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This study presents a novel multistage expressway fast charging station (EFCS) planning problem coordinated with the dynamic regional power structure (PS) transformation. Under the prerequisite of the EFCS network's sustainable operation, network accessibility, and orderly construction, a three‐step planning method oriented to the enhancement of energy saving and emission reduction (ESER) benefits and rationalization of facility utilization is developed: (i) EV‐expanded network, (ii) multiagent‐based dynamic traffic assignment (MA‐DTA), and (iii) deployment refinement. Embedding the MA‐DTA and customized refinement strategy into the iterative planning structure enables the integration of operations and planning of the EFCS network. A numerical experiment and an empirical study in the Shandong Peninsula urban agglomeration are conducted. It demonstrates that the method can find a high‐quality solution within acceptable computation time and is applicable to realistic large‐scale EFCS planning. The planning method can effectively play the role of economy and facility in inducing EV users' charging demands, thus enhancing the overall ESER benefits. The integration of operation and planning is proven effective in reasonably matching the supply and demand of facility service and charging loads in a full‐time period. Further, the multistage EFCS planning schemes during 2025–2045 are explored, and some insightful policy implications are revealed. [ABSTRACT FROM AUTHOR]

Background: Sleep deprivation (SD) is commonplace in modern society and there are large individual differences in the vulnerability to SD. We aim to identify the structural network differences based on diffusion tensor imaging (DTI) that contribute to the individual different vulnerability to SD. Methods: The number of psychomotor vigilance task (PVT) lapses was used to classify 49 healthy subjects on the basis of whether they were vulnerable or resistant to SD. DTI and graph theory approaches were used to investigate the topologic organization differences of the brain structural connectome between SD‐vulnerable and ‐resistant individuals. We measured the level of global efficiency and clustering in rich club and non‐rich club organizations. Results: We demonstrated that participants vulnerable to SD had less global efficiency, network strength, and local efficiency but longer shortest path length compared with participants resistant to SD. Lower efficiency was mainly distributed in the right insula, bilateral thalamus, bilateral frontal, temporal, and temporal lobes. Furthermore, a disrupted subnetwork was observed that consisted of widespread connections. Moreover, the vulnerable group showed significantly decreased strength of the rich club compared with the resistant group. The strength of rich club connectivity was found to be correlated negatively with PVT performance (r = −0.395, p = 0.005). We further tested the reliability of the results. Conclusion: The findings revealed that individual differences in resistance to SD are related to disrupted topologic efficiency connectome pattern, and our study may provide potential connectome‐based biomarkers for the early detection of the vulnerable degree to SD. [ABSTRACT FROM AUTHOR]

Objectives: During embryonic haematopoiesis, haematopoietic stem/progenitor cells (HSPCs) develop from hemogenic endothelial cells (HECs) though endothelial to haematopoietic transition (EHT). However, little is known about how EHT is regulated in human. Here, we report that GFI1 plays an essential role in enabling normal EHT during haematopoietic differentiation of human embryonic stem cells (hESCs). Results: GFI1 deletion in hESCs leads to a complete EHT defect due to a closed chromatin state of hematopoietic genes in HECs. Mechanically, directly regulates important signaling pathways essential for the EHT such as PI3K signaling.etc. Conclutions: Together, our findings reveal an essential role of GFI1 mediated epigenetic mechanism underlying human EHT during hematopoiesis. [ABSTRACT FROM AUTHOR]

Transmission lines are affected by aeolian vibration, sandstorms and acid rain, which cause structural damage and eventually lead to line breaking accidents. In this paper, the structural health monitoring technology of conductors is researched, and a structural monitoring system for conductors is designed. First, based on the structure of the ACSR (Aluminum Conductor Steel Reinforced) conductor and the dynamic equation, the relation between the natural frequencies and the structure of the conductor is obtained. Then, an online health monitoring system of the conductor structure is proposed, and key issues, such as the power supply solution of sensors, data preprocessing technology, multiple‐sensor synchronization method, are analyzed in detail. Finally, the structural health monitoring of overhead transmission lines designed in this paper is tested on 110‐kV experimental transmission lines. The experimental results show that from the system proposed the operation parameters of the conductors can be well obtained. [ABSTRACT FROM AUTHOR]

The absence of tumor antigens leads to a low response rate, which represents a major challenge in immune checkpoint blockade (ICB) therapy. Pyroptosis, which releases tumor antigens and damage‐associated molecular patterns (DAMPs) that induce antitumor immunity and boost ICB efficiency, potentially leads to injury when occurring in normal tissues. Therefore, a strategy and highly efficient agent to induce tumor‐specific pyroptosis but reduce pyroptosis in normal tissues is urgently required. Here, a smart tumor microenvironmental reactive oxygen species (ROS)/glutathione (GSH) dual‐responsive nano‐prodrug (denoted as MCPP) with high paclitaxel (PTX) and photosensitizer purpurin 18 (P18) loading is rationally designed. The ROS/GSH dual‐responsive system facilitates the nano‐prodrug response to high ROS/GSH in the tumor microenvironment and achieves optimal drug release in tumors. ROS generated by P18 after laser irradiation achieves controlled release and induces tumor cell pyroptosis with PTX by chemo‐photodynamic therapy. Pyroptotic tumor cells release DAMPs, thus initiating adaptive immunity, boosting ICB efficiency, achieving tumor regression, generating immunological memory, and preventing tumor recurrence. Mechanistically, chemo‐photodynamic therapy and control‐release PTX synergistically induce gasdermin E (GSDME)‐related pyroptosis. It is speculated that inspired chemo‐photodynamic therapy using the presented nano‐prodrug strategy can be a smart strategy to trigger pyroptosis and augment ICB efficiency. [ABSTRACT FROM AUTHOR]

Background and Purpose: IL‐1β produced by macrophages via the NOD‐, LRR‐ and pyrin domain‐containing 3 (NLRP3) inflammasome, mediates the inflammatory crosstalk between macrophages and adipocytes. In our previous study, (16S,20S,24R)‐12β‐acetoxy‐16,23‐epoxy‐24,25‐dihydroxy‐3β‐(β‐D‐xylopyranosyloxy)‐9,19‐cyclolanost‐22(23)‐ene (AEDC), a cycloartane triterpenoid isolated from Actaea vaginata (Ranunculaceae), was found to possess anti‐inflammatory effect on LPS‐treated RAW264.7 macrophages. This study was designed to investigate whether AEDC modulates macrophage–adipocyte crosstalk to alleviate adipose tissue inflammation. Experimental Approach The anti‐inflammatory effect of AEDC was evaluated on LPS plus ATP‐induced THP‐1 macrophages and C57BL/6J mice. The expression of autophagy‐related and NLRP3 inflammasome complex proteins was analysed by western blots, immunofluorescence staining and co‐immunoprecipitation. The pro‐inflammatory cytokines levels were determined by ELISA kits. The adipose tissue inflammation was evaluated by histological analysis and immunohistochemical staining. Key Results: AEDC (5 and 10 μM) activated autophagy, which in turn suppressed the NLRP3 inflammasome activation and IL‐1β secretion in THP‐1 macrophages. AEDC increased the expression of SIRT3 deacetylase and enhanced its deacetylating activity to reverse mitochondrial dysfunction and activate AMP‐activated protein kinase, which together induced autophagy. Moreover, AEDC (10 μM) attenuated macrophage conditioned medium‐induced inflammatory responses in adipocytes and blocked THP‐1 macrophages migration towards 3T3‐L1 adipocytes. In inflammation mice, AEDC (5 and 20 mg·kg−1) treatment reduced the levels of pro‐inflammatory cytokines in serum and epididymal adipose tissue and reduced macrophage infiltration to alleviate adipose tissue inflammation. Conclusion and Implications: AEDC attenuated the inflammatory crosstalk between macrophages and adipocytes through SIRT3‐autophagy‐mediated NLRP3 inflammasome inhibition, which might used for the treatment of adipose tissue inflammation‐related metabolic disorders. [ABSTRACT FROM AUTHOR]

Transition metal‐catalyzed direct decarboxylative transformations of aromatic carboxylic acids usually require high temperatures, which limit the substrate's scope, especially for late‐stage applications. The development of the selective decarbonylative of carboxylic acid derivatives, especially the most fundamental aroyl chlorides, with stable and cheap electrophiles under mild conditions is highly desirable and meaningful, but remains challenging. Herein, a strategy of nickel‐catalyzed decarbonylative alkylation of aroyl chlorides via phosphine/nitrogen ligand relay is reported. The simple phosphine ligand is found essential for the decarbonylation step, while the nitrogen ligand promotes the cross‐electrophile coupling. Such a ligand relay system can effectively and orderly carry out the catalytic process at room temperature, utilizing easily available aroyl chlorides as an aryl electrophile for reductive alkylation. This discovery provides a new strategy for direct decarbonylative coupling, features operationally simple, mild conditions, and excellent functional group tolerance. The mild approach is applied to the late‐stage methylation of various pharmaceuticals. Extensive experiments are carried out to provide insights into the reaction pathway and support the ligand relay process. [ABSTRACT FROM AUTHOR]

Background: Pembrolizumab (Pembro) in combination with chemotherapy has been approved for the treatment of pretreated advanced NSCLC in the United States and China for its significant efficacy. However, the cost‐effectiveness is unknown considering Pembro's high price. The impact of programmed death ligand 1 (PD‐L1) test on the cost‐effectiveness is also unknown. The current study assessed the cost‐effectiveness of combination therapy for nonsquamous NSCLC from the United States and China public payers' perspective. Materials and Methods: A literature‐based Markov model was conducted using KEYNOTE‐189 trial data to compare cost and quality‐adjusted life years (QALYs) of three treatment strategies for nonsquamous NSCLC: Pembro‐chemotherapy combination and chemotherapy strategy without PD‐L1 test, and treatment strategy according to their PD‐L1 status. Results: In base case analysis, the combination strategy generated an additional 0.78 QALYs and 0.59 QALYs over chemotherapy in the United States and China respectively, resulting in an ICER of $132 392/QALY in the United States and $92 533/QALY in China. In the PD‐L1 ≥1% base case, the ICERs were $77 754/QALY and $56 768/QALY respectively in the United States and China for PD‐L1 test strategy. In the PD‐L1 ≥50% base case, the ICERs were $44 731/QALY and $34 388/QALY respectively in the United States and China for PD‐L1 test strategy. Lowering Pembro price can also partly decrease the ICERs. Conclusion: Compared with chemotherapy, the combination strategy is not cost‐effective for the treatment of NSCLC in the American and Chinese health care system at WTP threshold of $100 000/QALY for the United States and $27 351/QALY for China. Using PD‐L1 test for patient selection and price reduction could improve the cost‐effective probabilities of immunotherapy for nonsquamous NSCLC. [ABSTRACT FROM AUTHOR]

Background: Extranodal marginal zone B‐cell lymphoma of mucosa‐associated lymphoid tissue (MALT lymphoma) in the oromaxillofacial head and neck region is rare, with limited data available. This retrospective study explored the clinical features, stage, treatment, and prognosis of this disease. Methods: Overall, 105 patients with MALT lymphomas in the oromaxillofacial head and neck region were included in this retrospective analysis. SPSS 22.0 software package was used for data analysis and a two‐tailed P value of ≤.05 was considered statistically significant. Primary endpoints of the study were the complete response (CR) rate, overall survival (OS), and progression‐free survival (PFS). Results: About 52% of the patients had long‐term xerostomia, autoimmune diseases, or chronic parotitis and 81% had diseases involving the large salivary glands. Ann Arbor staging of the patients was as follows: stages I/II, 73 patients and stages III/IV, 32 patients. In the 97 patients followed up, CR rate after initial treatment was 80%. Tumor progression was observed in 12 patients and 14 patients died. There was a significant difference between the rate of CR in localized (87%) and disseminated (67%) lymphoma patients (P =.02). The 5‐ and 10‐year PFS of the localized lymphoma patients were both 91%, whereas those of the disseminated lymphoma patients were 83% and 65%, respectively (P =.03). The 5‐year PFS rates of the chemotherapy and non‐chemotherapy groups in the disseminated lymphoma patients were 85% and 73% (P =.04). Meanwhile, the 5‐year PFS rates of the rituximab and non‐rituximab groups in the disseminated lymphoma patients were 100% and 70% (P =.03). In multivariate analysis, MALT Lymphoma International Prognostic Index (MALT‐IPI) was an independent prognostic factor affecting OS, whereas Ann Arbor staging affected PFS. Conclusions: This study suggests that the outcome after initial treatment of MALT lymphomas in the oromaxillofacial head and neck region is satisfactory and that this disease progresses slowly. The CR rate and PFS of localized lymphoma patients are better than those of disseminated lymphoma patients. Systemic treatment (chemotherapy or rituximab) may improve PFS in disseminated disease patients. MALT‐IPI and Ann Arbor staging are independent prognostic factors. [ABSTRACT FROM AUTHOR]

Summary: How cell wall elasticity, plasticity, and time‐dependent extension (creep) relate to one another, to plant cell wall structure and to cell growth remain unsettled topics. To examine these issues without the complexities of living tissues, we treated cell‐free strips of onion epidermal walls with various enzymes and other agents to assess which polysaccharides bear mechanical forces in‐plane and out‐of‐plane of the cell wall. This information is critical for integrating concepts of wall structure, wall material properties, tissue mechanics and mechanisms of cell growth. With atomic force microscopy we also monitored real‐time changes in the wall surface during treatments. Driselase, a potent cocktail of wall‐degrading enzymes, removed cellulose microfibrils in superficial lamellae sequentially, layer‐by‐layer, and softened the wall (reduced its mechanical stiffness), yet did not induce wall loosening (creep). In contrast Cel12A, a bifunctional xyloglucanase/cellulase, induced creep with only subtle changes in wall appearance. Both Driselase and Cel12A increased the tensile compliance, but differently for elastic and plastic components. Homogalacturonan solubilization by pectate lyase and calcium chelation greatly increased the indentation compliance without changing tensile compliances. Acidic buffer induced rapid cell wall creep via endogenous α‐expansins, with negligible effects on wall compliances. We conclude that these various wall properties are not tightly coupled and therefore reflect distinctive aspects of wall structure. Cross‐lamellate networks of cellulose microfibrils influenced creep and tensile stiffness whereas homogalacturonan influenced indentation mechanics. This information is crucial for constructing realistic molecular models that define how wall mechanics and growth depend on primary cell wall structure. Significance Statement: To assess how cell wall elasticity, plasticity and slow time‐dependent extension during growth relate to one another and to wall structure, we measured the biomechanical actions of various enzymes by uniaxial tensile testing, nano‐indentation, creep assays, and atomic force microscopy (AFM) imaging. These responses were separable, unlike those expected of a simple fiber‐reinforced hydrogel. Our results identify distinctive roles for homogalacturonan and cross‐lamellate networks of cellulose microfibrils in epidermal wall mechanics and growth. [ABSTRACT FROM AUTHOR]

Whole genome duplication, a prevalent force of evolution in plants, results in massive genome restructuring in different organisms. Roles of the resultant duplicated genes are poorly understood, both functionally and evolutionarily. In the present study, differentially expressed ethylene responsive factors (GhERF1s), anchored on Chr‐A07 and Chr‐D07, were isolated from a high‐yielding cotton hybrid (XZM2) and its parents. The GhERF1 was located in the B3 subgroup of the ethylene responsive factors subfamily involved in conferring tolerance to abiotic stress. Nucleotide sequence analysis of 524 diverse accessions, together with quantitative real‐time polymerase chain reaction analysis, elucidated that de‐functionalization of GhERF1‐7A occurred due to one base insertion following formation of the allotetraploid cotton. Our quantitative trait loci and association mapping analyses highlighted a role for GhERF1‐7A in conferring high boll number per plant in modern cotton cultivars. Overexpression of GhERF1‐7A in transgenic Arabidopsis resulted in a substantial increase in the number of siliques and total seed yield. Neo‐functionalization of GhERF1‐7A was also observed in modern cultivars rather than in races and/or landraces, further supporting its role in the development of high‐yielding cotton cultivars. Both de‐ and neo‐functionalization occurred in one of the duplicate genes, thus providing new genomic insight into the evolution of allotetraploid cotton species. Whole genome duplication usually results in massive genome restructuring. We report both de‐ and neo‐functionalization occurred in duplicate ethylene responsive factors of B3 subgroup of ERF subfamily, which involved in abiotic stress tolerance after the formation of allotetraploid cotton. Our finding provides a new genomic insight into the evolution of allotetraploid species. [ABSTRACT FROM AUTHOR]

Abstract: Positive cofactor 4 (PC4) participates in DNA damage repair and involved in nonhomologous end joining (NHEJ). Our previous results demonstrated that knockdown of PC4 downregulated the expression of XRCC4‐like factor (XLF) in esophageal squamous cell carcinoma. However, the mechanism how PC4 regulates the expression of XLF remains unclear. Here, we found that knockdown of PC4 increased radiosensitivity of non‐small cell lung cancer (NSCLC) both in vivo and in vitro. Furthermore, we found that PC4 knockdown downregulated the expression of XLF, whereas recovering XLF expression restored radioresistance in the PC4‐knockdown NSCLC cells. In addition, PC4 knockdown inhibited XLF expression by transcriptionally suppressing of XLF. Moreover, PC4 expression correlated with radiosensitivity and was an independent prognostic factor of progression‐free survival (PFS) in patients with NSCLC. These findings suggest that PC4 could be used as a promising therapeutic target for NSCLC. [ABSTRACT FROM AUTHOR]

Aims Pseudoginsenoside-F11 ( PF11), an ocotillol-type ginsenoside, has been reported to exert wide-ranging neuroprotective properties. The aim of this study was to investigate the effect and potential mechanisms of PF11 on the autophagic/lysosomal pathway following ischemic stroke. Methods Male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion ( pMCAO). Cerebral ischemia outcome, TUNEL staining, Fluoro-Jade B staining were carried out 24 hours poststroke. The autophagic/lysosomal-related proteins were measured. Results A single administration of PF11 significantly decreased the infarct area, reduced the brain water content, and improved neurological functions, even 4 hours after the onset of pMCAO. Meanwhile, PF11 lessened the ischemic insult-mediated loss of neurons and activation of astrocytes and microglia. Furthermore, PF11 attenuated pMCAO-induced accumulations of autophagosomes and apoptosis. We further observed a remarkable effect of PF11 in reversing the ischemic insult-induced accumulation of autophagosomes ( LC3- II) and abnormal aggregation of autophagic proteins ( SQSTM1 and ubiquitin). Furthermore, PF11 was capable of improving lysosomal function and lysosome/autophagosome fusion following pMCAO, and this change was reversed by the lysosomal inhibitor chloroquine. Also, the improvement of ischemic outcome and the antiapoptotic effect induced by PF11 was reversed by CQ. Conclusion These findings indicate that the autophagic flux is impaired in a rat model of pMCAO, and that PF11 exerts an excellent protective effect against ischemic stroke by alleviating autophagic/lysosomal defects. [ABSTRACT FROM AUTHOR]

Background Smoking is a leading cause of preventable death. Early studies based on samples of twins have linked the lifetime smoking practices to genetic predisposition. The flavin-containing monooxygenase ( FMO) protein family consists of a group of enzymes that metabolize drugs and xenobiotics. Both FMO1 and FMO3 were potentially susceptible genes for nicotine metabolism process. Methods In this study, we investigated the potential of FMO genes to confer risk of nicotine dependence via deep targeted sequencing in 2,820 study subjects comprising 1,583 nicotine dependents and 1,237 controls from European American and African American. Specifically, we focused on the two genomic segments including FMO1, FMO3, and pseudo gene FMO6P, and aimed to investigate the potential association between FMO genes and nicotine dependence. Both common and low-frequency/rare variants were analyzed using different algorithms. The potential functional significance of SNPs with association signal was investigated with relevant bioinformatics tools. Results We identified different clusters of significant common variants in European (with most significant SNP rs6674596, p = .0004, OR = 0.67, MAF_ EA = 0.14, FMO1) and African Americans (with the most significant SNP rs6608453, p = .001, OR = 0.64, MAF_ AA = 0.1, FMO6P). No significant signals were identified through haplotype-based analyses. Gene network investigation indicated that both FMO1 and FMO3 have a strong relation with a variety of genes belonging to CYP gene families (with combined score greater than 0.9). Most of the significant variants identified were SNPs located within intron regions or with unknown functional significance, indicating a need for future work to understand the underlying functional significance of these signals. Conclusions Our findings indicated significant association between FMO genes and nicotine dependence. Replications of our findings in other ethnic groups were needed in the future. Most of the significant variants identified were SNPs located within intronic regions or with unknown functional significance, indicating a need for future work to understand the underlying functional significance of these signals. [ABSTRACT FROM AUTHOR]

We used atomic force microscopy ( AFM), complemented with electron microscopy, to characterize the nanoscale and mesoscale structure of the outer (periclinal) cell wall of onion scale epidermis - a model system for relating wall structure to cell wall mechanics. The epidermal wall contains ~100 lamellae, each ~40 nm thick, containing 3.5-nm wide cellulose microfibrils oriented in a common direction within a lamella but varying by ~30 to 90° between adjacent lamellae. The wall thus has a crossed polylamellate, not helicoidal, wall structure. Montages of high-resolution AFM images of the newly deposited wall surface showed that single microfibrils merge into and out of short regions of microfibril bundles, thereby forming a reticulated network. Microfibril direction within a lamella did not change gradually or abruptly across the whole face of the cell, indicating continuity of the lamella across the outer wall. A layer of pectin at the wall surface obscured the underlying cellulose microfibrils when imaged by FESEM, but not by AFM. The AFM thus preferentially detects cellulose microfibrils by probing through the soft matrix in these hydrated walls. AFM-based nanomechanical maps revealed significant heterogeneity in cell wall stiffness and adhesiveness at the nm scale. By color coding and merging these maps, the spatial distribution of soft and rigid matrix polymers could be visualized in the context of the stiffer microfibrils. Without chemical extraction and dehydration, our results provide multiscale structural details of the primary cell wall in its near-native state, with implications for microfibrils motions in different lamellae during uniaxial and biaxial extensions. [ABSTRACT FROM AUTHOR]

( Pb1− x Ba x) ZrO3 ( x = 0, 0.025, 0.05, 0.075, 0.1) ceramics were synthesized by a traditional solid-state reaction method, and the pure phase was obtained of all sintered samples. For all compositions, substitution of Pb2+ by Ba2+ reduced the phase transition temperature of antiferroelectric to ferroelectric and Curie temperature. Polarization-electric field hysteresis loops were conducted and typical ferroelectric hysteresis loops were observed in higher temperature range. Impedance and dielectric measurements were studied on the high temperature relaxation. Relaxation behavior could be suppressed after annealing treatment in oxygen atmosphere. Value of activation energy calculated from impedance was lower than that calculated from conduction measurements. It was concluded that short-range hopping of oxygen vacancy contributes to the dielectric relaxation and long-distance movement of doubly ionized oxygen vacancies contributes to the conduction. [ABSTRACT FROM AUTHOR]

NaSr2Nb5O15 piezoelectric ceramics were sintered at different temperatures with or without atmospheric powder. The effects of atmospheric powder and sintering temperature on the dielectric, piezoelectric, and ferroelectric properties of the ceramics were analyzed. According to the modified Curie-Weiss law, we know that all these ceramics show an intermediate relaxor-like behavior between the normal and ideal relaxor ferroelectrics. Atmospheric powder affects significantly the properties of ceramics because the ceramics sintered without atmospheric powder lose lots of sodium. Furthermore, sintering temperature also significantly affects the properties of ceramics because the relative density of ceramics is enhanced when sintering temperature is increased. [ABSTRACT FROM AUTHOR]

Aims It has been well documented that angiotensin II type 1 ( AT1) receptor blockers ( ARBs) are known to attenuate neural damage and the c-Jun N-terminal protein kinase 3 ( JNK3) pathway and caspase-3 signal are involved in neuronal cell death following cerebral ischemia/reperfusion ( I/ R). In this study, we first showed that losartan could protect neurons against cerebral I/ R-induced injury. Methods Cerebral ischemia model was induced by four-vessel occlusion. Antisense oligodeoxynucleotides ( ODNs) against AT1 receptor and losartan were used to detect whether the AT1 receptor implicated in cerebral I/ R. Immunoprecipitation ( IP) and immunoblotting ( IB) were used to detect the interactions between β-arrestin-2 and AT1/apoptosis signal-regulating kinase 1 ( ASK1)/ MAP kinase kinase 4 ( MKK4) signaling module following cerebral I/ R. Results First, losartan decreased cerebral I/ R-induced neuronal death. Second, losartan depressed the β-arrestin-2-assembled AT1/ ASK1/ MKK4 signaling module. Third, losartan depressed the activation of c-jun, JNK3, Bcl-2, caspase-3 and the release of cytochrome c from mitochondria to cytoplasm. Conclusion Taken together, losartan could attenuate neural damage following the cerebral I/R via inhibiting the β-arrestin-2-assembled AT1/ ASK1/ MKK4 signaling module and depressing the activation of c-jun, JNK3, and caspase-3 and the release of cytochrome c. [ABSTRACT FROM AUTHOR]

In this study, several columns of different lengths were filled with composite soils sampled from the field at corresponding depths and then loaded intermittently with influent of a high phosphorus concentration to evaluate phosphorus fate and transport in soil. The results indicate that the height of the mass transfer zone, solvent pore velocity, and soil's life expectancy for phosphorus removal increased with depth, while the retained phosphorus per kilogram of soil and the linear adsorption equilibrium coefficient, R, decreased with depth. An equation was developed to link liquidphase phosphorus with solvent traveling time and soil depth. The results of X-ray diffraction and washout tests indicate that calcium-phosphorus precipitation and/or crystal growth occurred in the columns. The new protocol is useful for evaluation of phosphorus fate and transport in other subsurface systems, because it allows flexible adjustments in hydraulic loadings, feed solution, and sampling schemes. Water Environ. Res., 79, 2343 (2007). [ABSTRACT FROM AUTHOR]

A series of fiber-specific mutants, or germplasms, have been recently used in the study of fiber development. In the current study, scanning electron microscopy (SEM) was used to investigate developmental differences in lint and fuzz initiation in different genotypes ( Gossypium hirsutum) of upland cotton. These fiber mutants included dominant naked seed N1, recessive naked seed n2, Xuzhou-142 lintless-fuzzless (XZ142WX), Xinxiangxiaojilintless-fuzzless (XinWX), Xinxiangxiaojilinted-fuzzless (XinFLM), with TM-1, the cytogenetic and genetic experimental standard stock, as the control. Characteristics of fiber initiation were analyzed from –1 to +1 days post anthesis (dpa) and at 4 and 5 dpa for fuzz initiation. Our data suggested that lint initiation centered on day of anthesis (0 dpa), and elongated significantly at 1 dpa, while fuzz initiation began at 4 dpa, although the shape of fuzz protrusions differed from that of lint fibers. Fiber initiation occurred first on the ovule funicular crest. Compared to TM-1, there was a noted retardation in development and fiber protrusion in N1 and XinFLM. Microscopy data also demonstrated that lintless-fuzzless mutants (XZ142WX and XinWX) developed irregular protrusions during early developmental stages, which were unable to grow into fiber. [ABSTRACT FROM AUTHOR]

There is an increasing interest in the use of lanthanides in medicine. However, the mechanism of their accumulation in cells is not well understood. Lanthanide cations are similar to ferric ions with regard to transferrin binding, suggesting transferrin-receptor mediated transport is possible; however, this has not yet been confirmed. In order to clarify this mechanism, we investigated the binding of Yb3+ to apotransferrin by UV-Vis spectroscopy and stopped-flow spectrophotometry, and found that Yb3+ binds to apotransferrin at the specific iron sites in the presence of bicarbonate. The apparent binding constants of these sites showed that the affinity of Yb3+ is lower than that of Fe3+ and binding of Yb3+ in the N-lobe is kinetically favored while the C-lobe is thermodynamically favored. The first Yb3+ bound to the C-lobe quantitatively with a Yb/apotransferrin molar ratio of < 1, whereas the binding to the other site is weaker and approaches completeness by a higher molar ratio only. As demonstrated by 1 H NMR spectra, Yb3+ binding disturbed the conformation of apotransferrin in a manner similar to Fe3+ . Flow cytometric studies on the uptake of fluorescein isothiocyanate labeled Yb3+ -bound transferrin species by K562 cells showed that they bind to the cell receptors. Laser scanning confocal microscopic studies with fluorescein isothiocyanate labeled Yb3+ -bound transferrin and propidium iodide labeled DNA and RNA in cells indicated that the Yb3+ entered the cells. The Yb3+ -transferrin complex inhibited the uptake of the fluorescein labeled ferric-saturated transferrin (Fe2 -transferrin) complex into K562 cells. The results demonstrate that the complex of Yb3+ -transferrin complex was recognized by the transferrin receptor and that the transferrin-receptor-mediated mechanism is a possible... [ABSTRACT FROM AUTHOR]

A single‐arm helical antenna with the width of the arm varying periodically for a circularly polarised (CP) tilted beam is introduced. The proposed antenna radiates a CP tilted beam, when the following two conditions are met: (i) the circumference of the proposed antenna is >4λ0/3 (λ0 is the wavelength in free space at the centre frequency) and (ii) the width of the arm varies periodically. The designed procedure reveals that the maximum radiation direction of the tilted beam is not sensitive to a change in frequency. The simulated and measured results show that the designed antenna radiates a CP tilted beam with θmax = 32°. The measured 10 dB return loss bandwidth is 12.8% from 2.33 to 2.65 GHz, and the experimental results of the radiation pattern, gain and axial ratio are also presented. [ABSTRACT FROM AUTHOR]

Summary: Pteris vittata is an arsenic (As) hyperaccumulator that can accumulate several thousand mg As kg−1 DW in aboveground biomass. A key factor for its hyperaccumulation ability is its highly efficient As long‐distance translocation system. However, the underlying molecular mechanisms remain unknown.We isolated PvAsE1 through the full‐length cDNA over‐expression library of P. vittata and characterized it through a yeast system, RNAi gametophytes and sporophytes, subcellular‐location and in situ hybridization. Phylogenomic analysis was conducted to estimate the appearance time of PvAsE1.PvAsE1 was a plasma membrane‐oriented arsenite (AsIII) effluxer. The silencing of PvAsE1 reduced AsIII long‐distance translocation in P. vittata sporophytes. PvAsE1 was structurally similar to solute carrier (SLC)13 proteins. Its transcripts could be observed in parenchyma cells surrounding the xylem of roots. The appearance time was estimated at c. 52.7 Ma.PvAsE1 was a previously uncharacterized SLC13‐like AsIII effluxer, which may contribute to AsIII long‐distance translocation via xylem loading. PvAsE1 appeared late in fern evolution and might be an adaptive subject to the selection pressure at the Cretaceaou–Paleogene boundary. The identification of PvAsE1 provides clues for revealing the special As hyperaccumulation characteristics of P. vittata. [ABSTRACT FROM AUTHOR]

The adaptive threshold reception scheme for OFDM pulse‐width modulation (OFDM‐PWM)‐based visible light communication systems is presented. The authors first implement the adaptive threshold algorithm to modify the discrete OFDM‐PWM sampling signal. Then, the unit periodic integral is employed for the modified time‐domain sampling sequence to accurately calculate the pulse width of each OFDM‐PWM sample. The proposed reception scheme is robust to the additive white Gaussian noise superimposed on the amplitude of the received OFDM‐PWM signals. The experimental results show that the proposed adaptive threshold reception scheme has a better BER performance compared with the traditional OFDM. [ABSTRACT FROM AUTHOR]

Summary Fusarium head blight (FHB) and the presence of mycotoxin deoxynivalenol (DON) pose serious threats to wheat production and food safety worldwide. DON, as a virulence factor, is crucial for the spread of FHB pathogens on plants. However, germplasm resources that are naturally resistant to DON and DON‐producing FHB pathogens are inadequate in plants. Here, detoxifying bacteria genes responsible for DON epimerization were used to enhance the resistance of wheat to mycotoxin DON and FHB pathogens. We characterized the complete pathway and molecular basis leading to the thorough detoxification of DON via epimerization through two sequential reactions in the detoxifying bacterium Devosia sp. D6‐9. Epimerization efficiently eliminates the phytotoxicity of DON and neutralizes the effects of DON as a virulence factor. Notably, co‐expressing of the genes encoding quinoprotein dehydrogenase (QDDH) for DON oxidation in the first reaction step, and aldo‐keto reductase AKR13B2 for 3‐keto‐DON reduction in the second reaction step significantly reduced the accumulation of DON as virulence factor in wheat after the infection of pathogenic Fusarium, and accordingly conferred increased disease resistance to FHB by restricting the spread of pathogenic Fusarium in the transgenic plants. Stable and improved resistance was observed in greenhouse and field conditions over multiple generations. This successful approach presents a promising avenue for enhancing FHB resistance in crops and reducing mycotoxin contents in grains through detoxification of the virulence factor DON by exogenous resistance genes from microbes. [ABSTRACT FROM AUTHOR]

Auditory verbal hallucinations (AVH) are distinctive clinical manifestations of schizophrenia. While low‐frequency repetitive transcranial magnetic stimulation (rTMS) has demonstrated potential in mitigating AVH, the precise mechanisms by which it operates remain obscure. This study aimed to investigate alternations in structural connectivity and functional connectivity (SC‐FC) coupling among schizophrenia patients with AVH prior to and following treatment with 1 Hz rTMS that specifically targets the left temporoparietal junction. Initially, patients exhibited significantly reduced macroscopic whole brain level SC‐FC coupling compared to healthy controls. Notably, SC‐FC coupling increased significantly across multiple networks, including the somatomotor, dorsal attention, ventral attention, frontoparietal control, and default mode networks, following rTMS treatment. Significant alternations in SC‐FC coupling were noted in critical nodes comprising the somatomotor network and the default mode network, such as the precentral gyrus and the ventromedial prefrontal cortex, respectively. The alternations in SC‐FC coupling exhibited a correlation with the amelioration of clinical symptom. The results of our study illuminate the intricate relationship between white matter structures and neuronal activity in patients who are receiving low‐frequency rTMS. This advances our understanding of the foundational mechanisms underlying rTMS treatment for AVH. [ABSTRACT FROM AUTHOR]

Lipid metabolism is elevated in cancer to satisfy increased energy demands.2 Considering APOC2's known function in FA transport and metabolism, its upregulation is a plausible mechanism for cancer adaptation and growth. APOC2, cancer, lipid metabolism Keywords: APOC2; cancer; lipid metabolism EN APOC2 cancer lipid metabolism 1 5 5 07/01/21 20210601 NES 210601 Abbreviations AML acute myeloid leukemia APOC2 apolipoprotein C2 FA fatty acid OS overall survival Dear Editor, Apolipoprotein C2 (APOC2), an activator of lipoprotein lipase, participates in hydrolysis of triglycerides, very low-density lipoproteins, and high-density lipoproteins to release free fatty acids (FA).1 FA oxidation has emerged as an important source of energy for cancer survival and growth.2 Patterns of I APOC2 i genomics and transcriptomic alterations in cancer remained unexplored. [Extracted from the article]

Aims: To explore large‐scale brain network alterations and examine their clinical and neuropsychological relevance in patients with anti‐N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis. Methods: Twenty‐four patients with anti‐NMDAR encephalitis and 26 matched healthy controls (HCs) were enrolled in our study. Based on the multimodal MRI dataset, individual morphological, structural, and functional brain networks were constructed and compared between the two groups at multiple levels. The associations with clinical/neuropsychological variables and the discriminant ability of significant alterations were further studied. Results: Multimodal network analysis revealed that anti‐NMDAR encephalitis mainly affected morphological and structural networks, but subtle alterations were observed in functional networks. Intriguingly, decreased network local efficiency was observed for both morphological and structural networks and increased nodal centrality in the lateral orbital gyrus was convergently observed among the three types of networks in the patients. Moreover, the alterations, particularly those from structural networks, accounted largely for cognitive deficits of the patients and could distinguish the diseased individuals from the HCs with excellent performance (area under the curve =0.933). Conclusions: The current study provides a comprehensive view of characteristic multimodal network dysfunction in anti‐NMDAR encephalitis, which is crucial to establish new diagnostic biomarkers and promising therapeutic targets for the disease. [ABSTRACT FROM AUTHOR]

Objective: Lumbar spondylolisthesis (LS) is a common lumbar disease, and the prevalence of LS in different countries or regions was not consistent in the past. This study intends to make statistics on the prevalence of lumbar spondylolisthesis in middle‐aged people in Beijing community. Methods: This is an epidemiological study. 4548 people in Beijing community aged 50 to 64 years were recruited from the local communities by advertisements placed in housing estates and community centres for people to take part in a prospective cohort study from August from September 2013 to March 2014. There is no intervention on the subjects. RadiAnt DICOM Viewer is adopted to read the lateral CT positioning images of all the studied objects, adjust the image as bone window, observe and evaluate the slide of L1 to L5 vertebra in the lateral CT positioning image. Results: Among the 4,548 subjects included in the study, 2,490 (54.75%) were male and 2,058 (45.25%) were female. A total of 785 subjects had lumbar spondylolisthesis, with a total incidence of 17.26%. There was no significant difference between prevalence of males and females in the subgroup 50‐54 years old (13.55% males / 12.53% females) and 55‐59 years old (14.77% males / 14.93% females). But the prevalence of LS in 60‐64 years old females (28.57%) increased significantly, compared with 55‐59 years old females (14.93%) and 60‐64 years old males (18.76%). There were 847 levels that had slipped, L5S1 > L4/5 > L3/4 > L2/3 > L1/2. The retrolisthesis was the most, accounting for 61.51% (521/847), and the anterolisthesis was 38.49% (326/847), including anterolisthesis gradeI for 95.71% (312/326), anterolisthesis gradeII for 4.29% (14/326). Neither of anterolisthesis and retrolisthesis presented more than grade III. Among all the subjects, 318 had anterolisthesis, with a total incidence of 6.99%, and 467 subjects only had retrolisthesis. Conclusion: The total prevalence of LS in the middle‐aged people in Beijing community was 17.26%, 15.98% in males and 18.80% in females, and women are more likely to suffer from LS after 60 years old. [ABSTRACT FROM AUTHOR]

The large‐scale application of Si‐based anodes is impeded by their fast capacity decay, which is mainly attributed to the huge volume expansion upon cycling. The employment of functional binders is one efficient method to mitigate this issue. In this work, a four‐armed polyacrylic acid (4A‐PAA) homopolymer is explored as a remarkably effective binder for Si‐based anodes. The 4A‐PAA binder is prepared via an atom transfer radical polymerization, followed by ester hydrolysis. Compared to the conventional linear polyacrylic acid (PAA) binder, the 4A‐PAA not only shows enhanced toughness due to its decreased molecular regularity and intramolecular hydrogen bond but also exhibits increased binding strength because of its multidimensional binding structure. As a result, the SiOx/graphite electrode using the 4A‐PAA retains a capacity retention of 89.1% and a capacity of 558.1 mAh g−1 after 200 cycles at 0.16 A g−1, which are superior to the PAA electrode, corresponding to 80.4% and 469.3 mAh g−1, respectively. The improved performance is attributed to the employment of the 4A‐PAA, which mitigates the volume change of the SiOx/graphite anode. This work not only offers a promising binder for Si‐based anodes but also presents a universal solution for other anodes with high volume expansion during cycling. [ABSTRACT FROM AUTHOR]

In the Southern Great Plains (SGP) of the United States, encroachment of the native invasive woody legume, honey mesquite (Prosopis glandulosa Torr.), has caused a decline in C4 mid‐grass abundance. Prosopis glandulosa invasion has also facilitated growth of the C3 mid‐grass species, Texas wintergrass (Nassella leucotricha [Trin & Rupr.] Pohl) initially beneath its canopy but extending to interspaces between P. glandulosa as stand density increases. Little is known about the stability of the Prosopis/Nassella association or C4 grass recovery following P. glandulosa disturbance.We quantified C3 and C4 grass production in interspaces, and basal cover in interspaces and P. glandulosa subcanopy microsites for 9 years following P. glandulosa suppression (top‐kill) and compared this to untreated P. glandulosa woodland (woodland).The Prosopis/Nassella association limited the window of C4 mid‐grass recovery to only a few years. Nassella leucotricha dominated grass production during the first 3 years after top‐kill. C4 mid‐grass recovery began in year 4, but was interrupted by severe drought in years 5 through 7. Recovery resumed in year 8, due to above‐average summer rainfall, but P. glandulosa regrowth was large enough by this time to limit C4 mid‐grass production to a third of its potential.Nassella leucotricha basal cover remained dominant and stable in woodland subcanopy microsites, even during drought, and only briefly declined in top‐kill subcanopy microsites before returning to pretreatment levels by year 8 as P. glandulosa regrowth increased and provided shade.Synthesis and applications. A single suppression event had little impact on disrupting the Prosopis/Nassella association and allowing C4 mid‐grass recovery. The coupling of a deciduous, N‐fixing C3 woody species with this C3 perennial grass may be a vegetative "state" that is resistant to multiple woody suppression disturbances and permanently limits the transition back to C4 grassland. [ABSTRACT FROM AUTHOR]

Background and Purpose: Skeletal muscle is the predominant site for glucose disposal and fatty acid consumption. Emerging evidence indicates that the crosstalk between adipose tissue and skeletal muscle is critical in maintaining insulin sensitivity and lipid homeostasis. The current study was designed to investigate whether myricanol improves insulin sensitivity and alleviates adiposity through modulating skeletal muscle-adipose tissue crosstalk.Experimental Approach: The therapeutic effect of myricanol was evaluated on palmitic acid (PA)-treated C2C12 myotubes and high-fat diet (HFD)-fed mice. The crosstalk between myotubes and adipocytes was evaluated using Transwell assay. The cellular lipid content was examined by Nile red staining. The mitochondrial content was assessed by MitoTracker Green staining and citrate synthase activity, and the mitochondrial function was examined by Seahorse assay. Expression of mitochondria-related and insulin signalling pathway proteins was analysed by Western blot, and the irisin level was determined by elisa kit.Key Results: Myricanol increased mitochondrial quantity and function through activating AMP-activated protein kinase, resulting in reduced lipid accumulation and enhanced insulin-stimulated glucose uptake, in PA-treated C2C12 myotubes. Furthermore, myricanol stimulated irisin production and secretion from myotubes to reduce lipid content in 3T3-L1 adipocytes. In HFD-fed mice, myricanol treatment alleviated adiposity and insulin resistance through enhancing lipid utilization and irisin production in skeletal muscle and inducing browning of inguinal fat.Conclusions and Implications: Myricanol modulates skeletal muscle-adipose tissue crosstalk, to stimulate browning of adipose tissue and improve insulin sensitivity in skeletal muscle. Myricanol might be a potential candidate for treating insulin resistance and obesity. [ABSTRACT FROM AUTHOR]

Introduction: The pathogenesis of non‐cystic fibrosis bronchiectasis has not been clearly clarified. This study aimed to investigate the expression of ciliary regulating protein forkhead box protein j1 (Foxj1) on airway epithelium in non‐cystic fibrosis bronchiectasis and its association with airway cilia structure disorder and disease severity. Methods: Lung tissue sections excised from 47 patients with non‐cystic fibrosis bronchiectasis were included between January 2018 and June 2021. Specimens from 26 subjects who underwent a lobectomy due to lung nodule were chosen as controls. Clinical information was collected, and pathologic analysis was performed to assess the epithelial structure and expression of ciliary regulating Foxj1. Results: Of the 47 patients with non‐cystic fibrosis bronchiectasis, 25 were considered as mild, 12 were moderate whereas the remaining 10 cases were severe according to the bronchiectasis severity index score evaluation. Epithelial hyperplasia, hyperplasia of goblet cells and inflammatory cell infiltration were observed in non‐cystic fibrosis bronchiectasis, compared with control subjects. Cilia length in non‐cystic fibrosis bronchiectasis patients were shorter than that in the control group, (5.34 ± 0.89) μm versus (7.34 ± 0.71) μm, respectively (P = 0.002). The expression of Foxj1 was (2.69 ± 1.09) × 106 in non‐cystic fibrosis bronchiectasis, compared with (6.67 ± 1.15) × 106 in the control group (P = 0.001). Moreover, patients with lower expression of Foxj1 showed shorter airway cilia and worse in disease severity. Conclusion: Foxj1 declined in the airway epithelium of patients with non‐cystic fibrosis bronchiectasis, positively correlated to cilia length and might imply worse disease severity. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a high-risk pathogenic toxin for hepatic diseases. Excessive mitophagy is a hallmark in Cd-induced hepatotoxicity. However, the underlying mechanism remains obscure. Mitochondrial calcium uniporter (MCU) is a key regulator for mitochondrial and cellular homeostasis. Here, Cd exposure upregulated MCU expression and increased mitochondrial Ca2+ uptake are found. MCU inhibition through siRNA or by Ru360 significantly attenuates Cd-induced excessive mitophagy, thereby rescues mitochondrial dysfunction and increases hepatocyte viability. Heterozygous MCU knockout mice exhibit improved liver function, ameliorated pathological damage, less mitochondrial fragmentation, and mitophagy after Cd exposure. Mechanistically, Cd upregulates MCU expression through phosphorylation activation of cAMP-response element binding protein at Ser133(CREBS133) and subsequent binding of MCU promoter at the TGAGGTCT, ACGTCA, and CTCCGTGATGTA regions, leading to increased MCU gene transcription. The upregulated MCU intensively interacts with voltage-dependent anion-selective channel protein 1 (VDAC1), enhances its dimerization and ubiquitination, resulting in excessive mitophagy. This study reveals a novel mechanism, through which Cd upregulates MCU to enhance mitophagy and hepatotoxicity. [ABSTRACT FROM AUTHOR]

Amplitude of low‐frequency fluctuation (ALFF) has been widely used for localization of abnormal activity at the single‐voxel level in resting‐state fMRI (RS‐fMRI) studies. However, previous ALFF studies were based on fast Fourier transform (FFT‐ALFF). Our recent study found that ALFF based on wavelet transform (Wavelet‐ALFF) showed better sensitivity and reproducibility than FFT‐ALFF. The current study aimed to test the reliability and validity of Wavelet‐ALFF, and apply Wavelet‐ALFF to investigate the modulation effect of repetitive transcranial magnetic stimulation (rTMS). The reliability and validity were assessed on multicenter RS‐fMRI datasets under eyes closed (EC) and eyes open (EO) conditions (248 healthy participants in total). We then detected the sensitivity of Wavelet‐ALFF using a rTMS modulation dataset (24 healthy participants). For each dataset, Wavelet‐ALFF based on five mother wavelets (i.e., db2, bior4.4, morl, meyr and sym3) and FFT‐ALFF were calculated in the conventional band and five frequency sub‐bands. The results showed that the reliability of both inter‐scanner and intra‐scanner was higher with Wavelet‐ALFF than with FFT‐ALFF across multiple frequency bands, especially db2‐ALFF in the higher frequency band slow‐2 (0.1992–0.25 Hz). In terms of validity, the multicenter ECEO datasets showed that the effect sizes of Wavelet‐ALFF with all mother wavelets (especially for db2‐ALFF) were larger than those of FFT‐ALFF across multiple frequency bands. Furthermore, Wavelet‐ALFF detected a larger modulation effect than FFT‐ALFF. Collectively, Wavelet db2‐ALFF showed the best reliability and validity, suggesting that db2‐ALFF may offer a powerful metric for inspecting regional spontaneous brain activities in future studies. [ABSTRACT FROM AUTHOR]

The problem of the underwater structure disease of the bridge is increasingly obvious, which has seriously affected the safe operation of the bridge structure, so it is necessary to detect the underwater structure regularly. There are many kinds of bridge underwater structure diseases. This paper targets the bridge underwater structural crack diseases adopts multiple image recognition networks for verification, compares the advantages of different networks, and takes the YOLO‐v4 network as the main body to build a lightweight convolutional neural network.Mobilenetv3 replaced CSPDarkent as the backbone feature extraction network, while the feature layer scale of Mobilenetv3 was modified, and the extracted preliminary feature layer was input into the enhanced feature extraction network for feature fusion. The PANet networks are replaced by the depthwise separable convolution. Using ablation experiments to compare the performance of four algorithm combinations in lightweight networks. At the same time, the disease identification accuracy of each network and the performance of the network are tested in various experimental environments, and the feasibility of the lightweight network is verified in the application of bridge underwater structure damage identification. [ABSTRACT FROM AUTHOR]

Aplastic anaemia, cytokine-induced memory-like NK cell, natural killer cells, single-cell RNA sequencing We didn't detect NCAM (CD56) in the dataset and used CD7/KLRD1/KLRF1/NGK7/GNLY as specific NK cell markers.[3] As expected, all these eight clusters expressed high levels of NK cell-specific markers (Figure 1B). Keywords: aplastic anaemia; cytokine-induced memory-like NK cell; natural killer cells; single-cell RNA sequencing EN aplastic anaemia cytokine-induced memory-like NK cell natural killer cells single-cell RNA sequencing 1 6 6 12/29/22 20221201 NES 221201 Dear Editor, In recently, we reported the important contribution of nature killer (NK) cells in the pathogenesis of severe aplastic anaemia (SAA). (B) LogFC bar graph of DEGs identified in NK cells by comparing HC-BM cells with HC-PB cells. [Extracted from the article]

Aims Sildenafil, a phosphodiesterase type 5 inhibitor, has been found to produce functional recovery in ischemic rats by increasing the c GMP level and triggering neurogenesis. The aim of this study was to investigate further sildenafil mechanisms. Methods Male Sprague- Dawley rats underwent middle cerebral artery occlusion and reperfusion, followed by intraperitoneal or intravenous treatment of sildenafil starting 2 h later. Behavioral tests were performed on day 1 or day 7 after reperfusion, while cerebral infarction, edema, Nissl staining, Fluoro- Jade B staining, and electron microscopy studies were carried out 24 h poststroke. The c GMP-dependent Nogo-66 receptor ( Nogo- R) pathway, synaptophysin, PSD-95/neuronal nitric oxide synthases (n NOS), brain-derived neurotrophic factor ( BDNF)/tropomyosin-related kinase B ( Trk B), and nerve growth factor ( NGF)/tropomyosin-related kinase A ( Trk A) were measured. Results Sildenafil enhanced neurological recovery and inhibited infarction, even following delayed administration 4 h after stroke onset. Furthermore, sildenafil reduced the loss of neurons and modulated the expressions of the c GMP-dependent Nogo- R pathway. Moreover, sildenafil protected the structure of synapses and mediated the expressions of synaptophysin, PSD-95/n NOS, BDNF/ Trk B, and NGF/ Trk A. Conclusions Sildenafil produces significant neuroprotective effects on injured neurons in acute stroke, and these are mediated by the c GMP-dependent Nogo- R pathway, NGF/ Trk A, and BDNF/ Trk B. [ABSTRACT FROM AUTHOR]

The no‐reference image quality assessment (NR‐IQA) method can evaluate the distortions in an image without the reference image. However, due to the diversity of the image contents and distortion types, it is hard for the existing NR‐IQA algorithms to obtain competitive performance on both synthetically and authentically distorted images. To address the problem, a multiscale feature representation‐based NR‐IQA method that performs well for both synthetic and authentic distortions is proposed. This model consists of two parts: The feature extraction part and the feature fusion part. First, part of the Res2Net‐50 network is chosen as the feature extraction part due to its high ability in increasing the range of receptive fields. Then, the feature fusion part consisting of a novel residual block and two fully connected layers is designed to fuse the extracted features and realize the quality score mapping. After a series of stepwise optimization experiments, the most competitive network architecture consisting of the feature extraction part and the feature fusion part is obtained. Comprehensive experiments on the LIVE, TID2013, CSIQ, KADID‐10k, KonIQ‐10K, and LIVE challenge databases demonstrate that the proposed method can work powerfully on both the synthetic and authentic distortions and also has a strong generalization ability. [ABSTRACT FROM AUTHOR]

Background: Improving oral anticancer agent (OAA) initiation and adherence is the important quality‐of‐care issues, particularly since one fourth of anticancer agents being developed will be administered orally. Our objective was to identify provider‐ and patient‐level characteristics associated with OAA initiation and adherence among individuals with metastatic renal cell carcinoma (mRCC). Methods: We used state cancer registry data linked to multi‐payer claims data to identify patients with mRCC diagnosed in 2004–2015. Provider data were obtained from North Carolina Health Professions Data System and the National Plan & Provider Enumeration System. We estimated risk ratios (RRs) and corresponding 95% confidence limits (CLs) using modified Poisson regression to evaluate factors associated with OAA initiation and adherence. Results: Among the 207 (out of 687) patients who initiated an OAA following mRCC diagnosis and survived 90 days, median proportion of days covered was 0.91. Patients with a modal provider specializing in hematology/medical oncology were much more likely to initiate OAAs than those seen by other specialties. Additionally, patients with a female provider were more likely to initiate OAAs than those with a male provider. Compared to patients treated by providers practicing in both urban and rural areas, patients with providers practicing solely in urban areas were more likely to initiate OAAs, after controlling for patient‐level factors (RR = 1.37; 95% CL: 1.09–1.73). Medicare patients were less likely to be adherent than those with private insurance (RR = 0.61; 95% CL: 0.42–0.87). Conclusions: Our results suggest that provider‐ and patient‐level factors influence OAA initiation in patients with mRCC but only insurance type was associated with adherence. [ABSTRACT FROM AUTHOR]

Aims: The blood‐brain barrier (BBB) is a specialized and indispensable structure in brain blood vessels that is damaged during Alzheimer's disease (AD). CD147 is expressed on the BBB and deeply engaged in the AD pathological process. In this study, we aimed to provide a better understanding of the roles of CD147 in BBB function in health and neurodegenerative disease. Methods and Results: We measured CD147 expression in mouse brains and demonstrated that CD147 is exclusively expressed in brain endothelial cells (BECs), and its expression decreases with age. After constructing endothelial‐specific CD147 knockout mice, we performed RNA‐sequencing on BECs isolated from mice of different ages as well as a range of database analyses. We found that endothelial CD147 is essential for the dual functions of the BBB, including barrier maintenance and transporter regulation. This study also shows that CD147 plays a pivotal role in neurodegenerative diseases, particularly in AD. Conclusions: Our findings suggested that targeting CD147 in BECs may represent a novel therapeutic strategy, which promoted the design of future experimental investigations and the mechanistic understanding of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Polar growth during appressorium formation is vital for the penetration peg formation in the rice blast fungus, Magnaporthe oryzae. Previous research has shown that the Sln1‐septin‐exocyst complex, localized at the base of the appressorium in contact with the leaf surface, forms a ring structure that influences growth polarity and affects penetration peg formation, and is necessary for pathogenicity. Our previous research showed CK2 proteins assemble another ring structure positioned perpendicular to the Sln1‐septin‐exocyst complex. Our research showed that the CK2 ring needs to become correctly assembled for penetration peg function and subsequent plant infection. In the present study, we found that the ring structures of CK2 are absent in the appressorium of ΔMoSep3 septin deletion mutants lacking the septin ring of the Sln1‐septin‐exocyst complex. Sln1 affects the septin proteins that recruit the exocyst complex that localizes as another ring at the appressorium's bottom. Destruction of the exocyst complex by mutation also causes incorrect localization of the CK2 ring structure. In conclusion, CK2 probably takes part in reestablishing the appressorium' spolarity growth necessary for penetration peg formation. We can also conclude that the correct localization and assembly of one or more CK2 ring structures in the appressorium depend on the initial assembly of the Sln1‐septin‐exocyst complex two rings at the base of the appressorium. [ABSTRACT FROM AUTHOR]

A bacterial artificial chromosome (BAC) library was constructed for Gossypium hirsutum acc. TM-1, a genetic and genomic standard line for Upland cotton. The library consists of 147 456 clones with an average insert size of 122.8 kb ranging from 97 to 240 kb. About 96.0% of the clones have inserts over 100 kb. Therefore, this library represents theoretically 7.4 haploid genome equivalents based on an AD genome size of 2 425 Mb. Clones were stored in 384 384− well plates and arrayed into multiplex pools for rapid and reliable library screening. BAC screening was carried out by four-round polymerase chain reactions using 23 simple sequence repeats (SSR) markers, three sequence-related amplified polymorphism markers and one pair of primers for a gene associated with fiber development to test the quality of the library. Correspondingly, in total 92 positive BAC clones were identified with an average four positive clones per SSR marker, ranging from one to eight hits. Additionally, since these SSR markers have been localized to chromosome 12 (A12) and 26 (D12) according to the genetic map, these BAC clones are expected to serve as seeds for the physical mapping of these two homologous chromosomes, sequentially map-based cloning of quantitative trait loci or genes associated with important agronomic traits. [ABSTRACT FROM AUTHOR]

A method for estimation of the maximum substrate utilization rate (qmax) using batch reactors with denitrification biofilm was introduced and compared with the traditional method of using batch reactors with suspended growth for qmax estimation. The values of qmax obtained from the suspended-growth reactors (0.69 to 0.71 g N/g volatile suspended solids [VSS] ⋅ d) and from the attached-biomass reactors (0.74 to 0.85 g N/g VSS ⋅ d) are similar and within the range of the values reported in the literature (0.23 to 2.88 g N/g VSS ⋅ d). Therefore, the intrinsic kinetic parameter, qmax, can be obtained using attached-growth batch reactors, if the effectiveness factor, η, is approximately equal to 1 and the bulk concentration of the rate-limiting substrate, C, is much higher than the half-velocity constant, Ks. The attached-growth batch reactor method is unique, because the biomass used in the batch tests is the same as that present in the parent reactor under investigation. [ABSTRACT FROM AUTHOR]

Introduction: Two separate antiangiogenic tyrosine kinase inhibitors (TKIs) and immunotherapy (IO) combinations are FDA‐approved as front‐line treatment for metastatic renal cell carcinoma (mRCC). Little is known about off‐protocol and post‐front‐line experience with combination TKI–IO approaches. Methods: We conducted a retrospective analysis of mRCC patients who received combination TKI–IO post‐first‐line therapy between November 2015 and January 2019 at MD Anderson Cancer Center and Duke Cancer Institute. Chart review detailed patient characteristics, treatments, toxicity, and survival. Independent radiologists, blinded to clinical data, assessed best radiographic response using RECIST v1.1. Results: We identified 48 mRCC patients for inclusion: median age 65 years, 75.0% clear cell histology, 68.8% IMDC intermediate risk, and median two prior systemic therapies. TKI–IO combinations included nivolumab–cabozantinib (N +C; 24 patients), nivolumab–pazopanib (N+P; 13), nivolumab–axitinib (6), nivolumab–lenvatinib (2), and nivolumab–ipilimumab–cabozantinib (3). The median progression‐free survival was 11.6 months and the median overall survival was not reached. Response data were available in 45 patients: complete response (CR; n = 3, 6.7%), partial response (PR; 20, 44.4%), stable disease (SD; 19, 42.2%), and progressive disease (3, 6.7%). Overall response rate was 51% and disease control rate (CR+PR+SD) was 93%. Only one patient had a grade ≥3 adverse event. Conclusion: To our knowledge, this is the first case series reporting off‐label use of combination TKI–IO for mRCC. TKI–IO combinations, particularly N+P and N+C, are well tolerated and efficacious. Although further prospective research is essential, slow disease progression on IO or TKI monotherapy may be safely controlled with addition of either TKI or IO. [ABSTRACT FROM AUTHOR]

Primary dysmenorrhea (PDM) is cyclic menstrual pain in the absence of pelvic anomalies, and it is thought to be a sex‐hormone related disorder. Existing study has focused on the effects of menstrual cramps on brain function and structure, ignoring the psychological changes associated with menstrual pain. Here we examined whether pain empathy in PDM differs from healthy controls (HC) using task‐based functional magnetic resonance imaging (fMRI). Fifty‐seven PDM women and 53 matched HC were recruited, and data were collected at the luteal and menstruation phases, respectively. During fMRI scans, participants viewed pictures displaying exposure to painful situations and pictures without any pain cues and assessed the level of pain experienced by the person in the picture. Regarding the main effect of the pain pictures, our results showed that compared to viewing neutral pictures, viewing pain pictures caused significantly higher activation in the anterior insula (AI), anterior cingulate cortex, and the left inferior parietal lobule; and only the right AI exhibited a significant interaction effect (group × picture). Post‐hoc analyses confirmed that, relative to neutral pictures, the right AI failed to be activated in PDM women viewing painsss pictures. Additionally, there was no significant interaction effect between the luteal and menstruation phases. It suggests that intermittent pain can lead to abnormal empathy in PDM women, which does not vary with the pain or pain‐free phase. Our study may deepen the understanding of the relationship between recurrent spontaneous pain and empathy in a clinical disorder characterized by cyclic episodes of pain. [ABSTRACT FROM AUTHOR]

Knowledge of the molecular‐level chemistry of brown carbon (BrC) is important in reducing the uncertainties in aerosol radiative forcing. Time‐resolved ambient PM2.5 samples were collected during a severe pollution episode in January 2017 over Xi'an, China for a comprehensive nontarget and full scanning of BrC molecules and their absorption properties using electrospray ionization Fourier transform–ion cyclotron resonance mass spectrometry combined with partial least squares regression analysis, which apportioned the overall ultraviolet absorption to individual molecules. The estimated absorption of CHNO and CHNOS molecules exhibited nighttime prevalence, whereas CHOS, CHNS, CHN, CHO, CHS, and CH molecules presented a dynamic trend. Carbon conjugation was positively correlated with estimated absorption by CHO and CHNO molecules, while exhibiting a mixed relationship with CHNOS. Higher nitrogen content was associated with enhanced light‐absorption properties of BrC molecules, while higher oxygen and sulfur content appeared to be associated with photobleaching during secondary transformation. Plain Language Summary: Individual molecular absorption has significant implications for ambient brown carbon analysis, but existing studies mostly focused on bulk absorption properties for the sample as a whole. A novel method is presented here to evaluate individual brown carbon absorption at the molecular level through high resolution mass spectrometry, and partial least squares regression analysis was applied to PM2.5 samples collected during a heavy pollution episode in Xi'an, China. Nitrogen‐containing compounds were found to be the strongest contributor to brown carbon absorption, especially during the nighttime, while processes involving oxidation and sulfur addition appeared to weaken the molecular absorption. This study bridges the gap between real atmospheric PM2.5 absorption and knowledge from controlled laboratory studies, which support these findings. Key Points: The molecular absorption of CHNOS and CHNO exhibited significant diurnal variationConjugation and elevated N content were associated with BrC photo‐enhancementOxidation and elevated S content appeared to be associated with light photobleaching of BrC molecules [ABSTRACT FROM AUTHOR]

Background: Bronchobiliary fistula is a rare, but life‐threatening complication after ablation of hepatocellular carcinoma. Few cases of bronchobiliary fistula have been reported and the treatment is controversial. Methods: From 2006 to 2019, a total of 11 patients were diagnosed with bronchobiliary fistula after ablation and received nonsurgical treatment. Results: All 11 patients presented with cough and bilioptysis. There were only two patients in which MRI revealed an obvious fistulous tract connecting the pleural effusion and biliary lesions. Pleural effusion, liver abscess and hepatic biloma were found in other patients. Three patients died of uncontrolled bronchobiliary fistula. Conclusions: Bronchobiliary fistula is a rare post‐ablation complication but should be taken into consideration in clinical decisions. Minimally invasive interventional treatment is a relatively effective means of dealing with bronchobiliary fistula, but as for the more severe cases, greater clinical experience is required. [ABSTRACT FROM AUTHOR]