Search

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]

In this brief, a filtering power divider (FPD) with independently controllable four transmission zeros (TZs) and low insertion loss is designed and analyzed by using quad‐mode ring‐loaded resonator (QMRLR). The equivalent circuit of the proposed FPD is given, and the resonant characteristics of the resonator are analyzed. Due to the horizontal transmission interference of QMRLR, two TZs are realized. In addition, two TZs and one transmission pole are achieved by stepped impedance lines, achieving high selectivity within the passbands. The insertion loss is less than 0.5 dB, which is better than other FPDs. For demonstration, a prototype with center frequencies at 1.45 and 2.75 GHz is fabricated and measured. The measured and simulated results are presented with good agreement. [ABSTRACT FROM AUTHOR]

Carbon monoxide (CO) as an endogenous gaseous signaling molecule, is widely studied for its ability to inhibit cancer cell proliferation as gas therapy. However, the therapeutic efficiency of CO gas therapy is far from ideal due to the low availability of CO supply. Here, inspired by the band structure and Fenton‐related elements, MIL‐101(Cr)@CoOx nanoparticles are introduced for the first time to achieve ultrasound‐mediated synergistic therapy by combining CO gas therapy and chemodynamic therapy together effectively. MIL‐101(Cr)@CoOx can present substantial CO2 adsorption capacity for the BDC2− linkers and Co center, and enable to transformation of endogenous CO2 to CO efficiently under ultrasound irradiation due to the appropriate band structure and conduction band position. With the Co‐engaged Fenton‐like reaction, MIL‐101(Cr)@CoOx triggered the reactions to catalyze the over‐expressed intracellular H2O2 into cytotoxic hydroxyl radicals (·OH). The potential therapeutic outcome of chemodynamic therapy can be amplified by the ultrasonic cavitation‐induced conversion between Co3+ and Co2+ in vitro is demonstrated. The proliferation, ATP, and mitochondria functions of 4T1 mouse breast cancer cells are severely compromised by CO‐promoted ROS generation and the sono‐Fenton effect. Further, in vivo studies confirm that MIL‐101(Cr)@CoOx combined with ultrasound irradiation exhibits superior tumor suppression, and achieves the ultrasound‐mediated chemodynamic‐gas cancer therapy with higher precisions for personalized treatments. This new system offers a distinct concept for constructing smart ultrasound‐stimulus systems to realize synergetic cancer therapy. [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]

Spontaneous droplet jumping on micro‐/nano‐structured superhydrophobic surfaces has been exploited as an efficient means for enhancing steam condensation heat transfer. However, the good performance of such surfaces quickly decays with raising the degree of subcooling, due to the mismatch between the characteristic length scales and droplet sizes when they grow up. Herein, a novel strategy for multiscale droplet regulation is proposed by combining sub‐millimeter fin structure with a hierarchical microporous superhydrophobic surface. A superior condensation heat transfer performance is attained on such hierarchical superhydrophobic finned tube (F‐SHB), in comparison to the baseline case of superhydrophobic non‐finned (SHB) tube under well‐controlled test conditions. Although the droplet jumping is not as vigorous as that on the SHB tube, the finned geometry of the F‐SHB tube leads to a condensation heat transfer enhancement even under high degrees of subcooling up to 36 K, because of the accelerated departure of large droplets by imposing Laplace force gradient in the presence of V‐shaped sub‐millimeter fins. This multiscale enhancement strategy is shown to enable a cascading regulation over the entire lifespan of condensate droplets. The fabrication of F‐SHB tubes is facile and easy to be scaled up, showing great potential in practical steam condensation applications. [ABSTRACT FROM AUTHOR]

Organic compounds that can respond to external stimuli and exhibit fluorescence changes have drawn increasing attention recently because of their potential applications in intelligent displays, optical data storage, anticounterfeiting, bioimaging, and sensors. Herein, we have synthesized two new organic compounds based on frameworks of anthracene and pyridine groups: 4‐(anthracen‐9‐yl) pyridine (AN9P) and 4‐(anthracen‐2‐yl) pyridine (AN2P). Both compounds, in solution and solid state, including polycrystals and single crystals, display reversible fluorescence transformations under alternate acid and base treatments. AN9P and AN2P solutions could be regulated to emit white‐light luminescence. The photoluminescence of the AN9P and AN2P polycrystals showed fast fluorescence changes with wide ranges (>300 nm) upon alternate acid and base stimuli and still exhibited remarkable fluorescence emission with almost no attenuation after 15 cycles of the reversible process. Both experimental and computational results suggested that the heteroatom nitrogen in the AN9P and AN2P molecules significantly influenced the intra‐ and intermolecular electronic interactions during the reversible protonation and deprotonation processes, resulting in changes in their frontier molecular orbitals and fluorescence emission characteristics. Our results provide a new facile approach to design molecular structures that realize highly dynamic photoluminescence changes in both liquid solution and solid crystal. [ABSTRACT FROM AUTHOR]

BACKGROUND: Phosphatidylcholine (PC) is considered to be the major dietary source for choline, which is associated with atherosclerosis progress. Thus, phosphatidylglucose (PG) was prepared by enzymatic modification of PC to investigate the effects on atherosclerosis in apolipoprotein E deficient (ApoE−/−) mice, as well as to investigate its dose–response relationship. RESULTS: The results showed that dietary PG significantly decreased the atherosclerotic lesion area in a dose‐dependent manner. Further studies found that intervention with a 0.8 g kg−1 and 2 g kg−1 PG diet for 4 months significantly decreased free cholesterol level and thus reduced total cholesterol levels in serum. The results of cholesterol distribution among lipoproteins showed that dietary PG significantly decreased low‐density lipoprotein levels in ApoE−/− mice. In addition, only administration of high‐dose PG significantly reduced total cholesterol levels in liver tissues by 31.2%. Furthermore, mice treated with high‐dose PG had an expanded bile acid pool and increased the ratio of conjugated bile acids to unconjugated bile acids in the liver, serum and gallbladder by increasing hepatic gene expression of primary and conjugated bile acid synthesis. Additionally, low‐dose and high‐dose PG significantly increased total fecal sterols by 20.8% and 11.9%, respectively, by increasing sitosterol and ethylcoprostanol levels. CONCLUSION: These results indicate that PG alleviated atherosclerosis in a dose‐dependent manner by increasing cholesterol alienation to bile acids and cholesterol efflux. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

As a promising candidate for next‐generation energy storage devices, Zn metal battery excels with their good safety, high specific capacity, and economic attractiveness. However, it still suffers from a narrow electrochemical window, notorious dendrite formation, and sluggish Zn ion transfer. Aqueous electrolyte engineering has been regarded as an effective way to improve these. It is shown that by adding sodium polystyrene sulfonate (PSS) polymers into a dilute 1 m Zn(OTf)2 aqueous electrolyte, compact water shells with stronger hydrogen bonding and more ordered structures are formed around the polymer chains. As a result, a fast transport channel to the zinc ions is provided. The PSS chains also protect the zinc electrode from directly contacting the water molecules and thus suppress water decomposition. With these merits, a Zn//Cu cell demonstrates a high coulombic efficiency of ≈99% after 1500 h cycling. Meanwhile, a record‐high cumulative Zn plating capacity of 10 000 mA h cm−2 is obtained using a Zn||Zn cell. In addition, the Zn//C@V2O5 full cell achieves almost 100% capacity retention after 1000 cycles. This work provides a new strategy for designing advanced electrolyte systems excelling in ion transport kinetics. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) induces electric fields that depolarise or hyperpolarise neurons. Intermittent theta burst stimulation (iTBS), a patterned form of TMS that is delivered at the theta frequency (~5 Hz), induces neuroplasticity in the hippocampus, a brain region that is implicated in memory and learning. One form of plasticity that is unique to the hippocampus is adult neurogenesis; however, little is known about whether TMS or iTBS in particular affects newborn neurons. Here, we therefore applied repeated sessions of iTBS to male and female mice and measured the extent of adult neurogenesis and the morphological features of immature neurons. We found that repeated sessions of iTBS did not significantly increase the amount of neurogenesis or affect the gross dendritic morphology of new neurons, and there were no sex differences in neurogenesis rates or aspects of afferent morphology. In contrast, efferent properties of newborn neurons varied as a function of sex and stimulation. Chronic iTBS increased the size of mossy fibre terminals, which synapse onto Cornu Ammonis 3 (CA3) pyramidal neurons, but only in males. iTBS also increased the number of terminal‐associated filopodia, putative synapses onto inhibitory interneurons but only in male mice. This efferent plasticity could result from a general trophic effect, or it could reflect accelerated maturation of immature neurons. Given the important role of mossy fibre synapses in hippocampal learning, our results identify a neurobiological effect of iTBS that might be associated with sex‐specific changes in cognition. [ABSTRACT FROM AUTHOR]

The analysis of glycoproteins and the comparison of protein N‐glycosylation from different eukaryotic origins require unbiased and robust analytical workflows. The structural and functional analysis of vertebrate protein N‐glycosylation currently depends extensively on bacterial peptide‐N4‐(N‐acetyl‐β‐glucosaminyl) asparagine amidases (PNGases), which are indispensable enzymatic tools in releasing asparagine‐linked oligosaccharides (N‐glycans) from glycoproteins. So far, only limited PNGase candidates are available for N‐glycans analysis, and particularly the analysis of plant and invertebrate N‐glycans is hampered by the lack of suitable PNGases. Furthermore, liquid chromatography–mass spectrometry (LC–MS) workflows, such as hydrogen deuterium exchange mass spectrometry (HDX‐MS), require a highly efficient enzymatic release of N‐glycans at low pH values to facilitate the comprehensive structural analysis of glycoproteins. Herein, we describe a previously unstudied superacidic bacterial N‐glycanase (PNGase H+) originating from the soil bacterium Rudaea cellulosilytica (Rc), which has significantly improved enzymatic properties compared to previously described PNGase H+ variants. Active and soluble recombinant PNGase Rc was expressed at a higher protein level (3.8‐fold) and with higher specific activity (~56% increase) compared to the currently used PNGase H+ variant from Dyella japonicum (Dj). Recombinant PNGase Rc was able to deglycosylate the glycoproteins horseradish peroxidase and bovine lactoferrin significantly faster than PNGase Dj (10 min vs. 6 h). The versatility of PNGase Rc was demonstrated by releasing N‐glycans from a diverse array of samples such as peach fruit, king trumpet mushroom, mouse serum, and the soil nematode Caenorhabditis elegans. The presence of only two disulfide bonds shown in the AlphaFold protein model (so far all other superacidic PNGases possess more disulfide bonds) could be corroborated by intact mass‐ and peptide mapping analysis and provides a possible explanation for the improved recombinant expression yield of PNGase Rc. [ABSTRACT FROM AUTHOR]

Photoelectrochemical (PEC) cytosensors, a combination of the PEC process and the living‐cell assay, have emerged as a powerful tool in the analytical and biological science. This mini review provides a brief introduction of this arena and summaries the key steps about the development of PEC cytosensors with representative examples, followed by future prospects based on our own opinions. [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]

Ammonia (NH3), an air pollutant in the living environment, has many toxic effects on various tissues and organs. However, the underlying mechanisms of NH3‐induced tracheal cell autophagy remains poorly understood. In present study, chickens and LMH cells were used as NH3 exposure models to investigate toxic effects. The change of tracheal tissues ultrastructure showed that NH3 exposure induced autolysosomes. The differential expression of 12 circularRNAs (circRNAs) was induced by NH3 exposure using circRNAs transcriptome analysis in broiler tracheas. We further found that circ‐IFNLR1 was down‐regulated, and miR‐2188‐5p was up‐regulated in tracheal tissues under NH3 exposure. Bioinformatics analysis and dual luciferase reporter system showed that circ‐IFNLR1 bound directly to miR‐2188‐5p and regulated each other, and miR‐2188‐5p regulated RNF182. Overexpression of miR‐2188‐5p caused autophagy and its inhibition partially reversed autophagy in LMH cells which were caused by ammonia stimulation or knockdown of circ‐IFNLR1. The expressions of three autophagy‐related genes (LC3, Beclin 1, and BNIP3) were observably up‐regulated. Our results indicated that NH3 exposure caused autophagy through circ‐IFNLR1/miR‐2188‐5p/RNF182. These results provided new insights for the study of ammonia on environmental toxicology on ceRNA and circRNAs in vivo and vitro. [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]

The electronic transport properties of a 2D normal metal superconductor are studied by a nonequilibrium Green's function method. The normal metal is the non‐inverted HgTe/CdTe quantum well doped by electrons. It is found that Andreev reflection (AR) is enhanced in the weak disorder regime while weakened in the strong disorder regime. However, the AR coefficient can be perfect (TA=1) with vanished fluctuations in the moderate disorder regime, whereas other scattering processes are forbidden. The mechanism goes that Anderson disorder leads to a topological Anderson insulator with bulk states localized while edge states still extensive. Multiple ARs and spin‐momentum locking cooperate to vanish the normal reflection and leave AR only. A detailed numerical study shows that fixing the Fermi surface in conduction band, a large enough junction width, and a strong coupling between the normal and superconducting leads are necessary for perfect AR. [ABSTRACT FROM AUTHOR]

Tumor‐induced immune suppression mediated by myeloid‐derived suppressor cells (MDSCs) and insufficient immunogenicity are two major factors for the poor overall response rate to the immune checkpoint blockade (ICB). Here, a tumor microenvironment responsive nanoprodrug (FIT nanoparticles) is presented for co‐delivering tadalafil (TAD) and indocyanine green (ICG) photosensitizer to simultaneously targeting intratumor MDSCs and amplifying tumor immunogenicity. The resulting nanoprodrug shows high drug loading (nearly 100%), tumor‐specific release, and robust therapeutic efficacy by virtue of promoting immunogenic cell death (ICD) induction and alleviation of MDSCs for augmenting the photothermal immunotherapy. In an in vivo colon tumor model, the released TAD in the tumor can effectively ameliorate MDSCs immunosuppressive activity, while the photosensitizer ICG is capable of inducing ICD to promote sufficient dendritic cells maturation and T cell infiltration. The results reported here may provide a superior candidate of adjuvants for strengthening immune response and ICB efficacy. [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]

Background: Inhibition of the programmed cell death protein 1 (PD-1) pathway has demonstrated clinical benefit in metastatic urothelial cancer (mUC); however, response rates of 15% to 26% highlight the need for more effective therapies. Bruton tyrosine kinase (BTK) inhibition may suppress myeloid-derived suppressor cells (MDSCs) and improve T-cell activation.Methods: The Randomized Phase 2 Trial of Acalabrutinib and Pembrolizumab Immunotherapy Dual Checkpoint Inhibition in Platinum-Resistant Metastatic Urothelial Carcinoma (RAPID CHECK; also known as ACE-ST-005) was a randomized phase 2 trial evaluating the PD-1 inhibitor pembrolizumab with or without the BTK inhibitor acalabrutinib for patients with platinum-refractory mUC. The primary objectives were safety and objective response rates (ORRs) according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Immune profiling was performed to analyze circulating monocytic MDSCs and T cells.Results: Seventy-five patients were treated with pembrolizumab (n = 35) or pembrolizumab plus acalabrutinib (n = 40). The ORR was 26% with pembrolizumab (9% with a complete response [CR]) and 20% with pembrolizumab plus acalabrutinib (10% with a CR). The grade 3/4 adverse events (AEs) that occurred in ≥15% of the patients were anemia (20%) with pembrolizumab and fatigue (23%), increased alanine aminotransferase (23%), urinary tract infections (18%), and anemia (18%) with pembrolizumab plus acalabrutinib. One patient treated with pembrolizumab plus acalabrutinib had high MDSCs at the baseline, which significantly decreased at week 7. Overall, MDSCs were not correlated with a clinical response, but some subsets of CD8+ T cells did increase during the combination treatment.Conclusions: Both treatments were generally well tolerated, although serious AE rates were higher with the combination. Acalabrutinib plus pembrolizumab did not improve the ORR, PFS, or OS in comparison with pembrolizumab alone in mUC. Baseline and on-treatment peripheral monocytic MDSCs were not different in the treatment cohorts. Proliferating CD8+ T-cell subsets increased during treatment, particularly in the combination cohort. Ongoing studies are correlating these peripheral immunome findings with tissue-based immune cell infiltration. [ABSTRACT FROM AUTHOR]

Summary: Cytomegalovirus (CMV) DNAemia and disease are common complications in patients undergoing allogeneic haematopoietic stem cell transplantation (allo‐HSCT). Few studies have compared the efficacy and safety of the HSCT donor and third‐party CMV‐specific cytotoxic T lymphocytes (CMV‐CTLs) in the treatment of CMV DNAemia and disease. In this study, we retrospectively compared the efficacy and safety of HSCT donor and third‐party CMV‐CTLs in patients with refractory CMV DNAemia or disease after allo‐HSCT at our centre from January 2017 to September 2021. Fifty‐three patients who received CMV‐CTL therapy were enrolled, including 40 in the donor group and 13 in the third‐party group, and they were adults aged 18 years or older. Within 6 weeks of treatment, 26 (65.0%) and 9 (69.2%) patients achieved complete response in the donor and third‐party groups (p = 1.000). The 2‐year overall survival was 59.6% (95% CI 46.1%–77.1%) and 53.8% (32.6%–89.1%) in the donor and third‐party groups (p = 0.860). Four (10.0%) patients in the donor group and two (15.4%) patients in the third‐party group developed acute graft‐versus‐host disease within 3 months after CMV‐CTL infusions. In conclusion, our data suggest that donor and third‐party CMV‐CTLs have comparable efficacy and safety for refractory CMV DNAemia and disease. [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]

Introduction: Severe aplastic anemia (SAA) is a disease characterized by severe pancytopenia and hematopoietic failure of bone marrow. Natural killer (NK) cells are a class of large granular lymphocytes that perform killing and immunomodulatory functions. Our previous study demonstrated that NK cells played the "protective" role in SAA, which is weakened. However, the mechanism remains unclear. Methods: Peripheral blood NK cells from SAA patients and normal controls were sorted and total proteins were extracted. Then, mass spectrometry was performed to screen differentially expressed proteins (DEPs). Results: Significant differences in the expression levels of 93 proteins were observed in NK cells of SAA patients compared with normal controls. Among them, 48 were upregulated proteins, including histone H1.2, histone H1.3, heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1), and interferon regulatory factor 1 (IRF‐1), and 45 were downregulated proteins, including actin‐related complex (ARP2/3), histone H3, histone H4, phosphoglycerate kinase 1 (PGK1), talin‐1. Gene Ontology (GO) function indicated that the DEPs most involved were vesicle‐mediated transport, innate immune response, and DNA binding. KEGG analysis showed 3 upregulated and 12 downregulated pathways, in which cell endocytosis and FC‐γ receptor‐mediated phagocytosis were most closely related to NK cell functions. Conclusion: Our study is the first analysis of proteomic profile in NK cells in SAA and found many DEPs involving in dysfunction of NK cells, which provides potential targets for deeper research of inadequate immunomodulation. [ABSTRACT FROM AUTHOR]

Cyclobutanone C−C activation with a Rh(I) catalyst has great potential for the synthesis of fused‐ and bridged‐ring systems. However, this synthetic application is greatly limited because of the direct CO extrusion from cyclobutanone, which leads to formation of cyclopropane as a byproduct. The calculations rationalize the experimental puzzles: why PMe2Ph and XPhos ligands can prevent cyclopropane formation for C2‐ and C3‐substituted cyclobutanone, respectively. More importantly, we enriched ligand computationally to exemplify how to develop new ligands. The small monodentate or bidentate phosphine ligand can favor [4+2] cycloaddition over cyclopropanation in the C2‐substituted cyclobutanone system. For the C3‐substituted cyclobutanone system, [4+2–1] cycloaddition is favored and cyclopropanation can be avoided when the large monodentate phosphine ligand is present. The different ligand requirements for C2‐ and C3‐substituted cyclobutanones are attributed to different mechanisms. [ABSTRACT FROM AUTHOR]

Intestinal barrier dysfunction is a major complication of total parenteral nutrition (TPN). Our preliminary study revealed that intestinal P‐glycoprotein (P‐gp) was significantly downregulated under TPN treatment followed by disruption of barrier function, and thus the significance of early downregulation of P‐gp needs to be addressed. Herein, we report a pivotal role of P‐gp in the development of intestinal barrier dysfunction under TPN. Functional suppression of P‐gp may facilitate bacterial attachment to intestinal epithelial cells (IECs) and thereby induce degradation of tight junctions to trigger barrier dysfunction. By using a rat model of TPN, we found early downregulation of P‐gp function in ileum after 3‐day TPN, followed by disruption of barrier function after 7‐day TPN. By using Escherichia coli (E. coli) k88 and DH5α as type strains, we found significantly increased bacterial attachment to IECs in TPN group compared to sham. By using Caco‐2 cells as an IEC model in vitro, we found that functional suppression of P‐gp remarkably facilitated bacterial attachment to Caco‐2 cells, leading to subsequent disruption of intestinal barrier function. Of note, Occludin was significantly downregulated by bacterial attachment when P‐gp was functionally suppressed. Mechanistically, changes on Occludin were attributed to enhanced protein degradation instead of suppressed protein translation. Despite the half‐life of Occludin protein being unchanged by DH5α treatment alone, it was decreased by about 40% when P‐gp was simultaneously suppressed. Taken together, our findings revealed that early downregulation of intestinal P‐gp under TPN may be a potential therapeutic target to prevent the development of barrier dysfunction. [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]

A silver‐catalyzed nitration/annulation of α‐alkynyl arylols is reported by using tert‐butyl nitrite (TBN) as a NO2 radical precursor, from which a set of 3‐nitrated benzofurans were synthesized with moderate to good yields. This transformation initiated by an in situ generated NO2 radical proceeds efficiently under mild and neutral redox conditions, which provides a new pathway toward the 3‐nitrobenzofuran framework via catalytic difunctionalization of internal alkynes. [ABSTRACT FROM AUTHOR]

Milk fat globule‐EGF factor 8 (MFGE8) has been reported to play various roles in acute injury and inflammation response. However, the role of MFGE8 in liver injury is poorly investigated. The present research was designed to clarify the expression and function of MFGE8 in carbon tetrachloride (CCl4)‐induced liver injury. Using serum cytokine arrays, we selected a promising cytokine MFGE8 as the candidate in the process of hepatitis‐fibrosis‐hepatocellular carcinoma (HCC) progression, based on the elevated expression in both hepatic fibrosis and HCC models. We validated the increased expression of MFGE8 in liver tissues and serum samples of acute and chronic CCl4‐induced mice. Immunohistochemistry staining of mouse liver tissues indicated that elevated MFGE8 expression was mainly derived from the injured hepatocytes. In addition, MFGE8 expression in the supernatant of primary hepatocytes was accumulated with prolongation of culture time, and CCl4 treatment further increased the expression of MFGE8. Moreover, a strong correlation between serum MFGE8 expression and liver transaminase activities suggested that MFGE8 may be a novel candidate in liver injury. Intriguingly, mice pretreated with MFGE8 were protected from CCl4‐induced liver injury through antiapoptosis role in the early stage and proproliferation role in the late stage. MFGE8 reduced apoptosis by inhibiting the activation of IRE1α/ASK1/JNK pathway and promoted proliferation by phosphorylation of ERK and AKT. Moreover, serum MFGE8 expression was increased in hepatitis patients while decreased in liver cirrhosis patients. All the results suggest MFGE8 as a novel marker and promising therapeutic agent of liver injury. [ABSTRACT FROM AUTHOR]

Electrostatic interactions between a silylated isothiourea intermediate and an ester π system were explored by determining how variations in sterics and electronics affect the selectivity of a silylation‐based kinetic resolution. Sterics on the π systems affect the selectivity factors of alkyl 2‐hydroxycyclohexanecarboxylates, resulting in a strong correlation of selectivity factors to Charton values. Induction effects of electron‐withdrawing substituents on phenyl esters significantly enhance selectivity supporting an edge to face π–π interaction. The linear free energy relationships that were uncovered will aid in future incorporation of intermolecular electrostatic interactions towards controlling asymmetric reactions. [ABSTRACT FROM AUTHOR]

A Cu‐catalyzed [4+1] annulation of N‐aryl‐1,2,3,4‐tetrahydroisoquinolines (N‐aryl THIQs) with α‐diazoketones has been established under oxidative conditions, leading to the construction of a series of indolo[2,1‐a]isoquinolines with generally good yields. The reaction enables dediazotized dicarbonylation of α‐diazoketones, creating direct C(sp3)/C(sp2)−H bond bifunctionalization to access tetracyclic aza‐heterocyclic skeletons. Oxidation: Cu‐catalyzed [4+1] annulation of N‐aryl‐1,2,3,4‐tetrahydroisoquinolines (N‐aryl THIQs) with α‐diazoketones has been established under oxidative conditions, leading to the construction of a series of indolo[2,1‐a]isoquinolines with generally good yields. [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]

To reveal the effects of PrPC on cells’ biological processes and on gene expression. We established stable DF‐1 (PrPC‐knockdown (KD)) cells, and combined with DF‐1 (wt) and DF‐1 (PrPC‐overexpression (OE)) cells that we previously established we studied the effects of chicken PrPC (PrPC) on DF‐1 cells’ processes. Then by using high throughput sequencing technology (HTS) and bioinformatics, we analyzed the differentially expressed genes (DEGs) between these cells. The results show that compared with DF‐1 (wt) and DF‐1 (PrPC‐scramble), DF‐1 (PrPC–KD) are significantly decreased in adhesion, proliferation, formation rate of colony and cells number of colony, scratch wound healing rate, cells number of invasion and migration, S phase cell populations, but the apoptosis rate and G1 phase cell populations are significantly increased. Conversely, all of these features in DF‐1 (PrPC‐OE) are opposite. In addition, compared with DF‐1 (wt), we found that there are totally 1055 DE genes between DF‐1 (PrPC–KD) and DF‐1 (PrPC‐OE) cells. After Go and pathway enrichment analysis, we know that these DEGs are significantly enriched in cell, cell part, cellular process, and metabolic pathway. In short, we found that PrPC can promote DF‐1 cells’ processes except apoptosis. Furthermore, PrPC involves in the focal adhesion, cancer, ribosome, metabolic pathways, and so forth, and the overexpression of PrPC can promote the pathway of amoebiasis, but its down‐regulation can promote the pathway of serotonergic synapse. However, the details are keeping unknown and that would be our next research. [ABSTRACT FROM AUTHOR]

Abstract: A new sulfinate salt‐mediated radical relay for the completion of C(sp3)−H bond indenylation of cyclic ethers with readily available 2‐alkynylbenzonitriles by combining silver/tert‐butyl peroxide (TBHP) was established, providing a wide range of 3‐alkylated 1‐indenones with generally good yields. Interestingly, the current reaction system can tolerate an S‐centered radical and a C‐centered radical in one pot, in which the S‐centered radical promotes the formation of the C‐centered radical to induce a radical cascade without disturbing the reaction process. A reaction mechanism is also proposed based on control experiments. [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]

Aim: Chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) levels are not free from significant hepatic lesions. Recently, there has been an improved understanding of the clinical significance of quantitative hepatitis B core antibody levels (qAnti‐HBc) during CHB management. In this cross‐sectional study, we evaluated the utility of qAnti‐HBc in identifying significant liver inflammation in CHB patients. Methods: A total of 469 patients (training set, n = 363; validation set, n = 106) who underwent liver biopsy (LB) were included. The qAnti‐HBc levels were quantified and the relationship between histology and serum markers was systematically analyzed. Results: In the training set, qAnti‐HBc levels were found to have significant diagnostic value for moderate to severe liver inflammation (≥G2) in all patients (area under the receiver operating characteristic curve [AUROC] = 0.768; 95% confidence interval [CI], 0.721–0.810; P < 0.001) and in patients with normal or near‐normal ALT levels (AUROC = 0.767; 95% CI, 0.697–0.828; P < 0.001). Our novel index (AC index) for the identification of ≥G2 inflammation, which combined the qAnti‐HBc and ALT levels, significantly improved diagnostic performance (AUROC = 0.813; 95% CI, 0.768–0.852) compared to the use of ALT alone (AUROC = 0.779; 95% CI, 0.732–0.821) in all patients. In the validation set, the AC index showed an improved AUROC of 0.890 (95% CI, 0.814–0.942) and 0.867 (95% CI, 0.749–0.943) in all patients and patients with normal ALT levels, respectively. Conclusions: The qAnti‐HBc level predicts significant liver inflammation well, even in patients with normal or near‐normal ALT levels. Compared with the conventional ALT level, the AC index is a more reliable non‐invasive biomarker for significant liver inflammation in CHB patients. [ABSTRACT FROM AUTHOR]

The report in this issue by Pomerantz and colleagues demonstrates that men with metastatic prostate cancer harboring germline BRCA2 mutations are strongly associated with a prostate‐specific antigen response ≥50% during treatment with a platinum agent. However, more work will be required to classify other men who might benefit from platinum agents. See also pages 3532‐9. [ABSTRACT FROM AUTHOR]

A replacement procedure to construct orthogonal arrays of strength three was proposed by Suen et al. [7]. This method was later extended by Suen and Dey [8]. In this paper, we further explore the replacement procedure to obtain some new families of orthogonal arrays of strength three. [ABSTRACT FROM AUTHOR]

Insect olfactory receptors (iORs) with atypical 7‐transmembrane domains, unlike Chordata olfactory receptors, are not in the GPCR protein family. iORs selectively bind to volatile ligands in the environment and affect essential insect behaviors. In this study, we constructed a new platform (iORbase, https://www.iorbase.com) for the structural and functional analysis of iORs based on a combined algorithm for gene annotation and protein structure prediction. Moreover, it provides the option to calculate the binding affinities and binding residues between iORs and pheromone molecules by virtual screening of docking. Furthermore, iORbase supports the automatic structural and functional prediction of user‐submitted iORs or pheromones. iORbase contains the well‐analyzed results of approximately 6 000 iORs and their 3D protein structures identified from 59 insect species and 2 077 insect pheromones from the literature, as well as approximately 12 million pairs of simulated interactions between functional iORs and pheromones. We also built 4 online modules, iORPDB, iInteraction, iModelTM, and iOdorTool to easily retrieve and visualize the 3D structures and interactions. iORbase can help greatly improve the experimental efficiency and success rate, identify new insecticide targets, or develop electronic nose technology. This study will shed light on the olfactory recognition mechanism and evolutionary characteristics from the perspectives of omics and macroevolution. [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]

Ganoderma lucidum has become a potential model system for evaluating how environmental factors regulate the secondary metabolism of basidiomycetes. Heat stress (HS) is one of the most important environmental factors. It was previously reported that HS could induce the biosynthesis of ganoderic acids (GA). In this study, we found that HS increased GA biosynthesis and also significantly increased cell membrane fluidity. Furthermore, our results showed that addition of the membrane rigidifier dimethylsulfoxide (DMSO) could revert the increased GA biosynthesis elicited by HS. These results indicate that an increase in membrane fluidity is associated with HS-induced GA biosynthesis. Further evidence showed that the GA content was decreased in D9des-silenced strains and could be reverted to WT levels by addition of the membrane fluidizer benzyl alcohol (BA). In contrast, GA content was increased in D9des-overexpression strains and could be reverted to WT levels by the addition of DMSO. Furthermore, both membrane fluidity and GA biosynthesis induced by HS could be reverted by DMSO in WT and D9des-silenced strains. To the best of our knowledge, this is the first report demonstrating that membrane fluidity is involved in the regulation of heat stress induced secondary metabolism in filamentous fungi. [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]

Plate cooling is a complex process so that it cannot be described by a fixed model. So, the mathematical model requires self-adaptive ability to comply with the various parameters such as gauges and temperatures of plates. Considering the effect of influence factors on cooling process, an online variable scale grid (VSG) model for cooling is developed. VSG model builds a multi-dimension space system where each dimension is determined by the effect of each factor on heat transfer. Every plate can find a corresponding point in the space, according to its own process conditions. To guarantee the higher precision of temperature control, it adopts dimensionless treatment for all the factors to avoid the errors caused by different physical units. In order to reduce the computational cost, the technologies of finite element meshing and centroid calculation have been applied. When a new plate comes, the correlations between the new one and historical samples, centroids are described by Euclidean distance. Finally, the target value is estimated through the distance-weighted average method. The results of experiments and applications with real industrial data show that the proposed VSG is effective in the plate cooling control and has a wide application prospect. [ABSTRACT FROM AUTHOR]

Interconduit pit membranes, which are permeable regions in the primary cell wall that connect to adjacent conduits, play a crucial role in water relations and the movement of nutrients between xylem conduits. However, how pit membrane characteristics might influence water‐carbon coupling remains poorly investigated in cycads. We examined pit characteristics, the anatomical and photosynthetic traits of 13 cycads from a common garden, to determine if pit traits and their coordination are related to water relations and carbon economy. We found that the pit traits of cycads were highly variable and that cycads exhibited a similar tradeoff between pit density and pit area as other plant lineages. Unlike other plant lineages (1) pit membranes, pit apertures, and pit shapes of cycads were not coordinated as in angiosperms; (2) cycads exhibited larger pit membrane areas but lower pit densities relative to ferns and angiosperms, but smaller and similar pit membrane densities to non‐cycad gymnosperms; (3) cycad pit membrane areas and densities were partially coordinated with anatomical traits, with hydraulic supply of the rachis positively coordinated with photosynthesis, whereas pit aperture areas and fractions were negatively coordinated with photosynthetic traits; (4) cycad pit traits reflected adaptation to wetter habitats for Cycadaceae and drier habitats for Zamiaceae. The large variation in pit traits, the unique pit membrane size and density, and the partial coordination of pit traits with anatomical and physiological traits of the rachis and pinna among cycads may have facilitated their dominance in a variety of ecosystems from the Mesozoic to modern times. [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]

The photophysical properties of a series of silole derivatives, with hydrogen (TPS), bromine (BrTPS), and conjugated phenyl (HPS), triphenylsilyethynyl (BTPES), and dimethylfluorene (BFTPS) substituents at 2,5-positions in both gas and aggregate phases have been investigated computationally by employing the correlation function rate formalism coupled with a hybrid quantum/molecular mechanics (QM/MM) approach. It is found that the solid-state fluorescence quantum efficiency first increases sharply with the degree of π-conjugation of the 2,5-substituents, then levels off, and finally starts to decrease slightly. This is because the side-group conjugation tends to enhance the radiative decay rate in both gas and solid phases. However, a further increase in conjugation leads to saturation in the radiative decay rate but increases the non-raditiave decay rate due to the decreased energy gap. [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]

Wheat plants are ubiquitously simultaneously exposed to salinity and limited iron availability caused by soil saline‐alkalisation. Through this study, we found that both low Fe and NaCl severely inhibited the growth of seminal roots in wheat seedlings; however, sufficient Fe caused greater growth cessation of seminal roots than low Fe under salt stress. Low Fe improved the root meristematic division activity, not altering the mature cell sizes compared with sufficient Fe under salt stress. Foliar Fe spray and split‐root experiments showed that low Fe‐alleviating the salinity‐induced growth cessation of seminal roots was dependent on local low Fe signals in the roots. Ionomics combined with TEM/X‐ray few differences in the root Na+ uptake and vacuolar Na+ sequestration between two Fe levels under salt stress. Phytohormone profiling and metabolomics revealed salinity‐induced overaccumulation of ACC/ethylene and tryptophan/auxin in the roots under sufficient Fe than under low Fe. Differential gene expression, pharmacological inhibitor addition and the root growth performance of transgenic wheat plants revealed that the rootward auxin efflux and was responsible for the low Fe‐mediated amelioration of the salinity‐induced growth cessation of seminal roots. Our findings will provide novel insights into the modulation of crop root growth under salt stress. Summary statement: We found that low Fe ameliorated the salinity‐induced growth cessation of wheat seminal roots, and our findings will provide novel insights into the understanding of Fe involved nutrient interactions and the modulation of crop root growth under salt stress. [ABSTRACT FROM AUTHOR]

A major challenge for further promotion of lipase productivity in Penicillium expansum PE-12 is to find a suitable promoter that can function efficiently in this industrial strain. In this study, the 5′ flanking region of P. expansum lipase ( Ppel) containing a putative novel promoter sequence was characterized by fusing to [ABSTRACT FROM AUTHOR]