cancer risk (ILCR) ranged from 2.2 × 10−8 to 2.2 × 10−6. It is noted that the carcinogenic risk of consuming yellow croaker, which is one of the most popular seafood among people on the east coast of China, was the highest. In conclusion, trophic magnification implied a possible elevated risk through this marine food chain, and overfishing may have increased the uncertainty associated with TMF estimations. [ABSTRACT FROM AUTHOR]

In order to effectively prolong the lifetime of wireless sensor network and balance network energy consumption, a WSN clustering routing algorithm based on hybrid genetic tabu search (CRGT) is proposed. Firstly, in the stage of cluster head election, two parameters, the residual energy of nodes and the distance from nodes to Sink node, are introduced to optimize the threshold function to make the cluster head election more reasonable. Secondly, in the stage of clustering, ordinary nodes join the cluster with the lowest cost according to the cost function to balance the node energy. Finally, a hybrid genetic tabu search algorithm is introduced to select the optimal path with the least energy consumption during data transmission. The simulation results show that, compared with the other two clustering routing algorithms, CRGT algorithm effectively prolongs the network lifetime, and the energy consumption is more balanced. [ABSTRACT FROM AUTHOR]

Introduction: Recent studies in postmenopausal women have found associations of follicle-stimulating hormone (FSH) levels with both glucose metabolism and bone turnover. The objective of the study was to investigate whether FSH may contribute to suppressed bone turnover markers (BTMs) in postmenopausal women with type 2 diabetes (T2D). Materials and methods: 888 postmenopausal women with T2D, 352 nondiabetes (prediabetes plus normoglycemia) were included from the METAL study. HbA1c, sex hormones, 25-hydroxy vitamin D (25(OH)D), serum procollagen type I N-terminal propeptide (P1NP), and β-C-terminal telopeptide (β-CTX) were measured. Results: P1NP and β-CTX decreased in postmenopausal T2D women compared with nondiabetes controls (both p < 0.001). The major factors responsible for the changes in P1NP were HbA1c (β = − 0.050, p < 0.001), 25(OH)D (β = − 0.003, p = 0.006), FSH (β = 0.001, p = 0.044) and metformin (β = − 0.109, p < 0.001), for β-CTX were HbA1c (β = − 0.049, p < 0.001), body mass index (BMI) (β = − 0.011, p = 0.005), 25(OH)D (β = − 0.003, p = 0.003), FSH (β = 0.002, p = 0.022) and metformin (β = − 0.091, p = 0.001) in postmenopausal T2D women based on multivariate regression analysis. With the increase in HbA1c, FSH decreased significantly (p for trend < 0.001). Mediation analysis demonstrated that FSH partly mediated the suppression of LnP1NP and Lnβ-CTX by HbA1c (β = − 0.009 and − 0.010, respectively), and Lnβ-CTX by BMI (β = − 0.015) when multiple confounders were considered (all p < 0.05). Conclusion: HbA1c was the crucial determinant contributing to the suppression of BTMs. FSH might play a novel mediation role in BTM suppression due to HbA1c or BMI. [ABSTRACT FROM AUTHOR]

With the adjustment of social relations and interest patterns brought about by the comprehensive deepening reform in China, new and old contradictions are intertwined, various risks are increased, collective actions occasionally occur, and some new trends are observed. However, due to there is no authoritative database of collective action in China, it is difficult to observe the trend of collective actions. There has been significant research show that news coverage is an effective way to obtain collective action information. Thus, we examine the recent news coverage shift in terms of collective action. We collected 5354 news coverages from 2014 to 2018. Then, we constructed a collective action domain-specific word dictionary and presented a method to automatically detect temporal, spatial, and topical trends of collective action. The proposed framework is based on text mining analysis that collects data from news outlets and extracts valuable data for perceiving the collective action trends. The results show that the proposed method is an effective tool to identify the trends in collective action via machine learning. [ABSTRACT FROM AUTHOR]

Hadal trenches are the deepest and most remote regions of the ocean. The 11-kilometer deep Challenger Deep is the least explored due to the technical challenges of sampling hadal depths. It receives organic matter and heavy metals from the overlying water column that accumulate differently across its V-shaped topography. Here, we collected sediments across the slope and bottom-axis of the Challenger Deep that enable insights into its in situ microbial communities. Analyses of 586 metagenome-assembled genomes retrieved from 37 metagenomes show distinct diversity and metabolic capacities between bottom-axis and slope sites. 26% of prokaryotic 16S rDNA reads in metagenomes were novel, with novelty increasing with water and sediment depths. These predominantly heterotrophic microbes can recycle macromolecules and utilize simple and complex hydrocarbons as carbon sources. Metagenome and metatranscriptome data support reduction and biotransformation of arsenate for energy gain in sediments that present a two-fold greater accumulation of arsenic compared to non-hadal sites. Complete pathways for anaerobic ammonia oxidation are predominantly identified in genomes recovered from bottom-axis sediments compared to slope sites. Our results expand knowledge of microbially-mediated elemental cycling in hadal sediments, and reveal differences in distribution of processes involved in nitrogen loss across the trench. The V-shaped Challenger Deep in the Mariana Trench is the deepest part of the world's oceans. Using 586 prokaryotic metagenome-assembled genomes and metatranscriptomic data, this study explores metabolic capabilities and activities of microorganisms involved in elemental cycling in hadal sediments, and reveals the different distribution of processes between its bottom-axis and slope. [ABSTRACT FROM AUTHOR]

With the emergence of multidrug resistance (MDR) in many pathogens, bacterial infections are becoming a growing threat to public health. The frightening scenario is due largely to the formation of biofilms, in which the bacteria are extremely recalcitrant to the conventional antibiotic regimens. To address the emergence of MDR and biofilm-associated infections, numerous polymer-based materials have been designed and prepared recently. The subject of this perspective is the recent development of polymer-based materials that have been applied to combat multidrug-resistant pathogens, to prevent the formation of biofilms, or enhance the eradication efficacy to mature biofilms via killing biofilm-bacteria or dispersing biofilms. The advantages and shortcomings of these polymer-based materials are discussed, as well as the challenges we are facing in the clinical translation of these systems. [ABSTRACT FROM AUTHOR]

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A new cocrystal of baicalein, possessing three A-ring-hydroxyl groups and without B-ring-hydroxyl groups and 4,4′-bipyridine (BE·2BPY·H2O) has been prepared and characterized. The structural analyses and Hirshfeld surfaces show that baicalein is hydrogen-bonded to co-crystallized solvent water molecules featuring for example motifs that can be described with graph set R44(8) similar to those reported for the cocrystal of myricetin with 4,4′-bipyridine. A zipper-type architecture is observed in cocrystal BE·2BPY·H2O linking a baicalein, two 4,4′-bipyridine and a solvent water molecules via classical O–H⋯N and O–H⋯O and non-classical C–H⋯O hydrogen bonds into 2D sheets. Additionally, the cocrystal shows better solubility in 0.1 M HCl in comparison to pure baicalein. Cocrystal of baicalein with zipper-type architecture shows improved solubility compared to baicalein. [ABSTRACT FROM AUTHOR]

Although iron oxide (Fe3O4) nanoparticles have broad application prospects as magnetic resonance imaging (MRI) contrast agent, their biocompatibility and biotoxicity still need to be improved. In this study, we prepared Fe3O4@Angelica sinensis polysaccharide nanoparticles (Fe3O4@ASP NPs) with a 9 nm Fe3O4 core and ASP as the coating material. The Fe3O4@ASP NPs are superparamagnetic, can be taken up by liver and spleen macrophages in the circulatory system in vivo, and are a good-biocompatibility and low-toxicity transverse relaxation time (T2) and T2-star (T2*) magnetic resonance imaging (MRI) contrast agent for the liver. The cytotoxicity assessment using HeLa cells and the pathological tests in mice validate that Fe3O4@ASP NPs have low toxicity and good biocompatibility in vivo, which can be attributed to the ASP as a natural polysaccharide with good biocompatibility and its function of protecting the liver. Fe3O4@ASP NPs are a potential new MRI contrast agent with high signal intensity in vivo. [ABSTRACT FROM AUTHOR]

Hot-rolled high-Mg-alloyed Al–Mg alloy (Al–9.2Mg–0.8Mn–0.2Zr–0.15Ti, labeled as 5A12) plates were successfully friction stir welded at rotating rates ranging from 750 to 1500 r·min−1 at a constant welding speed of 50 mm·min−1. The joints were characterized by optical microscopy (OM), electron backscatter diffraction (EBSD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), electron-dispersive spectroscopy (EDS), and tensile testing. All the joints are volume defect-free and exhibit fine, equiaxed dynamic recrystallization (DRX) grains with high-angle grain boundaries (HAGBs) fractions of 88.6%–93.3% in the nugget zones (NZs). The DRX grain size and the second-phase particle size in the NZs have a parabolic relation with the rotating rate. Furthermore, among the joints tested, the joint prepared at 1000 r·min−1, which has the highest ultimate tensile strength ((478 ± 3) MPa) and the largest elongation to rupture (22.5% ± 1.4%)—approximately 87.5% and 145.2% those of the base metal, respectively, exhibits the smallest grain size of 2.93 μm, as well as the smallest particle size in the NZs. These excellent mechanical properties can be ascribed to the combined effects of the fine DRX grains with high fraction of HAGBs and the fine second-phase particles with a uniform distribution. [ABSTRACT FROM AUTHOR]

Increased expression of branched-chain amino acid transaminase 1 or 2 (BCAT1 and BCAT2) has been associated with aggressive phenotypes of different cancers. Here we identify a gain of function of BCAT1 glutamic acid to alanine mutation at codon 61 (BCAT1 E61A ) enriched around 2.8% in clinical gastric cancer samples. We found that BCAT1 E61A confers higher enzymatic activity to boost branched-chain amino acid (BCAA) catabolism, accelerate cell growth and motility and contribute to tumor development. BCAT1 directly interacts with RhoC, leading to elevation of RhoC activity. Notably, the BCAA-derived metabolite, branched-chain α-keto acid directly binds to the small GTPase protein RhoC and promotes its activity. BCAT1 knockout-suppressed cell motility could be rescued by expressing BCAT1 E61A or adding branched-chain α-keto acid. We also identified that candesartan acts as an inhibitor of BCAT1 E61A , thus repressing RhoC activity and cancer cell motility in vitro and preventing peritoneal metastasis in vivo. Our study reveals a link between BCAA metabolism and cell motility and proliferation through regulating RhoC activation, with potential therapeutic implications for cancers., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The link between branched-chain amino acids (BCAAs) and obesity has been known for decades but the functional role of BCAA metabolism in white adipose tissue (WAT) of obese individuals remains vague. Here, we show that mice with adipose tissue knockout of Bcat2, which converts BCAAs to branched-chain keto acids (BCKAs), are resistant to high-fat diet-induced obesity due to increased inguinal WAT browning and thermogenesis. Mechanistically, acetyl-CoA derived from BCKA suppresses WAT browning by acetylation of PR domain-containing protein 16 (PRDM16) at K915, disrupting the interaction between PRDM16 and peroxisome proliferator-activated receptor-γ (PPARγ) to maintain WAT characteristics. Depletion of BCKA-derived acetyl-CoA robustly prompts WAT browning and energy expenditure. In contrast, BCKA supplementation re-establishes high-fat diet-induced obesity in Bcat2 knockout mice. Moreover, telmisartan, an anti-hypertension drug, significantly represses Bcat2 activity via direct binding, resulting in enhanced WAT browning and reduced adiposity. Strikingly, BCKA supplementation reverses the lean phenotype conferred by telmisartan. Thus, we uncover the critical role of the BCAA-BCKA axis in WAT browning., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)