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Abstract As a critical payload of the gravitational wave detection interferometry system, the tilt-to-length (TTL) noise has a significant influence on the detection accuracy of the interferometry system. The non-geometric TTL (NG-TTL) noise, which is the main component of the TTL noise within the telescope, is closely related to the sensitive aberrations of the system’s small pupil. Due to the different environments of the earth and space, structural deformations of the telescope can cause significantly unfavorable changes in the sensitive aberrations at the small pupil. And its negative influence must be considered carefully during the whole structural design phase of the gravitational wave telescope. In this paper, the theoretical model of the NG-TTL noise within the telescope based on the Fringe Zernike polynomials has been summarized. An evaluation function of the NG-TTL noise within the telescope was proposed. A desensitization design method for the high-stability structure of the gravitational wave telescope was developed. The results show that under the same disturbances, the NG-TTL noise within the telescope was reduced to 0.1 pm·Hz− 1/2 from 2 pm·Hz− 1/2, taking the primary mirror (PM) as an example.

Abstract LiInSe2 crystals are promising semiconductor materials for neutron detectors due to the large neutron capture cross-sectional area of the specific isotopes (6Li) and high charge transport properties. However, the optoelectronic performance fails to reach the expected level due to the difficulty of controlling the crystal defects. Herein, we modulate the stoichiometric ratio to control the type of defects in single LiInSe2 crystals grown by the vertical Bridgman method. The UV‒vis–NIR transmission results indicate that the band gap of the yellow colored Li1.01In1Se2 sample is close to ~ 2.83 eV at room temperature, and this value is consistent with the theoretical band gap of LiInSe2 (~ 2.86 eV). Photoluminescence (PL) spectroscopy was used to analyze the defect concentration. The results indicate that the defect types in the yellow Li1.01In1Se2 single crystal are VSe + and LiIn 2−; these result from the introduction of excess Li and the suppression of the adverse defects in InLi 2+ and VLi −. These results demonstrate a feasible route for obtaining high-quality yellow 6LiInSe2 crystals and promote the application of 6LiInSe2 neutron detectors.

Abstract Diabetic encephalopathy (DE) is a severe complication of diabetes, but its pathogenesis remains unclear. This study aimed to investigate the roles and underlying mechanisms of high glucose (HG)- and advanced glycosylation end product (AGE)-induced oxidative stress (OS) in the cognitive decline in DE. The DE mouse model was established using a high-fat diet and streptozotocin, and its cognitive functions were evaluated using the Morris Water Maze, novel object recognition, and Y-maze test. The results revealed increased reactive oxygen species (ROS) generation, mitophagy inhibition, and decreased prohibitin 2 (PHB2) expression in the hippocampal neurons of DE mice and HG- or AGE-treated HT-22 cells. However, overexpression of PHB2 reduced ROS generation, reversed mitophagy inhibition, and improved mitochondrial function in the HG- or AGE-treated HT-22 cells and ameliorated cognitive decline, improved mitochondrial structural damage, and reversed mitophagy inhibition of hippocampal neurons in DE mice. Further analysis revealed that the Kelch-like ECH-associated protein 1 (Keap1)–nuclear factor erythroid 2-related factor 2 (Nrf2) pathway was involved in the HG- or AGE-mediated downregulation of PHB2 in HT-22 cells. These results demonstrate that HG- or AGE-induced OS inhibits the mitophagy of hippocampal neurons via the Keap1–Nrf2–PHB2 pathway, thereby contributing to the cognitive decline in DE.

Abstract Chronic lymphocytic leukemia (CLL) presents with heterogeneous clinical outcomes, suggesting varied underlying pathogenic mechanisms. This study aims to elucidate the impact of T follicular helper (Tfh) cells on CLL progression and prognosis. Gene expression profile data for CLL were collected from GSE22762 and GSE39671 datasets. Patients were divided into high and low groups using Tfh levels using the optimal cutoff value based on overall survival (OS) and time-to-first treatment (TTFT). Differential expression analysis was performed between these groups, followed by co-expression network analysis and single-sample Gene Set Enrichment Analysis (ssGSEA). Marker genes of Tfh cells were used to construct prognostic models. Additionally, 40 CLL patients were recruited and categorized based on median Tfh levels. Marker gene expression was assessed using RT-qPCR and Western Blot, and immune cell levels were determined through flow cytometry. The high group showed better prognosis compared to the low group. Among the 1121 differentially expressed genes identified, five co-expression networks were constructed, with the turquoise module showing the highest correlation with Tfh cells. Genes within this module significantly participate in cytokine-cytokine receptor interaction, PI3K-Akt signaling pathway, and natural killer cell mediated cytotoxicity. Tfh cells were significantly negatively correlated with activated B cells and positively correlated with Tregs. The Random Survival Forest (RSF) model identified 10 marker genes, and further analysis using Lasso regression and nomogram selected CLEC4A, RAE1, CD84, and PRDX1 as prognostic markers. In the high group, levels of CLEC4A and RAE1 were higher than in the low group, whereas CD84 and PRDX1 were lower. Flow cytometry revealed that the level of activated B cells in the high Tfh group was significantly lower than in the low Tfh group, while the level of Tregs is significantly higher in the high Tfh group. This study seeks to contribute to a more detailed understanding of the pathogenesis of CLL, delving into the prognostic significance of Tfh.

Abstract Understanding the spatiotemporal characteristics and comprehensive service capabilities of various ecosystem services is crucial for maintaining regional ecosystem security, and clarifying the driving mechanisms of ecosystem services plays a guarantee for achieving regional sustainable development. Based on the ecological issues of Shanxi Province (SXP) in China, an assessment system covering eight targeted ecosystem services were constructed to quantitatively analyze the spatio-temporal patterns and contribution rates of driving factors. The water conservation, sand fixation, environment purification and habitat quality in the Loess Hills of western SXP have improved, with significant increase in hotspots. The comprehensive service capacity of ecosystem services in the Fenwei Basin (central SXP) has deteriorated, and the coldspots have expanded. The water conservation, carbon storage, habitat quality and recreation culture in the Yanshan-Taihang Mountains (eastern SXP) were enhanced, while product supply, carbon storage and environment purification were deteriorated. Land use is the dominant influencing factor on product supply. Water and soil conservation, sand fixation, and environment purification are dominated by climate factors. Carbon storage, habitat quality and recreation culture are influenced by underlying surface conditions. The current study provided a research paradigm, which will help the government with appropriate management policies to ensure the effectiveness of ecological protection and restoration, and offers insights for facilitating ecological sustainability and economic transformation in resource-based regions worldwide.

Abstract Observational studies have shown that non-alcoholic fatty liver disease (NAFLD) is strongly associated with metabolic dysfunction. However, there is a paucity of research on whether changes in indicators of serum metabolism contribute to the development of NAFLD. This study was conducted with 4084 participants who underwent healthy physical examinations at Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China, in 2022 and 2023. Baseline and follow-up measurements, including anthropometric data, abdominal ultrasound and blood samples were collected. The diagnosis of NAFLD was based on the 2010 Chinese Guidelines on Diagnosis and Treatment of NAFLD. Multiple logistic regression was utilized to analyze the odds ratios (ORs) for the 1-year risk of NAFLD in connection with both baseline metabolic indicators and changes in metabolic indicators observed over the course of 1 year. A total of 3425 study participants who were free of NAFLD at baseline, including 1146 men and 2279 women, were included in the final analysis. The mean age was 34.43 ± 7.20 years. Participants who developed NAFLD were older, male and had higher levels of body mass index (BMI), blood pressure, fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), free triiodothyronine (fT3), uric acid (UA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST); and lower levels of high-density lipoprotein cholesterol (HDL-C) and free thyroxine (fT4) (all P values

Abstract Female urethral caruncle is the most common urethral mass in postmenopausal women, yet there is a lack of studies on its imaging. The aim of this study was to provide a summary of the clinical and ultrasound features as well as the precise location of female urethral caruncle. This study reviewed the clinical and ultrasonographic records of 20 consecutive women with pathologically confirmed urethral caruncle. Data on patient demographics, symptoms, and transperineal and transrectal ultrasound imaging features, including location, shape, margin, size, blood flow, and inner echo of the caruncle, were extracted. Each patient presented with only one mass at the urethral meatus. Most caruncles were located on the posterior lip (75%) of the urethra, presenting as oval (80%), mixed-echoic (50%), or hypo-echoic (40%) nodules with abundant linear (40%) or dendritic (60%) blood flow. The average distance between the bladder neck and the cranial end of the masses was 28 mm. Hyper-echogenic spots, cystic echo areas, and macrocalcifications were detected in thirteen caruncles (70%). This study shows that transperineal combined with transrectal ultrasound can be used to assess female urethral caruncle, and its relative location to the urethra can be accurately described, which is helpful for surgeons making preoperative localization and conversations.

Abstract The prevalence of non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancers, with the Wnt/β-catenin signaling pathway exhibiting robust activation in this particular subtype. The expression of FAM83A (family with sequence similarity 83, member A) has been found to be significantly upregulated in lung cancer, leading to the stabilization of β-catenin and activation of the Wnt signaling pathway. In this study, we conducted a screening of down-regulated miRNAs in lung cancer with FAM83A as the target. Ultimately, we identified miR-1 as a negative regulator of FAM83A and confirmed that FAM83A is a direct target gene of miR-1 through dual luciferase reporter assays. The overexpression of miR-1 significantly attenuated the expression level of FAM83A and suppressed the Wnt signaling pathway, leading to a reduction in the expression levels of downstream target genes AXIN2, CyclinD1, and C-MYC. Additionally, it decreased the nuclear translocation of β-catenin. In addition, overexpression of miR-1 accelerated the degradation of β-catenin by inhibiting FAM83A, promoted the assembly of β-catenin degradation complex, and inhibited the proliferation, migration and invasion of NSCLC cells. In summary, miR-1 may be a potential candidate miRNA for the treatment of NSCLC.

Abstract We explored physiological effects of the sodium-glucose co-transporter-2 inhibitor empagliflozin on intact experimentally hypertrophic murine hearts following transverse aortic constriction (TAC). Postoperative drug (2–6 weeks) challenge resulted in reduced late Na+ currents, and increased phosphorylated (p-)CaMK-II and Nav1.5 but not total (t)-CaMK-II, and Na+/Ca2+ exchanger expression, confirming previous cardiomyocyte-level reports. It rescued TAC-induced reductions in echocardiographic ejection fraction and fractional shortening, and diastolic anterior and posterior wall thickening. Dual voltage- and Ca2+-optical mapping of Langendorff-perfused hearts demonstrated that empagliflozin rescued TAC-induced increases in action potential durations at 80% recovery (APD80), Ca2+ transient peak signals and durations at 80% recovery (CaTD80), times to peak Ca2+ (TTP100) and Ca2+ decay constants (Decay30–90) during regular 10-Hz stimulation, and Ca2+ transient alternans with shortening cycle length. Isoproterenol shortened APD80 in sham-operated and TAC-only hearts, shortening CaTD80 and Decay30–90 but sparing TTP100 and Ca2+ transient alternans in all groups. All groups showed similar APD80, and TAC-only hearts showed greater CaTD80, heterogeneities following isoproterenol challenge. Empagliflozin abolished or reduced ventricular tachycardia and premature ventricular contractions and associated re-entrant conduction patterns, in isoproterenol-challenged TAC-operated hearts following successive burst pacing episodes. Empagliflozin thus rescues TAC-induced ventricular hypertrophy and systolic functional, Ca2+ homeostatic, and pro-arrhythmogenic changes in intact hearts.

Abstract Adipose tissue plays critical roles in an individual’s aging process. In this research, we use single-nucleus RNA sequencing to create highly detailed transcriptional maps of subcutaneous adipose tissue and visceral adipose tissue in young and aged mice. We comprehensively identify the various cell types within the white adipose tissue of mice, our study has elucidated seven distinct cell types within this tissue. Further analyses focus on adipocytes, fibro-adipogenic progenitors, and immune cells, revealing age-related declines in the synthetic metabolic activity of adipocytes, diminished immune regulation, and reduced maturation or proliferation of fibroblasts in undifferentiated adipocytes. We confirm the presence of distinct subpopulations of adipocytes, highlighting decreases in adipogenesis subgroups due to aging. Additionally, we uncover a reduction in immune cell subpopulations, driven by age-associated immune system dysregulation. Furthermore, pseudo-time analyses indicate that Adipocyte1 represents the 'nascent' phase of adipocyte development, while Adipocyte2 represents the 'mature' phase. We use cell–cell interaction to explore the age-dependent complexities of the interactions between FAPs and adipocytes, and observed increased expression of the inflammation-related Retn-Tlr4 interaction in older mice, while the anti-inflammatory Angpt1-Tek interaction was only detected in young mice. These transcriptional profiles serve as a valuable resource for understanding the functional genomics underlying metabolic disorders associated with aging in human adipose tissue.

Abstract Gravitational wave telescope place extremely high demands on structural thermal deformation, making material selection a critical issue. Carbon fiber reinforced polymer (CFRP) is an ideal choice for the support structure of telescope due to its low coefficient of thermal expansion (CTE) and designable properties. However, current research on the optimization of the CTE of CFRP is scarce, and conventional methods struggle to find layups that meet the requirements. In this paper, an unconventional layup optimization method is proposed to solve this problem. Initially defining the characteristics of the telescope structure and using different layup material for the main and side support rods to minimize thermal deformation. Subsequently, the NSGA-II algorithm is used to optimize the layups which are divided into conventional and unconventional layups. Specimens are then produced from these results and tested to assess the impact of processing errors on practical applications. The results demonstrate that the optimized CFRP meet the CTE requirements and, when applied to the structure, significantly reduces the thermal deformation in the eccentric direction compared to conventional designs. Additionally, a numerical analysis evaluates the effect of ply orientation errors on the performance of unconventional layups, discussing the method's limitations within these contexts.

Abstract This study aimed to develop a machine learning (ML)-based tool for early and accurate prediction of in-hospital mortality risk in patients with spontaneous intracerebral hemorrhage (sICH) in the intensive care unit (ICU). We did a retrospective study in our study and identified cases of sICH from the MIMIC IV (n = 1486) and Zhejiang Hospital databases (n = 110). The model was constructed using features selected through LASSO regression. Among five well-known models, the selection of the best model was based on the area under the curve (AUC) in the validation cohort. We further analyzed calibration and decision curves to assess prediction results and visualized the impact of each variable on the model through SHapley Additive exPlanations. To facilitate accessibility, we also created a visual online calculation page for the model. The XGBoost exhibited high accuracy in both internal validation (AUC = 0.907) and external validation (AUC = 0.787) sets. Calibration curve and decision curve analyses showed that the model had no significant bias as well as being useful for supporting clinical decisions. XGBoost is an effective algorithm for predicting in-hospital mortality in patients with sICH, indicating its potential significance in the development of early warning systems.

Abstract The increasing global phenomenon of soil salinization has prompted heightened interest in the physiological ecology of plant salt and alkali tolerance. Halostachys caspica belonging to Amaranthaceae, an exceptionally salt-tolerant halophyte, is widely distributed in the arid and saline-alkali regions of Xinjiang, in Northwest China. Soil salinization and alkalinization frequently co-occur in nature, but very few studies focus on the interactive effects of various salt and alkali stress on plants. In this study, the impacts on the H. caspica seed germination, germination recovery and seedling growth were investigated under the salt and alkali stress. The results showed that the seed germination percentage was not significantly reduced at low salinity at pH 5.30–9.60, but decreased with elevated salt concentration and pH. Immediately after, salt was removed, ungerminated seeds under high salt concentration treatment exhibited a higher recovery germination percentage, indicating seed germination of H. caspica was inhibited under the condition of high salt-alkali stress. Stepwise regression analysis indicated that, at the same salt concentrations, alkaline salts exerted a more severe inhibition on seed germination, compared to neutral salts. The detrimental effects of salinity or high pH alone were less serious than their combination. Salt concentration, pH value, and their interactions had inhibitory effects on seed germination, with salinity being the decisive factor, while pH played a secondary role in salt-alkali mixed stress.

Abstract In this paper, Voronoi cell finite element method (VCFEM) based on assumed flux hybrid formulation has been presented for heat conduction problem of particle reinforced composites material. The heat fluxes satisfying a priori internal thermal balance are directly approximated independently in the matrix and the inclusion respectively. The temperatures on element boundary and matrix-inclusion interface are interpolated by nodal temperature. The thermal balance on the interelement boundary and matrix-inclusion interface is relaxed and introduced into the functional by taking the temperature as Lagrange multiplier. In this way, a functional containing two variables of heat flux and temperature is proposed. Full field heat flux and effective thermal conductivity are obtained. Feasibility and effectiveness of the proposed approach are verified through several numerical examples.

Abstract Multiple myeloma (MM) progression involves diminished tumor antigen presentation and an immunosuppressive microenvironment, characterized by diminished expression of major histocompatibility complexes (MHC) class I molecule and elevated programmed death ligand 1 (PDL1) in MM cells, along with an enriched population of regulatory T cells (Tregs). To investigate Treg's influence on MM cells, we established a co-culture system using Tregs from MM patients and the MM cell lines (MM.1S and SK-MM-1) in vitro and assessed the effects of intervening in the relevant pathways connecting Tregs and MM cells in vivo. In vitro, Tregs induced transforming growth factor beta-1 (TGF-β1) production, downregulated MHC I members, and increased PDL1 expression in MM cells. Treg-derived TGF-β1 suppressed the cGAS-STING pathway, contributing to the loss of MHC I molecule expression and PDL1 upregulation. Correspondingly, neutralizing TGF-β1 or activating the cGAS-STING pathway restored MHC I and PDL1 expression, effectively countering the pro-tumorigenic effect of Tregs on MM cells in vivo. These data elucidated how Tregs influence tumor antigen presentation and immunosuppressive signal in MM cells, potentially providing therapeutic strategies, such as neutralizing TGF-β1 or activating the cGAS-STING pathway, to address the immune escape and immunosuppressive dynamics in MM.

Abstract The Circle of Willis perforation (cWp) mouse model is a key tool in subarachnoid hemorrhage (SAH) research; however, inconsistent bleeding volumes can challenge experimental reliability. To address this issue, we introduced the ROB Scoring System, a novel protocol integrating Rotarod Tests (RT), Open-field Tests (OT) video analysis, and daily Body Weight Loss (BWL) monitoring to precisely categorize SAH severity. Forty C57BL/6 mice underwent cWp SAH induction, categorized by ROB into severity subgroups (severe, moderate, mild). Validation compared ROB trends in subgroups, and ROB outcomes with autopsy results on postoperative days three and seven for acute and sub-acute evaluations. Mortality rates were analyzed via the survival log-rank test, revealing a significant difference among SAH subgroups (P

Abstract Non-pharmaceutical interventions (NPI) have great potential to improve cognitive function but limited investigation to discover NPI repurposing for Alzheimer's Disease (AD). This is the first study to develop an innovative framework to extract and represent NPI information from biomedical literature in a knowledge graph (KG), and train link prediction models to repurpose novel NPIs for AD prevention. We constructed a comprehensive KG, called ADInt, by extracting NPI information from biomedical literature. We used the previously-created SuppKG and NPI lexicon to identify NPI entities. Four KG embedding models (i.e., TransE, RotatE, DistMult and ComplEX) and two novel graph convolutional network models (i.e., R-GCN and CompGCN) were trained and compared to learn the representation of ADInt. Models were evaluated and compared on two test sets (time slice and clinical trial ground truth) and the best performing model was used to predict novel NPIs for AD. Discovery patterns were applied to generate mechanistic pathways for high scoring candidates. The ADInt has 162,212 nodes and 1,017,284 edges. R-GCN performed best in time slice (MR = 5.2054, Hits@10 = 0.8496) and clinical trial ground truth (MR = 3.4996, Hits@10 = 0.9192) test sets. After evaluation by domain experts, 10 novel dietary supplements and 10 complementary and integrative health were proposed from the score table calculated by R-GCN. Among proposed novel NPIs, we found plausible mechanistic pathways for photodynamic therapy and Choerospondias axillaris to prevent AD, and validated psychotherapy and manual therapy techniques using real-world data analysis. The proposed framework shows potential for discovering new NPIs for AD prevention and understanding their mechanistic pathways.

Abstract The addition of hollow glass microsphere into composites is a method to improve mechanical properties. However, the interfacial debonding of hollow microsphere inevitably causes a decrease in the mechanical properties of the material, which ultimately leads to the failure of the composites. In the numerical simulation of such hollow particle-reinforced composites, the ordinary displacement finite element requires a large number of meshes, which undoubtedly greatly increases the computational cost. In this paper, a new VCFEM is proposed to solve this problem by establishing a two-dimensional Voronoi cell finite element model, deriving the residual energy generalized function of hollow particle-reinforced composites, and calculating the interface debonding. The simulation results are compared with the commercial software MARC, ABAQUS to verify the effectiveness of this VCFEM. The results show that this VCFEM greatly improves the computational efficiency while ensuring the accuracy. Based on this model, this paper also investigates the effect of the generation of interfacial debonding on the overall structure and the effect of different wall thickness of hollow particles on the damage of element debonding.

Abstract Resolving the role of galactic processes in Solar System/Earth events necessitates a robust temporal model. However, astrophysical theory diverges with models varying from long-lasting spiral density waves with uniform pattern speeds and arm structures to others with fleeting and unpredictable features. Here, we address those issues with (1) an analysis of patterns of impact periodicity over periods of 10 to 250 million years (Myr) using circular statistics and (2), an independent logarithmic spiral arm model fitted to arm tangents of 870 micron dust. Comparison of the impact periodicity results with the best-fit spiral arm model suggests a galactic period of 660 Myr, i.e. 165 Myr to pass from one arm to the next in a four spiral arm model, with the most recent arm passage around 52 million years ago (Ma). The oldest impact ages imply that the emerging galactic chronology model is robust for at least the last 2 Gyr. The arm-passing time is consistent with spectral analyses of zircons across 3 Gyrs. Overall, the model provides a temporal framework against which to test hypotheses of galactic mechanisms for global events such as mass extinctions and superchrons.

Abstract The effect of MDANP effects on ER stress signalling not well known or elucidated. Endoplasmic reticulum (ER) stress plays a critical role in necrotizing enterocolitis (NEC) pathogenesis through the PERK-eIF2ɑ-QRICH1 axis. The present study aimed to explore the protective effects of MDANP in NEC development. Firstly, a function screening was designed to identify the candidate peptides in human milk, and then the identified peptides were validated in NEC patients. In vivo, NEC was induced in mice pups and divided into four groups: (1) control group, (2) NEC group, (3) MDANP + NEC group, and (4) NS + NEC group. In vitro, lentivirus-mediated QRICH1 silencing, was used to transfect NCM460 cell lines, then stimulated with LPS. After LPS stimulation, cells were treated with chemically synthesized MDANP, and the essential proteins in the QRICH1 signalling pathway in cells were tested and compared. After the small-scale screening, a peptide (SKSKKFRRPDIQYPDATDED) named MDANP was determined as the principal peptide. Its protective effect against NEC through inhibiting the expression of ERS key proteins and impeding the intestinal cells’ apoptosis was observed in the animal models. Furthermore, the inhibitive effect of MDANP on apoptosis of intestinal epithelial cells through modulating the PERK-eIF2ɑ-QRICH1 ERS pathway was also confirmed in vitro. Taken together, our data suggest that MDANP effectively ameliorates apoptosis in NEC through attenuating PERK-eIF2ɑ-QRICH1.

Abstract This study investigates the relationships among government intervention, industrial structure, and energy eco-efficiency (EE). Energy eco-efficiency was measured based on a non-radial directional distance function for 236 cities in China from 2005 to 2019. Additionally, the difference-in-difference model (DID) method and spatial econometric models were used to analyse the impact of government intervention and industrial structure on energy eco-efficiency and their spatial spill-over effects. Government intervention includes fiscal expenditures and policy orientation for new energy demonstration construction. Our results indicate that: China’s EE has a fluctuating upward trend and increased 17.85% in the period, and its spatial distribution imbalance gradually developed into a regional distribution balance. Moreover, government intervention and adjustment of the industrial structure improved urban energy eco-efficiency by 7.43% and 0.92%, respectively, which also has spatial spill-over effects in neighbouring regions. Furthermore, economic development, technological innovation, and foreign direct investment enable EE. However, urbanisation hinders the improvement of energy eco-efficiency. Finally, heterogeneity analysis showed that the policy of the new energy demonstration city has better effects on eastern and western cities in promoting EE.

Abstract Fine particulate matter (PM2.5) pollution remains a major threat to public health. As the physical barrier against inhaled air pollutants, airway epithelium is a primary target for PM2.5 and influenza viruses, two major environmental insults. Recent studies have shown that PM2.5 and influenza viruses may interact to aggravate airway inflammation, an essential event in the pathogenesis of diverse pulmonary diseases. Airway epithelium plays a critical role in lung health and disorders. Thus far, the mechanisms for the interactive effect of PM2.5 and the influenza virus on gene transcription of airway epithelial cells have not been fully uncovered. In this present pilot study, the transcriptome sequencing approach was introduced to identify responsive genes following individual and co-exposure to PM2.5 and influenza A (H3N2) viruses in a human bronchial epithelial cell line (BEAS-2B). Enrichment analysis revealed the function of differentially expressed genes (DEGs). Specifically, the DEGs enriched in the xenobiotic metabolism by the cytochrome P450 pathway were linked to PM2.5 exposure. In contrast, the DEGs enriched in environmental information processing and human diseases, such as viral protein interaction with cytokines and cytokine receptors and epithelial cell signaling in bacterial infection, were significantly related to H3N2 exposure. Meanwhile, co-exposure to PM2.5 and H3N2 affected G protein-coupled receptors on the cell surface. Thus, the results from this study provides insights into PM2.5- and influenza virus-induced airway inflammation and potential mechanisms.

Abstract In the advanced stage of cancer, the pain caused by bone metastasis is unbearable, but the mechanism of bone cancer pain (BCP) is very complicated and remains unclear. In this study, we used 4T1 mouse breast cancer cells to establish a bone cancer pain model to study the mechanism of BCP. Then the paw withdrawal mechanical threshold (PWMT) and the hematoxylin-eosin staining were used to reflect the erosion of cancer cells on tibia tissue. We also determined the role of proinflammatory factors (TNF-α, IL-17, etc.) in BCP by the enzyme-linked immunosorbent assay in mouse serum. When GSK690693, a new Akt inhibitor, was given and the absence of intermediate signal dominated by Akt is found, pain may be relieved by blocking the transmission of pain signal and raising the PWMT. In addition, we also found that GSK690693 inhibited the phosphorylation of Akt protein, resulting in a significant decrease in with-nolysinekinases 1 (WNK1) expression in the spinal cord tissue. In the BCP model, we confirmed that GSK690693 has a relieving effect on BCP, which may play an analgesic effect through PI3K-WNK1 signal pathway. At the same time, there is a close relationship between inflammatory factors and PI3K-WNK1 signal pathway. The PI3K/Akt pathway in the dorsal horn of the mouse spinal cord activates the downstream WNK1 protein, which promotes the release of inflammatory cytokines, which leads to the formation of BCP in mice. Inhibition of Akt can reduce the levels of IL-17 and TNF-α, cut off the downstream WNK1 protein signal receiving pathway, increase the PWMT and relieve BCP in mice. To clarify the analgesic target of BCP, to provide reference and theoretical support for the clinical effective treatment of BCP and the development of new high-efficiency analgesics.

Abstract As a major source of air pollution, particulate matter (PM) and associated toxic trace elements pose potentially serious threats to human health and environmental safety. As is known that plants can reduce air PM pollution. However, the relationship between PM of different sizes and toxic trace elements in foliar PM is still unclear. This study was performed to explore the association between PM of different sizes (PM2.5, PM10, PM>10) and toxic trace elements (As, Al, Cu, Zn, Cd, Fe, Pb) as well as the correlation among toxic trace elements of six roadside plant species (Cinnamomum camphora, Osmanthus fragrans, Magnolia grandiflora, Podocarpus macrophyllus, Loropetalum chinense var. rubrum and Pittosporum tobira) in Changsha, Hunan Province, China. Results showed that P. macrophyllus had the highest ability to retain PM, and C. camphora excelled in retaining PM2.5. The combination of P. macrophyllus and C. camphora was highly recommended to be planted in the subtropical city to effectively reduce PM. The toxic trace elements accumulated in foliar PM varied with plant species and PM size. Two-way ANOVA showed that most of the toxic trace elements were significantly influenced by plant species, PM size, and their interactions (P

Abstract Machine learning (ML) has been extensively involved in assistant disease diagnosis and prediction systems to emancipate the serious dependence on medical resources and improve healthcare quality. Moreover, with the booming of pre-training language models (PLMs), the application prospect and promotion potential of machine learning methods in the relevant field have been further inspired. PLMs have recently achieved tremendous success in diverse text processing tasks, whereas limited by the significant semantic gap between the pre-training corpus and the structured electronic health records (EHRs), PLMs cannot converge to anticipated disease diagnosis and prediction results. Unfortunately, establishing connections between PLMs and EHRs typically requires the extraction of curated predictor variables from structured EHR resources, which is tedious and labor-intensive, and even discards vast implicit information.In this work, we propose an Input Prompting and Discriminative language model with the Mixture-of-experts framework (IPDM) by promoting the model’s capabilities to learn knowledge from heterogeneous information and facilitating the feature-aware ability of the model. Furthermore, leveraging the prompt-tuning mechanism, IPDM can inherit the impacts of the pre-training in downstream tasks exclusively through minor modifications. IPDM remarkably outperforms existing models, proved by experiments on one disease diagnosis task and two disease prediction tasks. Finally, experiments with few-feature and few-sample demonstrate that IPDM achieves significant stability and impressive performance in predicting chronic diseases with unclear early-onset characteristics or sudden diseases with insufficient data, which verifies the superiority of IPDM over existing mainstream methods, and reveals the IPDM can powerfully address the aforementioned challenges via establishing a stable and low-resource medical diagnostic system for various clinical scenarios.

Abstract Rejuvenation of an old organism was achieved in heterochronic parabiosis experiments, implicating different soluble factors in this effect. Extracellular vesicles (EVs) are the secretory effectors of many cells, including cardiosphere-derived cells (CDCs) with demonstrated anti-senescent effect. 1. To determine the role of EVs (versus other blood fractions) on the rejuvenating effect of the young blood. 2. To evaluate the anti-aging properties of therapeutically administered EVs secreted by young-CDCs in an old organism. Neonatal blood fractioned in 4 components (whole blood, serum, EV-depleted serum and purified EVs) was used to treat old human cardiac stromal cells (CSPCs). CDCs were generated from neonatal rat hearts and the secreted CDC-EVs were purified. CDC-EVs were then tested in naturally-aged rats, using monthly injections over 4-months period. For validation in human samples, pediatric CDC-EVs were tested in aged human CSPCs and progeric fibroblasts. While the purified EVs reproduced the rejuvenating effects of the whole blood, CSPCs treated with EV-depleted serum exhibited the highest degree of senescence. Treatment with young CDC-EVs induce structural and functional improvements in the heart, lungs, skeletal muscle, and kidneys of old rats, while favorably modulating glucose metabolism and anti-senescence pathways. Lifespan was prolonged. EVs secreted by young CDCs exert broad-ranging anti-aging effects in aged rodents and in cellular models of human senescence. Our work not only identifies CDC-EVs as possible therapeutic candidates for a wide range of age-related pathologies, but also raises the question of whether EVs function as endogenous modulators of senescence.

Abstract The microstructure of minerals and rocks can significantly alter reaction rates. This study focuses on identifying transport paths in low porosity rocks based on the hypothesis that grain boundary widening accelerates reactions in which one mineral is replaced by another (replacement reaction). We conducted a time series of replacement experiments of three limestones (CaCO3) of different microstructures and solid impurity contents using FeCl2. Reacted solids were analyzed using chemical imaging, small angle X-ray and neutron scattering and Raman spectroscopy. In high porosity limestones replacement is reaction controlled and complete replacement was observed within 2 days. In low porosity limestones that contain 1–2% dolomite impurities and are dominated by grain boundaries, a reaction rim was observed whose width did not change with reaction time. Siderite (FeCO3) nucleation was observed in all parts of the rock cores indicating the percolation of the solution throughout the complete core. Dolomite impurities were identified to act as nucleation sites leading to growth of crystals that exert force on the CaCO3 grains. Widening of grain boundaries beyond what is expected based on dissolution and thermal grain expansion was observed in the low porosity marble containing dolomite impurities. This leads to a self-perpetuating cycle of grain boundary widening and reaction acceleration instead of reaction front propagation.

Abstract Omeprazole and sodium bicarbonate dry suspension are effective treatments for acid-related disorders. This study compared the bioequivalence and safety of the two formulations of omeprazole and sodium bicarbonate powder and assessed how CYP2C19 gene polymorphisms affect pharmacokinetics (PK). A single-center, randomized, single-dose, 2-sequence and 2-period crossover method was performed in forty healthy Chinese subjects. Blood samples were collected after a single dose for PK (AUC0–∞, AUC0–t, and Cmax) analysis. The concentrations of Omeprazole in human plasma were determined by HPLC–MS/MS. Besides, the gene polymorphisms of CYP2C19 were assessed by Sanger sequencing. The geometric mean ratios (90% confidence interval) [GMR (95% CI)] of Test/Reference preparation for Cmax: 95.2% (88.48%, 102.43%), AUC0–t: 97.47% (94.4%, 101.02%), AUC0–∞: 97.68% (94.27%, 101.21%) were within the range of 80.00–125.00%. The non-parametric test showed no statistical difference in Tmax between the two groups (p > 0.05). All drugs were well tolerated, no severe adverse reactions occurred, and no significant differences in adverse events between the two drugs. For CYP2C19 gene polymorphisms, the results showed that of 40 subjects, 12 subjects were extensive metabolizers, 24 were intermediate metabolizers, and 4 were poor metabolizers, the frequency of metabolic genotypes were 30%, 60%, and 10%. And the allele distributions for CYP2C19 were *1, *2, and *3 at 60%, 38.75%, and 1.25%. Both the CYP2C19 alleles and metabolic genotypes were consistent with other studies in Chinese. The results of PK parameters showed that different genotypes of CYP2C19 lead to significant differences in t1/2, AUC0–t, AUC0–∞ and Cmax, but no significant differences in Tmax in each group. At the same time, we confirmed that the PK parameters of the test and reference had no differences between the males and females. This study has shown that the pharmacokinetic parameters of the two formulations are not significantly different, which showed bioequivalence and exemplary safety. CYP2C19 gene polymorphism significantly differed in the PK parameters of omeprazole sodium bicarbonate powder.

Abstract In angiosperms, self-incompatibility (SI) is a common and widespread mechanism for plant prevention of inbreeding, and late-acting self-incompatibility (LSI) may be ancestral in the group. In this work, we studied Schima superba, a species in Theaceae that is a commercially important timer and fire-resistant tree, and revealed its LSI mechanism. Hormones, enzymes, transcriptomes, and proteins were compared between self-pollination (SP) and outcross pollination (OP) in the styles and ovaries from 0 to 120 h after pollination. The self-pollen tubes grew to the bottom of the style and entered the ovary within 48 h but failed to penetrate the ovule. Meanwhile, the hormone and peroxidase levels dramatically changed. Transcriptome and proteome analyses explored the molecular mechanisms of LSI and candidate genes related to LSI in S. superba. Overall, 586.71 million reads were obtained, and 79,642 (39.08%) unigenes were annotated. KEGG and GO analysis showed that there were 4531 differentially expressed genes (DEGs) and 82 differentially expressed proteins (DEPs) at 48 h in self- (SP) versus outcross pollination (OP). Among these, 160 DEGs and 33 DEPs were involved in pollen–pistil interactions. “Pollen–pistil interaction,” “signal recognition,” and “component of membrane” were downregulated in SP, whereas “cell wall and membrane biosynthetic process,” and “oxidoreductase activity” were upregulated. The DEGs involved with S-RNases and SCF during SP suggested that the LSI occurred at 48 h in the ovary and that the LSI in S. superba was under gametophyte control. Calcium ion increase and release, mitochondrial function loss, and ROS disruption further aggravated PCD progress and cell death. The LSI of S. superba, which happened 48 h after pollination, was a key time point. The incompatibility PT ceased growth in the ovary because of S-RNase recognition and PCD in this organ. This study highlights the LSI molecular mechanism in S. superba and provides a reference to other species in Theaceae.

Abstract Urethral stricture is related to scar tissue fibrosis, but its pathogenesis is still unclear. This study aims to explore the regulatory mechanism of circular RNA (circRNA) in the occurrence and development of urethral stricture. CircRNA microarray was employed to analyze circRNA expression profiles between human urethral scar tissue and normal urethral tissue. The results of circRNA microarray showed that there were 296 differentially expressed genes between urethral scar tissue and normal urethral tissue. The enrichment analysis of Kyoto encyclopedia of genes and genomes showed that these circRNAs were significantly correlated with ECM–receptor interaction. The first nine differentially expressed circRNA were selected to predict the circRNA–miRNA network. RT-qPCR results showed that circ_0047339 was upregulated considerably in urethral scar tissue. Urethral scar fibroblasts were isolated from human urethral scar tissue and cultured in vitro. After silencing circ_0047339, the proliferation of urethral scar cells decreased significantly, and the expressions of Collagen I (COL-1) and α-smooth muscle actin (α-SMA) also reduced. As a competing endogenous RNA, circ_0047339 could increase the expression of TSP-1 by competitively binding miR-4691-5p. In addition, miR-4691-5p mimic transfection could inhibit the proliferation of urethral scar fibroblasts and the presentation of thrombospondin-1 (TSP-1), α-SMA and COL-1, while circ_0047339 overexpression eliminated this inhibition. Our results showed that circ_0047339 might promote the growth and fibrosis of urethral scar fibroblasts through miR-4691-5p/TSP-1 axis, thus promoting the development of urethral stricture.

Abstract Plant growth environment plays an important role in shaping soil microbial communities. To understand the response of soil rhizosphere microbial communities in Oplopanax elatus Nakai plant to a changed growth conditions from natural habitation to cultivation after transplant. Here, a comparative study of soil chemical properties and microbial community using high-throughput sequencing was conducted under cultivated conditions (CT) and natural conditions (WT), in Changbai Mountain, Northeast of China. The results showed that rhizosphere soil in CT had higher pH and lower content of soil organic matter (SOM) and available nitrogen compared to WT. These changes influenced rhizosphere soil microbial communities, resulting in higher soil bacterial and fungi richness and diversity in CT soil, and increased the relative abundance of bacterial phyla Acidobacteria, Chloroflexi, Gemmatimonadetes, Firmicutes and Patescibacteria, and the fungi phyla Mortierellomycota and Zoopagomycota, while decreased bacterial phyla Actinobacteria, WPS-2, Gemmatimonadetes, and Verrucomicrobia, and the fungi phyla Ascomycota, and Basidiomycota. Redundancy analysis analysis indicated soil pH and SOM were the primarily environmental drivers in shaping the rhizosphere soil microbial community in O. elatus under varied growth conditions. Therefore, more attention on soil nutrition management especially organic fertilizer inputs should be paid in O. elatus cultivation.

Abstract Nitrogen is an essential core element in walnut seedling growth and development. However, nitrogen starvation and excessive nitrogen stress can cause stunted growth and development of walnut seedlings, and environmental pollution is also of concern. Therefore, it is necessary to study the mechanism of walnut seedling resistance to nitrogen stress. In this study, morphological and physiological observations and transcriptome sequencing of walnut seedlings under nitrogen starvation and excess nitrogen stress were performed. The results showed that walnut seedlings under nitrogen starvation and excess stress could adapt to the changes in the nitrogen environment by changing the coordination of their root morphology and physiological indexes. Based on an analysis of transcriptome data, 4911 differential genes (DEGs) were obtained (2180 were upregulated and 2731 were downregulated) in a comparison of nitrogen starvation and control groups. A total of 9497 DEGs (5091 upregulated and 4406 downregulated) were obtained in the comparison between the nitrogen overdose and control groups. When these DEGs were analysed, the differential genes in both groups were found to be significantly enriched in the plant’s circadian pathway. Therefore, we selected the circadian rhythm as the focus for further analysis. We made some discoveries by analysing the gene co-expression network of nitrogen metabolism, circadian rhythm, and hormone signal transduction. (a) Nitrite nitrogen (NO2 −) or Glu may act as a nitrogen signal to the circadian clock. (b) Nitrogen signalling may be input into the circadian clock by regulating changes in the abundance of the CRY1 gene. (c) After the nitrogen signal enters the circadian clock, the expression of the LHY gene is upregulated, which causes a phase shift in the circadian clock. (d) The RVE protein may send information about the circadian clock’s response to nitrogen stress back to the nitrogen metabolic pathway via the hormone transduction pathway. In conclusion, various metabolic pathways in the roots of walnut seedlings coordinated with one another to resist the ill effects of nitrogen stress on the root cells, and these coordination relationships were regulated by the circadian clock. This study is expected to provide valuable information on the circadian clock regulation of plant resistance to nitrogen stress.

Abstract To detect the prognostic factors associated with initial reattachment after primary pars plana vitrectomy (PPV) with air tamponade for rhegmatogenous retinal detachment (RRD). We retrospectively reviewed 92 eyes of 92 patients with RRD. All eyes underwent PPV with air tamponade and a follow-up of at least 6 months. Initial anatomical success was defined as reattachment of the retina by a single operation. We performed univariate analysis to detect the presence of any difference between eyes with a successful initial reattachment and those that failed. We also performed multivariate logistic regression analysis to assess the influence of each preoperative factor on initial success. The rate of initial reattachment success was 93.5%. The percentage of retinal detachment involving the inferior quadrants in the initial success group was less than that in the initial failure group, and the difference was statistically significant (P = 0.043). There were no significant differences noted for other factors, such as symptom duration (P = 0.078) or location of retinal breaks (P = 0.065). Multiple logistic regression analysis using preoperative factors indicated that older age (odds ratio, 0.90; 95% confidence interval, 0.82–0.97; P = 0.010) and non-involvement of inferior quadrants (odds ratio, 9.90; 95% confidence interval, 1.36–71.92; P = 0.023) were significantly associated with initial success. PPV combined with air may be an effective treatment for some simple RRDs (proliferative vitreoretinopathy [PVR] grade ≤ C1). Non-involvement of the inferior quadrants and older age at presentation are associated with a greater likelihood of anatomic success. The volume of air in the eye after surgery is also very important, which may also affect the reduction of retinal detachment.

Abstract To compare the efficacy of internal limiting membrane (ILM) flap covering to that of ILM flap insertion for the treatment of macular hole retinal detachment (MHRD) in highly myopic eyes with axial length (AL) ≥ 30 mm. We retrospectively analysed the medical records of 48 MHRD patients with high myopia (AL ≥ 30 mm). According to different surgical methods, the patients were divided into a covering group (23 eyes) and an insertion group (25 eyes). The rate of retinal reattachment and MH closure were compared between the two groups, and the related factors affecting the initial anatomical results were analysed. After primary vitrectomy and single silicone oil removal, there were 18 eyes (78.3%) in the covering group, and 20 eyes (80.0%) in the insertion group had retinal reattachment (P = 1.000). Moreover, 16 eyes (69.6%) in the covering group and 17 eyes (68.0%) in the insertion group had their MHs sealed (P = 0.907). The best-corrected visual acuity (BCVA) at 12 months and the improvement in BCVA postoperatively in the two groups were not statistically significant (P = 0.543, 0.955). Logistic regression analysis showed that elongated AL (OR = 1.844, 95% CI 1.037–3.280, P = 0.037) and higher choroidal atrophy (OR = 2.986, 95% CI 1.011–8.821, P = 0.048) were risk factors affecting initial anatomical success. For extremely high-myopia MHRD with AL ≥ 30 mm, ILM flap covering and insertion can both effectively seal the MH and promote retinal reattachment, but the visual function improvement may still be limited. The longer the AL and the higher the choroidal atrophy, the greater is the risk of initial anatomical failure.

Abstract Bladder cancer (BLCA) is the most common malignancy whose early diagnosis can ensure a better prognosis. However, the predictive accuracy of commonly used predictors, including patients’ general condition, histological grade, and pathological stage, is insufficient to identify the patients who need invasive treatment. Autophagy is regarded as a vital factor in maintaining mitochondrial function and energy homeostasis in cancer cells. Whether autophagy-related genes (ARGs) can predict the prognosis of BLCA patients deserves to be investigated. Based on BLCA data retrieved from the Cancer Genome Atlas and ARGs list obtained from the Human Autophagy Database website, we identified prognosis-related differentially expressed ARGs (PDEARGs) through Wilcox text and constructed a PDEARGs-based prognostic model through multivariate Cox regression analysis. The predictive accuracy, independent forecasting capability, and the correlation between present model and clinical variables or tumor microenvironment were evaluated through R software. Enrichment analysis of PDEARGs was performed to explore the underlying mechanism, and a systematic prognostic signature with nomogram was constructed by integrating clinical variables and the aforementioned PDEARGs-based model. We found that the risk score generated by PDEARGs-based model could effectively reflect deteriorated clinical variables and tumor-promoting microenvironment. Additionally, several immune-related gene ontology terms were significantly enriched by PDEARGs, which might provide insights for present model and propose potential therapeutic targets for BLCA patients. Finally, a systematic prognostic signature with promoted clinical utility and predictive accuracy was constructed to assist clinician decision. PDEARGs are valuable prognostic predictors and potential therapeutic targets for BLCA patients.

Abstract OPC UA PubSub Over TSN is the core of the Industrial Internet and guarantees flexible interaction features for multiple parties in real-time for industrial communication. To achieve the transmission of time-triggered traffic in PubSub NetworkMessage, routing and scheduling data need to be analyzed. Traditional routing and scheduling methods have disadvantages such as low calculation efficiency, slow convergence speed, and poor reliability. Therefore, a routing and scheduling method for OPC UA PubSub NetworkMessage time-triggered traffic based on an improved ant colony algorithm is proposed. First, we analyze the network topology model, traffic model, and traffic transmission constraints of TSN; then, we apply the K-means clustering algorithm, the KSP algorithm based on the shortest path idea, and an improved ant colony algorithm for traffic classification, routing, and scheduling calculation. Experimental results show that this method can effectively reduce the delay increase caused by link congestion, improve the ability to schedule time-triggered traffic, and accelerate the convergence rate of iteration.

Abstract There is still a lack of competing risk analysis of patients with papillary renal cell carcinoma (pRCC) following surgery. We performed the cumulative incidence function (CIF) to estimate the absolute risks of cancer-specific mortality (CSM) and other-cause mortality (OCM) of pRCC over time, and constructed a nomogram predicting the probability of 2-, 3- and 5-year CSM based on competing risk regression. A total of 5993 pRCC patients who underwent nephrectomy between 2010 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The 2-, 3-, 5-year CSM rates were 3.2%, 4.4% and 6.5%, respectively, and that of OCM were 3.2%, 5.0% and 9.3%, respectively. The estimates of 5-year cumulative mortality were most pronounced among patients aged > 75 years in OCM (17.0%). On multivariable analyses, age, tumor grade, T stage, N stage, and with or without bone, liver and lung metastases were identified as independent predictors of CSM following surgery and were integrated to generate the nomogram. The nomogram achieved a satisfactory discrimination with the AUCt of 0.730 at 5-year, and the calibration curves presented impressive agreements. Taken together, age-related OCM is a significant portion of all-cause mortality in elderly patients and our nomogram can be used for decision-making and patient counselling.

Abstract Atom segmentation and localization, noise reduction and deblurring of atomic-resolution scanning transmission electron microscopy (STEM) images with high precision and robustness is a challenging task. Although several conventional algorithms, such has thresholding, edge detection and clustering, can achieve reasonable performance in some predefined sceneries, they tend to fail when interferences from the background are strong and unpredictable. Particularly, for atomic-resolution STEM images, so far there is no well-established algorithm that is robust enough to segment or detect all atomic columns when there is large thickness variation in a recorded image. Herein, we report the development of a training library and a deep learning method that can perform robust and precise atom segmentation, localization, denoising, and super-resolution processing of experimental images. Despite using simulated images as training datasets, the deep-learning model can self-adapt to experimental STEM images and shows outstanding performance in atom detection and localization in challenging contrast conditions and the precision consistently outperforms the state-of-the-art two-dimensional Gaussian fit method. Taking a step further, we have deployed our deep-learning models to a desktop app with a graphical user interface and the app is free and open-source. We have also built a TEM ImageNet project website for easy browsing and downloading of the training data.

Abstract Few histological prognostic indicators for end-stage renal disease (ESRD) have been validated in diabetic patients. This biopsy-based study aimed to identify nephropathological risk factors for ESRD in Chinese patients with type 2 diabetes. Histological features of 322 Chinese type 2 diabetic patients with biopsy-confirmed diabetic nephropathy (DN) were retrospectively analysed. Cox proportional hazards analysis was used to estimate the hazard ratio (HR) for ESRD. Single glomerular proteomics and immunohistochemistry were used to identify differentially expressed proteins and enriched pathways in glomeruli. During the median follow-up period of 24 months, 144 (45%) patients progressed to ESRD. In multivariable models, the Renal Pathology Society classification failed to predict ESRD, although the solidified glomerulosclerosis (score 1: HR 1.65, 95% confidence interval [CI] 1.04–2.60; score 2: HR 2.48, 95% CI 1.40–4.37) and extracapillary hypercellularity (HR 2.68, 95% CI 1.55–4.62) were identified as independent risk factors. Additionally, single glomerular proteomics, combined with immunohistochemistry, revealed that complement C9 and apolipoprotein E were highly expressed in solidified glomerulosclerosis. Therefore, solidified glomerulosclerosis and extracapillary hypercellularity predict diabetic ESRD in Chinese patients. Single glomerular proteomics identified solidified glomerulosclerosis as a unique pathological change that may be associated with complement overactivation and abnormal lipid metabolism.

Abstract This study aimed to develop a three-dimensional (3D) colour reproduction system to improve the aesthetic effects of dental prostheses. The system’s colour accuracy was also evaluated. Based on the concept of colour management, 96 colour patches were selected to develop colour profiles for an intraoral scanner and a 3D printer using polynomial regression. The colour differences Δ$${E}_{ab}^{\ast }$$ Eab⁎ between colour patches reproduced using different colour profiles and the original colour patches were analysed to select the best combinations of colour profiles. The 3D colour reproduction system with the best-performing (i.e. third-order polynomial regression) colour profiles was finally evaluated using tooth and gum shades. The median Δ$${E}_{ab}^{\ast }$$ Eab⁎ was 6.940 ranging from 1.504 to 32.660. In terms of tooth and gum shade, the median Δ$${E}_{ab}^{\ast }$$ Eab⁎ was 6.313, and half of the shade blocks were above the mismatch threshold (Δ$${E}_{ab}^{\ast }$$ Eab⁎ > 6.80). In conclusion, the colour management based on polynomial regression can decrease the colour difference of the 3D colour reproduction system, but not to clinically acceptable levels. Further advances are needed to improve the methods and hardware.

Abstract As a transcription factor, E2F2 participates in regulation of numerous genes. To investigate the role and mechnism of E2F2 in RA, expression of E2F2 in synovial tissue was detected. Proliferation, invasion, and secretion of inflammatory cytokines were measured after E2F2 was knocked-down in RASFs by siRNA transfection. Induction of TNF-α, IL-6, and LPS on expression and nuclear translocation of E2F2, and signal pathways involved in the process were tested. ChIP was used to investigate direct binding of NF-кB to the promoter of E2F2, and E2F2 to the promoter of IL-6. The correlation between mRNA levels of E2F2 and IL-6 or TNF-α in secreted in supernatant of RASFs were also investigated. As a result, silencing E2F2 could inhibit the proliferation and invasion of RASFs. LPS, IL-6 can stimulate the expression of E2F2 in RASFs both via the NF-кB pathway, while TNF-α via the ERK pathway. TNF-α can facilitate the nuclear translocation of E2F2 and TNF-α can bind to promoter of E2F2, and then E2F2 can bind to the promoter of IL-6 directly. Significant correlations was found between levels of E2F2 and IL-6/TNF-α in synoviocytes of RA patients. Our findings indicate that E2F2 may play an important role in pathogenesis of RA.

Abstract CD40 ligand (CD40L), a member of the tumor necrosis factor (TNF) superfamily, binds to CD40, leading to many effects depending on target cell type. Platelets express CD40L and are a major source of soluble CD40L. CD40L has been shown to potentiate platelet activation and thrombus formation, involving both CD40-dependent and -independent mechanisms. A family of proteins called TNF receptor associated factors (TRAFs) plays key roles in mediating CD40L-CD40 signaling. Platelets express several TRAFs. It has been shown that TRAF2 plays a role in CD40L-mediated platelet activation. Here we show that platelet also express TRAF3, which plays a negative role in regulating platelet activation. Thrombin- or collagen-induced platelet aggregation and secretion are increased in TRAF3 knockout mice. The expression levels of collagen receptor GPVI and integrin αIIbβ3 in platelets were not affected by deletion of TRAF3, suggesting that increased platelet activation in the TRAF3 knockout mice was not due to increased expression platelet receptors. Time to formation of thrombi in a FeCl3-induced thrombosis model was significantly shortened in the TRAF3 knockout mice. However, mouse tail-bleeding times were not affected by deletion of TRAF3. Thus, TRAF3 plays a negative role in platelet activation and in thrombus formation in vivo.

Abstract Coalbed methane (CBM) and shale gas become two most important unconventional natural gas resources in US. The fractal dimension, known as the degree of self-similarity or irregularity, is an important parameter to quantitatively characterize gas storage capacity and gas transport properties in pores of rock matrix. In this study, two coal and two shale samples were evaluated to estimate fractal dimensions using combined small angle X-ray scattering (SAXS), small angle neutron scattering (SANS) and low-pressure N2 adsorption techniques. The results show that surface fractal dimension D s of inaccessible pores is greater than that for total pores based on SANS results for all four tested samples. D s of accessible pores estimated by N2 desorption is greater than that for N2 adsorption for each linear section of each tested sample. Based on in situ SANS results, D s slightly decreases with increasing argon injecting pressure for San Juan coal. D s decreases with increasing methane and CO2 injecting pressure for samples with high D s . However, D s significantly increases when CO2 became liquid phase for samples with low D s . Furthermore, D s almost didn’t change after methane and argon penetrations for all these samples except Marcellus outcrop shale.

Abstract Coumarin and its derivatives are widely used as fragrances in industrial products and have medical value. The goal of the present study was to discover genes and pathways related to coumarin biosynthesis in Melilotus albus using transcriptome analysis. The genes of five M. albus near-isogenic lines (NILs) that had different coumarin content and β-glucosidase activity according to the investigation of pedigree were quantified and then analysed by RNA-Seq. Using transcriptome analysis, differentially expressed genes (DEGs) were identified in two pairwise comparisons that differed in coumarin content as well as in two pairwise comparisons that differed in β-glucosidase activity. Gene expression pattern analysis suggested similar transcriptional trends in the genotypes with the same coumarin levels. Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) database of DEGs was used to identify functional pathways associated with coumarin biosynthesis. We identified 111 unigenes, with several DEGs among them possibly being related to coumarin synthesis pathways. Unigenes encoding a hexokinase, an abscisic acid receptor, a phenylalanine ammonia-lyase (PAL) and two peroxidases particularly showed correspondence with the coumarin content of different genotypes. These results will contribute to a better understanding of the coumarin biosynthesis in M. albus.

Abstarct Microbial enhanced coalbed methane (ME-CBM) recovery is critically examined as a viable technology for natural gas recovery from coalbed methane (CBM) reservoirs. Since the majority of gas-in-place (GIP) is stored as an adsorbed phase in fine pores of coal matrix, the nano-pore structure directly influences gas storage and transport properties. Only limited studies have quantified the alteration of the nano-pore structure due to ME-CBM treatment. This study examines the evolution of the pore structure using a combination of small angle X-ray scattering (SAXS), low-pressure N2 and CO2 adsorption (LPGA) and high-pressure methane adsorption methods. The results show that the surface fractal dimension decreases for the two bioconverted coals compared to the untreated coal. After bio-treatment, the mesopore surface area and pore volume decrease with the average pore diameter increases, while the micropore surface area increases with pore volume decreases. Both inaccessible meso-/micropore size distributions decrease after bioconversion, while the accessible micropore size distribution increases, making a portion of closed micropore network accessible. In addition, the methane adsorption capacities increase after bio-treatment, which is confirmed by the increase of micropore surface area. A conceptual physical model of methanogenesis is proposed based on the evolution of the pore structure.

Abstract In this study, genomic DNA was screened for novel Na+/H+ antiporter genes from Halomonas zhaodongensis by selection in Escherichia coli KNabc lacking three major Na+/H+ antiporters. Co-expression of two genes designated umpAB, encoding paired homologous unknown membrane proteins belonging to DUF1538 (domain of unknown function with No. 1538) family, were found to confer E. coli KNabc the tolerance to 0.4 M NaCl and 30 mM LiCl, and an alkaline pH resistance at 8.0. Western blot and co-immunoprecipitation establish that UmpAB localize as a hetero-dimer in the cytoplasmic membranes. Functional analysis reveals that UmpAB exhibit pH-dependent Na+(Li+, K+)/H+ antiport activity at a wide pH range of 6.5 to 9.5 with an optimal pH at 9.0. Neither UmpA nor UmpB showed homology with known single-gene or multi-gene Na+/H+ antiporters, or such proteins as ChaA, MdfA, TetA(L), Nap and PsmrAB with Na+/H+ antiport activity. Phylogenetic analysis confirms that UmpAB should belong to DUF1538 family, which are significantly distant with the above-mentioned proteins with Na+/H+ antiport activity. Taken together, we propose that UmpAB represent a novel two-component Na+(Li+, K+)/H+ antiporter. To the best of our knowledge, this is the first report on the functional analysis of unknown membrane proteins belonging to DUF1538 family.

Abstract The characteristics of intestinal microbial communities may be affected by changes in the pathophysiology of patients with end-stage liver disease. Here, we focused on the characteristics of intestinal fecal microbial communities in post-liver transplantation (LT) patients in comparison with those in the same individuals pre-LT and in healthy individuals. The fecal microbial communities were analyzed via MiSeq-PE250 sequencing of the V4 region of 16S ribosomal RNA and were then compared between groups. We found that the gut microbiota of patients with severe liver disease who were awaiting LT was significantly different from that of healthy controls, as represented by the first principal component (p = 0.0066). Additionally, the second principal component represented a significant difference in the gut microbiota of patients between pre-LT and post-LT surgery (p = 0.03125). After LT, there was a significant decrease in the abundance of certain microbial species, such as Actinobacillus, Escherichia, and Shigella, and a significant increase in the abundance of other microbial species, such as Micromonosporaceae, Desulfobacterales, the Sarcina genus of Eubacteriaceae, and Akkermansia. Based on KEGG profiles, 15 functional modules were enriched and 21 functional modules were less represented in the post-LT samples compared with the pre-LT samples. Our study demonstrates that fecal microbial communities were significantly altered by LT.

Abstract Some evidences show that residual tumor after thermal ablation will progress rapidly. However, its mechanisms remain unclear. Here, we assessed whether activated HSCs could regulate stem cell-like property of residual tumor after incomplete thermal ablation to promote tumor progression. Human HCC cell lines were exposed to sublethal heat treatment to simulate the peripheral zone of thermal ablation. After residual HCC cells were cultured with conditional medium (CM) from activated HSCs, parameters of the stem cell-like phenotypes were analyzed. Nude mice bearing heat-exposed residual HCC cells and HSCs were subjected to metformin treatment to thwarter tumor progression. CM from activated primary HSCs or LX-2 cells significantly induced the stem cell-like phenotypes of residual HCC cells after heat treatment. These effects were significantly abrogated by neutralizing periostin (POSTN) in the CM. POSTN regulated the stemness of heat-exposed residual HCC cells via activation of integrin β1/AKT/GSK-3β/β-catenin/TCF4/Nanog signaling pathway. Metformin significantly inhibited in vivo progression of heat-exposed residual HCC via suppressing POSTN secretion and decreasing cancer stem cell marker expression. Our data propose a new mechanism of activated HSCs promoting the stemness traits of residual HCC cells after incomplete thermal ablation and suggest metformin as a potential drug to reverse this process.

Abstract Real-time quantitative phase imaging has tremendous potential in investigating live biological specimens in vitro. Here we report on a wideband sensitivity-enhanced interferometric microscopy for quantitative phase imaging in real time by employing two quadriwave lateral shearing interferometers based on randomly encoded hybrid gratings with different lateral shears. Theoretical framework to analyze the measurement sensitivity is firstly proposed, from which the optimal lateral shear pair for sensitivity enhancement is also derived. To accelerate the phase retrieval algorithm for real-time visualization, we develop a fully vectorized path-independent differential leveling phase unwrapping algorithm ready for parallel computing, and the framerate for retrieving the phase from each pair of two 4 mega pixel interferograms is able to reach 47.85 frames per second. Experiment results demonstrate that the wideband sensitivity-enhanced interferometric microscopy is capable of eliminating all the periodical error caused by spectral leaking problem and reducing the temporal standard deviation to the half level compared with phase directly retrieved by the interferogram. Due to its high adaptability, the wideband sensitivity-enhanced interferometric microscopy is promising in retrofitting existing microscopes to quantitative phase microscopes with high measurement precision and real-time visualization.