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Abstract Background Computed tomography (CT) is the usual modality for diagnosing stroke, but conventional CT angiography reconstructions have limitations. Methods A phantom with tubes of known diameters and wall thickness was scanned for wall detectability, wall thickness, and contrast-to-noise ratio (CNR) on conventional and spectral black-blood (SBB) images. The clinical study included 34 stroke patients. Diagnostic certainty and conspicuity of normal/abnormal intracranial vessels using SBB were compared to conventional. Sensitivity/specificity/accuracy of SBB and conventional were compared for plaque detectability. CNR of the wall/lumen and quantitative comparison of remodeling index, plaque burden, and eccentricity were obtained for SBB imaging and high-resolution magnetic resonance imaging (hrMRI). Results The phantom study showed improved detectability of tube walls using SBB (108/108, 100% versus conventional 81/108, 75%, p

Abstract Although it is well documented that mountains tend to exhibit high biodiversity, how geological processes affect the assemblage of montane floras is a matter of ongoing research. Here, we explore landform-specific differences among montane floras based on a dataset comprising 17,576 angiosperm species representing 140 Chinese mountain floras, which we define as the collection of all angiosperm species growing on a specific mountain. Our results show that igneous bedrock (granitic and karst-granitic landforms) is correlated with higher species richness and phylogenetic overdispersion, while the opposite is true for sedimentary bedrock (karst, Danxia, and desert landforms), which is correlated with phylogenetic clustering. Furthermore, we show that landform type was the primary determinant of the assembly of evolutionarily older species within floras, while climate was a greater determinant for younger species. Our study indicates that landform type not only affects montane species richness, but also contributes to the composition of montane floras. To explain the assembly and differentiation of mountain floras, we propose the ‘floristic geo-lithology hypothesis’, which highlights the role of bedrock and landform processes in montane floristic assembly and provides insights for future research on speciation, migration, and biodiversity in montane regions.

Abstract Background Mind wandering is a common phenomenon in daily life. However, the manifestations and cognitive correlates of mind wandering in different subclinical populations remain unclear. In this study, these aspects were examined in individuals with schizotypal traits and individuals with depressive symptoms, i.e., subclinical populations of patients with schizophrenia and depression. Methods Forty-two individuals with schizotypal traits, 42 individuals with subclinical depression, and 42 controls were recruited to complete a mind wandering thought sampling task (state level) and a mind wandering questionnaire (trait level). Measures of rumination and cognitive functions (attention, inhibition, and working memory) were also completed by participants. Results Both subclinical groups exhibited more state and trait mind wandering than did the control group. Furthermore, individuals with schizotypal traits demonstrated more trait mind wandering than individuals with subclinical depression. Rumination, sustained attention, and working memory were associated with mind wandering. In addition, mind wandering in individuals with subclinical depression can be accounted for by rumination or attention, while mind wandering in individuals with high schizotypal traits cannot be accounted for by rumination, attention, or working memory. Conclusions The results suggest that individuals with high schizotypal traits and subclinical depression have different patterns of mind wandering and mechanisms. These findings have implications for understanding the unique profile of mind wandering in subclinical individuals.

Abstract The elderly frequently present impaired blood–brain barrier which is closely associated with various neurodegenerative diseases. However, how the albumin, the most abundant protein in the plasma, leaking through the disrupted BBB, contributes to the neuropathology remains poorly understood. We here demonstrated that mouse serum albumin-activated microglia induced astrocytes to A1 phenotype to remarkably increase levels of Elovl1, an astrocytic synthase for very long-chain saturated fatty acids, significantly promoting VLSFAs secretion and causing neuronal lippoapoptosis through endoplasmic reticulum stress response pathway. Moreover, MSA-activated microglia triggered remarkable tau phosphorylation at multiple sites through NLRP3 inflammasome pathway. Intracerebroventricular injection of MSA into the brains of C57BL/6J mice to a similar concentration as in patient brains induced neuronal apoptosis, neuroinflammation, increased tau phosphorylation, and decreased the spatial learning and memory abilities, while Elovl1 knockdown significantly prevented the deleterious effect of MSA. Overall, our study here revealed that MSA induced tau phosphorylation and neuron apoptosis based on MSA-activated microglia and astrocytes, respectively, showing the critical roles of MSA in initiating the occurrence of tauopathies and cognitive decline, and providing potential therapeutic targets for MSA-induced neuropathology in multiple neurodegenerative disorders.

Abstract The neurotoxic α-synuclein (α-syn) oligomers play an important role in the occurrence and development of Parkinson’s disease (PD), but the factors affecting α-syn generation and neurotoxicity remain unclear. We here first found that thrombomodulin (TM) significantly decreased in the plasma of PD patients and brains of A53T α-syn mice, and the increased TM in primary neurons reduced α-syn generation by inhibiting transcription factor p-c-jun production through Erk1/2 signaling pathway. Moreover, TM decreased α-syn neurotoxicity by reducing the levels of oxidative stress and inhibiting PAR1-p53-Bax signaling pathway. In contrast, TM downregulation increased the expression and neurotoxicity of α-syn in primary neurons. When TM plasmids were specifically delivered to neurons in the brains of A53T α-syn mice by adeno-associated virus (AAV), TM significantly reduced α-syn expression and deposition, and ameliorated the neuronal apoptosis, oxidative stress, gliosis and motor deficits in the mouse models, whereas TM knockdown exacerbated these neuropathology and motor dysfunction. Our present findings demonstrate that TM plays a neuroprotective role in PD pathology and symptoms, and it could be a novel therapeutic target in efforts to combat PD. Schematic representation of signaling pathways of TM involved in the expression and neurotoxicity of α-syn. A TM decreased RAGE, and resulting in the lowered production of p-Erk1/2 and p-c-Jun, and finally reduce α-syn generation. α-syn oligomers which formed from monomers increase the expression of p-p38, p53, C-caspase9, C-caspase3 and Bax, decrease the level of Bcl-2, cause mitochondrial damage and lead to oxidative stress, thus inducing neuronal apoptosis. TM can reduce intracellular oxidative stress and inhibit p53-Bax signaling by activating APC and PAR-1. B The binding of α-syn oligomers to TLR4 may induce the expression of IL-1β, which is subsequently secreted into the extracellular space. This secreted IL-1β then binds to its receptor, prompting p65 to translocate from the cytoplasm into the nucleus. This translocation downregulates the expression of KLF2, ultimately leading to the suppression of TM expression. By Figdraw.

A reaction model for γ+p→J/ψ+p photoproduction, which exposes the cc¯ content of the photon in making the transition γ→cc¯+P→J/ψ and couples the intermediate cc¯ system to the proton's valence quarks via Pomeron (P) exchange, is used to deliver a description of available data, viz. both differential and total cross sections from near threshold, where data has newly been acquired, to invariant mass W≈300GeV. The study suggests that it is premature to link existing γ+p→J/ψ+p data with, for instance, in-proton gluon distributions, the quantum chromodynamics trace anomaly, or pentaquark production. Further developments in reaction theory and higher precision data are necessary before the validity of any such connections can be assessed.

Abstract Owing to the increasing market demand of Codonopsis Radix, the cropper blindly cultivates to expand planting area for economic benefits, which seriously affects the quality of Codonopsis Radix. Therefore, this study synthesized 207 batches of Codonopsis Radix and 115 ecological factors, and analyzed the suitable planting areas of Codonopsis pilosula under current and future climate change based on Geographic Information System (GIS) and MaxEnt model. Secondly, we evaluated the quality of Codonopsis Radix based on the all-in-one functional factor including chromatographic fingerprint, the index components, the effective compounds groups, the nutritional components, and the nutritional elements, and the quality regionalization of Codonopsis Radix was analyzed. Finally, the ecological factors affecting the accumulation of effective components of Codonopsis Radix were analyzed. This study found for the first time that the highly suitable area of Codonopsis pilosula was mainly distributed in the Weihe River system and the Bailongjiang River system in Gansu Province. There were differences in the quality of Codonopsis Radix from different ecologically suitable areas based on the all-in-one functional factors, and the comprehensive high-quality area of Codonopsis Radix was mainly distributed in Longnan and Longxi district of Gansu Province. The precipitation, temperature and altitude play a key role in the accumulation of chemical components in the 10 ecological factors affecting the distribution of Codonopsis pilosula. Under future climatic conditions, the highly suitable area of Codonopsis pilosula is decreased.

Abstract Background Efforts to precisely assess tumor-specific T-cell immune responses still face major challenges, and the potential molecular mechanisms mediating hepatocellular carcinoma (HCC) microenvironment imbalance after incomplete radiofrequency ablation (iRFA) are unclear. This study aimed to provide further insight into the integrated transcriptomic and proteogenomic landscape and identify a new target involved in HCC progression following iRFA. Methods Peripheral blood and matched tissue samples were collected from 10 RFA-treated HCC patients. Multiplex immunostaining and flow cytometry were used to assess local and systemic immune responses. Differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were explored via transcriptomic and proteogenomic analyses. Proteinase-3 (PRTN3) was identified in these analyses. And then, the ability of PRTN3 to predict overall survival (OS) was assessed in 70 HCC patients with early recurrence after RFA. In vitro CCK-8, wound healing and transwell assays were conducted to observe interactions between Kupffer cells (KCs) and HCC cells induced by PRTN3. The protein levels of multiple oncogenic factors and signaling pathway components were detected by western blotting. A xenograft mouse model was built to observe the tumorigenic effect of PRTN3 overexpression on HCC. Results Multiplex immunostaining revealed no immediate significant change in local immune cell counts in periablational tumor tissues after 30 min of iRFA. Flow cytometry showed significantly increased levels of CD4+ T cells, CD4+CD8+ T cells, and CD4+CD25+CD127− Tregs and significantly decreased the levels of CD16+CD56+ natural killer cells on day 5 after cRFA (p

All sources of power which can initiate unlocking or unlatching of any cabin doors must be isolated from the latching and locking systems prior to flight, and the key structural parts of flight safety must be able to bear the structural limit loads and ultimate loads, and the method of continuous airworthiness event monitoring based on risk management must depend on the adequate of monitoring data.The airworthiness requirements are interpreted in combination with actual cases, which has a certain referent to aircraft cabin door researchers and aircraft continuous airworthiness researchers.Based on this, taking the accident investigation report of United Airlines Flight 811 as the blueprint, and according to the current domestic airworthiness regulations and normative documents, the method of analytical interpretation is used to study the exposed problems.The results show that the design of the driving system of the front cargo compartment latch of Flight 811 did not meet the airworthiness requirements that it was necessary to disconnect the latch before flight and could not restore power to the cabin door during flight.The design of L-shaped anchor for the front cargo hold door of Flight 811 did not meet the requirements of load design and verification in airworthiness regulations.FAA made mistakes in its assessment of the safety impact and airworthiness risk level of the opening of the front cargo hold door of the aircraft in flight.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) for patients with periampullary diverticulum (PAD) remains a challenge. This study aims to investigate the factors and techniques related to successful and safe ERCP in patients with PAD. Methods: We enrolled patients who underwent ERCP in a large tertiary center. The difficult cannulation rate, technical success rate, clinical success rate, and adverse events (AEs) rate were compared between patients with or without PAD. Three independent logistic regression models were established to identify factors and techniques associated with difficult cannulation, clinical success, and AEs. Results: Five thousand five hundred and ninety patients were included, of which 705 (12.6%) were diagnosed with PAD. Patients with PAD had a significantly higher difficult cannulation rate compared with patients without PAD (10.6% vs 8.0%, P < 0.0001), but the rates of technical success (clinical success (95.2% vs 95.2%, P = 0.951), and AEs (16.5% vs 14.4%, P = 0.156) were similar. Type I PAD (odds ratio [OR] = 2.114, 95% confidence interval [CI]:1.05-5.25) and ERCP indication for pancreatic diseases (OR = 1.196, 95%CI: 1.053-1.261) were independently associated with difficult cannulation. Small endoscopic sphincterotomy (EST) with balloon dilatation (OR = 1.581, 95%CI: 1.044-2.393) was independently associated with clinical success. Somatostatin injection showed no preventive effect on post-ERCP pancreatitis (OR = 1.144, 95%CI: 1.044-1.254). Moreover, the auxiliary cannulation techniques were safe for PAD patients. Conclusions: PAD did not affect ERCP outcomes. However, the choice of techniques and AE prophylactic measures should be more specific, especially for patients with type I PAD.

Dysfunction of enteropeptidase (EP) can result in pancreatitis, a life-threatening disease. Yang et al. report a series of EP structures representing the EP catalytic cycle and propose a mechanistic model of enzyme function.

Introduction: Renal ischemia-reperfusion injury (IRI) is one of the major causes of acute kidney injury, and its mechanism is complex involving multiple factors, while delayed ischemic preconditioning (DIPC) has a protective effect on the above process. In our previous study, we found that DIPC can exert its protection on renal IRI by inhibiting the maturation of dendritic cells (DCs), but the mechanism has not been clarified. This study aimed to investigate the protective mechanism of DIPC on renal IRI in mice through Treg mediated by immature DCs (imDCs). Methods: The IRI mice model, DIPC treatment, and conditional CD11c+ DCs (CD11c-DTR) knockout mice were used to perform our study. The maturation and differentiation of DCs and Treg cells in the kidney and spleen were analyzed by flow cytometry. HE staining was used to evaluate the pathology of the kidney tissue. The level of creatinine (Cr), oxidative stress factors (SOD, MDA), and inflammatory factors (TNF-α, IL-10, IL-4) were also measured. Then, imDCs were co-cultured with HK-2 cells, and apoptosis was analyzed with flow cytometry and PI-Hoechst 33,342 fluorescence staining to assess the apoptosis rate of HK-2 cells under hypoxic-reoxygenated (H/R) conditions. Results: DIPC could decrease renal Cr levels, alleviate pathological renal damage, and reduce oxidative stress and inflammation caused by IRI. Moreover, DIPC could decrease the number of mature DCs (mDCs) and increase Treg lymphocyte infiltration in the kidney tissue, while the reduction of DCs reversed this process. In addition, our in vitro experiment found that in the H/R model, the apoptosis of HK-2 cells decreased which were co-cultured with imDCs. Conclusion: DIPC can regulate the differentiation of DCs into imDCs, thus affecting the differentiation level and distribution of Treg cells to exert its protective effect on renal IRI.

Abstract Using a symmetry-preserving regularisation of a vector $$\times $$ × vector contact interaction (SCI), we complete a systematic treatment of twelve semileptonic transitions with vector meson final states: $$D\rightarrow \rho $$ D → ρ , $$D_{(s)}\rightarrow K^*$$ D ( s ) → K ∗ , $$D_s\rightarrow \phi $$ D s → ϕ , $$B\rightarrow \rho $$ B → ρ , $$B_s\rightarrow K^*$$ B s → K ∗ , $$B_{(s)}\rightarrow D_{(s)}^*$$ B ( s ) → D ( s ) ∗ , $$B_c \rightarrow B_{(s)}^*, J/\psi , D^*$$ B c → B ( s ) ∗ , J / ψ , D ∗ ; and thereby finalise a unified analysis of semileptonic decays of heavy + heavy and heavy + light pseudoscalar mesons to both pseudoscalar and vector meson final states. The analysis is marked by algebraic simplicity, few parameters, and the ability to consistently describe systems from Nambu-Goldstone modes to heavy + heavy mesons. Regarding the behaviour of the transition form factors, the SCI results compare well wherever sound experimental or independent theory analyses are available; hence, the SCI branching fraction predictions should be a reasonable guide. Considering the ratios $$R(D_{(s)}^{(*)})$$ R ( D ( s ) ( ∗ ) ) , $$R(J/\psi )$$ R ( J / ψ ) , $$R(\eta _c)$$ R ( η c ) , whose values are key tests of lepton universality in weak interactions, the SCI values agree with Standard Model predictions. The $$B_{(s)}\rightarrow D_{(s)}^*$$ B ( s ) → D ( s ) ∗ transitions are used to predict the precursor functions that evolve into the universal Isgur–Wise function in the heavy-quark limit, with results that conform with those from other sources where such are available. The study also exposes effects on the transition form factors that flow from interference between emergent hadron mass from the strong interaction and Higgs boson couplings via current-quark masses, including flavour symmetry violation.

Trichosporeae is the largest and most taxonomically difficult tribe of Gesneriaceae due to its diverse morphology. Previous studies have not clarified the phylogenetic relationships within this tribe on several DNA markers, including the generic relationships within subtribes. Recently, plastid phylogenomics have been successfully employed to resolve the phylogenetic relationships at different taxonomic levels. In this study, plastid phylogenomics were used to explore the relationships within Trichosporeae. Eleven plastomes of Hemiboea were newly reported. Comparative analyses, phylogeny and morphological character evolution within Trichosporeae were conducted on 79 species representing seven subtribes. The Hemiboea plastomes range from 152,742 bp to 153,695 bp in length. Within Trichosporeae, the sampled plastomes range from 152,196 bp to 156,614 bp and GC content from 37.2% to 37.8%. A total of 121–133 genes were annotated in each species, including 80–91 protein-coding genes, 34–37 tRNA genes, and 8 rRNA genes. The contraction and expansion of IR borders were not detected, and gene rearrangements and inversions did not occur. The 13 hypervariable regions were proposed as the potential molecular markers for species identification. A total of 24,299 SNPs and 3,378 indels were inferred, and most of the SNPs were functionally missense and silent variations. There were 1968 SSRs, 2055 tandem repeats and 2802 dispersed repeats. The RSCU and ENC values indicated that the codon usage pattern was conserved in Trichosporeae. Both the phylogenetic frameworks based on the whole plastome and 80 CDSs were basically concordant. The sister relationships between Loxocarpinae and Didymocarpinae were confirmed, and Oreocharis was a sister group of Hemiboea with high support. The morphological characters showed a complex evolutionary pattern of Trichosporeae. Our findings may contribute to future research on genetic diversity, morphological evolutionary patterns, and conservation of the tribe Trichosporeae.

Theory suggests that in high-energy elastic hadron+hadron scattering, t-channel exchange of a family of colourless crossing-odd states – the odderon – may generate differences between pp¯ and pp cross-sections in the neighbourhood of the diffractive minimum. Using a mathematical approach based on interpolation via continued fractions enhanced by statistical sampling, we develop robust comparisons between pp¯ elastic differential cross-sections measured at √s=1.96 TeV by the D0 Collaboration at the Tevatron and function-form-unbiased extrapolations to this energy of kindred pp measurements at √s/TeV=2.76,7,8,13 by the TOTEM Collaboration at the LHC and a combination of these data with earlier cross-section measurements at √s/GeV=23.5,30.7,44.7,52.8,62.5 made at the intersecting storage rings. Focusing on a domain that straddles the diffractive minimum in the pp¯ and pp cross-sections, we find that these two cross-sections differ at the (2.2−2.6)σ level; hence, supply evidence with this level of significance for the existence of the odderon. If combined with evidence obtained through different experiment-theory comparisons, whose significance is reported to lie in the range (3.4−4.6)σ, one arrives at a (4.0−5.2)σ signal for the odderon.

Wireless sensor networks (WSNs) are widely used in various fields such as military, industrial, and transportation for real-time monitoring, sensing, and data collection of different environments or objects. However, the development of WSNs is hindered by several limitations, including energy, storage space, computing power, and data transmission rate. Among these, the availability of power energy plays a crucial role as it directly determines the lifespan of WSN. To extend the life cycle of WSN, two key approaches are power supply improvement and energy conservation. Therefore, we propose an energy harvesting system and a low-energy-consumption mechanism for WSNs. Firstly, we delved into the energy harvesting technology of WSNs, explored the utilization of solar energy and mechanical vibration energy to ensure a continuous and dependable power supply to the sensor nodes, and analyzed the voltage output characteristics of bistable piezoelectric cantilever. Secondly, we proposed a neighbor discovery mechanism that utilizes a separation beacon, is based on reply to ACK, and can facilitate the identification of neighboring nodes. This mechanism operates at a certain duty cycle ratio, significantly reduces idle listening time and results in substantial energy savings. In comparison to the Disco and U-connect protocols, our proposed mechanism achieved a remarkable reduction of 66.67% and 75% in the worst discovery delay, respectively. Furthermore, we introduced a data fusion mechanism based on integer wavelet transform. This mechanism effectively eliminates data redundancy caused by spatiotemporal correlation, resulting in a data compression rate of 5.42. Additionally, it significantly reduces energy consumption associated with data transmission by the nodes.

Auxin (indole-3-acetic acid, IAA) has a considerable impact on the regulation of plant carbohydrate levels and growth, but the mechanism by which it regulates sugar levels in plants has received little attention. In this study, we found that exogenous IAA altered fructose (Fru), glucose (Glc), and sucrose (Suc) concentrations in shoot tips mainly by regulating MdSUSY1, MdFRK2, MdHxK1 and MdSDH2 transcript levels. Additionally, we used 5-year-old ‘Royal Gala’ apple trees to further verify that these genes play primary roles in regulating sink strength. The results showed that MdSUSY1, MdFRK2, MdHxK1/3 and MdSDH2 might be major contributors to sink strength regulation. Taken together, these results provide new insight into the regulation of the carbohydrate metabolism mechanism, which will be helpful for regulating sink strength and yield.

The original specimens of both Prunus zappeyana and P. zappeyana var. subsimplex were found to belong to more than one taxon. In addition, P. zappeyana var. subsimplex was found to be invalid because, when the name was published, two separate descriptions were given to two cited collections, but not to the taxon, making the name unaccompanied with a description or diagnosis of this taxon (Art. 38.1 (a)). Therefore, a lectotype of P. zappeyana was designated under Art. 9.11 of ICN, by which P. zappeyana was placed in the synonymy of P. veitchii.

Our previous study demonstrated that chronic intermittent hypobaric hypoxia (CIHH) protects vascular endothelium function through ameliorating autophagy in mesenteric arteries of metabolic syndrome (MS) rats. This study aimed to investigate the role of adenosine mono-phosphate-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR) signaling in CIHH effect. Six-week-old male Sprague-Dawley rats were divided into control (CON), MS model, CIHH treatment (CIHH), and MS + CIHH groups. Serum pro-inflammatory cytokines were measured. The endothelium dependent relaxation (EDR), endothelial ultrastructure and autophagosomes were observed in mesenteric arteries. The expression of phosphor (p)-AMPKα, p-mTOR, autophagy-related and endoplasmic reticulum stress-related proteins, p-endothelial nitric oxide synthase, and cathepsin D were assayed. In MS rats, pro-inflammatory cytokines were increased, EDR was attenuated, and endothelial integrity was impaired. In addition, the expression level of p-AMPKα and cathepsin D was down-regulated, but the level of p-mTOR was up-regulated. While in MS + CIHH rats, all aforementioned abnormalities were ameliorated, and the beneficial effect of CIHH was cancelled by AMPKα inhibitor. In conclusion, AMPK-mTOR signaling pathway participates in the protection of CIHH on vascular endothelium of MS rats.

Abstract A symmetry-preserving regularisation of a vector $$\times $$ × vector contact interaction (SCI) is used to deliver a unified treatment of semileptonic transitions involving $$\pi $$ π , K, $$D_{(s)}$$ D ( s ) , $$B_{(s,c)}$$ B ( s , c ) initial states. The framework is characterised by algebraic simplicity, few parameters, and the ability to simultaneously treat systems from Nambu–Goldstone modes to heavy+heavy mesons. Although the SCI form factors are typically somewhat stiff, the results are comparable with experiment and rigorous theory results. Hence, predictions for the five unmeasured $$B_{s,c}$$ B s , c branching fractions should be a reasonable guide. The analysis provides insights into the effects of Higgs boson couplings via current-quark masses on the transition form factors; and results on $$B_{(s)}\rightarrow D_{(s)}$$ B ( s ) → D ( s ) transitions yield a prediction for the Isgur–Wise function in fair agreement with contemporary data.

Background: Calcium silicate biomaterials (CSB) have witnessed rapid development in the past 30 years. This study aimed to accomplish a comprehensive bibliometric analysis of the published research literature on CSB for biomedical applications and explore the research hotspot and current status.Methods: Articles related to CSB published in the last three decades (1990–2020) were retrieved from Web of Science Core Collection. The R bibliometrix package and VOSviewer were used to construct publication outputs and collaborative networking among authors, their institutes, countries, journals’ matrices and keywords plus.Results: A total of 872 publications fulfilling the search criteria were included. CSB is mainly reported for bone tissues and dental applications. Among researchers, Chang J from Chinese Academy of Sciences and Gandolfi MG from the University of Bologna are the most productive author in these two fields, respectively. China was the leading contributor to the research on CSB in the medical field. A total of 130 keywords appeared more ten or more times were identified. The term “mineral trioxide aggregate” ranked first with 268 occurrences. The co-occurrence analysis identified three major clusters: CSB in dentistry, bone tissue and vitro bioactivity.Conclusion: Calcium silicate biomaterials have a promising scope for various biomedical applications ranging from regeneration of hard tissues (bone and teeth) to skin, tumor, cardiac muscle and other soft tissues. This study may help researchers further understand the frontiers of the field.

Pancreatic adenosquamous carcinoma (ASPC) is a rare subtype of pancreatic cancer with lethal malignancy, and few studies have focused on the heterogeneity of ASPC. Here, we performed a single-cell sequencing procedure on pancreatic tumor tissue from an ASPC patient and a patient with high-grade intraductal papillary mucinous neoplasm (IPMN). Through the combined analysis of single-cell sequencing data from five pancreatic ductal adenocarcinoma (PDAC) patients, one IPMN patient, and one ASPC patient in a public database, we identified 11 main types of cells, including macrophages, B cells, cancer stem cells, ductal cells, fibroblasts, endo/stellate cells, neutrophils, acinar cells, T cells, natural killer (NK) cells, dendritic cells, and mast cells. Then, the different characteristics and differentiation paths of the immune microenvironment among IPMN, ASPC, and PDAC in macrophages, T cells, and cancer-associated fibroblasts (CAFs) were identified through multiple bioinformatics analyses. Two novel special cancer-associated fibroblasts were identified as nCAFs and imCAFs. Then, cancer cells in duct cells were identified using the infercnv software. Two ASPC-specific subgroups of cancer cells with squamous cell features were identified. Finally, the identified specific CAFs and cancer cells were mapped to TCGA-PAAD cohort through the cibersoftx software. All of these identified subgroups were calculated to have a significant prognostic value in pancreatic cancer patients. These findings will promote the clinical application of single-cell sequencing data of pancreatic cancer and deepen our understanding of ASPC.

Classical cavernous sinus embolism is a rare clinical finding, presented most commonly by complaints of headache, diplopia, visual field defects, facial pain, and progressive neurological deficits. Many patients exhibit symptoms of III, IV, and VI nerve palsies. We hereby report a rare case of aseptic cavernous sinus embolism developed in a 75-year-old male with primary lung cancer who presented with binocular diplopia due to unilateral third and sixth cranial nerve palsies with pupil-sparing. The possibility of cavernous sinus cancer embolus should be considered if the routine examination excluded metastases, infiltration, carcinomatous meningitis, or the paraneoplastic process. 18F-FDG PET imaging may provide a promising diagnostic modality for the diagnosis of cancer embolus.

Cathepsin B (CTSB) is a lysosomal protease implicated in the progression of various diseases. A large number of CTSB-related studies have been conducted to date. However, there is no comprehensive bibliometric analysis on this subject. In our study, we performed quantitative analysis of CTSB-related publications retrieved from the Science Citation Index Expanded (SCIE) of the Web of Science Core Collection (reference period: 2011–2021). A total of 3,062 original articles and reviews were retrieved. The largest number of publications were from USA (n = 847, 27.66%). The research output of each country showed positive correlation with gross domestic product (GDP) (r = 0.9745, P < 0.0001). Active collaborations between countries/regions were also observed. Reinheckel T and Sloane BF were perhaps the most impactful researchers in the research landscape of CTSB. Plos ONE was the most prevalent (119/3,062, 3.89%) and cited journal (3,021 citations). Comprehensive analysis of the top citations, co-citations, and keywords was performed to acquire the theoretical basis and hotspots of CTSB-related research. The main topics included CTSB-related cancers and inflammatory diseases, CTSB-associated cell death pattern, and the applications of CTSB. These results provide comprehensive insights into the current status of global CTSB-related research especially in pancreas, which is worthy of continued follow-up by practitioners and clinicians in this field.

BackgroundEnteropeptidase (EP) is a type II transmembrane serine protease and a physiological activator of trypsinogen. Extensive studies related to EP have been conducted to date. However, no bibliometric analysis has systematically investigated this theme. Our study aimed to visualize the current landscape and frontier trends of scientific achievements on EP, provide an overview of the past 120 years and insights for researchers and clinicians to facilitate future collaborative research and clinical intervention.MethodsQuantitative analysis of publications relating to EP from 1900 to 2020 was interpreted and graphed through the Science Citation Index Expanded of Web of Science Core Collection (limited to SCIE). Microsoft office 2019, GraphPad Prism 8, VOSviewer, and R-bibliometrix were used to conduct the bibliometric analysis.ResultsFrom 1900 to 2020, a total of 1,034 publications were retrieved. The USA had the largest number of publications, making the greatest contribution to the topic (n = 260, 25.15%). Active collaborations between countries/regions were also enrolled. Grant and Hermontaylor were perhaps the most impactful researchers in the landscape of EP. Protein Expression and Purification and the Journal of Biological Chemistry were the most prevalent (79/1,034, 7.64%) and cited journals (n = 2,626), respectively. Using the top 15 citations and co-citations achievements clarified the theoretical basis of the EP research field. Important topics mainly include the structure of EP, the affective factors for activating substrates by EP, EP-related disorders, and inhibitors of EP.ConclusionBased on the bibliometric analysis, we have gained a comprehensive analysis of the global status and research frontiers of studies investigating EP, which provides some guidance and reference for researchers and clinicians engaged in EP research.

Continuum Schwinger function methods for the strong-interaction bound-state problem are used to arrive at a unified set of parameter-free predictions for the semileptonic K→π, D→π,K and Ds→K, B(s)→π(K) transition form factors and the associated branching fractions. The form factors are a leading source of uncertainty in all such calculations: our results agree quantitatively with available data and provide benchmarks for the hitherto unmeasured Ds→K0, B¯s→K+ form factors. The analysis delivers a value of |Vcs|=0.974(10) and also predictions for all branching fraction ratios in the pseudoscalar meson sector that can be used to test lepton flavour universality. Quantitative comparisons are provided between extant theory and the recent measurement of BBs0→K−μ+νμ. Here, further, refined measurements would be useful in moving toward a more accurate value of |Vub|.

Background: Contact heat evoked potentials (CHEPs) is used to diagnose small fiber neuropathy (SFN). We established the normal values of CHEPs parameters in Chinese adults, optimized the test technique, and determined its reproducibility.Methods: We recruited 151 healthy adults (80 men; mean age, 37 ± 14 years). CHEPs was performed on the right forearm to determine the optimal number of stimuli, and then conducted at different sites to establish normal values, determine the effects of demographic characteristics and baseline temperature, and assess the short- (30 min) and long-term (1 year) reproducibility. N2 latency/height varied with age and sex, while P2 latency/height and N2–P2 amplitude varied with age. The optimal number of stimuli was three.Results: N2 latency/height (t = 5.45, P < 0.001) and P2 latency/height (χ2 = −4.06, P < 0.001) decreased and N2–P2 amplitude (t = −5.01, P < 0.001) and visual analog scale score (χ2 = −5.84, P < 0.001) increased with increased baseline temperature (35 vs. 32°C). CHEPs parameters did not differ with time (baseline vs. 30 min vs. 1 year).Conclusion: We established normal CHEPs values in Chinese adults. We found that CHEPs parameters changed with baseline temperature and that the short- and long-term test reproducibility were satisfactory.

Purpose: Cerebral aspergillosis (CA) is a rare but often fatal, difficult-to-diagnose, opportunistic infection. The utility of metagenomic next-generation sequencing (mNGS) for diagnosis of CA is unclear. We evaluated the usefulness of mNGS of the cerebrospinal fluid (CSF) for the diagnosis of CA.Methods: This prospective study involved seven consecutive patients with confirmed CA in whom CSF mNGS was performed. Serum (1→3)-β-D-glucan and galactomannan levels were determined, and histopathological examination and mNGS of the CSF were conducted. CSF specimens from three non-infected patients were used as positive controls.Results: mNGS of the CSF was positive in six of the seven confirmed CA cases (85.71% sensitivity). In the cryptococcal meningitis group (control), mNGS of the CSF was positive for Aspergillus in two patients (84.62% specificity). The positive likelihood ratio, negative likelihood ratio, and Youden’s index of mNGS for CA in the CSF were 5.565, 0.169, and 0.7, respectively. Among the six mNGS-positive cases, more than two Aspergillus species were found in four (4/6, 66.67%). In the positive controls, the addition of one A. fumigatus spore yielded a standardised species-specific read number (SDSSRN) of 25.45 by mNGS; the detection rate would be 0.98 if SDSSRN was 2.Conclusion: mNGS facilitates the diagnosis of CA and may reduce the need for cerebral biopsy in patients with suspected CA.Trial Registration Number: Chinese Clinical Trial Registry, ChiCTR1800020442.

Repulsive guidance molecule A (RGMa) is a potent inhibitor of axonal growth and a regulator of neuronal cell death. It is up-regulated following neuronal injury and accumulates in chronic neurodegenerative diseases. Neutralizing RGMa has the potential to promote neuroregeneration and neuroprotection. Previously we reported that a rat anti-N terminal RGMa (N-RGMa) antibody r5F9 and its humanized version h5F9 (ABT-207) promote neuroprotection and neuroregeneration in preclinical neurodegenerative disease models. However, due to its cross-reactivity to RGMc/hemojuvelin, ABT-207 causes iron accumulation in vivo, which could present a safety liability. Here we report the generation and characterization of a novel RGMa-selective anti-N-RGMa antibody elezanumab, which is currently under Phase 2 clinical evaluation in multiple disease indications. Elezanumab, a human monoclonal antibody generated by in vitro PROfusion mRNA display technology, competes with ABT-207 in binding to N-RGMa but lacks RGMc cross-reactivity with no impact on iron metabolism. It neutralizes repulsive activity of soluble RGMa in vitro and blocks membrane RGMa mediated BMP signaling. In the optic nerve crush and optic neuritis models, elezanumab promotes axonal regeneration and prevents retinal nerve fiber layer degeneration. In the spinal targeted experimental autoimmune encephalomyelitis (EAE) model, elezanumab promotes axonal regeneration and remyelination, decreases inflammatory lesion area and improves functional recovery. Finally, in the mouse cuprizone model, elezanumab reduces demyelination, which is consistent with its inhibitory effect on BMP signaling. Taken together, these preclinical data demonstrate that elezanumab has neuroregenerative and neuroprotective activities without impact on iron metabolism, thus providing a compelling rationale for its clinical development in neurodegenerative diseases.

With the aim of extracting the pion charge radius, we analyse extant precise pion+electron elastic scattering data on Q2∈[0.015,0.144] GeV2 using a method based on interpolation via continued fractions augmented by statistical sampling. The scheme avoids any assumptions on the form of function used for the representation of data and subsequent extrapolation onto Q2≃0. Combining results obtained from the two available data sets, we obtain rπ=0.640(7) fm, a value 2.4σ below today's commonly quoted average. The tension may be relieved by collection and similar analysis of new precise data that densely cover a domain which reaches well below Q2=0.015 GeV2. Considering available kaon+electron elastic scattering data sets, our analysis reveals that they contain insufficient information to extract an objective result for the charged-kaon radius, rK. New data with much improved precision, low-Q2 reach and coverage are necessary before a sound result for rK can be recorded.

Glioblastoma multiforme (GBM) is the most common and malignant brain tumor, and almost half of the patients carrying EGFR-driven tumor with PTEN deficiency are resistant to EGFR-targeted therapy. EGFR amplification and/or mutation is reported in various epithelial tumors. This series of studies aimed to identify a potent compound against EGFR-driven tumor. We screened a chemical library containing over 600 individual compounds purified from Traditional Chinese Medicine against GBM cells with EGFR amplification and found that cinobufagin, the major active ingredient of Chansu, inhibited the proliferation of EGFR amplified GBM cells and PTEN deficiency enhanced its anti-proliferation effects. Cinobufagin also strongly inhibited the proliferation of carcinoma cell lines with wild-type or mutant EGFR expression. In contrast, the compound only weakly inhibited the proliferation of cancer cells with low or without EGFR expression. Cinobufagin blocked EGFR phosphorylation and its downstream signaling, which additionally induced apoptosis and cytotoxicity in EGFR amplified cancer cells. In vivo, cinobufagin blocked EGFR signaling, inhibited cell proliferation, and elicited apoptosis, thereby suppressing tumor growth in both subcutaneous and intracranial U87MG-EGFR xenograft mouse models and increasing the median survival of nude mice bearing intracranial U87MG-EGFR tumors. Cinobufagin is a potential therapeutic agent for treating malignant glioma and other human cancers expressing EGFR.

Naringenin (5,7,4′-trihydroxyflavanone), belonging to the flavanone subclass, is associated with beneficial effects such as anti-oxidation, anticancer, anti-inflammatory, and anti-diabetic effects. Drug metabolism plays an essential role in drug discovery and clinical safety. However, due to the interference of numerous endogenous substances in metabolic samples, the identification and efficient characterization of drug metabolites are difficult. Here, ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry was used to obtain mass spectral information of plasma (processed by three methods), urine, feces, liver tissue, and liver microsome samples. Moreover, a novel analytical strategy named “ion induction and deduction” was proposed to systematically screen and identify naringenin metabolites in vivo and in vitro. The analysis strategy was accomplished by the establishment of multiple “net-hubs” and the induction and deduction of fragmentation behavior. Finally, 78 naringenin metabolites were detected and identified from samples of rat plasma, urine, feces, liver tissue, and liver microsomes, of which 67 were detected in vivo and 13 were detected in vitro. Naringenin primarily underwent glucuronidation, sulfation, oxidation, methylation, ring fission, and conversion into phenolic acid and their composite reactions. The current study provides significant help in extracting target information from complex samples and sets the foundation for other pharmacology and toxicology research.

Previous behavioral studies have shown that sharing painful experiences can strengthen social bonds and promote mutual prosociality, yet the neural mechanisms underlying this phenomenon remain unclear. We hypothesized that sharing a painful experience induces brain-to-brain synchronization and mutual empathy for each other's pain between pain-takers and pain-observers, which then leads to enhanced social bonding. To test this hypothesis, we adopted an electroencephalographic (EEG) hyper-scanning technique to assess neuronal and behavioral activity during a Pain-Sharing task in which high- or low-intensity pain stimulation was randomly delivered to one participant of a dyad on different experimental trials. Single-brain analysis showed that sensorimotor α-oscillation power was suppressed more when expecting high-intensity pain than when expecting low-intensity pain similarly for self-directed or partner-directed pain. Dual-brain analysis revealed that expecting high-intensity pain induced greater brain-to-brain synchronization of sensorimotor α-oscillation phases between pain-takers and pain-observers than did expecting low-intensity pain. Mediation analysis further revealed that brain-to-brain synchronization of sensorimotor α-oscillations mediated the effects of pain-stimulation intensity on mutual affective sharing for partner-directed pain. This mutual affective empathy during the task predicted the social bonding, as indexed by prosocial inclinations measured after the task. These results support the hypothesis that sharing a painful experience triggers emotional resonance between pairs of individuals through brain-to-brain synchronization of neuronal α-oscillations recorded over the sensorimotor cortex, and this emotional resonance further strengthens social bonds and motivates prosocial behavior within pairs of individuals.

Balanced time perspective refers to the ability to flexibly switch between different temporal foci in an adaptive manner according to the current context. Functional connectivity within the default mode network (DMN) has been suggested to support balanced time perspective. The coupling between the DMN and fronto-parietal network (FPN) may drive many important expressions of internally directed cognition. However, it remains unclear whether balanced time perspective is supported by the interaction between the FPN and DMN. To examine these issues, we recruited 91 participants (52 males with mean age of 19.6, and 39 females with mean age of 20.0) to undergo resting-state brain imaging scan and to complete a questionnaire measuring balanced time perspective. Seed-based voxel-wise functional connectivity analyses implicated midline DMN regions including the anterior medial prefrontal cortex (amPFC) and posterior cingulate cortex (PCC) along with the anterior cingulate cortex (ACC), precuneus, and cerebellum in supporting a balanced time perspective. More importantly, functional connectivity between the right amPFC and right dorsal lateral prefrontal cortex (DLPFC) in the FPN was found to associate with balanced time perspective. Our findings suggest the importance of coordinated brain activity in supporting a balanced time perspective.

Jute fibers are commonly used as reinforcement in composite materials manufacture due to its excellent mechanical properties. In this study, alkali (NaOH) and silane coupling agent KH570 treatment were conducted on component jute nonwovens to improve the bonding strength of jute/PLA composite interface. The jute/PLA composites were prepared from treated jute nonwovens and PLA films by molding method. The results show that alkali treatment can significantly improve the tensile, flexural and dynamic thermomechanical properties of jute/PLA composites. The composites treated with 1% NaOH exhibits the maximum tensile strength while the composites treated with 5% NaOH presents the maximum flexural strength and the minimum loss in the dynamic thermo-mechanical process. Moreover, the tensile and flexural strength of the composite treated with the combination of 5% NaOH-5% KH570 is significantly stronger than that when they act alone. This research can provide an optimal treatment strategy for the jute/PLA degradable composites with higher mechanical and thermos-mechanical tolerance. [ABSTRACT FROM AUTHOR]