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Abstract Mammalian TIP60 is a multi-functional enzyme with histone acetylation and histone dimer exchange activities. It plays roles in diverse cellular processes including transcription, DNA repair, cell cycle control, and embryonic development. Here we report the cryo-electron microscopy structures of the human TIP60 complex with the core subcomplex and TRRAP module refined to 3.2-Å resolution. The structures show that EP400 acts as a backbone integrating the motor module, the ARP module, and the TRRAP module. The RUVBL1-RUVBL2 hexamer serves as a rigid core for the assembly of EP400 ATPase and YL1 in the motor module. In the ARP module, an ACTL6A-ACTB heterodimer and an extra ACTL6A make hydrophobic contacts with EP400 HSA helix, buttressed by network interactions among DMAP1, EPC1, and EP400. The ARP module stably associates with the motor module but is flexibly tethered to the TRRAP module, exhibiting a unique feature of human TIP60. The architecture of the nucleosome-bound human TIP60 reveals an unengaged nucleosome that is located between the core subcomplex and the TRRAP module. Our work illustrates the molecular architecture of human TIP60 and provides architectural insights into how this complex is bound by the nucleosome.

Abstract Background Sjögren’s Syndrome (SS) is a rare chronic autoimmune disorder primarily affecting adult females, characterized by chronic inflammation and salivary and lacrimal gland dysfunction. It is often associated with systemic lupus erythematosus, rheumatoid arthritis and kidney disease, which can lead to increased mortality. Early diagnosis is critical, but traditional methods for diagnosing SS, mainly through histopathological evaluation of salivary gland tissue, have limitations. Methods The study used 100 labial gland biopsy, creating whole-slide images (WSIs) for analysis. The proposed model, named Cell-tissue-graph-based pathological image analysis model (CTG-PAM) and based on graph theory, characterizes single-cell feature, cell-cell feature, and cell-tissue feature. Building upon these features, CTG-PAM achieves cellular-level classification, enabling lymphocyte recognition. Furthermore, it leverages connected component analysis techniques in the cell graph structure to perform SS diagnosis based on lymphocyte counts. Findings CTG-PAM outperforms traditional deep learning methods in diagnosing SS. Its area under the receiver operating characteristic curve (AUC) is 1.0 for the internal validation dataset and 0.8035 for the external test dataset. This indicates high accuracy. The sensitivity of CTG-PAM for the external dataset is 98.21%, while the accuracy is 93.75%. In comparison, the sensitivity and accuracy for traditional deep learning methods (ResNet-50) are lower. The study also shows that CTG-PAM’s diagnostic accuracy is closer to skilled pathologists compared to beginners. Interpretation Our findings indicate that CTG-PAM is a reliable method for diagnosing SS. Additionally, CTG-PAM shows promise in enhancing the prognosis of SS patients and holds significant potential for the differential diagnosis of both non-neoplastic and neoplastic diseases. The AI model potentially extends its application to diagnosing immune cells in tumor microenvironments.

Abstract Cancer treatment continues to shift from utilizing traditional therapies to targeted ones, such as protein kinase inhibitors and immunotherapy. Mobilizing dendritic cells (DC) and other myeloid cells with antigen presenting and cancer cell killing capacities is an attractive but not fully exploited approach. Here, we show that PIKFYVE is a shared gene target of clinically relevant protein kinase inhibitors and high expression of this gene in DCs is associated with poor patient response to immune checkpoint blockade (ICB) therapy. Genetic and pharmacological studies demonstrate that PIKfyve ablation enhances the function of CD11c+ cells (predominantly dendritic cells) via selectively altering the non-canonical NF-κB pathway. Both loss of Pikfyve in CD11c+ cells and treatment with apilimod, a potent and specific PIKfyve inhibitor, restrained tumor growth, enhanced DC-dependent T cell immunity, and potentiated ICB efficacy in tumor-bearing mouse models. Furthermore, the combination of a vaccine adjuvant and apilimod reduced tumor progression in vivo. Thus, PIKfyve negatively regulates the function of CD11c+ cells, and PIKfyve inhibition has promise for cancer immunotherapy and vaccine treatment strategies.

Abstract Background Gut microbiota(GM) have been proven associated with lots of gastrointestinal diseases, but its causal relationship with Gastroesophageal reflux disease(GERD) and Barrett’s esophagus(BE) hasn’t been explored. We aimed to uncover the causal relation between GM and GERD/BE and potential mediators by utilizing Mendelian Randomization(MR) analysis. Methods Summary statistics of GM(comprising 301 bacteria taxa and 205 metabolism pathways) were extracted from MiBioGen Consortium(N = 18,340) and Dutch Microbiome Project(N = 7,738), GERD and BE from a multitrait meta-analysis(NGERD=602,604, NBE=56,429). Bidirectional two-sample MR analysis and linkage disequilibrium score regression(LDSC) were used to explore the genetic correlation between GM and GERD/BE. Mediation MR analysis was performed for the risk factors of GERD/BE, including Body mass index(BMI), weight, type 2 diabetes, major depressive disorder(MDD), smoking initiation, alcohol consumption, and dietary intake(including carbohydrate, sugar, fat, protein intake), to detect the potential mediators between GM and GERD/BE. Results 11 bacterial taxa and 13 metabolism pathways were found associated with GERD, and 18 taxa and 5 pathways exhibited causal relationship with BE. Mediation MR analysis suggested weight and BMI played a crucial role in these relationships. LDSC identified 1 taxon and 4 metabolism pathways related to GERD, and 1 taxon related to BE. Specie Faecalibacterium prausnitzii had a suggestive impact on both GERD(OR = 1.087, 95%CI = 1.01–1.17) and BE(OR = 1.388, 95%CI = 1.03–1.86) and LDSC had determined their correlation. Reverse MR indicated that BE impacted 10 taxa and 4 pathways. Conclusions This study established a causal link between gut microbiota and GERD/BE, and identified the probable mediators. It offers new insights into the role of gut microbiota in the development and progression of GERD and BE in the host.

Abstract Minimal hepatic encephalopathy (MHE) has a substantial impact on the clinical outcomes and quality of life (QOL) of patients with cirrhosis. However, timely diagnosis and intervention are challenging due to sophisticated diagnostic methods. In this study, 673 healthy controls and 905 patients with cirrhosis were screened, and 660 healthy controls and 757 patients with cirrhosis, divided into the test (292 patients) and validation (465 patients) cohort, were analyzed after screening. A diagnostic model of the Stroop test (Stroop‐CN) was constructed by multivariate linear regression based on the results of healthy controls. The prevalence of MHE and the comparison results with psychometric hepatic encephalopathy score through the Stroop‐CN model were stable in the test and validation cohorts. Moreover, the prevalence of MHE remained significantly higher in patients with worse disease conditions marked as high Child–Pugh grades and the Model for End‐stage Liver Disease and Sodium (MELD‐Na) scores in the test and validation cohort. The EuroQol 5‐D questionnaire revealed that patients with MHE had a worse QOL than those without MHE both in the test and validation cohort. In conclusion, an easy and practical Stroop‐CN model for MHE diagnosis based on the EncephalApp is established. It is found that a considerable number of Chinese patients with cirrhosis experience MHE, which significantly impacts their QOL.

Abstract Histone variant H2A.Z is found at promoters and regulates transcription. The ATP-dependent chromatin remodeler SRCAP complex (SRCAP-C) promotes the replacement of canonical histone H2A–H2B dimer with H2A.Z–H2B dimer. Here, we determined structures of human SRCAP-C bound to H2A-containing nucleosome at near-atomic resolution. The SRCAP subunit integrates a 6-subunit actin-related protein (ARP) module and an ATPase-containing motor module. The ATPase-associated ARP module encircles half of the nucleosome along the DNA and may restrain net DNA translocation, a unique feature of SRCAP-C. The motor module adopts distinct nucleosome binding modes in the apo (nucleotide-free), ADP-bound, and ADP-BeFx-bound states, suggesting that ATPase-driven movement destabilizes H2A–H2B by unwrapping the entry DNA and pulls H2A–H2B out of nucleosome through the ZNHIT1 subunit. Structure-guided chromatin immunoprecipitation sequencing analysis confirmed the requirement of H2A-contacting ZNHIT1 in maintaining H2A.Z occupancy on the genome. Our study provides structural insights into the mechanism of H2A-H2A.Z exchange mediated by SRCAP-C.

Abstract Background Public health initiatives, including human biomonitoring, have been impacted by unique challenges since the onset of the COVID-19 pandemic, compounding a decades-long trend of declining public participation. To combat low public participation rates, public health professionals often employ extensive engagement approaches including in-person interactions related to enrollment and sampling, success of which is an essential component of a statistically defensible study. The onset of the COVID-19 pandemic challenged public health programs to diversify engagement and sampling approaches, limiting direct interactions for the health and safety of the population. This study explores biomonitoring recruitment strategies through non-contact mechanisms and evaluate the application feasibility for population-based studies. Methods The Iowa Biomonitoring Program at the State Hygienic Laboratory developed a human biomonitoring study that utilized a multifaceted, distance-based approach. Traditional techniques, such as mailed recruitment invitations and phone-based discussions, were coupled with internet-based surveys and self-collected, shipped urine and water samples. Participation rates were evaluated by employing different mailing methods, and the demographics of enrolled participants were examined. Results This non-human contact approach achieved a nearly 14% participation rate among a rural population, well above our target rates. Our improved mailing strategy for targeting initially unresponsive participants yielded a significantly increase in the participation rates. The respondents were predominantly individuals with educational attainment of at least high school level. Among all the eligible participants, 83% submitted self-collected samples, a rate comparable to the National Health and Nutrition Examination Survey which involved in-person interviews. Conclusions The practice of engaging a rural population during the COVID-19 pandemic by transitioning from face-to-face interactions to a combination of mailing and internet-based approaches resulted in higher-than-expected participant recruitment and sample collection rates. Given the declining trend in the response rates for population-based survey studies, our results suggest conducting human biomonitoring without direct human interaction is feasible, which provides further opportunity to improve response rates and the relevance and reach of public health initiatives.

BackgroundPatients undergoing gastrointestinal surgery often experience hypotension following general anesthesia induction due to insufficient volume. This study aimed to assess whether pre-rehydration guided by carotid corrected flow time (FTc) could mitigate post-induction hypotension induced by general anesthesia.MethodsPatients undergoing resection of gastrointestinal tumors were assigned to either the conventional treatment group (Group C) or the fluid treatment group based on FTc (Group F). Within Group F, patients were further divided into Group A (carotid FTc

Chestnut blight (caused by Cryphonectria parasitica), together with Phytophthora root rot (caused by Phytophthora cinnamomi), has nearly extirpated American chestnut (Castanea dentata) from its native range. In contrast to the susceptibility of American chestnut, many Chinese chestnut (C. mollissima) genotypes are resistant to blight. In this research, we performed a series of genome-wide association studies for blight resistance originating from three unrelated Chinese chestnut trees (Mahogany, Nanking and M16) and a Quantitative Trait Locus (QTL) study on a Mahogany-derived inter-species F2 family. We evaluated trees for resistance to blight after artificial inoculation with two fungal strains and scored nine morpho-phenological traits that are the hallmarks of species differentiation between American and Chinese chestnuts. Results support a moderately complex genetic architecture for blight resistance, as 31 QTLs were found on 12 chromosomes across all studies. Additionally, although most morpho-phenological trait QTLs overlap or are adjacent to blight resistance QTLs, they tend to aggregate in a few genomic regions. Finally, comparison between QTL intervals for blight resistance and those previously published for Phytophthora root rot resistance, revealed five common disease resistance regions on chromosomes 1, 5, and 11. Our results suggest that it will be difficult, but still possible to eliminate Chinese chestnut alleles for the morpho-phenological traits while achieving relatively high blight resistance in a backcross hybrid tree. We see potential for a breeding scheme that utilizes marker-assisted selection early for relatively large effect QTLs followed by genome selection in later generations for smaller effect genomic regions.

Objectives: This study was aimed at analyzing the burden and trend of Alzheimer's disease and other dementias attributed to smoking (SADD) in the Belt and Road Initiative (BRI) countries during 1990–2019. Methods: Data from The 2019 Global Burden of Disease Study was used to extract information on the burden of SADD in terms of the numbers and age-standardized rate of mortality (ASMR) and disability-adjusted life years (ASDALR) in the BRI countries for 1990–2019. The average annual percent change (AAPC) was used to analyze the temporal trends of ASDALR from 1990 to 2019 and in the final decade by Joinpoint regression analysis. Results: The DALYs of SADD were the highest in China, India, and the Russian Federation in 1990 and in Lebanon, Montenegro and Bosnia, and Herzegovina in 2019. From 1990 to 2019, the ASDALR in China had increased from 55.50/105 to 66.18/105, but decreased from 2010 to 2019, while that of India had declined from 32.84/105 to 29.35/105, but increased from 2010 to 2019. The ASDALR showed the fastest increase in the Russian Federation, with AAPC of 1.97% (95% confidence interval [CI]: 1.77%, 2.16%), and the fastest decline in Sri Lanka, with AAPC of −2.69% (95% CI: 2.79%, −2.59%). ASMR and ASDALR from SADD showed a substantial decline during 1990–2019 both globally and in the different socio-demographic index (SDI) regions (all P

Abstract Background Age-related hearing loss (ARHL) signifies the bilateral, symmetrical, sensorineural hearing loss that commonly occurs in elderly individuals. Several studies have suggested a higher risk of dementia among patients diagnosed with ARHL. Although the precise causal association between ARHL and cognitive decline remains unclear, ARHL has been recognized as one of the most significant factors that can be modified to reduce the risk of developing dementia potentially. Mild cognitive impairment (MCI) typically serves as the initial stage in the transition from normal cognitive function to dementia. Consequently, the objective of our randomized controlled trial (RCT) is to further investigate whether the use of hearing aids can enhance cognitive function in older adults diagnosed with ARHL and MCI. Methods and design This study is a parallel-arm, randomized controlled trial conducted at multiple centers in Shanghai, China. We aim to enlist a total of 688 older adults (age ≥ 60) diagnosed with moderate-to-severe ARHL and MCI from our four research centers. Participants will be assigned randomly to either the hearing aid fitting group or the health education group using block randomization with varying block sizes. Audiometry, cognitive function assessments, and other relevant data will be collected at baseline, as well as at 6, 12, and 24 months post-intervention by audiologists and trained researchers. The primary outcome of our study is the rate of progression to dementia among the two groups of participants. Additionally, various evaluations will be conducted to measure hearing improvement and changes in cognitive function. Apart from the final study results, we also plan to conduct an interim analysis using data from 12-month follow-up. Discussion In recent years, there has been a notable lack of randomized controlled trials (RCTs) investigating the possible causal relationship between hearing fitting and the improvement of cognitive function. Our findings may demonstrate that hearing rehabilitation can be a valuable tool in managing ARHL and preventing cognitive decline, which will contribute to the development of a comprehensive framework for the prevention and control of cognitive decline. Trial registration Chinese Clinical Trial Registry chictr.org.cn ChiCTR2000036139. Registered on 21 August 2020.

As an important genus in Orchidaceae, Cymbidium has rich ecological diversity and significant economic value. DNA binding with one zinc finger (Dof) proteins are pivotal plant-specific transcription factors that play crucial roles in the growth, development, and stress response of plants. Although the Dof genes have been identified and functionally analyzed in numerous plants, exploration in Orchidaceae remains limited. We conducted a thorough analysis of the Dof gene family in Cymbidium goeringii, C. ensifolium, and C. sinensis. In total, 91 Dof genes (27 CgDofs, 34 CeDofs, 30 CsDofs) were identified, and Dof genes were divided into five groups (I–V) based on phylogenetic analysis. All Dof proteins have motif 1 and motif 2 conserved domains and over half of the genes contained introns. Chromosomal localization and collinearity analysis of Dof genes revealed their evolutionary relationships and potential gene duplication events. Analysis of cis-elements in CgDofs, CeDofs, and CsDofs promoters showed that light-responsive cis-elements were the most common, followed by hormone-responsive elements, plant growth-related elements, and abiotic stress response elements. Dof proteins in three Cymbidium species primarily exhibit a random coil structure, while homology modeling exhibited significant similarity. In addition, RT-qPCR analysis showed that the expression levels of nine CgDofs changed greatly under heat stress. CgDof03, CgDof22, CgDof27, CgDof08, and CgDof23 showed varying degrees of upregulation. Most upregulated genes under heat stress belong to group I, indicating that the Dof genes in group I have great potential for high-temperature resistance. In conclusion, our study systematically demonstrated the molecular characteristics of Dof genes in different Cymbidium species, preliminarily revealed the patterns of heat stress, and provided a reference for further exploration of stress breeding in orchids.

Background: Hypothalamic neuroinflammation is associated with disorders of lipid metabolism. Considering the anti-neuroinflammation effects of sodium-glucose cotransporter 2(SGLT2) inhibitors, a central administration of Dapagliflozin is postulated to provide hypothalamic protection and change lipid metabolism in kidney against diabetic kidney disease (DKD). Methods: Blood samples of DKD patients were collected. Male Sprague-Dawley (SD) rats with 30 mg/kg streptozotocin and a high-fat diet, db/db mice and palmitic acid (PA)-stimulated BV2 microglia were used for study models. 0.28 mg/3ul dapagliflozin was injected into the lateral ventricle in db/db mice. Genes and protein expression levels were determined by qPCR, western blotting, immunofluorescence, and immunohistochemistry staining. Secreted IL-1β and IL-6 were quantified by ELISA. Oil red O staining, lipidomic, and non-targeted metabolomics were performed to evaluate abnormal lipid metabolism in kidney. Results: The decrease of serum MCPIP1 was an independent risk factor for renal progression in DKD patients (OR=1.22, 95 %CI: 1.02–1.45, P = 0.033). Higher microglia marker IBA1 and lower MCPIP1 in the hypothalamus, as well as lipid droplet deposition increasing in the kidney were observed in DKD rats. Central dapagliflozin could reduce the blood sugar, hypothalamic inflammatory cytokines, lipid droplet deposition in renal tubular. Lipidomics and metabolomics results showed that dapagliflozin changed 37 lipids and 19 metabolites considered on promoting lipolysis. These lipid metabolism changes were attributed to dapagliflozin by upregulating MCPIP1, and inhibiting cytokines in the microglia induced by PA. Conclusions: Central administrated Dapagliflozin elicits an anti-inflammatory effect by upregulating MCPIP1 levels in microglia and changes lipid metabolism in kidney of DKD.

Abstract Background Giant hepatic hemangiomas are rare and can cause serious complications that contribute to a high risk of perinatal mortality. The purpose of this article is to review the prenatal imaging features, treatment, pathology, and prognosis of an atypical fetal giant hepatic hemangioma and to discuss the differential diagnosis of fetal hepatic masses. Case presentation A gravida 9, para 0 woman at 32 gestational weeks came to our institution for prenatal ultrasound diagnosis. A complex, heterogeneous hepatic mass measuring 5.2 × 4.1 × 3.7 cm was discovered in the fetus using conventional two-dimensional ultrasound. The mass was solid and had both a high peak systolic velocity (PSV) of the feeding artery and intratumoral venous flow. Fetal magnetic resonance imaging (MRI) revealed a clear, hypointense T1-W and hyperintense T2-W solid hepatic mass. Prenatal diagnosis was very difficult due to the overlap of benign and malignant imaging features on prenatal ultrasound and MRI. Even postnatally, neither contrast-enhanced MRI nor contrast-enhanced computed tomography (CT) was useful in accurately diagnosing this hepatic mass. Due to persistently elevated Alpha-fetoprotein (AFP), a laparotomy was performed. Histopathological examination of the mass showed atypical features such as hepatic sinus dilation, hyperemia, and hepatic chordal hyperplasia. The patient was ultimately diagnosed with a giant hemangioma, and the prognosis was satisfactory. Conclusions When a hepatic vascular mass is found in a third trimester fetus a hemangioma should be considered as a possible diagnosis. However, prenatal diagnosis of fetal hepatic hemangiomas can be challenging due to atypical histopathological findings. Imaging and histopathological assays can provide useful information for the diagnosis and treatment of fetal hepatic masses.

Furandicarboxylic acid is considered one of the most representative biomass matrix platforms and has been widely used to synthesize various novel biomaterials. In this study, a series of copolymerized poly (aryl ether ketone) resins with excellent properties have been prepared by combining the nonlinear structure of furan ketone with the weakly polarized cyclohexane structure. And the relationship between the structure and properties of the resins has been systematically studied. The results showed that the synthesized resins had excellent thermal properties, and the 5% thermal decomposition temperature could reach up to 478 °C. In addition, the resin exhibits good solubility and can be dissolved in the most common solvents. Its water absorption is deficient, at only 0.71%. At 10 GHz, the lowest dielectric constant of the resin is 3.05. Most importantly, using bio-based monomers in this study provides an environmentally friendly strategy for material design and synthesis, providing a green way to develop high-performance low-dielectric materials.

Combating health insurance fraud is of utmost importance to physicians, patients, and health insurers. To delve into the mechanisms of health insurance fraud between doctors and patients, this study employed evolutionary game theory to construct a model that comprehensively considers moral hazard, fraud cost, reward, punishment, bribes from patients, and other factors. Through theoretical analysis and numerical simulation of the model, the study discovered that the evolution of governance behavior in health insurance fraud is closely linked to its initial construction of the payment matrix and the initial selection of parameters for the payment matrix. Additionally, increasing penalties for fraudulent behavior, increasing the cost of fraud for both doctors and patients, and reducing moral hazard for both can effectively drive the final strategy of the system toward a non-fraudulent state. The study aims to provide valuable insights and recommendations to doctors, patients, and medical insurance institutions in establishing a sound governance environment for managing fraud behavior in health insurance.

Background Ambient fine particulate matter ≤ 2.5 µm (PM2.5) air pollution exposure has been identified as a global health threat, the epidemiological evidence suggests that PM2.5 increased the risk of chronic kidney disease (CKD) among the diabetes mellitus (DM) patients. Despite the growing body of research on PM2.5 exposure, there has been limited investigation into its impact on the kidneys and the underlying mechanisms. Past studies have demonstrated that PM2.5 exposure can lead to lipid metabolism disorder, which has been linked to the development and progression of diabetic kidney disease (DKD). Methods In this study, db/db mice were exposed to different dosage PM2.5 for 8 weeks. The effect of PM2.5 exposure was analysis by assessment of renal function, pathological staining, immunohistochemical (IHC), quantitative real-time PCR (qPCR) and liquid chromatography with tandem mass spectrometry (LC–MS/MS) based metabolomic analyses. Results The increasing of Oil Red staining area and adipose differentiation related protein (ADRP) expression detected by IHC staining indicated more ectopic lipid accumulation in kidney after PM2.5 exposure, and the increasing of SREBP-1 and the declining of ATGL detected by IHC staining and qPCR indicated the disorder of lipid synthesisandlipolysis in DKD mice kidney after PM2.5 exposure. The expressions of high mobility group nucleosome binding protein 1 (HMGN1) and kidney injury molecule 1 (KIM-1) that are associated with kidney damage increased in kidney after PM2.5 exposure. Correlation analysis indicated that there was a relationship between HMGN1-KIM-1 and lipid metabolic markers. In addition, kidneys of mice were analyzed using LC–MS/MS based metabolomic analyses. PM2.5 exposure altered metabolic profiles in the mice kidney, including 50 metabolites. In conclusion the results of this study show that PM2.5 exposure lead to abnormal renal function and further promotes renal injury by disturbance of renal lipid metabolism and alter metabolic profiles.

Sea surface temperature (SST) is an important parameter for monitoring ocean phenomena. Driven by ocean satellite Big Data, deep neural networks have achieved state-of-the-art performance in forecasting fields of oceanic phenomena. However, when there are some changes in the data set, the performance of these models drops significantly. In order to address this issue, this article develops a robust strong stability-preserving generative adversarial network model (SSPGAN) to forecast SST. The main objective of this article is to continue to produce accurate SST predictions even in the presence of minor data perturbations. The SSPGAN consists of a generator of a deep learning model and a strong stability preserving discriminator. The generator aims to generate SST that are close to the future true SST using SST from the past. The discriminator simultaneously tries to tell the generated SST apart from the real SST. The robust of the discriminator and the overall model is enhanced by the strong stability preserving network. Experiments confirm the SSPGAN's accuracy and robust for predicting SST in the presence of small data perturbations. In this study, we employ the Wasserstein metric to quantify the gap between the actual SST distribution and the generated SST with a perturbation. In addition, this article also analyzes the robust conditions of the deep neural network when the data are disturbed.

BAF and PBAF are SWI/SNF family chromatin remodeling complexes that create nucleosome-depleted regions for transcription activation. Here the authors report the structure of a 13-subunit human PBAF in complex with acetylated nucleosome in ADP-BeF3-bound state that provides structural insights into PBAF-mediated nucleosome association.

In this work, a bimetallic sulfide-coupled graphene hybrid was designed and constructed for capacitive energy storage. The hybrid structure involved decorating copper–cobalt–sulfide (CuCo2S4) nanoparticles onto graphene layers, with the nanoparticles anchored within the graphene layers, forming a hybrid energy storage system. In this hybrid structure, rGO can work as the substrate and current collector to support the uniform distribution of the nanoparticles and provides efficient transportation of electrons into and out of the electrode. In the meantime, CuCo2S4-active materials are expected to offer an evident enhancement in electrochemical activities, due to the rich valence change provided by Cu and Co. Benefiting from the integrated structure of CuCo2S4 nanoparticles and highly conductive graphene substrates, the prepared CuCo2S4@rGO electrode exhibited a favorable capacitive performance in 1 M KOH. At 1 A g−1, CuCo2S4@rGO achieved a specific capacitance of 410 F g−1. The capacitance retention at 8 A g−1 was 70% of that observed at 1 A g−1, affirming the material’s excellent rate capability. At the current density of 5 A g−1, the electrode underwent 10,000 charge–discharge cycles, retaining 98% of its initial capacity, which indicates minimal capacity decay and showcasing excellent cycling performance.

This paper presents an experimental investigation on the damage characteristics and microstructures of hybrid fiber reinforced concrete (HFRC) subjected to the freeze-thaw（F-T）cycles and compound- salt attack. The effect of steel fiber content and steel-polypropylene fiber hybridization on the apparent morphology, mass loss, relative dynamic elastic modulus (RDEM), mechanical strengths in terms of compressive and flexural strengths were studied. The damage mechanism was explored based on an analysis of pore structures of specimens. The results showed that the F-T cycle has adverse effect on the physical and mechanical properties of specimens. The addition of fibers alleviates the damage degree of concrete, and the fiber hybridization shows more pronounced effect. Results from the porosity analysis indicate the pore sizes of 1.2HFRC are mainly distributed within 40 nm and those of OC are within 60 nm. The volume of larger pore size of 1.2HFRC increases less than the others after salt F-T cycles. Finally, based on Weibull distribution function, evolution equations for the salt-frozen damage of HFRC are developed by a combination of strength attenuation and RDEM degradation. The research results provide theoretical basis and reference for the practical application and building maintenance of fiber reinforced concrete.

Abstract Background Plasmodium vivax rhoptry-associated membrane antigen (RAMA) is a glycophosphatidylinositol-anchored membrane protein currently under consideration as a malaria vaccine candidate. Immunoglobulin G (IgG) antibodies induced by P. vivax RAMA (PvRAMA) have been proved to persist over 12 months in the sera of people infected with P. vivax. It has also been shown that through stimulation of peripheral blood mononuclear cells with PvRAMA in vitro, the antigen can induce CD4+ T cells to produce interleukin-10. However, the genetic diversity of the RAMA gene in isolates of P. vivax (pvrama) and the immunogenicity of PvRAMA in animals remain unclear. Methods Genomic DNA was extracted from blood samples (n = 25) of patients in Jiangsu Province, China with imported infections of P. vivax from endemic countries in South and Southeast Asia. The extract genomic DNA was used as templates to amplify the P. vivax rama gene (pvrama) by PCR, and the PCR products were then sequenced and analyzed by the DnaSP, MEGA, and GeneDoc software packages. Recombinant PvRAMA (rPvRAMA) protein was expressed and purified, and then used to immunize mice. Levels of total IgG and different IgG subclasses of rPvRAMA-immunized mice were evaluated by enzyme-linked immunosorbent assay. Also, spleen cells of rPvRAMA-immunized mice were stimulated with rPvRAMA in vitro and levels of T cells were measured by flow cytometry. Results The average pairwise nucleotide diversity (π) of the pvrama gene was 0.00190, and the haplotype diversity (Hd) was 0.982. The C-terminal of PvRAMA showed lower haplotype diversity compared to the N-terminal and was completely conserved at amino acid sites related to erythrocyte binding. To further characterize immunogenicity of the C-terminal of PvRAMA, mice were immunized with rPvRAMA antigen. The rPvRAMA protein induced antibody responses, with the end-point titer ranging from 1:10,000 to 1:5,120,000. IgG1 was the predominant IgG subclass in rPvRAMA-immunized mice, followed by IgG2b. In addition, levels of CD4+ and CD8+ T cells in the rPvRAMA-stimulated group were significantly higher than those in the phosphate-buffered saline-stimulated group (normal control group). Conclusions The high conservation at specific amino acid sites and the high immunogenicity of the C-terminal of PvRAMA indicate the presence of conserved epitopes able to generate broadly reactive humoral and cellular immune responses. These findings support the potential of PvRAMA to serve as a vaccine candidate against P. vivax infection. Graphical Abstract

Background/purpose: Cement-retained restorations have the advantages of passive fit, less complexity of clinical and laboratory methods, cost, esthetics, and dimensional stability over screw-retained restorations, especially in multiple abutment implant-supported prostheses. A common and difficult technical problem with cement-retained implant prostheses is abutment screw loosening. Three-dimensional (3D) printing is a technology that has been rapidly developed and has become widely accepted in dentistry. The aim of this study was to establish a novel method of using 3D implant planning guide to locate the abutment screw in cement-retained implant prosthesis. Materials and methods: Six standard gypsum complete denture models were used to locate the abutment screw. An implant analog (4.5 mm in diameter and 12 mm in length) was placed in the drilling hole (5 mm in diameter and 14 mm in depth). After scanning with a 3D scanner, the 3D printing software was used to design the abutment screw location guide, which was printed by a resin-based 3D printer. Results: A total of 30 abutment screws were located and removed using the guide. The locating guide's actual diameter was 2.4 mm. The drilling point was accurate and precise, and no excessive loss of the abutment was noticed. Conclusion: The guide would help the dentist in locating the abutment screw access channel, resulting in a more precise and accurate drilling point. The guide for locating the abutment screw enhances the accuracy of screw channel access and reduces damage to the crown and abutment.

Abstract Kidney functions, including electrolyte and water reabsorption and secretion, could be influenced by circulating hormones. The pituitary gland produces a variety of hormones and cytokines; however, the influence of these factors on the kidney has not been well explained and explored. To provide more in-depth information and insights to support the pituitary–kidney axis connection, we used mouse pituitary and kidney single-cell transcriptomics data from the GEO database for further analysis. Based on a ligand–receptor pair analysis, cell–cell interaction patterns between the pituitary and kidney cell types were described. Key ligand–receptor pairs, such as GH-GHR, PTN-SDC2, PTN-SDC4, and DLK1-NOTCH3, were relatively active in the pituitary–kidney axis. These ligand–receptor pairs mainly target proximal tubule cells, principal cells, the loop of Henle, intercalated cells, pericytes, mesangial cells, and fibroblasts, and these cells are related to physiological processes, such as substance reabsorption, angiogenesis, and tissue repair. Our results suggested that the pituitary gland might directly regulate kidney function by secreting multiple hormones or cytokines and indicated that the above ligand–receptor pairs might represent a new research focus for studies on kidney function or kidney disease.

Persistent organic pollutant (POP) remediation is important for protecting the environment and human health but can be expensive. Here, the authors report on the creation of a plant-based remediation material which can absorb high levels of POPs and then provide the nutrients needed for fungal degradation and detoxification.

Summary: Three-dimensional structure and dynamics are essential for protein function. Advancements in hydrogen-deuterium exchange (HDX) techniques enable probing protein dynamic information in physiologically relevant conditions. HDX-coupled mass spectrometry (HDX-MS) has been broadly applied in pharmaceutical industries. However, it is challenging to obtain dynamics information at the single amino acid resolution and time consuming to perform the experiments and process the data. Here, we demonstrate the first deep learning model, artificial intelligence-based HDX (AI-HDX), that predicts intrinsic protein dynamics based on the protein sequence. It uncovers the protein structural dynamics by combining deep learning, experimental HDX, sequence alignment, and protein structure prediction. AI-HDX can be broadly applied to drug discovery, protein engineering, and biomedical studies. As a demonstration, we elucidated receptor-binding domain structural dynamics as a potential mechanism of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody efficacy and immune escape. AI-HDX fundamentally differs from the current AI tools for protein analysis and may transform protein design for various applications.

For the black start-up of DC micro-grids, three-phase charging resistors are required to limit the uncontrollable surge current. The main drawback of this start-up method is the difficulty in determining the appropriate resistance value to achieve a rapid start-up and limit the surge current with the change of grid parameters. To address this problem, this article proposes a soft start-up method for the DC micro-grid based on an improved two-level voltage source converter (VSC). Specifically, an silicon controlled rectifier and anti-parallel diode are added in each up-bridge-arm in the improved VSC. By conducting a dynamic control strategy of the firing angle on the SCRs, the start-up current can always be maintained near a given value to achieve rapid start-up. Moreover, the improved VSC has DC fault ride-through capability. The simulation results based on PSCAD/EMTDC are provided to validate the feasibility of the proposed start-up method.

This study investigates the feasibility of using biodegradable secondary alcohol ethoxylate (SAE) non-ionic surfactant as a building block for the formation of reverse micelles, functioning as reactive dye carriers for the dyeing of cotton fabric in non-aqueous octane medium. Ten dyeing parameters were optimised, by a one-factor-at-a-time approach, namely: (i) effect of colour fixation agent; (ii) surfactant-to-water mole ratio; (iii) surfactant-to-co-surfactant mole ratio; (iv) volume of soda ash; (v) volume of dye; (vi) solvent-to-cotton ratio; (vii) dyeing temperature; (viii) dyeing time; (ix) fixation time; (x) soda-ash-to-cotton ratio. The colour properties, fastness properties and physical properties of SAE-dyed samples were experimentally compared with the conventional water-dyed samples. The optimised condition was found when SAE samples were dyed as follows: (a) 1:20 surfactant-to-water ratio; (b) 1:8 surfactant-to-co-surfactant ratio; (c) 10:1 solvent ratio; (d) 40 min dyeing time; (e) 60 min fixation time; and (f) 70 °C dyeing and fixation temperature. The results showed that SAE-dyed samples have better colour strength, lower reflectance percentage and comparable levelness, fastness and physical properties than that of water-dyed samples. SEM images revealed that the dyed cotton fibres had no severe surface damage caused by an SAE-based reverse micellar dyeing system. The TEM image depicts that the reverse micelle was of nanoscale, spherical-shaped and had a core–shell structure, validating the presence of reverse micelle as a reactive dye carrier and the potential of an SAE-based reverse micellar system for dyeing of cotton fabrics.

The temperature field of the clutch assembly is critical for the clutch design and operation life. Current modeling methods of the temperature of the clutch assembly suffer from insufficient accuracy or a limited time scale for the complicated multi-physics coupling between the contact force, friction-generated heat, heat transfer, and thermal deformation in the clutch assembly in harsh operation conditions. In order to improve the accuracy of temperature field simulation and achieve long-term time scale, a new approach to modeling the temperature is proposed based on CFD simulation and decoupling technology. Firstly, the flow-thermal bi-directional coupling method is employed to determine the convective boundary conditions between the clutch assembly and the ambient air, improving the model’s accuracy. Secondly, the thermal-solid decoupling method is then used to reduce the computational time. The temperature of the clutch assembly during the continuous engagement and disengagement process is performed using this approach and verified by the rig test. The results demonstrate that the temperature of the outer, middle, and inner diameters of the pressure plate by the model agrees well with that by the rig test. For the first engagement and disengagement processes, the proportion of simulated temperature deviations exceeding 5 °C from the measured data is only 3.03%. For the last engagement and disengagement process, while the maximum temperature of the clutch is above 350 °C, the maximum temperature deviation between simulation and measurement is 4.99%. It proves that the approach proposed for modeling the dry clutch assembly temperature field has high accuracy while achieving long-term time-scale simulation.

Polybutene-1 with form I crystals exhibits excellent creep resistance and environmental stress crack resistance. The filaments of polybutene-1 and its random copolymer with 4 mol% ethylene co-units were produced via extrusion melt spinning, which are expected to be in form I states and show outstanding mechanical properties. The variances in microstructure, crystallization–melting behavior, and mechanical properties between homopolymer and copolymer filaments were analyzed using SEM, SAXS/WAXD, DSC, and tensile tests. The crystallization of form II and subsequent phase transition into form I finished after the melt-spinning process in the copolymer sample while small amounts of form II crystals remained in homopolymer filaments. Surprisingly, copolymer filaments exhibited higher tensile strength and Young’s modulus than homopolymer filaments, while the homopolymer films showed better mechanical properties than copolymer films. The high degree of orientation and long fibrous crystals play a critical role in the superior properties of copolymer filaments. The results indicate that the existence of ethylene increases the chain flexibility and benefits the formation of intercrystalline links during spinning, which contributes to an enhancement of mechanical properties. The structure–property correlation of melt-spun PB-1 filaments provides a reference for the development of polymer fibers with excellent creep resistance.

Abstract This study aimed to compare MRI quality between conventional fast spin echo T2 weighted imaging (FSE T2WI) with periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) FSE T2WI for patients with various porcelain fused to metal (PFM) crown and analyze the value of PROPELLER technique in reducing metal artifacts. Conventional FSE T2WI and PROPELLER FSE T2WI sequences for axial imaging of head were applied in participants with different PFM crowns: cobalt-chromium (Co–Cr) alloy, pure titanium (Ti), gold–palladium (Au–Pd) alloy. Two radiologists evaluated overall image quality of section in PFM using a 5-point scale qualitatively and measured the maximum artifact area and artifact signal-to-noise ratio (SNR) quantitatively. Fifty-nine participants were evaluated. The metal crown with the least artifacts and the optimum image quality shown in conventional FSE T2WI and PROPELLER FSE T2WI were in Au–Pd alloy, Ti, and Co–Cr alloy order. PROPELLER FSE T2WI was superior to conventional FSE T2WI in improving image quality and reducing artifact area for Co-Cr alloy (17.0 ± 0.2% smaller artifact area, p

Purpose Acteoside (Act), a phenylethanoid compound that was first isolated from mullein, has been widely used for the investigation of anti-inflammatory and anti-fibrotic effect. However, the mechanism of Act against unilateral ureteral obstruction (UUO)-mediated renal injury is largely unknown. Therefore, this study aimed to explore the effects of Act on UUO rats and possible mechanisms. Methods A total of 20 Sprague-Dawley (SD) rats were divided randomly into three groups (n ≥ 6): (i) sham-operated group (Sham); (ii) UUO group (UUO+Saline); and (iii) UUO + Act 40 mg/kg/day, (UUO+Act); Continuous gavage administration for 2 weeks postoperatively, while the rats in Sham and UUO+saline groups were given equal amounts of saline. All rats were sacrificed after 14 days, the urine and blood samples were collected for biochemical analysis, the renal tissues were collected for pathological staining and immunohistochemistry. Correlations between individual proteins were analyzed by Pearson correlation analysis. Results The results of renal function indexes and histopathological staining showed that Act could improve renal function by reducing serum creatinine, blood urea nitrogen and urine protein at the same time, Act could alleviate renal inflammation and fibrosis. In addition, the results of immunohistochemistry showed that Act could reduce the expression of inflammation and kidney injury-related proteins F4/80, Mcp-1, KIM-1 proteins, as well as the expression of fibrosis-related protein α-SMA and β-catenin. More importantly, Act can also reduce the expression of HMGN1, TLR4 and TREM-1 proteins. Conclusion These data demonstrate that Act can ameliorate UUO-induced renal inflammation and fibrosis in rats probably through triggering HMGN1/TLR4/TREM-1 pathway.

Background and Objectives: This study aimed to assess the knowledge, attitudes, and practice (KAP) of patients regarding dental caries prevention in a university hospital in Guangzhou, China. Materials and Methods: A hospital-based KAP survey was conducted in a cross-sectional manner at the First Affiliated Hospital in Guangzhou, China, from 1 September to 30 September 2022. Questionnaires were distributed to eligible patients, resulting in the participation of 251 individuals. The questionnaire consisted of five sections capturing socio-demographic data and exploring participants’ knowledge, attitudes, practice, and accurate preventive dental caries knowledge. Descriptive statistics and a generalized linear model with univariate tests were used for analysis. Results: The study results show that the knowledge score 7.97 (±0.91) and attitudes score 7.67 (±0.89) among the participants were good while the practice score was 6.80 (±0.81) moderate. The majority of participants identified tooth infections (81.3%), bacteria (92%), and sugar (89.2%) as the main causes of gum bleeding and tooth decay. Brushing (96%) and fluoride (80.5%) were also recognized as essential for preventing tooth decay. Of oral diseases, 94% were recognized as potentially affecting overall health. The vast majority ranging from 92.8% to 98%, believed that oral health is crucial to overall health and that regular check-ups and proper brushing habits are beneficial. There is a significant association of gender with age (p = 0.018), occupation (p = 0.050), lifestyle habit (p = 0.012), and knowledge score; whole education is significantly associated with practice score (p = 0.050). Conclusions: The majority of patients exhibited accurate knowledge and attitudes with moderate practice towards dental caries prevention, with socio-demographic factors playing a major role. However, effective implementation of dental health education programs across the healthcare system is still required to further enhance outcomes.

Abstract Population screening played a substantial role in safely reopening the economy and avoiding new outbreaks of COVID-19. PCR-based pooled screening makes it possible to test the population with limited resources by pooling multiple individual samples. Our study compared different population-wide screening methods as transmission-mitigating interventions, including pooled PCR, individual PCR, and antigen screening. Incorporating testing-isolation process and individual-level viral load trajectories into an epidemic model, we further studied the impacts of testing-isolation on test sensitivities. Results show that the testing-isolation process could maintain a stable test sensitivity during the outbreak by removing most infected individuals, especially during the epidemic decline. Moreover, we compared the efficiency, accuracy, and cost of different screening methods during the pandemic. Our results show that PCR-based pooled screening is cost-effective in reversing the pandemic at low prevalence. When the prevalence is high, PCR-based pooled screening may not stop the outbreak. In contrast, antigen screening with sufficient frequency could reverse the epidemic, despite the high cost and the large numbers of false positives in the screening process.

Objective(s): To explore the effect of verbascoside on renal fibrosis in unilateral ureteral obstruction (UUO) rats.Materials and Methods: Twenty Sprague-Dawley rats were randomly distributed into sham-operated, UUO, and UUO+Verbascoside groups. After two weeks of rat model construction, urine and blood samples were collected for biochemical analysis while kidney tissues were harvested for hematoxylin and eosin (H&E), Masson’s Trichrome, and immunohistochemistry staining. Pearson coefficient was used to analyze the correlation between the two proteins. Results: Verbascoside improved UUO-induced renal dysfunction as detected by decreased serum creatinine, urea nitrogen, and urinary protein excretion rate. In UUO rats, H&E staining result revealed increased total nucleated cell number, and Masson’s Trichrome staining results showed tubular interstitial fibrosis with the deposition of collagen fibrils. Besides, expressions of fibrosis-related proteins including collagen type I (COL-I), α-smooth muscle actin (a-SMA), and tissue inhibitor of metalloproteinase 2 (TIMP2) expressed higher in the UUO group. Moreover, macrophage infiltration-related factors such as CD68+, F4/80+ cells, and suppressor of cytokine signaling-3 (SOCS3) were significantly higher in the UUO group than in sham-operated rats. However, after administration with verbascoside, the accumulation of collagen fibrils and total nucleated cell numbers were mitigated. Likewise, macrophage infiltration was extenuated and fibrosis-related proteins were down-regulated in the UUO+Verbascoside rats. Correlation analysis indicated that macrophage infiltration-related markers were related to fibrosis-related factors.Conclusion: Verbascoside could alleviate renal fibrosis in UUO rats probably through ameliorating macrophage infiltration.

Objective: Immune inflammatory cells and cytokines play an important role in the occurrence and development of diabetic nephropathy (DN). Acteoside has been reported to regulate the inflammation and immune response. The study aims to investigate the effects of acteoside on the expressions of MCP-1 and TGF-β 1 on nephropathy in diabetic mice. Methods: C57BL/6J mice in the model group were given a single intraperitoneal injection of STZ (150 mg/kg). Model mice were divided randomly into two groups: 5 without treatment, 5 treated with acteoside. After continuous administration for 8 weeks, serum, urine, and kidney tissue were collected, then, ralated biochemical parameters, pathological characteristics and MCP-1 and TGF-β1 mRNA or protein were detected. The NRK-52E cells were divided into three groups as follows: the normal control group (NC group), the high glucose group (HS group), the high glucose+acteoside group (HS+ACT group). The expressions of MCP-1 and TGF-β 1 in the mRNA and protein levels were assessed with RT-PCR, western blot and ELISA. Results: The expressions of MCP-1 and TGF-β 1 were significantly enhanced in DN group and dramatically reduced after acteoside treatment. Compared with those in NC group, the expressions of MCP-1 and TGF-β 1 in NRK-52E cell of HS group were significantly enhanced, while both were significantly decreased in HS+ACT group compared with HS group. Conclusion: Our findings indicate that Acteoside has protective effects on DN via inhibiting the expressions of MCP-1 and TGF-β 1 .

Nemaline myopathy (NM) is a rare, hereditary heterogeneous myopathy. Fetal NM has a more severe disease course and a poorer prognosis and is usually lethal during the first few months of life. Hence, early prenatal diagnosis is especially important for clinical interventions and patient counseling. We report the case of a fetus with NM due to KLHL40 gene variation leading to arthrogryposis multiplex congenita (AMC). The ultrasonography and histopathology results revealed an enhanced echo intensity and decreased muscle thickness, which may be novel features providing early clues for the prenatal diagnosis of NM. Moreover, to our knowledge, this article is the first report to describe a case of NM associated with complex congenital heart disease (CHD).

Plasmodium vivax is the most widespread human malaria parasite. The spleen is one of the most significant immune organs in the course of Plasmodium infection, and it contains splenic fibroblasts (SFs), which supports immunologic function by secreting type I collagen (collagen I). Plasmodium proteins have rarely been found to be involved in collagen alterations in the spleen during infection. Here, we selected the protein P. vivax tryptophan-rich antigen 23 (PvTRAg23), which is expressed by the spleen-dependent gene Pv-fam-a and is a member of the PvTRAgs family of export proteins, suggesting that it might have an effect on SFs. The protein specifically reduced the level of collagen I in human splenic fibroblasts (HSFs) and bound to cells with vimentin as receptors. However, such collagen changes were not mediated by binding to vimentin, but rather activating the NF-κBp65 pathway to produce inflammatory cytokines. Collagen impaired synthesis accompanied by extracellular matrix-related changes occurred in the spleen of mice infected with P. yoelii 17XNL. Overall, this study is the first one to report and verify the role of Plasmodium proteins on collagen in HSF in vitro. Results will contribute to further understanding of host spleen structural changes and immune responses after Plasmodium infection.

Fungi work as decomposers to break down organic carbon, deposit recalcitrant carbon, and transform other elements such as nitrogen. The decomposition of biomass is a key function of wood-decaying basidiomycetes and ascomycetes, which have the potential for the bioremediation of hazardous chemicals present in the environment. Due to their adaptation to different environments, fungal strains have a diverse set of phenotypic traits. This study evaluated 320 basidiomycetes isolates across 74 species for their rate and efficiency of degrading organic dye. We found that dye-decolorization capacity varies among and within species. Among the top rapid dye-decolorizing fungi isolates, we further performed genome-wide gene family analysis and investigated the genomic mechanism for their most capable dye-degradation capacity. Class II peroxidase and DyP-type peroxidase were enriched in the fast-decomposer genomes. Gene families including lignin decomposition genes, reduction-oxidation genes, hydrophobin, and secreted peptidases were expanded in the fast-decomposer species. This work provides new insights into persistent organic pollutant removal by fungal isolates at both phenotypic and genotypic levels.

Background: The goal of this work was to compare the serum vitamin D level in women with uterine leiomyoma to that of controls, and to examine its association with the etiopathogenesis of this disease. Methods: This case-control study included 110 premenopausal women referred to a university hospital from January 2020 to December 2020. The study group consisted of 55 cases who underwent surgery for uterine fibroids, while the control group was comprised of 55 subjects without uterine fibroids. The number and volume of existing fibroids in each subject was assessed by transvaginal ultrasonography. Serum vitamin D status was determined by radioimmunoassay for 25-hydroxyvitamin D. Results: Average serum 25-hydroxyvitamin D levels in patients with uterine fibroids (20.52 ± 6.17 ng/mL) were significantly lower than in controls (24.18 ± 6.88 ng/mL; p = 0.004). Deficiency in 25-hydroxyvitamin D (i.e.,

Summary: Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment (TME). However, the relationship between the phenotype and metabolic pattern of TAMs remains poorly understood. We performed single-cell transcriptome profiling on hepatic TAMs from mice bearing liver metastatic tumors. We find that TAMs manifest high heterogeneity at the levels of transcription, development, metabolism, and function. Integrative analyses and validation experiments indicate that increased purine metabolism is a feature of TAMs with pro-tumor and terminal differentiation phenotypes. Like mouse TAMs, human TAMs are highly heterogeneous. Human TAMs with increased purine metabolism exhibit a pro-tumor phenotype and correlate with poor therapeutic efficacy to immune checkpoint blockade. Altogether, our work demonstrates that TAMs are developmentally, metabolically, and functionally heterogeneous and purine metabolism may be a key metabolic feature of a pro-tumor macrophage population.

Context Processing with vinegar could enhance the efficacy and reduce the toxicity of Curcuma phaeocaulis Valeton. (Zingiberaceae), a Chinese herbal medicine with anti-inflammatory and antitumor activities. Objective This study investigated the vinegar processing effects by evaluating anti-angiogenic effect and toxicity of C. phaeocaulis through zebrafish and rat models. Materials and methods Zebrafish embryos (AB and FLk-GFP strain) were applied to evaluate toxicity, cardiotoxicity and anti-angiogenic activity of volatile oil, and water decoction of the raw and vinegar-processed C. phaeocaulis. Meanwhile, a blood stasis syndrome rat model was applied to study the toxicity by measuring the ovarian and uterine coefficient. Results Curcuma phaeocaulis volatile oil and its vinegar-processed products in zebrafish had an LC50 of 67.315 and 95.755 μg/mL, respectively. Curcuma phaeocaulis water decoction and its vinegar-processed products had an LC50 of 161.440 and 206.239 μg/mL, respectively. The toxicity of vinegar-processed products was significantly lower than the raw, and the development characteristic of zebrafish embryos at different times confirmed these results. The volatile oil of vinegar-processed products could inhibit the growth of intersegmental blood vessels at the dose of 20 μg/mL, while the raw materials did not exhibit such effect at the same concentration. The rat experiment also confirmed that the volatile oil could reduce toxicity of ovarian and uterine. Discussion and conclusions The study indicated that processing using vinegar could decrease toxicity and increase anti-angiogenic activity of C. phaeocaulis, which could be applied for clinical treatment. Further in-depth study on the synergism and detoxification mechanism of vinegar processing technology is needed.

Fiber-reinforced resin matrix composites have been widely used in aerospace, construction, transportation and other industries due to their excellent mechanical properties and flexible structural design. However, due to the influence of the molding process, the composites are easily delaminated, which greatly reduces the structural stiffness of the components. This is a common problem in the processing of fiber-reinforced composite components. In this paper, through the combination of finite element simulation analysis and experimental research, drilling parameter analysis was carried out for prefabricated laminated composites, and the influence of different processing parameters on the processing axial force was qualitatively compared. The inhibition rule of variable parameter drilling on the damage propagation of initial laminated drilling was explored, which further improves the drilling connection quality of composite panels with laminated materials.

With the rapid development of high-frequency communication and large-scale integrated circuits, insulating dielectric materials require a low dielectric constant and dielectric loss. Poly (aryl ether ketone) resins (PAEK) have garnered considerable attention as an intriguing class of engineering thermoplastics possessing excellent chemical and thermal properties. However, the high permittivity of PAEK becomes an obstacle to its application in the field of high-frequency communication and large-scale integrated circuits. Therefore, reducing the dielectric constant and dielectric loss of PAEK while maintaining its excellent performance is critical to expanding the PAEK applications mentioned above. This study synthesized a series of poly (aryl ether ketone) resins that are low dielectric, highly thermally resistant, and soluble, containing cyclohexyl and diphenyl fluorene. The effects of cyclohexyl contents on the properties of a PAEK resin were studied systematically. The results showed that weakly-polarized cyclohexyl could reduce the molecular polarization of PAEK, resulting in low permittivity and high transmittance. The permittivity of PAEK is 2.95–3.26@10GHz, and the transmittance is 65–85%. In addition, the resin has excellent solubility and can be dissolved in NMP, DMF, DMAc, and other solvents at room temperature. Furthermore, cyclohexyl provided PAEK with excellent thermal properties, including a glass transition temperature of 239–245 °C and a 5% thermogravimetric temperature, under a nitrogen atmosphere of 469–534 °C. This makes it a promising candidate for use in high-frequency communications and large-scale integrated circuits.

Considered herein is the initial-boundary value problem for a semilinear parabolic equation with a memory term and non-local source wt−ΔBw−ΔBwt+∫0tg(t−τ)ΔBw(τ)dτ=|w|p−1w−1|B|∫B|w|p−1wdx1x1dx′ on a manifold with conical singularity, where the Fuchsian type Laplace operator ΔB is an asymmetry elliptic operator with conical degeneration on the boundary x1=0. Firstly, we discuss the symmetrical structure of invariant sets with the help of potential well theory. Then, the problem can be decomposed into two symmetric cases: if w0∈W and Π(w0)>0, the global existence for the weak solutions will be discussed by a series of energy estimates under some appropriate assumptions on the relaxation function, initial data and the symmetric structure of invariant sets. On the contrary, if w0∈V and Π(w0)<0, the nonexistence of global solutions, i.e., the solutions blow up in finite time, is obtained by using the convexity technique.

Internal delamination damage in composite connection structures can occur in the process of the overloading of a high-speed bearing, with alternating force loads, high or low temperatures, and the humid or hot environment loads. Mechanical drilling and riveting are usually used at the delamination position and outside its envelope, to inhibit delamination expansion. However, delamination damage can change the structural stress state of the original structure. It is difficult to achieve a better inhibition effect using conventional drilling mechanisms and process methods with intact composite panels, and new damage forms can even be introduced into the drilling process due to unreasonable parameter settings. Therefore, this paper combined finite element simulation technology and experimental processing technology, to analyze the influence of different delamination dimensions and positions on processing quality. The results showed that the feed speed and rotating speed had significant effects on the axial force of composite laminates. In particular, in the case of a low speed and high feed, the axial force will increase significantly.

Abstract This paper deals with a class of Petrovsky system with nonlinear damping w t t + Δ B 2 w − k 2 Δ B w t + a w t | w t | m − 2 = b w | w | p − 2 $$\begin{aligned} w_{tt}+\Delta _{\mathbb{B}}^{2}w-k_{2} \Delta _{\mathbb{B}}w_{t}+aw_{t} \vert w_{t} \vert ^{m-2}=bw \vert w \vert ^{p-2} \end{aligned}$$ on a manifold with conical singularity, where Δ B $\Delta _{\mathbb{B}}$ is a Fuchsian-type Laplace operator with totally characteristic degeneracy on the boundary x 1 = 0 $x_{1}=0$ . We first prove the global existence of solutions under conditions without relation between m and p, and establish an exponential decay rate. Furthermore, we obtain a finite time blow-up result for local solutions with low initial energy E ( 0 ) < d $E(0)< d$ .

This paper deals with the blow-up phenomena for a nonlinear pseudo-parabolic equation with a memory term $u_{t}-\triangle{u}-\triangle{u}_{t}+\int_{0}^{t}g(t-\tau)\triangle{u}(\tau)d\tau=|{u}|^{p}{u}$ in a bounded domain, with the initial and Dirichlet boundary conditions. We first obtain the finite time blow-up results for the solutions with initial data at non-positive energy level as well as arbitrary positive energy level, and give some upper bounds for the blow-up time $T^{*}$ depending on the sign and size of initial energy $E(0)$. In addition, a lower bound for the life span $T^{*}$ is derived by means of a differential inequality technique if blow-up does occur.

The dynamic architecture of the human brain has been consistently observed. However, there is still limited modeling work to elucidate how neuronal circuits are hierarchically and flexibly organized in functional systems. Here we proposed a reachable probability approach based on non-homogeneous Markov chains, to characterize all possible connectivity flows and the hierarchical structure of brain functional systems at the dynamic level. We proved at the theoretical level the convergence of the functional brain network system, and demonstrated that this approach is able to detect network steady states across connectivity structure, particularly in areas of the default mode network. We further explored the dynamically hierarchical functional organization centered at the primary sensory cortices. We observed smaller optimal reachable steps to their local functional regions, and differentiated patterns in larger optimal reachable steps for primary perceptual modalities. The reachable paths with the largest and second largest transition probabilities between primary sensory seeds via multisensory integration regions were also tracked to explore the flexibility and plasticity of the multisensory integration. The present work provides a novel approach to depict both the stable and flexible hierarchical connectivity organization of the human brain.

Introduction To date, there is little research assessing the efficacy of a proximal humeral internal locking system (PHILOS) plate plus an allogeneic fibula inserted obliquely in the treatment of 2-part proximal humerus fractures (PHFs) with calcar comminution in patients >60 years old with severe osteoporosis. The aim of this study was to retrospectively evaluate the outcomes of elderly patients with osteoporotic 2-part PHFs combined with medial column (calcar) instability or disruption who experienced a PHILOS plate plus an allogeneic fibula inserted obliquely. Materials and Methods One hundred and twelve consecutive elderly patients with severe osteoporotic 2-part PHFs combined with calcar instability or disruption who were treated with a PHILOS plate plus an allogeneic fibula inserted obliquely were retrospectively identified from 3 tertiary medical centres during 2014–2019. The primary outcomes were the Constant scores and American Shoulder and Elbow Surgeons (ASES) scores; secondary outcome was the rate of key orthopaedic complications. Results Median follow-up was 24 (15.3–27.6) months. Significant improvements in the median Constant scores were observed (39 [26–58 points] prior to surgery vs 81 [67–95 points] at final follow-up). The median ASES scores improved from 43 (26–64 points) prior to surgery to 83 (65–96 points) at final follow-up. The percentage of key orthopaedic complications was 25.6% (22/86). Four (4.7%) cases had loss of reduction, 4 (4.7%) experienced aseptic loosening, 1 (.8%) had non-union, 4 (4.7%) suffered a periprosthetic fracture, 3 (3.5%) experienced a revision surgery, 1 (.8%) had a dislocation and 5 (5.8%) suffered an unbearable shoulder pain. Conclusion For elderly patients with osteoporotic 2-part PHFs combined with calcar instability or disruption, PHILOS plate combined with an allogeneic fibula inserted obliquely might have recognisable advantages in decreasing the loss of fixation and preventing medial calcar collapse.